Ginkgo biloba and Its Chemical Components in the Management of Alzheimer's Disease.

The pathogenesis of Alzheimer's disease (AD), a degenerative disease of the central nervous system, remains unclear. The main manifestations of AD include cognitive and behavioral disorders, neuropsychiatric symptoms, neuroinflammation, amyloid plaques, and neurofibrillary tangles. However, current drugs for AD once the dementia stage has been reached only treat symptoms and do not delay progression, and the research and development of targeted drugs for AD have reached a bottleneck. Thus, other treatment options are needed. Bioactive ingredients derived from plants are promising therapeutic agents. Specifically, Ginkgo biloba (Gb) extracts exert anti-oxidant, anticancer, neuroplastic, neurotransmitter-modulating, blood fluidity, and anti-inflammatory effects, offering alternative options in the treatment of cardiovascular, metabolic, and neurodegenerative diseases. The main chemical components of Gb include flavonoids, terpene lactones, proanthocyanidins, organic acids, polysaccharides, and amino acids. Gb and its extracts have shown remarkable therapeutic effects on various neurodegenerative diseases, including AD, with few adverse reactions. Thus, high-quality Gb extracts are a well-established treatment option for AD. In this review, we summarize the insights derived from traditional Chinese medicine, experimental models, and emerging clinical trials on the role of Gb and its chemical components in the treatment of the main clinical manifestations of AD.

Extending the Grading of Recommendations Assessment, Development and Evaluation (GRADE) in Traditional Chinese Medicine (TCM): The GRADE-TCM.

AIM: To extend and form the "Grading of Recommendations Assessment, Development and Evaluation in Traditional Chinese Medicine" (GRADE-TCM). METHODS: Methodologies were systematically reviewed and analyzed concerning evidence-based TCM guidelines worldwide. A survey questionnaire was developed based on the literature review and open-end expert interviews. Then, we performed expert consensus, discussion meeting, opinion collection, external examination, and the GRADE-TCM was formed eventually. RESULTS: 265 Chinese and English TCM guidelines were included and analyzed. Five experts completed the open-end interviews. Ten methodological entries were summarized, screened and selected. One round of consensus was conducted, including a total of 22 experts and 220 valid questionnaire entries, concerning 1) selection of the GRADE, 2) GRADE-TCM upgrading criteria, 3) GRADE-TCM evaluation standard, 4) principles of consensus and recommendation, and 5) presentation of the GRADE-TCM and recommendation. Finally, consensus was reached on the above 10 entries, and the results were of high importance (with voting percentages ranging from 50 % to 81.82 % for "very important" rating) and strong reliability (with the Cr ranging from 0.93 to 0.99). Expert discussion meeting (with 40 experts), opinion collection (in two online platforms) and external examination (with 14 third-party experts) were conducted, and the GRADE-TCM was established eventually. CONCLUSION: GRADE-TCM provides a new extended evidence-based evaluation standard for TCM guidelines. In GRADE-TCM, international evidence-based norms, characteristics of TCM intervention, and inheritance of TCM culture were combined organically and followed. This is helpful for localization of the GRADE in TCM and internationalization of TCM guidelines.

Fully connected-convolutional (FC-CNN) neural network based on hyperspectral images for rapid identification of P. ginseng growth years.

P. ginseng is a precious traditional Chinese functional food, which is used for both medicinal and food purposes, and has various effects such as immunomodulation, anti-tumor and anti-oxidation. The growth year of P. ginseng has an important impact on its medicinal and economic values. Fast and nondestructive identification of the growth year of P. ginseng is crucial for its quality evaluation. In this paper, we propose a FC-CNN network that incorporates spectral and spatial features of hyperspectral images to characterize P. ginseng from different growth years. The importance ranking of the spectra was obtained using the random forest method for optimal band selection. Based on the hyperspectral reflectance data of P. ginseng after radiometric calibration and the images of the best five VNIR bands and five SWIR bands selected, the year-by-year identification of P. ginseng age and its identification experiments for food and medicinal purposes were conducted, and the FC-CNN network and its FCNN and CNN branch networks were tested and compared in terms of their effectiveness in the identification of P. ginseng growth years. It has been experimentally verified that the best year-by-year recognition was achieved by utilizing images from five visible and near-infrared important bands and all spectral curves, and the recognition accuracy of food and medicinal use reached 100%. The FC-CNN network is significantly better than its branching model in the effect of edible and medicinal identification. The results show that for P. ginseng growth year identification, VNIR images have much more useful information than SWIR images. Meanwhile, the FC-CNN network utilizing the spectral and spatial features of hyperspectral images is an effective method for the identification of P. ginseng growth year.

