Evaluation on the traditional safe use of Kochiae Fructus oriented by antioxidant properties and oral safety of its ethanolic extract.

Kochiae Fructus (KF) is a traditional Chinese medicine, which has been used to delay aging and treat inflammation, such as rubella, eczema, cutaneous pruritus, etc. In order to fully understand the traditional medicinal value of KF, we evaluated the antioxidant properties and oral safety of its ethanolic extract. Considering flavonoids and phenolics in medicinal plants generally have strong antioxidant activity, we firstly detected the total flavonoids and phenolics contents of KFEE and its fractions. Secondly, we evaluated the antioxidant activities of KFEE and its fractions. Finally, we evaluated the oral safety of KFEE by the acute and 28-day subacute toxicities. The n-butanol fraction (ENBF) possessed the highest phenolics and flavonoids with values of 77.30 ± 3.17 mg gallic acid equivalents/g and 228.81 ± 7.56 mg rutin equivalents/g, respectively. The results of antioxidant tests showed that ENBF possessed potent antioxidant ability. Among them, the high antioxidation capacity observed in ENBF could be attributed to its rich content of flavonoids and phenolics. The results of toxicological studies showed that the LD50 value of KFEE was 6000 mg/kg BW, and the no observed adverse effect level (NOAEL) of KFEE was 600 mg/kg BW. According to the standards of the American Academy of Sciences for the classification of toxic substances, KFEE can be classified as practically non-toxic substance, which provided valuable evidence for the oral safety of KF as a natural aging delay medicine.

HBB contributes to individualized aconitine-induced cardiotoxicity in mice via interfering with ABHD5/AMPK/HDAC4 axis.

The root of Aconitum carmichaelii Debx. (Fuzi) is an herbal medicine used in China that exerts significant efficacy in rescuing patients from severe diseases. A key toxic compound in Fuzi, aconitine (AC), could trigger unpredictable cardiotoxicities with high-individualization, thus hinders safe application of Fuzi. In this study we investigated the individual differences of AC-induced cardiotoxicities, the biomarkers and underlying mechanisms. Diversity Outbred (DO) mice were used as a genetically heterogeneous model for mimicking individualization clinically. The mice were orally administered AC (0.3, 0.6, 0.9 mg· kg-1 ·d-1) for 7 d. We found that AC-triggered cardiotoxicities in DO mice shared similar characteristics to those observed in clinic patients. Most importantly, significant individual differences were found in DO mice (variation coefficients: 34.08%-53.17%). RNA-sequencing in AC-tolerant and AC-sensitive mice revealed that hemoglobin subunit beta (HBB), a toxic-responsive protein in blood with 89% homology to human, was specifically enriched in AC-sensitive mice. Moreover, we found that HBB overexpression could significantly exacerbate AC-induced cardiotoxicity while HBB knockdown markedly attenuated cell death of cardiomyocytes. We revealed that AC could trigger hemolysis, and specifically bind to HBB in cell-free hemoglobin (cf-Hb), which could excessively promote NO scavenge and decrease cardioprotective S-nitrosylation. Meanwhile, AC bound to HBB enhanced the binding of HBB to ABHD5 and AMPK, which correspondingly decreased HDAC-NT generation and led to cardiomyocytes death. This study not only demonstrates HBB achievement a novel target of AC in blood, but provides the first clue for HBB as a novel biomarker in determining the individual differences of Fuzi-triggered cardiotoxicity.

Rotor-based image-guided therapy of glioblastoma.

Glioblastoma (GBM), deep in the brain, is more challenging to diagnose and treat than other tumors. Such challenges have blocked the development of high-impact therapeutic approaches that combine reliable diagnosis with targeted therapy. Herein, effective cyanine dyes (IRLy) with the near-infrared two region (NIR-II) adsorption and aggregation-induced emission (AIE) have been developed via an "extended conjugation & molecular rotor" strategy for multimodal imaging and phototherapy of deep orthotopic GBM. IRLy was synthesized successfully through a rational molecular rotor modification with stronger penetration, higher signal-to-noise ratio, and a high photothermal conversion efficiency (PCE) up to ∼60%, which can achieve efficient NIR-II photo-response. The multifunctional nanoparticles (Tf-IRLy NPs) were further fabricated to cross the blood-brain barrier (BBB) introducing transferrin (Tf) as a targeting ligand. Tf-IRLy NPs showed high biosafety and good tumor enrichment for GBM in vitro and in vivo, and thus enabled accurate, efficient, and less invasive NIR-II multimodal imaging and photothermal therapy. This versatile Tf-IRLy nanosystem can provide a reference for the efficient, precise and low-invasive multi-synergistic brain targeted photo-theranostics. In addition, the "extended conjugation & molecular rotor" strategy can be used to guide the design of other photothermal agents.

