Unveiling the Mechanism of the ChaiShao Shugan Formula Against Triple-Negative Breast Cancer.

Background: The ChaiShao Shugan Formula (CSSGF) is a traditional Chinese medicine formula with recently identified therapeutic value in triple-negative breast cancer (TNBC). This study aimed to elucidate the underlying mechanism of CSSGF in TNBC treatment. Methods: TNBC targets were analyzed using R and data were from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The major ingredients and related protein targets of CSSGF were explored via the Traditional Chinese Medicine Systems Pharmacology database, and an ingredient-target network was constructed via Cytoscape to identify hub genes. The STRING database was used to construct the PPI network. GO and KEGG enrichment analyses were performed via R to obtain the main targets. The online tool Kaplan‒Meier plotter was used to identify the prognostic genes. Molecular docking was applied to the core target genes and active ingredients. MDA-MB-231 and MCF-7 cell lines were used to verify the efficacy of the various drugs. Results: A total of 4562 genes were screened as TNBC target genes. The PPI network consisted of 89 nodes and 845 edges. Our study indicated that quercetin, beta-sitosterol, luteolin and catechin might be the core ingredients of CSSGF, and EGFR and c-Myc might be the latent therapeutic targets of CSSGF in the treatment of TNBC. GO and KEGG analyses indicated that the anticancer effect of CSSGF on TNBC was mainly associated with DNA binding, transcription factor binding, and other biological processes. The related signaling pathways mainly involved the TNF-a, IL-17, and apoptosis pathways. The molecular docking data indicated that quercetin, beta-sitosterol, luteolin, and catechin had high affinity for EGFR, JUN, Caspase-3 and ESR1, respectively. In vitro, we found that CSSGF could suppress the expression of c-Myc or promote the expression of EGFR. In addition, we found that quercetin downregulates c-Myc expression in two BC cell lines. Conclusion: This study revealed the effective ingredients and latent molecular mechanism of action of CSSGF against TNBC and confirmed that quercetin could target c-Myc to induce anti-BC effects.

Propofol Modulates Gallbladder Cancer Progression via miR-4430/SLC19A3 Axis.

Background/Aim: Propofol is a common anesthetic used during surgery. MircoRNA (miRNA), especially miR-4430, is currently a research hotspot in GBC. This study investigates whether propofol regulates GBC through the miR-4430/SLC19A3 axis. Materials and methods: NOZ and SGC996 cells, human gallbladder cancer cell lines, were obtained from BLUEFBIO (Shanghai, China). The cells were treated with propofol, and the experimental setup included a control group. qRT-PCR was used to measure the content of miR-4430 and solute carrier family 19 member 3 (SLC19A3). The cell viability, migration, and apoptosis were analyzed by colony formation assay, wound healing assay, and flow cytometry, respectively. Western blot tested the levels of SLC91A3, cyclin D-dependent kinases 6 (CDK6), and Bax proteins. Mechanically, dual-luciferase reporter assay notarized the link of miR-4430 with SLC19A3. Results: Propofol significantly repressed the proliferation of GBC cells, as indicated by a pronounced reduction in colony formation in both NOZ and SGC996 cells (P = .025, 95% CI:1.2, 2.4). The inhibitory effect of propofol was reversed by the enhanced expression of miR-4430 in GBC cells. Furthermore, SLC19A3 was identified as a direct target of miR-4430. Silencing SLC19A3 reversed the altered cell behavior observed in propofol-treated GBC cells (P = .019, 95% CI:1.6, 3.5). Additionally, overexpression of SLC19A3 significantly attenuated both cell proliferation and migration influenced by miR-4430 in propofol-treated GBC cells (P = .034, 95% CI:1.4, 2.8). Conclusion: Propofol changed the cell behaviors of GBC by modulating the miR-4430/SLC19A3 axis.

Gut microbiota contributes to bisphenol A-induced maternal intestinal and placental apoptosis, oxidative stress, and fetal growth restriction in pregnant ewe model by regulating gut-placental axis.

