Clinical Efficacy and Gut Microbiota Regulating-Related Effect of Si-Jun-Zi Decoction in Postoperative Non-Small Cell Lung Cancer Patients: A Prospective Observational Study.

BACKGROUND: Postoperative non-small cell lung cancer (NSCLC) patients frequently encounter a deteriorated quality of life (QOL), disturbed immune response, and disordered homeostasis. Si-Jun-Zi Decoction (SJZD), a well-known traditional Chinese herbal formula, is frequently employed in clinical application for many years. Exploration is underway to investigate the potential therapeutic effect of SJZD for treating postoperative NSCLC. OBJECTIVE: To assess the efficacy of SJZD on QOLs, hematological parameters, and regulations of gut microbiota in postoperative NSCLC patients. METHODS: A prospective observational cohort study was conducted, enrolling 65 postoperative NSCLC patients between May 10, 2020 and March 15, 2021 in Yueyang Hospital, with 33 patients in SJZD group and 32 patients in control (CON) group. The SJZD group comprised of patients who received standard treatments and the SJZD decoction, while the CON group consisted of those only underwent standard treatments. The treatment period was 4 weeks. The primary outcome was QOL. The secondary outcomes involved serum immune cell and inflammation factor levels, safety, and alterations in gut microbiota. RESULTS: SJZD group showed significant enhancements in cognitive functioning (P = .048) at week 1 and physical functioning (P = .019) at week 4. Lung cancer-specific symptoms included dyspnea (P = .001), coughing (P = .008), hemoptysis (P = .034), peripheral neuropathy (P = .019), and pain (arm or shoulder, P = .020, other parts, P = .019) eased significantly in the fourth week. Anemia indicators such as red blood cell count (P = .003 at week 1, P = .029 at week 4) and hemoglobin (P = .016 at week 1, P = .048 at week 4) were significantly elevated by SJZD. SJZD upregulated blood cell cluster differentiation (CD)3+ (P = .001 at week 1, P < .001 at week 4), CD3+CD4+ (P = .012 at week 1), CD3+CD8+ (P = .027 at week 1), CD19+ (P = .003 at week 4), increased anti-inflammatory interleukin (IL)-10 (P = .004 at week 1, P = .003 at week 4), and decreased pro-inflammatory IL-8 (P = .004 at week 1, p = .005 at week 4). Analysis of gut microbiota indicated that SJZD had a significant impact on increasing microbial abundance and diversity, enriching probiotic microbes, and regulating microbial biological functions. CONCLUSIONS: SJZD appears to be an effective and safe treatment for postoperative NSCLC patients. As a preliminary observational study, this study provides a foundation for further research.

Predicting the mechanism of action of YQYYJD prescription in the treatment of non-small cell lung cancer using transcriptomics analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: The efficacy of the herbal formula Yiqi Yangyin Jiedu (YQYYJD) in the treatment of advanced lung cancer has been reported in clinical trials. However, the key anti-lung cancer herbs and molecular mechanisms underlying its inhibition of lung cancer are not well-understood. AIM OF THE STUDY: To identify the key anti-lung cancer herbs in the YQYYJD formula and investigate their therapeutic effect and potential mechanism of action in non-small cell lung cancer (NSCLC) using transcriptomics and bioinformatics techniques. MATERIALS AND METHODS: A mouse Lewis lung carcinoma (LLC) subcutaneous inhibitory tumor model was established with 6 mice in each group. Mice were treated with the YQYYJD split formula: Yiqi Formula (YQ), Yangyin Formula (YY), and Ruanjian Jiedu Formula (RJJD) for 14 days. The tumor volume and mouse weight were recorded, and the status of tumor occurrence was further observed by taking photos. The tumor was stained with hematoxylin-eosin to observe its histopathological changes. Immunohistochemistry was used to detect the expression of the proliferation marker Ki67 and the apoptotic marker Caspase-3 in tumor tissues. Flow cytometry was used to detect the number of CD4+ and CD8+ T cells and cytokines interleukin-2 (IL-2) and interferon-gamma (IFN-γ) in the spleen and tumor tissues. The differential genes of key drugs against tumors were obtained by transcriptome sequencing of tumors. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) enrichment analyses were performed on differential genes to obtain pathways and biological processes where targets were aggregated. TIMER2.0 and TISIDB databases were used to evaluate the impact of drugs on immune cell infiltration and immune-related genes. The binding activity of the key targets and compounds was verified by molecular docking. RESULTS: YQ, YY, and RJJD inhibited the growth of subcutaneous transplanted tumors in LLC mice to varying degrees and achieved antitumor effects by inhibiting the expression of tumor cell proliferation, apoptosis, and metastasis-related proteins. Among the three disassembled prescriptions, YQ better inhibited the growth of subcutaneous transplanted tumors in LLC mice, significantly promoted tumor necrosis, significantly increased the expression of Caspase-3 protein in tumor tissue, and significantly decreased the expression of Ki-67 (P < 0.05), thereby increasing the infiltration of CD8+ T cells. YQ significantly increased the expression of CD4+ and CD8+ T cells in tumor and splenic tissues of tumor-bearing mice and up-regulated the expression of IL-2 and IFN-γ. Transcriptome sequencing and bioinformatics results showed that after YQ intervention, differentially expressed genes were enriched in more than one tumor-related pathway and multiple immune regulation-related biological functions. There were 12 key immune-related target genes. CONCLUSION: YQ was the key disassembled prescription of YQYYJD, exerting significant antitumor effects and immune regulation effects on NSCLC. It may have relieved T cell exhaustion and regulated the immune microenvironment to exert antitumor effects by changing lung cancer-related targets, pathways, and biological processes.