Discovery and Development of Luvangetin from Zanthoxylum avicennae as a New Fungicide Candidate for Fusarium verticillioides.

Pathogenic fungi pose a significant threat to crop yields and human healthy, and the subsequent fungicide resistance has greatly aggravated these agricultural and medical challenges. Hence, the development of new fungicides with higher efficiency and greater environmental friendliness is urgently required. In this study, luvangetin, isolated and identified from the root of Zanthoxylum avicennae, exhibited wide-spectrum antifungal activity in vivo and in vitro. Integrated omics and in vitro and in vivo transcriptional analyses revealed that luvangetin inhibited GAL4-like Zn(II)2Cys6 transcriptional factor-mediated transcription, particularly the FvFUM21-mediated FUM cluster gene expression, and decreased the biosynthesis of fumonisins inFusarium verticillioides. Moreover, luvangetin binds to the double-stranded DNA helix in vitro in the groove mode. We isolated and identified luvangetin, a natural metabolite from a traditional Chinese edible medicinal plant and uncovered its multipathogen resistance mechanism. This study is the first to reveal the mechanism underlying the antifungal activity of luvangetin and provides a promising direction for the future use of plant-derived natural products to prevent and control plant and animal pathogenic fungi.

Qingkailing granule alleviates pulmonary fibrosis by inhibiting PI3K/AKT and SRC/STAT3 signaling pathways.

Pulmonary fibrosis (PF) poses a significant challenge with limited treatment options and a high mortality rate of approximately 45 %. Qingkailing Granule (QKL), derived from the Angong Niuhuang Pill, shows promise in addressing pulmonary conditions. Using a comprehensive approach, combining network pharmacology analysis with experimental validation, this study explores the therapeutic effects and mechanisms of QKL against PF for the first time. In vivo, QKL reduced collagen deposition and suppressed proinflammatory cytokines in a bleomycin-induced PF mouse model. In vitro studies demonstrated QKL's efficacy in protecting cells from bleomycin-induced injury and reducing collagen accumulation and cell migration in TGF-ß1-induced pulmonary fibrosis cell models. Network pharmacology analysis revealed potential mechanisms, confirmed by western blotting, involving the modulation of PI3K/AKT and SRC/STAT3 signaling pathways. Molecular docking simulations highlighted interactions between QKL's active compounds and key proteins, showing inhibitory effects on epithelial damage and fibrosis. Collectively, these findings underscore the therapeutic potential of QKL in alleviating pulmonary inflammation and fibrosis through the downregulation of PI3K/AKT and SRC/STAT3 signaling pathways, with a pivotal role attributed to its active compounds.

Glycyrrhizic acid treatment ameliorates anxiety-like behaviour via GLT1 and Per1/2-dependent pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicinal herb, Glycyrrhiza. URALENSIS: Fisch. (licorice root, chinese name: Gancao) has a variety of medicinal values and is widely used clinically. Its main active ingredient, glycyrrhizic acid (GA), is believed to have a neuroprotective effect. However, the underlying biological mechanisms of GA on stress-induced anxiety disorders are still unclear. AIM OF THE STUDY: To investigate the anti-anxiety effect of GA and its underlying mechanism. METHODS: We selected the anxiety model induced by repeated chronic restraint stress (CRS) for 2 h on each of 7 consecutive days. GA (4, 20, 100 mg/kg) was injected intraperitoneally once daily for 1 week. The potential GA receptors were identified using whole-cell patches and computer-assisted docking of molecules. High-throughput RNA sequencing, adeno-associated virus-mediated gene regulation, Western blotting, and RT-qPCR were used to assess the underlying molecular pathways. RESULTS: GA alleviate depression-like and anxiety-like behaviors in CRS mice. GA decreased synaptic transmission by facilitating glutamate reuptaking in mPFC. Meanwhile, long-term GA treatment increased the expression of clock genes Per1 and Per2. Suppressing both Per1 and Per2 abolished the anxiolytic effects of GA treatment. CONCLUSION: Our study suggests that GA may be developed for the treatment of stress-induced anxiety disorders, and its mechanism is related to GLT1 and Per1/2-dependent pathways. This presents a novel approach to discovering potent therapeutic drugs.