BACKGROUND: Bisphenol A (BPA) is an environmental contaminant with endocrine-disrupting properties that induce fetal growth restriction (FGR). Previous studies on pregnant ewes revealed that BPA exposure causes placental apoptosis and oxidative stress (OS) and decreases placental efficiency, consequently leading to FGR. Nonetheless, the response of gut microbiota to BPA exposure and its role in aggravating BPA-mediated apoptosis, autophagy, mitochondrial dysfunction, endoplasmic reticulum stress (ERS), and OS of the maternal placenta and intestine are unclear in an ovine model of gestation. RESULTS: Two pregnant ewe groups (n = 8/group) were given either a subcutaneous (sc) injection of corn oil (CON group) or BPA (5 mg/kg/day) dissolved in corn oil (BPA group) once daily, from day 40 to day 110 of gestation. The maternal colonic digesta and the ileum and placental tissue samples were collected to measure the biomarkers of autophagy, apoptosis, mitochondrial dysfunction, ERS, and OS. To investigate the link between gut microbiota and the BPA-induced FGR in pregnant ewes, gut microbiota transplantation (GMT) was conducted in two pregnant mice groups (n = 10/group) from day 0 to day 18 of gestation after removing their intestinal microbiota by antibiotics. The results indicated that BPA aggravates apoptosis, ERS and autophagy, mitochondrial function injury of the placenta and ileum, and gut microbiota dysbiosis in pregnant ewes. GMT indicated that BPA-induced ERS, autophagy, and apoptosis in the ileum and placenta are attributed to gut microbiota dysbiosis resulting from BPA exposure. CONCLUSIONS: Our findings indicate the underlying role of gut microbiota dysbiosis and gut-placental axis behind the BPA-mediated maternal intestinal and placental apoptosis, OS, and FGR. The findings further provide novel insights into modulating the balance of gut microbiota through medication or probiotics, functioning via the gut-placental axis, to alleviate gut-derived placental impairment or FGR. Video Abstract.

Baduanjin exercise intervention trial: research protocol of a randomised controlled trial for frail kidney transplant recipients.

INTRODUCTION: Frailty is one of the most common comorbidities in kidney transplant recipients (KTRs). Physical, psychological and social frailty could be improved by exercise intervention. Baduanjin, also known as Eight-section Brocades, is a type of traditional Chinese medicine exercise characterised by the interplay between physical postures and movements, breathing and mind. It can help frail patients strengthen their upper and lower body muscles, improve their mood, quality of life and frailty. However, the effectiveness of Baduanjin on frail KTRs remains unknown. Therefore, we will conduct a randomised controlled trial (RCT) to evaluate the effectiveness of Baduanjin on frail KTRs. METHODS AND ANALYSIS: This protocol describes an assessor and analyst blinded, parallel RCT for frail KTRs comparing Baduanjin group (n=72) with care-as-usual group (n=72). The primary outcomes are frailty assessed by Frailty Phenotype scale and Tilburg Frailty Indicator scale, and muscle strength assessed by a grip strength metre. The secondary outcomes are quality of life assessed by Medical Outcomes Study 36-Item Short-Form Health Survey (MOS SF-36) and depression assessed by the Hospital Anxiety and Depression Scale. All these data will be collected at the baseline, after 3, 6, 9 and 12 months, respectively. Two-way mixed analysis of variance (ANOVA) will be used to test the effectiveness of Baduanjin exercise. Qualitative interviews with participants in the intervention group will also be performed after 6 months. Themes will be extracted from interview transcripts using NVivo software. ETHICS AND DISSEMINATION: The Ethics Committees of Beijing University of Chinese Medicine (2022BZYLL1018) and China-Japan Friendship Hospital (2022-KY-250) had approved the study. The organ donors were all from China-Japan Friendship Hospital. They provided informed consent and they were not executed prisoners. We have provided BMJ Open with documentation from the hospital that indicates that the organs will be harvested ethically. The findings of this study will be disseminated through peer-reviewed journals, international conferences, media reports and briefings. TRIAL REGISTRATION NUMBER: ChiCTR2100041730.

[Aqueous extract of Epimedium sagittatum mitigates pulmonary fibrosis in mice].

This study aims to investigate the intervention effect of the aqueous extract of Epimedium sagittatum Maxim on the mouse model of bleomycin(BLM)-induced pulmonary fibrosis, so as to provide data support for the clinical treatment of pulmonary fibrosis. Ninety male C57BL/6N mice were randomized into normal(n=10), model(BLM, n=20), pirfenidone(PFD, 270 mg·kg~(-1), n=15), and low-, medium-, and high-dose E. sagittatum extract(1.67 g·kg~(-1), n=15; 3.33 g·kg~(-1), n=15; 6.67 g·kg~(-1), n=15) groups. The model of pulmonary fibrosis was established by intratracheal instillation of BLM(5 mg·kg~(-1)) in the other five groups except the normal group, which was treated with an equal amount of normal saline. On the day following the modeling, each group was treated with the corresponding drug by gavage for 21 days. During this period, the survival rate of the mice was counted. After gavage, the lung index was calculated, and the morphology and collagen deposition of the lung tissue were observed by hematoxylin-eosin(HE) and Masson staining, respectively. The levels of reactive oxygen species(ROS) in lung cell suspensions were measured by flow cytometry. The levels of glutathione peroxidase(GSH-Px), total superoxide dismutase(T-SOD), and malondialdehyde(MDA) the in lung tissue were measured. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling(TUNEL) was employed to examine the apoptosis of lung tissue cells. The content of interleukin-6(IL-6), chemokine C-C motif ligand 2(CCL-2), matrix metalloproteinase-8(MMP-8), transforming growth factor-beta 1(TGF-ß1), alpha-smooth muscle actin(α-SMA), E-cadherin, collagen Ⅰ, and fibronectin in the lung tissue was measured by enzyme-linked immunosorbent assay(ELISA). The expression levels of F4/80, Ly-6G, TGF-ß1, and collagen Ⅰ in the lung tissue were determined by immunohistochemistry. The mRNA levels of CCL-2, IL-6, and MMP-7 in the lung tissue were determined by qRT-PCR. The content of hydroxyproline(HYP) in the lung tissue was determined by alkaline hydrolysation. The expression of α-SMA and E-cadherin was detected by immunofluorescence, and the protein levels of α-SMA, vimentin, E-cadherin in the lung tissue were determined by Western blot. The results showed the aqueous extract of E. sagittatum increased the survival rate, decreased the lung index, alleviated the pathological injury, collagen deposition, and oxidative stress in the lung tissue, and reduced the apoptotic cells. Furthermore, the aqueous extract of E. sagittatum down-regulated the protein levels of F4/80 and Ly-6G and the mRNA levels of CCL-2, IL-6, and MMP-7 in the lung tissue, reduced the content of IL-6, CCL-2, and MMP-8 in the alveolar lavage fluid. In addition, it lowered the levels of HYP, TGF-ß1, α-SMA, collagen Ⅰ, fibronectin, and vimentin, and elevated the levels of E-cadherin in the lung tissue. The aqueous extract of E. sagittatum can inhibit collagen deposition, alleviate oxidative stress, and reduce inflammatory response by regulating the expression of the molecules associated with epithelial-mesenchymal transition, thus alleviating the symptoms of bleomycin-induced pulmonary fibrosis in mice.