UPLC-QTOF-MS based metabolomics unravels the modulatory effect of ginseng water extracts on rats with Qi-deficiency.

Ginseng is commonly used as a nutritional supplement and daily wellness product due to its ability to invigorate qi. As a result, individuals with Qi-deficiency often use ginseng as a health supplement. Ginsenosides and polysaccharides are the primary components of ginseng. However, the therapeutic effects and mechanisms of action of these components in Qi-deficiency remain unclear. This study aimed to determine the modulatory effects and mechanisms of ginseng water extract, ginsenosides, and ginseng polysaccharides in a rat model of Qi-deficiency using metabolomics and network analysis. The rat model of Qi-deficiency was established via swimming fatigue and a restricted diet. Oral administration of different ginseng water extracts for 30 days primarily alleviated oxidative stress and disrupted energy metabolism and immune response dysfunction caused by Qi-deficiency in rats. Ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used for untargeted serum metabolomic analysis. Based on the analysis results, the active constituents of ginseng significantly reversed the changes in serum biomarkers related to Qi-deficiency in rats, particularly energy, amino acid, and unsaturated fatty acid metabolism. Furthermore, analysis of the metabolite-gene network suggested that the anti-Qi-deficiency effects of the ginseng components were mainly associated with toll-like receptor (TLR) signaling and inflammatory response. Additional verification revealed that treatment with the ginseng components effectively reduced the inflammatory response and activation of the myocardial TLR4/NF-κB pathway induced by Qi-deficiency, especially the ginseng water extracts. Therefore, ginseng could be an effective preventive measure against the progression of Qi-deficiency by regulating metabolic and inflammatory responses.

In-depth investigation of the therapeutic effect of Tribulus terrestris L. on type 2 diabetes based on intestinal microbiota and feces metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Tribulus terrestris L. (TT) is extensively documented in the Tibetan medical literature 'Si Bu Yi Dian', has been used to treat diabetes mellitus for more than a thousand years. However, the underlying mechanisms and comprehensive effects of TT on diabetes have yet to be investigated. AIM OF THE STUDY: The aim of the study was to systemically elucidate the potential mechanisms of TT in treating diabetes mellitus, and further investigate the therapeutic effects of the water extract, small molecular components and saccharides from TT. MATERIALS AND METHODS: Fecal metabolomics was employed to draw the metabolic profile based on UHPLC-Q-TOF-MS/MS. The V3-V4 hypervariable regions of the bacteria 16S rRNA gene were amplified to explore the structural changes of the intestinal microbiome after TT intervention and to analyze the differential microbiota. The microbial metabolites SCFAs were determined by GC-MS, and the BAs and tryptophan metabolites were quantified by UPLC-TQ-MS. Spearman correlation analysis was carried out to comprehensively investigate the relationship among the endogenous metabolites profile, intestinal microbiota and their metabolites. RESULTS: TT exhibited remarkably therapeutic effect on T2DM rats, as evidenced by improved glucolipid metabolism and intestinal barrier integrity, ameliorated inflammation and remission in insulin resistance. A total of 24 endogenous biomarkers were screened through fecal metabolomics studies, which were mainly related to tryptophan metabolism, fatty acid metabolism, bile acid metabolism, steroid hormone biosynthesis and arachidonic acid metabolism. Investigations on microbiomics revealed that TT significantly modulated 18 differential bacterial genera and reversed the disordered gut microbial in diabetes rats. Moreover, TT notably altered the content of gut microbiota metabolites, both in serum and fecal samples. Significant correlation among microbial community, metabolites and T2DM-related indicators was revealed. CONCLUSIONS: The multiple components of TT regulate the metabolic homeostasis of the organism and the balance of intestinal microbiota and its metabolites, which might mediate the anti-diabetic capacity of TT.

[Mechanism of acteoside in prevention and treatment of gouty arthritis based on liver metabolomics].