The Impact of Early Psychological Intervention Under Hospital-led HIV/AIDS Case Management on Patients' Well-being.

Objective: To explore the influence of early psychological intervention on AIDS patients receiving hospital-led case management. Methods: Between December 2022 and May 2023, 100 cases of AIDS patients were gathered at the Fifth Hospital of Shijiazhuang. They were randomly assigned to either a psychological intervention group or a conventional intervention group. Each group consists of 50 individuals affected by AIDS. The conventional intervention group received care through traditional care models. In contrast, the psychological intervention group received immediate psychological support upon being screened positive for HIV antibodies, in addition to the conventional intervention group. The intervention period for both groups lasted 3 months, during which medication adherence, adverse emotional conditions, self-management skills, and quality of life were compared. Results: During the intervention period, the psychological intervention group exhibited higher medication adherence than the conventional intervention group. Post-intervention, the levels of anxiety as assessed by the SAS and the degree of depression as evaluated by the SDS of the conventional intervention group were higher than those of the psychological intervention group. Additionally, the psychological intervention group demonstrated higher scores in 7 dimensions the total score on the self-management ability scale, and a higher score in the WHOQOL-HIV-BREF compared to the conventional intervention group. Conclusion: In the context of hospital-led case management for AIDS, early psychological intervention in patients has been shown to enhance medication adherence, reduce negative emotions, improve self-management skills, and enhance overall quality of life.

Elucidating the distinctive regulatory effects and mechanisms of active compounds in Salvia miltiorrhiza Bunge via network pharmacology: Unveiling their roles in the modulation of platelet activation and thrombus formation.

Salvia miltiorrhiza Bunge. (DS), as an important traditional Chinese medicine (TCM), has a long history of usage for promoting blood circulation and removing blood stasis. Modern studies have shown that the chemical components of DS have many biological activities such as cardiovascular protection, anti-arrhythmia, anti-atherosclerosis, improvement of microcirculation, protection of myocardium, inhibition and removal of platelet aggregation. Nevertheless, the action mechanism of DS as well its active compounds on platelet activation has not been fully uncovered. This study aimed to find out the potential targets and mechanisms of DS in the modulation of platelet activation and thrombosis, using network pharmacology and biological experimental. These compounds with anti-thrombotic activity in DS, cryptotanshinone (CPT), isoeugenol (ISO) and tanshinone IIA (TSA), together with the corresponding targets being Src, Akt and RhoA are screened by network pharmacology. We confirmed that ISO, CPT and TSA dose-dependently inhibited platelet activation in vitro, mainly by inhibiting agonist-induced clot retraction, aggregation and P-selectin and ATP release. The western blot findings indicated that ISO, CPT, and TSA led to reduced levels of p-Akt and p-ERK in activated platelets. Additionally, ISO and TSA were observed to decrease p-cSrc expression while increasing RhoA expression. ISO, CPT, and TSA demonstrated a potential to restrict the advancement of carotid arterial thrombosis in vivo. We confirm that ISO, CPT and TSA are the key anti-thrombotic active compounds in DS. These active compounds exhibit unique inhibitory effects on platelet activation and thrombus formation by modulating the Akt/ERK and cSrc/RhoA signaling pathways.

Ganoderma lucidum spore oil synergistically enhances the function of cyclophosphamide in the prevention of breast cancer metastasis.

BACKGROUND: Ganoderma lucidum ( G . lucidum ) is a traditional Chinese herbal medicine that has shown potential as an alternative adjuvant therapy for cancer patients. However, the mechanisms and adjuvant therapeutic effects of G . lucidum in cancer treatment remain unclear. METHODS: In this work, G . lucidum spore oil (GanoOil), a newly developed oily G . lucidum spore extract was used to investigate the mechanisms and adjuvant therapeutic effects of GanoOil in conjunction with the chemotherapeutic drug cyclophosphamide (CTX) for preventing breast cancer metastasis. RESULTS: In the model of lung metastasis, orally administered GanoOil increased the population of CD8 + T cells and interleukin (IL)-6 cytokine levels in mouse blood, whereas also enhancing the activity of natural killer cells in the spleen. Furthermore, the combination of GanoOil and CTX effectively suppressed the lung metastasis of circulating breast cancer cells, alleviated CTX-induced weight loss, and reduced the ratio of lung and spleen weight to body weight in mice. Moreover, high concentrations of GanoOil exhibited no significant toxicity or side effects in both in vitro and in vivo experiments. CONCLUSION: In conclusion, GanoOil is a safe drug that can enhance immune activity in mice to achieve therapeutic effects on cancer, and can also synergistically inhibit tumor metastasis with CTX.