Dietary rumen-protected L-arginine or N-carbamylglutamate enhances placental amino acid transport and suppresses angiogenesis and steroid anabolism in underfed pregnant ewes.

This study aimed to investigate the effects of dietary supplementation of underfed Hu ewes from d 35 to 110 of gestation with either rumen-protected L-arginine (RP-Arg) or N-carbamylglutamate (NCG) on placental amino acid (AA) transport, angiogenic gene expression, and steroid anabolism. On d 35 of gestation, 32 Hu ewes carrying twin fetuses were randomly divided into four treatment groups, each consisting of eight ewes, and were fed the following diets: A diet providing 100% of NRC's nutrient requirements for pregnant ewes (CON); A diet providing 50% of NRC's nutrient requirements for pregnant ewes (RES); RES diet plus 5 g/d NCG (RES + NCG); or RES diet plus 20 g/d RP-Arg (RES + ARG). On the d 110 of pregnancy, blood samples were taken from the mother, and samples were collected from type A cotyledons (COT; the fetal portions of the placenta). The levels of 17ß-estradiol and progesterone in the maternal serum and both the capillary area density (CAD) and capillary surface density (CSD) in type A COT were decreased in response to Arg or NCG supplementation when compared to the RES group. The concentrations of arginine, leucine, putrescine and spermidine in type A COT were higher (P < 0.05) in the RES + ARG or RES + NCG group than in the RES group. The mRNA expression levels of inducible nitric oxide synthase (iNOS) and solute carrier family 15, member 1 (SLC15A1) were increased (P < 0.05) while those of progesterone receptor (PGR) and fibroblast growth factor 2 (FGF2) were decreased in type A COT by supplementation with either NCG or RP-Arg compared to the RES group. The results suggest that providing underfed pregnant ewes from d 35 to 110 of gestation with a diet supplemented with NCG or RP-Arg improves placental AA transport, and reduces the expression of angiogenic growth factor genes and steroid anabolism, leading to better fetal development.

Gut microbiota-associated taurine metabolism dysregulation in a mouse model of Parkinson's disease.

IMPORTANCE: PD is recognized as a multisystem disease concerning GI dysfunction and microbiota dysbiosis but still lacks ideal therapies. Recently, aberrant microbiota-derived metabolites are emerging as important participants in PD etiology. However, the alterations of gut microbiota community and serum untargeted metabolite profile have not been fully investigated in a PD mice model. Here, we discover sharply reduced levels of Lactobacillus and taurine in MPTP-treated mice. Moreover, Lactobacillus, Adlercreutzia, and taurine-related metabolites showed the most significant correlation with pathological and GI performance of PD mice. The abundances of microbial transporter and enzymes participating in the degeneration of taurine were disturbed in PD mice. Most importantly, taurine supplement ameliorates MPTP-induced motor deficits, DA neuron loss, and microglial activation. Our data highlight the impaired taurine-based microbiome-metabolism axis during the progression of PD and reveal a novel and previously unrecognized role of genera in modulating taurine metabolism.

Efficacy and safety of Xian-Lian-Jie-Du optimization decoction as an adjuvant treatment for prevention of recurrence in patients with stage IIIB/IIIC colon cancer: study protocol for a multicentre, randomized controlled trial.