This study aims to reveal the effect of acteoside on gouty arthritis(GA) in rats based on liver metabolomics. The ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to search for the potential biomarkers and metabolic pathways. SD rats were randomly assigned into blank, model, colchicine(0.3 mg·kg~(-1)), and high-, medium-, low-dose(200, 100, and 50 mg·kg~(-1), respectively) acteoside groups(n=7). The rats were administrated once a day for 7 continuous days. Monosodium urate(MSU) was used to induce GA model in rats during administration. The degree of joint swelling and pathological changes of synovial tissue in rats were observed, and the levels of interleukin(IL)-1ß, IL-18 and tumor necrosis factor(TNF)-α in the synovial tissue of rats were measured. UPLC-Q-TOF-MS was employed to collect rat liver data, and Progenesis QI and EZ info were used for data analysis. Human Metabolomics Database(HMDB) and Kyoto Encyclopedia of Genes and Genomes(KEGG) were employed to predict the potential biomarkers and metabolic pathways. The results showed that acteoside alleviated joint swelling, reduced synovial tissue damage, and lowered the levels of inflammatory cytokines in GA rats. A total of 19 common biomarkers were identified, 17 of which can be regulated by acteoside. Seven metabolic pathways were enriched, such as glycerophospholipid metabolism, linoleic acid metabolism, and taurine and hypotaurine metabolism, among which glycerophospholipid metabolism was strongly disturbed. The metabolomics analysis suggested that acteoside may down-regulate the expression of inflammatory cytokines and alleviate the symptoms of GA rats by regulating glycerophospholipid metabolism, linoleic acid metabolism, and taurine and hypotaurine metabolism. The findings provide a reference for future research and development of acteoside.

Beyond traditional therapies: a network meta-analysis on the treatment efficacy for chronic phantom limb pain.

BACKGROUND: Phantom limb pain (PLP) frequently affects individuals with limb amputations. When PLP evolves into its chronic phase, known as chronic PLP, traditional therapies often fall short in providing sufficient relief. The optimal intervention for chronic PLP remains unclear. OBJECTIVE: The objectives of this network meta-analysis (NMA) were to examine the efficacy of different treatments on pain intensity for patients with chronic PLP. EVIDENCE REVIEW: We searched Medline, EMBASE, Cochrane CENTRAL, Scopus, and CINAHL EBSCO, focusing on randomized controlled trials (RCTs) that evaluated interventions such as neuromodulation, neural block, pharmacological methods, and alternative treatments. An NMA was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary outcome was pain score improvement, and the secondary outcomes were adverse events. FINDINGS: The NMA, incorporating 12 RCTs, indicated that neuromodulation, specifically repetitive transcranial magnetic stimulation, provided the most substantial pain improvement when compared with placebo/sham groups (mean difference=-2.9 points, 95% CI=-4.62 to -1.18; quality of evidence (QoE): moderate). Pharmacological intervention using morphine was associated with a significant increase in adverse event rate (OR=6.04, 95% CI=2.26 to 16.12; QoE: low). CONCLUSIONS: The NMA suggests that neuromodulation using repetitive transcranial magnetic stimulation may be associated with significantly larger pain improvement for chronic PLP. However, the paucity of studies, varying patient characteristics across each trial, and absence of long-term results underscore the necessity for more comprehensive, large-scale RCTs. PROSPERO REGISTRATION NUMBER: CRD42023455949.

Integrated ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry-based components analysis and network pharmacology strategy of Gancao Xiexin Decoction in treating gastric ulcer.

Gancao Xiexin Decoction (GCXXD) is a traditional Chinese decoction that is often used in treating gastric ulcers. However, the substance basis and mechanism of action remain unclear. In this study, in vivo and in vitro components of GCXXD were analyzed by ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry. The compound Discover platform was used to ultimately enable rapid identification of compounds. Acquire X intelligent data acquisition technology software was innovatively adopted. In the process of collecting drug-containing plasma, all components detected in blank plasma samples were excluded to eliminate the interference and influence of endogenous components in plasma, making the analysis results more accurate and reliable. At the same time, the possibility of selecting precursor parent ions with low concentration levels within the chromatographic peak can be increased, improving the coverage and integrality of the detection of components in vivo. Also, the targeted network pharmacology strategy combined with molecular docking was established to explore the mechanism of GCXXD in treating gastric ulcers. As a result, 113 components were identified, 41 of which could enter the bloodstream and exert therapeutic effects in vivo. The main effective components are glycyrrhizic acid, 6-gingerol, jatrorrhizine, wogonin, palmatine, and liquiritigenin, main targets in vivo were related to ALB, IL6, and VEGF, which play an important role in anti-inflammatory and promoting angiogenesis. In summary, this study adopted a comprehensive analysis strategy to reveal the pharmacodynamic material basis and mechanism of GCXXD against gastric ulcers, providing a scientific basis for its clinical application.