GraphGPT: A Graph Enhanced Generative Pretrained Transformer for Conditioned Molecular Generation.

Condition-based molecular generation can generate a large number of molecules with particular properties, expanding the virtual drug screening library, and accelerating the process of drug discovery. In this study, we combined a molecular graph structure and sequential representations using a generative pretrained transformer (GPT) architecture for generating molecules conditionally. The incorporation of graph structure information facilitated a better comprehension of molecular topological features, and the augmentation of a sequential contextual understanding of GPT architecture facilitated molecular generation. The experiments indicate that our model efficiently produces molecules with the desired properties, with valid and unique metrics that are close to 100%. Faced with the typical task of generating molecules based on a scaffold in drug discovery, our model is able to preserve scaffold information and generate molecules with low similarity and specified properties.

Terpenoid Glucosides from Gentiana macrophylla That Attenuate TNF-α Induced Pulmonary Inflammation in A549 Cells.

Four previously undescribed terpenoid glucosides, including one sesquiterpenoid di-glucoside (1), two new iridoid glucosides (2, 3), and a new triterpenoid tri-glucoside (4), were isolated from a 70% ethanol extract of the root of Gentiana macrophylla (Gentianaceae), along with eight known terpenoids. Their structures were determined by spectroscopic techniques, including 1D, 2D NMR, and HRMS (ESI), as well as chemical methods. The absolute configuration of compound 1 was determined by quantum chemical calculation of its theoretical electronic circular dichroism (ECD) spectrum. The sugar moieties of all the new compounds were confirmed to be D-glucose by GC analysis after acid hydrolysis and acetylation. Anti-pulmonary inflammation activity of the iridoids were evaluated on a TNF-α induced inflammation model in A549 cells. Compound 2 could significantly alleviate the release of proinflammatory cytokines IL-1ß and IL-8 and increase the expression of anti-inflammatory cytokine IL-10.

Phytochemicals for the treatment of metabolic diseases: Evidence from clinical studies.

With the continuous improvement of people's living standard, the incidence of metabolic diseases is gradually increasing in recent years. There is growing interest in finding drugs to treat metabolic diseases from natural compounds due to their good efficacy and limited side effects. Over the past few decades, many phytochemicals derived from natural plants, such as berberine, curcumin, quercetin, resveratrol, rutin, and hesperidin, have been shown to have good pharmacological activity against metabolic diseases in preclinical studies. More importantly, clinical trials using these phytochemicals to treat metabolic diseases have been increasing. This review comprehensively summarizes the clinical progress of phytochemicals derived from natural plants in the treatment of several metabolic diseases, including type 2 diabetes mellitus (T2DM), obesity and non-alcoholic fatty liver disease (NAFLD). Accumulating clinical evidence shows that a total of 18 phytochemicals have good therapeutic effects on the three metabolic diseases by lowering blood glucose and lipid levels, reducing insulin resistance, enhancing insulin sensitivity, increasing energy expenditure, improving liver function, and relieving inflammation and oxidative stress. The information will help us better understand the medicinal value of these phytochemicals and promote their clinical application in the treatment of metabolic diseases.

Electroacupuncture alleviates PTSD-like behaviors by modulating hippocampal synaptic plasticity via Wnt/ß-catenin signaling pathway.