INTRODUCTION: Colon cancer remains one of the most prevalent cancers worldwide. Unfortunately, there are no recognized and effective therapeutic strategies to prevent tumor recurrence after radical resection and chemotherapy, and the disease-free survival (DFS) in patients with stage IIIB or IIIC disease remains unsatisfactory. Xian-Lian-Jie-Du optimization decoction (XLJDOD) is a Chinese herbal medicine (CHM) empirical prescription, which has been validated experimentally and clinically that could inhibit the progression of colorectal cancer and ameliorate the symptoms. The purpose of this study is to evaluate the efficacy and safety of XLJDOD in prevention of recurrence of colon cancer. METHODS: This study is a multi-center, double-blind, randomized, placebo-controlled trial conducted at 13 hospitals of China. Following the completion of surgery and adjuvant 5- fluorouracil-based chemotherapy, a total of 730 subjects with stage IIIB or IIIC colon cancer will be randomized in a 1:1 ratio to an intervention group (n = 365; XLJDOD compound granule) and a control group (n = 365; Placebo). Patients will receive 6-month treatments and be followed up with 3 monthly assessments for 2 years. The primary outcome is 2-year DFS rate and the secondary outcomes are 1, 2-year relapse rate (RR), overall survival (OS) and quality of life (QoL). Safety outcomes such as adverse events will be also assessed. A small number of subgroup analysis will be carried out to explore the heterogeneity of effects of XLJDOD. DISCUSSION: The outcomes from this randomized controlled trial will provide objective evidences to evaluate XLJDOD's role as an adjuvant treatment in colon cancer. TRIAL REGISTRATION: www. CLINICALTRIALS: gov , identifier: NCT05709249. Registered on 31 Jan 2023.

Acupuncture and Doxylamine-Pyridoxine for Nausea and Vomiting in Pregnancy : A Randomized, Controlled, 2 × 2 Factorial Trial.

BACKGROUND: An effective and safe treatment for nausea and vomiting of pregnancy (NVP) is lacking. OBJECTIVE: To assess the efficacy and safety of acupuncture, doxylamine-pyridoxine, and a combination of both in women with moderate to severe NVP. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial. (ClinicalTrials.gov: NCT04401384). SETTING: 13 tertiary hospitals in mainland China from 21 June 2020 to 2 February 2022. PARTICIPANTS: 352 women in early pregnancy with moderate to severe NVP. INTERVENTION: Participants received daily active or sham acupuncture for 30 minutes and doxylamine-pyridoxine or placebo for 14 days. MEASUREMENTS: The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at the end of the intervention at day 15 relative to baseline. Secondary outcomes included quality of life, adverse events, and maternal and perinatal complications. RESULTS: No significant interaction was detected between the interventions (P = 0.69). Participants receiving acupuncture (mean difference [MD], -0.7 [95% CI, -1.3 to -0.1]), doxylamine-pyridoxine (MD, -1.0 [CI, -1.6 to -0.4]), and the combination of both (MD, -1.6 [CI, -2.2 to -0.9]) had a larger reduction in PUQE score over the treatment course than their respective control groups (sham acupuncture, placebo, and sham acupuncture plus placebo). Compared with placebo, a higher risk for births with children who were small for gestational age was observed with doxylamine-pyridoxine (odds ratio, 3.8 [CI, 1.0 to 14.1]). LIMITATION: The placebo effects of the interventions and natural regression of the disease were not evaluated. CONCLUSION: Both acupuncture and doxylamine-pyridoxine alone are efficacious for moderate and severe NVP. However, the clinical importance of this effect is uncertain because of its modest magnitude. The combination of acupuncture and doxylamine-pyridoxine may yield a potentially larger benefit than each treatment alone. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Project of Heilongjiang Province "TouYan" Innovation Team.

[LC-MS analysis of 2-(2-phenylethyl) chromones in sodium chloride-treated suspension cells of Aquilaria sinensis].

Qualitative and quantitative analysis of 2-(2-phenylethyl) chromones in sodium chloride(NaCl)-treated suspension cells of Aquilaria sinensis was conducted by UPLC-Q-Exactive-MS and UPLC-QQQ-MS/MS. Both analyses were performed on a Waters T3 column(2.1 mm×50 mm, 1.8 µm) with 0.1% formic acid aqueous solution(A)-acetonitrile(B) as mobile phases at gradient elution. MS data were collected by electrospray ionization in positive ion mode. Forty-seven phenylethylchromones was identified from NaCl-treated suspension cell samples of A. sinensis using UPLC-Q-Exactive-MS, including 22 flindersia-type 2-(2-phenylethyl) chromones and their glycosides, 10 5,6,7,8-tetrahydro-2-(2-phenylethyl) chromones and 15 mono-epoxy or diepoxy-5,6,7,8-tetrahydro-2-(2-phenylethyl) chromones. Additionally, 25 phenylethylchromones were quantitated by UPLC-QQQ-MS/MS. Overall, the rapid and efficient qualitative and quantitative analysis of phenylethylchromones in NaCl-treated suspension cells of A. sinensis by two LC-MS techniques, provides an important reference for the yield of phenylethylchromones in Aquilariae Lignum Resinatum using in vitro culture and other biotechnologies.