[Effects of Polystyrene Microplastics Combined with Cadmium Contamination on Soil Physicochemical Properties and Physiological Ecology of Lactuca sativa].

Contaminants such as microplastics (MPs) and heavy metals are commonly found in soils, both of which are extremely difficult to degrade and can easily form compound contamination, altering the physicochemical properties of the soil and thus potentially changing the growth and physiological and ecological characteristics of plants. In order to study the effects of the combined contamination of soil MPs and heavy metals on soil properties and plant growth, polystyrene microplastics (PS-MPs) with a particle size of 3 µm and the heavy metal cadmium were selected in the study. The changes in the physicochemical properties of soil and their effects on lettuce (Lactuca sativa) seed germination and seedling growth were studied at various exposure concentrations of PS-MPs (0, 10, 50, 100, 200, and 400 mg·kg-1) and combined with different Cd contamination concentrations (0, 1.2, and 6.0 mg·kg-1), respectively. The results showed that soil organic matter (SOM), available phosphorus (AP), alkali-hydrolysable nitrogen (AHN), and available kalium (AK) showed significant decreases as the intensity of PS-MPs combined with Cd contamination increased. Simultaneously, PS-MPs combined with Cd contamination also significantly reduced the germination rate of lettuce seeds, but low concentrations of PS-MPs slowed down the effect of Cd (6.0 mg·kg-1) contamination on lettuce seeds, and high concentrations of PS-MPs enhanced the effect of Cd (6.0 mg·kg-1). The fresh weight, dry weight, and plant height of lettuce seedlings showed an increasing and then decreasing trend with increasing exposure to PS-MPs. Chlorophyll content, superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) showed a decreasing trend, whereas malondialdehyde (MDA) content showed an overall increasing trend under different Cd concentrations. The main physicochemical indicators of the soil were negatively correlated with MDA of lettuce seedlings, whereas other indicators of the seedlings were positively correlated. The combined contamination of PS-MPs and Cd could affect the germination of plant seeds and the physiological and ecological characteristics of seedlings by changing the physicochemical properties of the soil. Both exposure to single PS-MPs contaminants and the combination of PS-MPs with Cd inhibited the germination of lettuce seeds and affected the physiological activities of their seedlings, and the inhibition was significantly increased with increasing exposure. Low exposure to PS-MPs or the combination of PS-MPs with Cd contamination exhibited a promotive effect on lettuce seedling growth. High exposure to PS-MPs combined with Cd contamination exhibited significant ecological effects on lettuce seedlings, and high exposure to PS-MPs exacerbated the ecotoxicological effects of Cd contaminants on lettuce seedlings, and PS-MPs and Cd exhibited synergistic effects. The results can provide some reference for assessing the ecological effects of MPs and heavy metal pollution in soil-plant systems.

UPLC-Q-TOF/MS based serum and urine metabolomics strategy to analyze the mechanism of nervonic acid in treating Alzheimer's disease.

Nervonic acid is a natural component of breast milk and is frequently used as a food additive due to its excellent neuroprotective effects. Although it has been reported that nervonic acid may play a role in the recovery of human cognitive impairment, its specific mechanism of action is still unclear. In this study, the results of serum biochemical indexes showed that nervonic acid improved inflammation and reduced amyloid ß peptide (Aß) deposition and tau protein phosphorylation in Alzheimer's disease (AD) rats. Subsequently, we further used a metabolomics approach to investigate the potential mechanism of action of nervonic acid in the treatment of AD. The results of serum and urine metabolomics study showed that the intervention of nervonic acid significantly reversed the metabolic profile disorder in AD rats. A total of 52 metabolites were identified. They mainly involved linoleic acid metabolism, alpha-linolenic acid metabolism, phenylalanine metabolism and arachidonic acid metabolism, and all these metabolic pathways were associated with the emergence of inflammation in vivo. It suggests that the therapeutic effect of nervonic acid on AD is likely to be produced by ameliorating inflammation. The results obtained in this study provide new insights into the mechanism of nervonic acid treatment of AD and lay a foundation for the clinical application of nervonic acid in the treatment of Alzheimer's disease.