Abnormalities in hippocampal synaptic plasticity contribute to the pathogenesis of post-traumatic stress disorder (PTSD). The Wnt/ß-catenin signaling pathway is critical for the regulation of synaptic plasticity. PTSD symptoms can be alleviated by correcting impaired neural plasticity in the hippocampus (Hipp). Electroacupuncture (EA) has a therapeutic effect by relieving PTSD-like behaviors. However, little is known about whether the Wnt/ß-catenin pathway is involved in EA-mediated improvements of PTSD symptoms. In this study, we found that enhanced single prolonged stress (ESPS)-induced PTSD led to abnormal neural plasticity, characterized by the decline of dendritic spines, the expression of postsynaptic density 95 (PSD95), and synaptophysin (Syn) in the stressed Hipp along with the reduction of Wnt3a and ß-catenin, and increased GSK-3ß. EA significantly alleviated PTSD-like behaviors, as assessed by the open field test, elevated platform maze test and conditioning fear test. This was paralleled by correcting abnormal neural plasticity by promoting the expression of PSD95 and Syn, as well as the number of dendritic spines in the Hipp. Importantly, EA exerted anti-PTSD effects by augmenting the expression levels of Wnt3a and ß-catenin, and decreasing that of GSK-3ß. The effects mediated by EA were abolished by XAV939, an inhibitor of the Wnt/ß-catenin pathway. This suggests that EA relieved ESPS-induced PTSD-like behaviors, which can largely be ascribed to impaired neural plasticity in the Hipp. These findings provide new insights into possible mechanisms linking neural plasticity in the Hipp as potential novel targets for PTSD treatment in EA therapy.

Moxibustion ameliorates cerebral ischemia-reperfusion injury by regulating ferroptosis in rats.

Moxibustion is an effective treatment for the clinical management of acute cerebral infarction. However, its exact mechanism of action is still not fully understood. This study aimed to investigate the protective effect of moxibustion on cerebral ischemia-reperfusion injury (CIRI) in rats. Middle cerebral artery occlusion/reperfusion (MCAO/R) was used to construct a CIRI rat model, all animals were randomly divided into four groups including sham operation group, MCAO/R group (MCAO/R), moxibustion therapy + MCAO/R (Moxi) and ferrostatin-1 + MCAO/R (Fer-1) group. In the Moxi group, moxibustion treatment was initiated 24 h after modeling, once a day for 30 mins each time for 7 days. Moreover, the Fer-1 group received intraperitoneal injections of Fer-1 12 h after modeling, once a day for a total of 7 days. The results showed that moxibustion could reduce nerve function damage and neuronal death. Additionally, moxibustion could reduce the production of lipid peroxides such as lipid peroxide, malondialchehyche and ACSL4 to regulate lipid metabolism, promote the production of glutathione and glutathione peroxidase 4 and reduce the expression of hepcidin by inhibiting the production of inflammatory factor interleukin-6, therefore, downregulating the expression of SLC40A1, reducing the iron level in the cerebral cortex, reducing the accumulation of reactive oxygen species and inhibiting ferroptosis. Based on our studies, it can be concluded that moxibustion has the ability to inhibit ferroptosis of nerve cells post CIRI and plays a protective role in the brain. This protective role can be attributed to the regulation of iron metabolism of nerve cells, reduction of iron deposition in the hippocampus and lowering the level of lipid peroxidation.

Iron metabolism: An emerging therapeutic target underlying the anti-Alzheimer's disease effect of ginseng.

Finding neuroprotective drugs with fewer side effects and more efficacy has become a major problem as the global prevalence of Alzheimer's disease (AD) rises. Natural drugs have risen to prominence as potential medication candidates. Ginseng has a long history of use in China, and it has a wide range of pharmacological actions that can help with neurological issues. Iron loaded in the brain has been linked to AD pathogenesis. We reviewed the regulation of iron metabolism and its studies in AD and explored how ginseng might regulate iron metabolism and prevent or treat AD. Researchers utilized network pharmacology analysis to identify key factive components of ginseng that protect against AD by regulating ferroptosis. Ginseng and its active ingredients may benefit AD by regulating iron metabolism and targeting ferroptosis genes to inhibit the ferroptosis process. The results present new ideas for ginseng pharmacological studies and initiatives for further research into AD-related drugs. To provide comprehensive information on the neuroprotective use of ginseng to modulate iron metabolism, reveal its potential to treat AD, and provide insights for future research opportunities.

[Study on mechanisms of acupuncture underlying improvement of CUMS-induced depression in rats based on tandem mass spectrometry proteomics technique].