Chuanxiong improves angiogenesis via the PI3K/AKT/Ras/MAPK pathway based on network pharmacology and DESI-MSI metabolomics.

Introduction: Chuanxiong, a traditional Chinese medicine, has been proved to treat a variety of cardiovascular and cerebrovascular diseases by promoting angiogenesis. However, the mechanisms of Chuanxiong's pro-angiogenesis is currently unknown. This study aimed to uncover the effect and mechanisms of Chuanxiong promoting angiogenesis in vivo and in vitro. Methods: First, potential targets were predicted by network pharmacology analysis, and PPI network was established and the pathways were enriched. Then, the chorioallantoic membrane test on quails was applied to assess the proangiogenic effects in vivo. As well, to evaluate the effects in vitro, real-time PCR, western blot analysis, the scratch test, and the tube formation experiment were used. Subsequently, the major metabolic pathways were analyzed using non-targeted metabolomics. Results: As a result of network pharmacological analysis, 51 collective targets of Chuanxiong and angiogenesis were identified, which are mainly associated with PI3K/AKT/Ras/MAPK pathway. And the biological verification results showed that Chuanxiong could increase the vessel numbers and vessel area in qCAM models. Meanwhile, Chuanxiong contributed to HUVEC proliferation, tube formation, migration, by encouraging scratch healing rates and boosting tube branch points. In addition, the levels of VEGFR2, MAPK and PI3K were elevated compared to the control group. The western blot analysis also confirmed Chuanxiong could promote an increase in AKT, FOXO1 and Ras. Furtheremore, metabolomic results showed that the proangiogenic effect of Chuanxiong is associated with glycine, serine and threonine metabolism. Discussion: In conclusion, this study clarified that Chuanxiong could promote angiogenesis in vivo and in vitro via regulating PI3K/AKT/Ras/MAPK pathway.

MET Inhibits the Proliferation of EC Cells by Increasing MPA Sensitivity.

Context: The high resistance rate and high recurrence rate of progesterone only as a treatment for endometrial cancer (EC) limit its clinical application. Metformin (MET) may have antitumor ability. Combining MET and medroxyprogesterone acetate (MPA) may strengthen their inhibitory effects on proliferation of EC cells, but MET's mechanisms remain unclear. Objective: The study intended to identify the specific molecular mechanism that MET combined with MPA uses against EC progression. Design: The research team performed a controlled animal study. Setting: The study took place at Xuzhou Medical University in Xuzhou, China. Animals: The animals were16 female non-obese diabetic-severe combined immunodeficient (NOD-SCID) nude mice, about 12 to 16 g in weight. Interventions: The research team divided randomly, the mice into four groups and induced EC in all groups, four in each group: (1) The control group which received received normal saline, (2) the MPA group, which received 100 mg/kg of MPA; (3) the MET group, which received metformin at the rate of 200 mg/kg, each gavage volume was 0.1ml; (4) the MET+MPA group, which received 100 mg/kg of MPA and 200 mg/kg of MET. Outcome measures: The research team: (1) used a CCK-8 kit, an EdU assay, and a flow-cytometry assay to measure cancer-cell proliferation, count, and viability; determine the cell cycle; and measure apoptosis; (2) performed a Western blot analysis to determine the expression of the PR, CD133, pAkt, totalAkt, p-mTOR, and totalTOR antibodies; and (3) determined the size and volume of tumors in vivo and used immunohistochemical staining to determine expression of the Ki67 protein. Results: The MET+MPA group had a significantly lower number of cancer cells than the MET or MDA groups (both P < .001). That group also had significantly more stagnated cancer cells in the G0/G1 phase and significantly fewer cancer cells in the S phase or G2/M phase control, MET, or MPA groups (all P < .01). The MET+MPA group's PCNA and Ki-67 protein expression was significantly lower than that of the MET and MPA group. The EDU assay yielded similar results. Additionally, the MET+MPA group had significantly higher PR expression than that of to MET or MPA group (both P < .001). The MET and MPA groups' expression of CD133, p-Akt, and p-mTOR were significantly lower than those of the control group, while the MET+MPA group's levels were significantly lower than those of the MET and MPA groups. In-vivo experiments revealed that the MET and MPA groups did show decreased tumor size and volume. The MET+MPA group had tumor weights that were significantly lower and tumor volumes were significantly smaller than those of the MET and MPA groups (all P < .001). Immunohistochemical analysis revealed that the MET+MPA group's levels of the Ki-67 antigen were significantly lower than those of the MET and MPA groups. Conclusions: MET inhibited the proliferation of EC cells by increasing MPA-sensitivity, which was dependent on the inhibition of the CD133 expression and the Akt/mTOR pathway. In addition, if MET acts as an effective progestin sensitizer, it certainly offers promising therapeutic prospects for patients with early-stage EC or overgrown endometrium who have fertility requirements.