Analysis of the clinical characteristics in 18 patients with novel coronavirus pneumonia: Observational study.

The aim of the present study was to analyze the clinical features, treatments, and short-term prognoses of 18 patients with novel coronavirus pneumonia (NCP) in order to provide reference for further clinical prevention and control of the epidemic. From January 29 to February 29, 2020, data from 18 patients with NCP who were positive for the 2019 novel coronavirus nucleic acid test were collected, and their clinical manifestations, laboratory tests, imaging features, and treatment protocols were analyzed retrospectively. From among the 18 patients with NCP, 9 (50%) were imported cases and 9 (50%) had contact histories with confirmed adult patients. Clinical classification was mainly of the normal type (16 cases, 88.9%). Fever and cough were common clinical symptoms, and the main laboratory indices were lymphocytopenia and leukocytopenia. The main imaging findings yielded ground-glass opacity in 12 cases (66.7%) and patchy opacity in 9 cases (50%). All 18 patients were treated with antiviral therapy and targeted treatment in accordance with their symptoms, returned negative nucleic acid tests (9-23 days) after their treatment, and were cured and discharged by March 5, 2020. During the early stages in Deyang, most patients with NCP were input cases; in the later stages, the main route of infection was close contact within the family. Close contact history in epidemiology, nucleic acid detection, and chest imaging were important references for diagnosis. Antiviral therapy resulted in good therapeutic effects. Adopting multi-departmental consultation and remote consultation in combination with traditional Chinese medicine treatment and psychological counseling may result in a good short-term prognosis.

Effect of acupuncture on arthritic pathological injury in rats with type â ¡ collagen-induced rheumatoid arthritis. / é’ˆåˆºæ”¹å–„â ¡åž‹èƒ¶åŽŸè›‹ç™½è¯±å¯¼æ€§å ³èŠ‚ç‚Žå¤§é¼ ç‚Žæ€§ååº”çš„æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To observe the effect of acupuncture stimulation of "Yanglingquan"(GB34), "Zusanli"(ST36) and "Xuanzhong" (GB39) on arthritis index (AI), joint synovial membrane pathology, serum-related immunoinflammatory factors, and expressions of tumor suppressor gene mt-p53, nuclear factor kappa B (NF-κB) and peroxisome proliferator activated receptor gamma (PPARγ) in knee joint synovial tissue of rats with type Ⅱ collagen-induced arthritis (CIA), so as to explore its possible mechanisms underlying improvement of rheumatoid arthritis (RA). METHODS: Male SD rats were used in the present study. The CIA model was established by subcutaneous injection of collagen emulsion (200 µL/rat) in the tail root region on the first day and repeat (100 µL/rat) once on the 9th day. Eighteen successful CIA rats were randomized into model, medication and acupuncture groups, with 6 rats in each group. Other 6 normal rats were used as the normal control group. For rats of the medication group, leflunomide (1.9 mg/kg) was administrated by gavage, once a day, and for rats of the acupuncture group, manual acupuncture stimulation was applied to bilateral GB34, ST36, GB39 for 30 min, once a day, for 12 weeks. The arthritis index (AI) score (0-4 points) was evaluated once every week. The contents of IL-6, IL-17 and TNF-α in the serum were determined by ELISA. Histopathological changes of the ankle joint were observed by H.E. staining. The protein and mRNA expression levels of mt-p53, NF-κB p65, and PPARγ in the knee joint synovial tissue were determined by Western blot and quantitative real time PCR, separately. RESULTS: Compared with the normal control group, the AI scores at different time-points after modeling, contents of serum TNF-α, IL-6 and IL-17, expression levels of mt-p53, NF-κB p65, PPARγ proteins and mRNAs were significantly increased in the model group (P<0.01, P<0.05). In comparison with the model group, the AI scores at the 10th week in the medication group and at the 3rd, 9th and 10th week in the acupuncture group, contents of serum TNF-α, IL-6 and IL-17, and the expression levels of mt-p53 and NF-κB p65 proteins in both medication and acupuncture groups, as well as mt-p53 and NF-κB p65 mRNAs in the medication group were apparently decreased (P<0.01, P<0.05), while the expression levels of PPARγ protein in both medication and acupuncture group and PPARγ mRNA in the medication group were significantly up-regulated (P<0.05, P<0.01). No significant differences were found between the acupuncture and medication groups in down-regulating the AI score and serum TNF-α, IL-6 and IL-17 contents. The effect of acupuncture was weaker than that of medication in down-regulating the expression of mt-p53 and NF-κB p65 proteins and mRNAs and in up-regulating PPARγ mRNA (P<0.01). H.E. results showed ankle cartilage hyperplasia, reduced joint cavity, mild fibroproliferation and inflammatory cell infiltration in the surrounding soft tissue of the ankle joint in rats of the model group, which was milder in both medication and acupuncture groups. CONCLUSIONS: Acupuncture stimulation can improve the degree of joint inflammation and swelling in CIA rats, which may be related to its effects in inhibiting the overexpression of immunoinflammatory factors in serum and regulating expression of mt-p53, NF-κB p65, PPARγ mRNAs and proteins in the synovial tissue.