OBJECTIVE: To investigate the possible mechanism of "regulating qi and relieving depression" acupuncture underlying improvement of chronic unpredictable mild stress (CUMS)-induced depression in rats by using Tandem Mass Tags(TMT) quantitative proteomics technique. METHODS: Thirty-six male SD rats were randomly divided into control, model and acupuncture groups, with 12 rats in each group. The depression model was induced by CUMS stress for 21 days. After the depression model was successfully established, the rats in the acupuncture group received manual acupuncture stimulation at "Baihui" (GV20) and "Yintang" (GV24+) for 20 min, once daily for 21 days. Open field test, sugar water preference test and forced swimming test (FST) were used to evaluate the behavioral changes. TMT quantitative proteomics was used to obtain differential proteins in the hippocampus tissue and related signaling pathways enrichment was analyzed, followed by verifying differential protein pathways by using Western blot and immunofluorescence methods. RESULTS: Behavior tests showed that on the 21st and 42nd days, the horizontal crossing times, walking distance and percentage of sugar water consumption were significantly decreased (P<0.05), while the immobility time of FST was obviously increased (P<0.05) in the model group relevant to the control group. After acupuncture intervention, the horizontal crossing times, walking distance and percentage of sugar water consumption were significantly increased (P<0.05), and the immobility time was apparently decreased (P<0.05) in the acupuncture group relevant to the model group. The TMT quantitative proteomics of hippocampus tissue displayed that of the 71 differential proteins (model group vs control group), 32 was down-regulated and 39 up-regulated in the model group; and among the above 71 differential proteins, there were 20 differential proteins between acupuncture group and model group, 15 down-regulated and 5 up-regulated in the acupuncture group (vs the model group). The expression of Mapk8ipl was up-regulated in the model group (vs the control group) and down-regulated in the acupuncture group (vs the model group). GO and KEGG enrichment analysis showed that these acupuncture-related differential proteins mainly involve the regulation of blood coagulation system, MAPK signaling pathway, etc. We selected the MAPK/JNK signaling pathway related to depression for verification. Western blot showed that the expression levels of c-JUN and phosphorylated c-JUN terminal kinase (p-JNK) proteins in the hippocampus were up-regulated in the model group relevant to the control group (P<0.05); while the expression levels of c-JUN and p-JNK proteins in the hippocampus were down-regulated in the acupuncture group relevant to the model group (P<0.05). The results of immunofluorescence showed that the mean fluorescence intensity of c-JUN and p-JNK in hippocampal CA1, CA3 and DG regions was increased in the model group relevant to the control group (P<0.05), while the mean fluorescence intensity of c-JUN and p-JNK in hippocampal CA1, CA3 and DG regions was obviously lower in the acupuncture group than in the model group (P<0.05). CONCLUSION: Acupuncture for "regulating qi and relieving depression" can significantly improve depression-like behavior in CUMS-induced depression model rats, which involves multiple targets and multiple pathways, including MAPK/JNK signaling.

Network meta-analysis of 8 types of traditional Chinese medicine injection combined with chemotherapy in colorectal cancer treatment.