Efficacy of Aidi injection combined with chemotherapy, radiotherapy or chemoradiotherapy for unresectable esophageal cancer treatment: A meta-analysis and systematic review of 29 randomized controlled trials based on Asian populations (China).

OBJECTIVES: This study aimed to assess the efficacy of Aidi combined with standard treatment, including radiotherapy (R), chemotherapy (C), or chemoradiotherapy (CR), for unresectable esophageal cancer (EC). METHODS: Eight online databases were queried to collect randomized controlled trials (RCTs) published from database construction to August 2022. Patients in the control group underwent standard treatment with R, C, or CR, whereas those in the experimental group underwent Aidi combined with standard treatment. RESULTS: In this meta-analysis, 29 reports with 2079 patients were included. The results showed that the Aidi-based combination therapy groups had higher objective response rates (ORRs), disease control rates (DCRs), one-year overall survival (OS) and improvement and stability of Karnofsky performance status (KPS) than the control group (risk ratio (RR) = 1.24 (95% CI = 1.17-1.33), 1.09 (95% CI = 1.05-1.14), 1.50 (95% CI = 1.31-1.72), and 1.28 (95% CI = 1.16-1.41)). The Aidi-based combination therapy groups also had lower total incidence rates of bone marrow suppression (BMS), chemotherapy-induced nausea and vomiting (CINV) and radiation esophagitis (RE) than the control group (RR = 0.48 (95% CI = 0.41-0.56), 0.46 (95% CI = 0.36-0.58), and 0.49 (95% CI = 0.38-0.62)). In addition, subgroup analysis suggested that the optimal dose and cycle of Aidi injection combined therapy was 80-100 ml/time and 30 days/2 cycles. The efficacy of Aidi combined with DP (docetaxel + cisplatin) was better than the Aidi combined with PF (cisplatin plus fluorouracil). CONCLUSION: Aidi-based combination therapy showed high efficacy for unresectable EC treatment and reduced the incidence rates of adverse events. However, further studies including higher-quality RCTs are needed to validate these findings. TRIAL REGISTRATION NUMBER: INPLASY 202290020.

Anti-proliferative and anti-inflammatory eudesmanolides from the flowers of Sphagneticola trilobata (L.) Pruski.

Twenty-six eudesmanolides including six undescribed compounds were isolated from the flowers of Sphagneticola trilobata (L.) Pruski. Their structures were elucidated based on the interpretation of spectroscopic techniques, NMR calculation, and DP4+ analysis. The stereochemistry of (1S,4S,5R,6S,7R,8S,9R,10S,11S)-1,4,8- trihydroxy-6-isobutyryloxy-11-methyleudesman-9,12-olide (1) was demonstrated by single crystal X-ray diffraction. All eudesmanolides were evaluated for their anti-proliferative activities against four human tumor cell lines (HepG2, HeLa, SGC-7901, and MCF-7). 1α,4ß-Dihydroxy-6α-methacryloxy-8ß-isobutyryloxyeudesman-9,12-olide (3) and wedelolide B (8) showed pronounced cytotoxic effects against AGS cell line with IC50 values of 1.31 and 0.89 µM, respectively. Their anti-proliferative activities against AGS cells were exerted through a dose-dependent apoptosis pathway, as verified by cell and nucleus morphological assessment, clone formation assay, and Western blot analysis. Furthermore, 1α,4ß,8ß-trihydroxy-6ß-methacryloxyeudesman-9,12-olide (2) and 1α,4ß,9ß-trihydroxy-6α-isobutyryloxy- 11α-13-methacryloxyprostatolide (7) performed significant inhibitory effects on lipopolysaccharide-stimulated nitric oxide production in RAW 264.7 macrophages with IC50 values of 11.82 and 11.05 µM, respectively. Moreover, compounds 2 and 7 could block the nuclear translocation of NF-κB and reduce the expression of iNOS, COX-2, IL-1ß, and IL-6 to exert anti-inflammatory effects. This study provides evidence for the utilization of the eudesmanolides from S. trilobata as lead compounds for further research due to their cytotoxic potential.

Effects of a Macroporous Resin Extract of Dendrobium officinale Leaves in Rats with Hyperuricemia Induced by Anthropomorphic Unhealthy Lifestyle.