Phytochemical Constituents from the Seeds of Capsella bursa-pastoris and Their Antioxidant Activities.

Phytochemical investigation of 70% EtOH extract of the seeds of Capsella bursa-pastoris led to the isolation of a new cyclobutane organic acid (1), and fourteen known compounds, including two organosulfur compounds (2, 3), two quinonoids (4, 5), five flavonoids (6-10), three sterols (11-13) and two other types (14, 15). The structures of the compounds were elucidated by extensive spectroscopic analyses as well as comparison of their spectroscopic data with those reported in the literature. The antioxidant capacities of all compounds and extractive fractions were evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging test and ferric reducing antioxidant power (FRAP) assay. Then the antioxidative substances were evaluated for their neuroprotective effects against H2O2-induced HT22 cell injury. The results indicated the strong scavenging ability to free radical of the extractive fractions and compounds 1-3, 8-10 and 13, and the ferric reducing antioxidant power of the extractive fractions and compounds 1-3, 8 and 10, which were close to or higher than that of the positive control trolox. The EtOAc fraction, n-BuOH fraction, and compounds 1, 3 and 8 can protect HT-22 cells from oxidative damage.

Near-Infrared II Hemicyanine Dye with Large Stokes Shift Designed by TICT Regulation for Boosting Imaging-Guided Photothermal Therapy.

The serious threat that cancer poses to human health highlights the significance of early detection and effective treatment. The integration of fluorescence diagnosis and photothermal therapy in NIR-II has gained attention due to its high sensitivity, fast response, and noninvasiveness. Fluorescence, produced by the radiative relaxation process of electrons in a molecule, and photothermal, generated by the nonradiative relaxation process of electrons in a molecule, are competing photophysical processes. Hence, it is a challenge for the molecule to balance between the properties of fluorescence and photothermal. In this study, a NIR-II hemicyanine with TICT character is designed to obtain molecules with both better fluorescence and photothermal properties, utilizing positively charged pyridine salt and triphenylamine as electron acceptor and donor, respectively, and oxole as the conjugated π-bridge. HCY-995, one of the synthesized compounds, has a quantum yield of 0.09%, photothermal conversion efficiency of 54.90%, and a significant Stoke shift of 232 nm, which makes it appropriate for the integration of photothermal therapy and high-resolution imaging. This study provides new insights into the development of NIR-II molecules with fluorescent and photothermal integrated properties.

Heat-stone massage for patients with chronic musculoskeletal pain: a protocol for multicenter randomized controlled trial.