OBJECTIVE: This study conducted a network meta-analysis to comprehensively compare the efficacy and safety of 8 types of traditional Chinese medicine injection combined with chemotherapy in colorectal cancer treatment. METHODS: We searched relevant previous studies from databases including Pubmed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Service System (SinMed), VIP, and Wanfang Database. The searched studies spanned from the inception of databases to December 2022. The included randomized controlled trials were screened; data were extracted; and bias risk was assessed. The network meta-analysis was performed using Revman 5.4 software, R software, and STATA software. RESULTS: Fifty randomized controlled studies were included, including 8 types of traditional Chinese medicine injection. The results showed that Aidi injection [OR 1.65,95%CI (1.33,2.05)], compound Kushenshen injection [OR 2.72,95%CI (2.12,3.51)], Kangai injection [OR 2.16,95%CI (1.56,3.02)], and Shenqi Fuzheng injection [OR 1.97,95%CI (1.24,3.15)] combined with chemotherapy in colorectal cancer treatment had a significantly higher objective response rate (p < 0.05) than single chemotherapy, and compound Kushen injection + chemotherapy [OR 2.72,95%CI (2.12,3.51)] regimen ranked the highest. The disease control rate of Aidi injection, Brucea javanica oil emulsion injection [OR 4.1,95%CI (1.74,10.43)], compound Kushen injection [OR 2.43,95%CI (1.73,3.44), Kangai injection[OR 2.31,95%CI (1.51,3.58)], Kanglaite injection[OR 3.18,95%CI (1.52,6.9)], and Shenqi Fuzheng injection[OR 2.6,95%CI (1.22,5.92)] combined with chemotherapy in the treatment of colorectal cancer was significantly improved (p < 0.05), and Brucea javanica oil emulsion injection + chemotherapy[OR 4.1,95%CI (1.74,10.43)] regimen ranked the highest. The incidence of leukopenia reduction in the treatment of colorectal cancer was significantly reduced by Aidi injection[OR 0.32,95%CI (0.24,0.43)], Brucea javanica oil emulsion injection [OR 0.34,95%CI (0.17,0.68)] compound Kushen injection [OR 0.27,95%CI (0.17,0.40)], Kangai injection [OR 0.23,95%CI (0.14,0.37)], and Kanglaite injection [OR 0.20,95%CI (0.09,0.45)] combined with chemotherapy (p < 0.05), and Kanglaite injection + chemotherapy [OR 0.20,95%CI (0.09,0.45)] regimen ranked the highest. Aidi injection [OR 0.48,95%CI (0.3,0.74)], Brucea javanica oil emulsion injection [OR 0.09,95%CI (0.01,0.43)], and Kangai injection [OR 0.47,95%CI (0.22,0.96)] combined with chemotherapy in the treatment of colorectal cancer significantly reduced the incidence of thrombocytopenia reduction (p < 0.05), and Brucea javanica oil emulsion injection + chemotherapy [OR 0.09,95%CI (0.01,0.43)] regimen ranked the highest. Aidi injection [OR 0.49,95%CI (0.32, 0.74)], Kangai injection [OR 0.26,95%CI (0.09,0.71)] combined with chemotherapy in the treatment of colorectal cancer significantly reduced the incidence of hemoglobin reduction (p < 0.05), and Kangai injection + chemotherapy [OR 0.26,95%CI (0.09,0.71)] regimen ranked the highest. Aidi injection [OR 0.38,95%CI (0.28,0.52)], compound Kushen injection [OR 0.23,95%CI (0.15,0.36)] and Kangai injection [OR 0.19,95%CI (0.12,0.30)] combined with chemotherapy in the treatment of colorectal cancer significantly reduced the incidence of nausea and vomiting (p < 0.05), and Kangai injection + chemotherapy[OR 0.19,95%CI (0.12,0.30)] regimen ranked the highest. Aidi injection [OR 0.51,95%CI (0.35,0.74)], compound Kushenshen injection [OR 0.27,95%CI (0.15,0.47)], and Kanglaite injection [OR 0.31,95%CI (0.13,0.69)] combined with chemotherapy in the treatment of colorectal cancer significantly reduced the incidence of abdominal pain and diarrhea (p < 0.05), and compound Kushen injection + chemotherapy [OR 0.27,95%CI (0.15,0.47)] regimen ranked the highest. CONCLUSION: Aidi injection, Brucea javanica oil emulsion injection, compound Kushen injection, Kangai injection, Shenqi Fuzheng injection, Kanglaite injection, Shenfu injection, and Xiaoaiping injection combined with chemotherapy functioned more effectively than single chemotherapy did in colorectal cancer treatment. Nevertheless, limited by the treatment quality and methodology of different intervention measures included in the study, this conclusion is expected to be scrutinized in higher-quality and rigorously designed randomized controlled trials. PROSPERO registration No.: CRD42023392398.

Quantifying the Contributions of Environmental Factors to Prostate Cancer and Detecting Risk-Related Diet Metrics and Racial Disparities.

The relevance of nongenetic factors to prostate cancer (PCa) has been elusive. We aimed to quantify the contributions of environmental factors to PCa and identify risk-related diet metrics and relevant racial disparities. We performed a unique analysis of the Diet History Questionnaire data of 41 830 European Americans (EAs) and 1282 African Americans (AAs) in the PLCO project. The independent variables in the regression models consisted of age at trial entry, race, family history of prostate cancer (PCa-fh), diabetes history, body mass index (BMI), lifestyle (smoking and coffee consumption), marital status, and a specific nutrient/food factor (X). P < .05 and a 95% confidence interval excluding zero were adopted as the criteria for determining a significant difference (effect). We established a priority ranking among PCa risk-related genetic and environmental factors according to the deviances explained by them in the multivariate Cox-PH regression analysis: age > PCa-fh > diabetes ⩾ race > lifestyle ⩾marital-status ⩾BMI > X. We confirmed previous studies showing that (1) high protein and saturated fat levels in diet were related to increased PCa risk, (2) high-level supplementary selenium intake was harmful rather than beneficial for preventing PCa, and (3) supplementary vitamin B6 was beneficial for preventing benign PCa. We obtained the following novel findings: high-level organ meat intake was an independent predictor for increased aggressive PCa risk; supplementary iron, copper and magnesium increased benign PCa risk; and the AA diet was "healthy" in terms of the relatively lower protein and fat levels and was "unhealthy" in that it more commonly contained organ meat. In conclusion, we established a priority ranking among the contributing factors for PCa and identified several risk-related diet metrics and the racial disparities. Our findings suggested some new approaches to prevent PCa such as restriction of organ meat intake and supplementary microminerals.