Aim: Hyperuricemia (HUA) has received increased attention in the last few decades due to its global prevalence. Our previous study found that administration of a macroporous resin extract of Dendrobium officinale leaves (DoMRE) to rats with HUA that was induced by exposure to potassium oxazine combined with fructose and a high-purine diet led to a significant reduction in serum uric acid (SUA) levels. The aim of this study was to explore the effects of DoMRE on hyperuricemia induced by anthropomorphic unhealthy lifestyle and to elucidate its possible mechanisms of action. Methods: Dosages (5.0 and 10.0 g/kg/day) of DoMRE were administered to rats daily after induction of HUA by anthropomorphic unhealthy lifestyle for 12 weeks. The levels of UA in the serum, urine, and feces; the levels of creatinine (Cr) in the serum and urine; and the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum were all measured using an automatic biochemical analyzer. The activities of xanthine oxidase (XOD) and adenosine deaminase (ADA) in the serum, liver, and intestine tissue supernatant were measured using appropriate kits for each biological target. The expressions levels of UA transporters (ABCG2 and GLUT9), tight junction (TJ) proteins (ZO-1 and occludin), and inflammatory factors (IL-6, IL-8, and TNF-α) in the intestine were assayed by immunohistochemical (IHC) staining. Hematoxylin and eosin (H&E) staining was used to assess histological changes in the renal and intestinal tissues. Results: DoMRE treatment significantly reduced SUA levels and concomitantly increased fecal UA (FUA) levels and the fractional excretion of UA (FEUA) in HUA rats. Furthermore, DoMRE significantly reduced both the XOD activity in the serum, liver, and intestine and the ADA activity in the liver and intestine. DoMRE also effectively regulated the expression of GLUT9 and ABCG2 in the intestine, and it significantly upregulated the expression of the intestinal TJ proteins ZO-1 and occludin. Therefore, DoMRE reduced the damage to the intestinal barrier function caused by the increased production of inflammatory factors due to HUA to ensure normal intestinal UA excretion. Conclusion: DoMRE demonstrated anti-HUA effects in the HUA rat model induced by an anthropomorphic unhealthy lifestyle, and the molecular mechanism appeared to involve the regulation of urate transport-related transporters (ABCG2 and GLUT9) in the intestine, protection of the intestinal barrier function to promote UA excretion, and inhibition of XOD and ADA activity in the liver and intestine to inhibit UA production in the HUA-induced rats.

Supramolecular self-assembled AIE molecules are used in the search for target proteins in norcantharidin.

Norcantharidin (NCTD), a demethylated derivative of cantharidin, is an anticancer active component in traditional Chinese medicine. At present, the main methods for finding its target proteins are pharmacological methods and biophysical screening, which cannot achieve the purpose of efficient and accurate screening. Here we established a new analytical method for specific fishing and assisted imaging for norcantharidin target proteins. For the AIE supramolecule probe, the benzophenone azide (BPA) fluorescent nanoparticles with strong AIE properties were encapsulated in biocompatible DSPE-PEG that covalently coupled with NCTD (named BPA@NCTD NPs). The target proteins of NCTD can be captured by BPA@NCTD NPs, and then be detected to investigate the potential signaling pathways. The screened differential proteins were analysed through the protein and signaling pathway database, and multiple signaling pathways were obtained and verified. The mechanism of norcantharidin in inhibiting the migration and invasion of A549 cells through the P53 signaling pathway was confirmed by Western blot experiments. Our research showed that AIE supramolecule probe BPA@NCTD NPs has the dual functions of specific screening of A549 cells target proteins and biological imaging, which not only offers a good anti-fluorescence quenching ability for the dynamic imaging process of NCTD, but also provides a novel and efficient specific method for efficient analysis of target proteins and signal pathways.

Differential vulnerability of thalamic nuclei in multiple sclerosis.

OBJECTIVES: Investigating differential vulnerability of thalamic nuclei in multiple sclerosis (MS). METHODS: In a secondary analysis of prospectively collected datasets, we pooled 136 patients with MS or clinically isolated syndrome and 71 healthy controls all scanned with conventional 3D-T1 and white-matter-nulled magnetization-prepared rapid gradient echo (WMn-MPRAGE) and tested for cognitive performance. T1-based thalamic segmentation was compared with the reference WMn-MPRAGE method. Volumes of thalamic nuclei were compared according to clinical phenotypes and cognitive profile. RESULTS: T1- and WMn-MPRAGE provided comparable segmentations (0.84 ± 0.13 < volume-similarity-index < 0.95 ± 0.03). Medial and posterior thalamic groups were significantly more affected than anterior and lateral groups. Cognitive impairment related to volume loss of the anterior group. CONCLUSION: Thalamic nuclei closest to the third ventricle are more affected, with cognitive consequences.

The longitudinal association between onion consumption and risk of depressive symptoms: results from the TCLSIH Cohort study and the UK Biobank.