Introduction: Chronic musculoskeletal pain bothers the quality of life for approximately 1.71 billion people worldwide. Although pharmacological therapies play an important role in controlling chronic pain, overuse of opioids, persistent or recurrent symptoms, and pain-related disability burden still need to be addressed. Heat-stone massage is using the heated stone to stimulate muscles and ligaments followed by massage for relax, which can potentially treat the chronic musculoskeletal pain. To determine the efficacy and safety of heat-stone massage for patients with chronic musculoskeletal pain is needed. Methods and analysis: This multicenter, 2-arm, randomized, positive drug-controlled trial will include a total of 120 patients with chronic musculoskeletal pain. The intervention group will receive a 2 week heat-stone massage, 3 times per week, whereas the control group will receive the flurbiprofen plaster twice per day for 2 weeks. The primary end point is the change in Global Pain Scale from baseline to the end of the 2 week intervention. The secondary outcomes include the pain severity (Numerical Rating Scale), pain acceptance (Chronic Pain Acceptance Questionnaire), self-management (Health Education Impact Questionnaire), self-efficacy (Pain Self-Efficacy Questionnaire), anxiety and depression (Hospital Anxiety and Depression Scale), quality of life (Short Form-36). The intention-to-treat dataset will be used for analysis. Discussion: The pain management remains the research topic that patients always pay close attention to. This will be the first randomized clinical trial to evaluate whether heat-stone massage, a non-pharmacological therapy, is effective in the chronic musculoskeletal pain management. The results will provide evidence for new option of daily practice. Clinical trial registration: World Health Organization Chinese Clinical Trial Registry [ChiCTR2200065654; https://www.chictr.org.cn/showproj.html?proj=185403]; International Traditional Medicine Clinical Trial Registry [ITMCTR2022000104; http://itmctr.ccebtcm.org.cn/en-US/Home/ProjectView?pid=51776b6f-77b8-4811-9b5a-a0fec10f2cee].

An integrated approach based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, network pharmacology, and molecular docking to study the key effective compounds and mechanism of action of Platycodi Radix in the treatment of chronic obstructive pulmonary disease.

Platycodi Radix (PR) is a valuable herb that is widely used in the treatment of chronic obstructive pulmonary disease in clinics. However, the mechanism of action for the treatment of chronic obstructive pulmonary disease remains unclear due to the lack of in vivo studies. Our study established a novel integrated strategy based on ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry, network pharmacology, and molecular docking to systematically analyze the tissue distribution and active compounds of PR in vivo and the therapeutic mechanism of chronic obstructive pulmonary disease. First, tissue distribution studies have shown that the lung is the organ with the highest distribution of PR compounds. Subsequently, network pharmacology results showed that the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and mitogen-activated protein kinase signaling pathway were the critical mechanisms of PR against chronic obstructive pulmonary disease. Ultimately, molecular docking results showed that the key targets were stably bound to the corresponding active compounds of PR. Our study is of great significance for the screening of the key effective compounds and the study of the mechanism of action in traditional Chinese medicine and provides data to support the further development and utilization of PR.

The role of experiential avoidance in the early stages of an online mindfulness-based intervention: Two mediation studies.

Objectives There is evidence to suggest that only 2-4 weeks of mindfulness-based interventions (MBIs) can already alleviate emotional stress. The current studies sought to examine whether experiential avoidance mediated the effects of MBIs on emotional distress during an early stage of the intervention. Methods: Chinese participants with high emotional distress were recruited. Study 1 included 324 participants, randomly assigned to an online MBI (N = 171) or a control group (N = 153). Experiential avoidance and general emotional distress were measured at baseline and after the 3rd week of the intervention. Study 2 included 158 participants, randomly assigned to an online MBI (N = 79) or a control group (N = 79). Experiential avoidance and emotional distress were measured at baseline and weekly in the first three weeks. Results: Compared to the control group, experiential avoidance and emotional distress were significantly improved in the MBI group during the first three weeks of the intervention (Cohen's d = 0.22-0.63). Moreover, changes in experiential avoidance mediated the effects of MBI on emotional distress in the early stage in both contemporary and lagged mediation models. Discussion: Experiential avoidance is an important mediator during the early-stage of MBIs for alleviating emotional distress.

Therapeutic effect of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves on ischemic stroke via the microbiota-gut-brain axis.

Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves (ESL) are widely used to treat ischemic stroke (IS); however, the specific mechanism remains unclear. The microbiota-gut-brain axis plays a critical role in IS and has become a potential therapeutic target. This study aimed to reveal and verify the therapeutic effect of ESL on IS through the microbiota-gut-brain axis. Ultra-high-performance liquid chromatography coupled with mass spectrometry-based untargeted/targeted metabolomics combined with 16S rRNA microbiota sequencing strategy were used to investigate the regulatory effect of ESL on the metabolism and intestinal microenvironment after IS. Lactobacillus reuteri and Clostridium butyricum were used to treat rats with IS to verify that elevated levels of probiotics are key factors in the therapeutic effect of ESL. The results showed that IS significantly altered the accumulation of 41 biomarkers, while ESL restored their concentrations back to normal. Moreover, ESL alleviated the dysbiosis of gut microbiota brought on by IS, by reducing the abundance of pathogens and increasing the abundance of probiotics (e.g., Lactobacillus reuteri and Clostridium butyricum); this could reduce post-stroke injury, thereby having a certain protective effect on IS. This study reveals that ESL plays an important role in treating IS through the microbiota-gut-brain axis, maintaining metabolic homeostasis in vivo.

Enterolactone and trabectedin suppress epithelial ovarian cancer synergistically via upregulating THBS1.

Epithelial ovarian cancer (EOC) is the most common and fatal subtype of ovarian malignancies, with no effective therapeutics available. Our previous studies have demonstrated extraordinary suppressive efficacy of enterolactone (ENL) on EOC. A chemotherapeutic agent, trabectedin (Trabe), is shown to be effective on ovarian cancer, especially when combined with other therapeutics, such as pegylated liposomal doxorubicin or oxaliplatin. Thrombospondin 1 (THBS1), a kind of matrix glycoprotein, plays important roles against cancer development through inhibiting angiogenesis but whether it is involved in the suppression of EOC by ENL or Trabe remains unknown. To test combined suppressive effects of ENL and Trabe on EOC and possible involvement of THBS1 in the anticancer activities of ENL and Trabe. The EOC cell line ES-2 was transfected with overexpressed THBS1 by lentivirus vector. We employed tube formation assay to evaluate the anti-angiogenesis activity of ENL and of its combined use with Trabe after THBS1 overexpression and established drug intervention and xenograft nude mouse cancer models to assess the in vivo effects of the hypothesized synergistic suppression between the agents and the involvement of THBS1. Mouse fecal samples were collected for 16S rDNA sequencing and microbiota analysis. We detected strong inhibitory activities of ENL and Trabe against the proliferation and migration of cancer cells and observed synergistic effects between ENL and Trabe in suppressing EOC. ENL and Trabe, given either separately or in combination, could suppress the tube formation capability of human microvascular endothelial cells, and this inhibitory effect became even stronger with THBS1 overexpression. In the ENL plus Trabe combination group, the expression of tissue inhibitor of metalloproteinases 3 and cluster of differentiation 36 was both upregulated, whereas matrix metalloproteinase 9, vascular endothelial growth factor, and cluster of differentiation 47 were all decreased. With the overexpression of THBS1, the results became even more pronounced. In animal experiments, combined use of ENL and Trabe showed superior inhibitory effects to either single agent and significantly suppressed tumor growth, and the overexpression of THBS1 further enhanced the anti-cancer activities of the drug combination group. ENL and Trabe synergistically suppress EOC and THBS1 could remarkably facilitate the synergistic anticancer effects of ENL and Trabe.

Research progress on carbon materials in tumor photothermal therapy.

At present, cancer remains one of the leading causes of human death worldwide, and surgery, radiotherapy and chemotherapy are still the main methods of cancer treatment. However, these treatments have their drawbacks. Surgical treatment often struggles with the complete removal of tumor tissue, leading to a high risk of cancer recurrence. Additionally, chemotherapy drugs have a significant impact on overall health and can easily result in drug resistance. The high risk and mortality of cancer and other reasons promote scientific researchers to unremittingly develop and find a more accurate and faster diagnosis strategy and effective cancer treatment method. Photothermal therapy, which utilizes near-infrared light, offers deeper tissue penetration and minimal damage to surrounding healthy tissues. Compared to conventional radiotherapy and other treatment methods, photothermal therapy boasts several advantages, including high efficiency, non-invasiveness, simplicity, minimal toxicity, and fewer side effects. Photothermal nanomaterials can be categorized as either organic or inorganic materials. This review primarily focuses on the behavior of carbon materials as inorganic materials and their role in tumor photothermal treatment. Furthermore, the challenges faced by carbon materials in photothermal treatment are discussed.