Core Target and Key Signal Pathway of Xiaoluo in the Treatment of Thyroid Cancer.

Context: At present, hormone therapy and surgery are the main treatments for thyroid cancer, and they have a quick effect but a high recurrence rate. Also, the side effects are significant. it's extremely urgent to explore treatments that can take into account both therapeutic benefits and side effects. Objective: The study intended to explore whether Xiaoluo has an inhibitory effect on the proliferation of thyroid-cancer cells in vitro and to examine the core target and key signaling pathway of Xiaoluo in the treatment of thyroid cancer, using the thyroid-cancer cell line SW579. Design: The research team performed an in-vitro study. Setting: The study took place at the College of Pharmacy at Harbin University of Commerce in Harbin, China. Outcome Measures: The research team used a Western blot analysis to detect the expression of apoptosis proteins-B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and Caspase-3-and the activity related to the signaling pathways phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT)/ mammalian target of rapamycin 1 (mTORC1). The team measured optical densities and inhibition rates for the 1, 2, 5, 10, and 15 mg/mL Xiaokuo groups and for a negative control group. The research team measured apoptosis, expression of Bcl-2, Bax, and Caspase-3, and expression of P13K, AKT, and mTor for the 10 µmol/L LY294002, 10 mg/mL Xiaoluo, 100 ng/mL IGF-1, and 100 ng/mL IGF-1+10 mg/mL Xiaoluo groups and for the blank control group. Results: The inhibition of SW579 cell proliferation increased with each increase in the Xiaoluo concentration from 1-15 mg/mL, and the inhibition rate reached 49.63% when the concentration was 15 mg/ml. The Xiaoluo group's late and total apoptosis rates were significantly higher (both P < .01) than those of the blank control group. The Xiaoluo group's expression of the Bcl-2 protein was significantly lower (P < .05), and its expressions of Bax and Caspase-3 were significantly higher (both P < .01) than those of the blank control group. The Xiaoluo group's expressions of P-PI3K, P-Akt, and P-MTOR were significantly lower than those of the blank group (all P < .01). These findings were comparable to those that occurred with use of the PI3K/AKT/mTORC1 signaling pathway inhibitor LY294002. Conclusions: Xiaoluo exerts its antithyroid-cancer effects through the induction of apoptosis in thyroid cancer cells through the inhibition of the PI3K/AKT/mTORC1 signaling pathway. Xiaoluo may serve as a potential therapeutic agent for the treatment of thyroid cancer.

Qihuang needle therapy in senile cervical spondylotic radiculopathy.

Background: Neurogenic cervical spondylosis [cervical spondylotic radiculopathy (CSR)] accounts for ~50-60% of all types of cervical spondylosis, and its incidence is the highest among all types of cervical spondylosis. Objective: The present study aimed to investigate the clinical efficacy of the Qihuang needle in the treatment of senile cervical radiculopathy. Methods: A total of 55 elderly patients with neurogenic cervical spondylosis were randomly divided into the general acupuncture group (27 cases) and the Qihuang acupuncture group (28 cases). The treatment given to these patients lasted for three sessions. The VAS scores and the Tanaka Yasuhisa Scale scores were compared before the treatment, after the first treatment, after the first session, and at the end of the session. Results: The basic data of the two groups before the treatment showed no difference. The VAS scores in the mackerel acupuncture group decreased significantly, whereas in the Tanaka Kangjiu Scale scores, the efficiency rates of the first and second courses of treatment increased significantly. Conclusion: The Qihuang needle therapy is recommended for the treatment of cervical spondylosis of the nerve root type. The said therapy is characterized by selection of fewer acupoints, a quick operation time, and no needle retention.