Background and aims: Onions have shown antidepressant effects but relevant evidence from people was limited. Thus, we aimed to explore the prospective association between onion consumption and risk of depressive symptoms in the general population. Methods: We used data from 2 cohorts: the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) cohort included 7739 participants (males, 57.6%) with a mean age of 39.5 years, and the UK Biobank included 169 806 individuals (males, 45.2%) with a mean age of 55.7 years. In the TCLSIH cohort, onion consumption was assessed by a validated food frequency questionnaire from May 2013; depressive symptoms were evaluated by the Chinese version of the Self-Rating Depression Scale (SDS scores ≥ 45) and were assessed up to 2018. In the UK Biobank, onion consumption was measured by 1-5 times validated 24-hour dietary recalls in 2006-2010; depressive symptoms were determined through the linked hospital records and death registries and were assessed up to 2018. Multivariable Cox proportional hazards models were employed to determine the association between onion consumption and risk of depressive symptoms. Results: A total of 1098 and 1924 cases of depressive symptoms were identified during 15 004 person-years and 1 243 832 person-years of follow-up in the TCLSIH cohort and the UK Biobank, respectively. After adjusting for many confounding factors, the fully adjusted HRs (95% CI) of depressive symptoms comparing the higher levels to the lowest level of onion consumption were 0.78 (0.65, 0.94), 0.73 (0.61, 0.87), and 0.77 (0.64, 0.92) in the TCLSIH cohort (p for trend = 0.01); and were 0.79 (0.68, 0.93), 0.81 (0.69, 0.94), and 0.97 (0.85, 1.12) in the UK Biobank (p for trend = 0.07). Similar associations were observed in the sensitivity analyses. Conclusion: Our results indicated that habitual onion consumption was associated with a lower risk of depressive symptoms in two cohorts. However, this association was not statistically significant in the highest level of onion consumption in the UK Biobank.

Data fusion of electronic noses and electronic tongues aids in botanical origin identification on imbalanced Codonopsis Radix samples.

Codonopsis Radix (CR) is an edible food and traditional Chinese herb medicine in China. Various varieties of Codonopsis Radix have different tastes. To make the flavor of processed food stable, two kinds of electronic sensory devices, electronic nose and electronic tongue, were used to establish a discrimination model to identify the botanical origin of each sample. The optimal model built on the 88 batches of samples was selected from the models trained with all combination of two pretreatment methods and three classification methods. A comparison were performed on the models trained on the data collected by electronic nose and electronic tongue. The results showed that the model trained on the fused dataset outperformed the models trained separately on the electronic nose data and electronic tongue data. The two preprocessing approaches could improve the prediction performance of all classification methods. Classification and Regression Tree approach performed better than Partial Least Square Discriminant Analysis and Linear Discriminant Analysis in terms of accuracy. But Classification and Regression Tree tends to assign the samples of minority class to the majority class. Meanwhile, Partial Least Square Discriminant Analysis keeps a good balance between the identification requirements of all the two groups of samples. Taking all the results above, the model built using the Partial Least Square Discriminant Analysis method on the fused data after z-score was used to identify the botanical origin of Codonopsis Radix.

[Mechanism of "Ephedrae Herba-Descurainiae Semen Lepidii Semen" combination in treatment of bronchial asthma based on network pharmacology and experimental verification].

This study aims to investigate mechanism of "Ephedrae Herba-Descurainiae Semen Lepidii Semen" combination(MT) in the treatment of bronchial asthma based on network pharmacology and in vivo experiment, which is expected to lay a theoretical basis for clinical application of the combination. First, the potential targets of MT in the treatment of bronchial asthma were predicted based on network pharmacology, and the "Chinese medicine-active component-target-pathway-disease" network was constructed, followed by Gene Oncology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the potential targets. Molecular docking was used to determine the binding activity of key candidate active components to hub genes. Ovalbumin(OVA, intraperitoneal injection for sensitization and nebulization for excitation) was used to induce bronchial asthma in rats. Rats were classified into control group(CON), model group(M), dexamethasone group(DEX, 0.075 mg·kg~(-1)), and MT(1∶1.5) group. Hematoxylin and eosin(HE), Masson, and periodic acid-Schiff(PAS) staining were performed to observe the effect of MT on pathological changes of lungs and trachea and goblet cell proliferation in asthma rats. The levels of transforming growth factor(TGF)-ß1, interleukin(IL)6, and IL10 in rat serum were detected by enzyme-linked immunosorbent assay(ELISA), and the mRNA and protein levels of mitogen-activated protein kinase 8(MAPK8), cyclin D1(CCND1), IL6, epidermal growth factor receptor(EGFR), phosphatidylinositol 3-kinase(PI3 K), and protein kinase B(Akt) by qRT-PCR and Western blot. Network pharmacology predicted that MAPK8, CCND1, IL6, and EGFR were the potential targets of MT in the treatment of asthma, which may be related to PI3 K/Akt signaling pathway. Quercetin and ß-sitosterol in MT acted on a lot of targets related to asthma, and molecular docking results showed that quercetin and ß-sitosterol had strong binding activity to MAPK, PI3 K, and Akt. In vivo experiment showed that MT could effectively alleviate the symptoms of OVA-induced asthma rats, improve the pathological changes of lung tissue, reduce the production of goblet cells, inhibit the inflammatory response of asthma rats, suppress the expression of MAPK8, CCND1, IL6, and EGFR, and regulate the PI3 K/Akt signaling pathway. Therefore, MT may relieve the symptoms and inhibit inflammation of asthma rats by regulating the PI3 K/Akt signaling pathway, and quercetin and ß-sitosterol are the candidate active components.