Predicting autism spectrum disorder using maternal risk factors: A multi-center machine learning study.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a complex environmental etiology involving maternal risk factors, which have been combined with machine learning to predict ASD. However, limited studies have considered the factors throughout preconception, perinatal, and postnatal periods, and even fewer have been conducted in multi-center. In this study, five predictive models were developed using 57 maternal risk factors from a cohort across ten cities (ASD:1232, typically developing[TD]: 1090). The extreme gradient boosting model performed best, achieving an accuracy of 66.2 % on the external cohort from three cities (ASD:266, TD:353). The most important risk factors were identified as unstable emotions and lack of multivitamin supplementation using Shapley values. ASD risk scores were calculated based on predicted probabilities from the optimal model and divided into low, medium, and high-risk groups. The logistic analysis indicated that the high-risk group had a significantly increased risk of ASD compared to the low-risk group. Our study demonstrated the potential of machine learning models in predicting the risk for ASD based on maternal factors. The developed model provided insights into the maternal emotion and nutrition factors associated with ASD and highlighted the potential clinical applicability of the developed model in identifying high-risk populations.

Engineered macrophage-derived cellular vesicles for NIR-II fluorescence imaging-guided precise cancer photo-immunotherapy.

Significant progress has been made in cancer immunotherapy; however, challenges such as interpatient variability, limited treatment response, and severe side effects persist. Although nanoimmunotherapy has emerged as a promising approach, the construction of precise and efficient nanosystems remain formidable challenges. Herein, a multifunctional nanoplatform was developed using macrophage-derived cellular vesicles (MCVs) for NIR-II imaging-guided precise cancer photo-immunotherapy. MCVs exhibited excellent tumor targeting and TAMs re-education effects, serving as both delivery carriers and therapeutic agents. Through amide bond, indocyanine green (ICG) was conjugated to the surface of MCVs, enabling in vivo tracking of MCVs distribution. Notably, ICG exhibited dual functionality as a NIR-II fluorescent agent and possessed photodynamic and photothermal effects, enabling the conversion of light energy into chemical or heat energy to eliminate tumor cells. This precision phototherapy triggered immunogenic cell death (ICD) of tumor, thereby activating the anti-tumor immune response. Additionally, MCVs loaded with R848, a toll-like receptor agonist, augmented the ICD-induced anti-tumor immunity. Animal experiments confirmed that MCVs-mediated photoimmunotherapy promoted T cell infiltration, inhibited tumor growth, and improved survival rates. In conclusion, we have developed a promising precision immunotherapy strategy capable of enhancing the immune response while mitigating off-target effects. These findings offer encouraging prospects for clinical translation.

Effect of controlling nitrogen and phosphorus release from sediment using a biological aluminum-based P-inactivation agent (BA-PIA).

A biological aluminum-based P-inactivation agent (BA-PIA) has been developed and demonstrated to effectively remove nitrogen and phosphorus; however, whether it can control the release of nitrogen and phosphorus in sediment still needs study. This study aimed to examine the effect of BA-PIA on controlling sediment nitrogen and phosphorus release. BA-PIA was prepared by artificial aeration. The use of BA-PIA in controlling nitrogen and phosphorus release was studied using water and sediment from a landscape lake in static simulation experiments. The sediment microbial community was analyzed using high-throughput sequencing. Static simulation showed that the reduction rates of total nitrogen (TN) and total phosphorus (TP) by BA-PIA were 66.8 ± 1.46% and 96.0 ± 0.98%, respectively. In addition, capping of BA-PIA promotes the conversion of easily released nitrogen (free nitrogen) in the sediment to stable nitrogen (acid-hydrolyzable nitrogen). The content of weakly adsorbed phosphorus and iron-adsorbed phosphorus in the sediment was reduced. The relative abundance of nitrifying bacteria, denitrifying bacteria, and microorganisms carrying phosphatase genes (such as Actinobacteria) in the sediment increased by 109.78%. The capping of BA-PIA not only effectively removed the nitrogen and phosphorus in water but greatly reduced the risk of nitrogen and phosphorus release from sediment. BA-PIA was able to make up for the deficiency of the aluminum-based phosphorus-locking agent (Al-PIA) that only removes phosphorus, giving it improved application prospects.

Association of feeding patterns in infancy with later autism symptoms and neurodevelopment: a national multicentre survey.

BACKGROUND: We aimed to compare differences in infant feeding patterns (breastfeeding and complementary food supplementation) between children with the autism spectrum disorder (ASD) and typically developing (TD) children through a multicentre study. The relationship between these patterns and later core symptoms and neurodevelopment in children with ASD was also investigated. METHODS: We analysed breastfeeding and complementary feeding patterns in 1389 children with ASD and 1190 TD children. The Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016) was used to assess neurodevelopmental levels. The Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), Childhood Autism Rating Scale (CARS), and ASD Warning Behavior Subscale of the CNBS-R2016 were used to assess ASD symptoms. RESULTS: Children with ASD had a shorter breastfeeding duration in infancy (8 (3-12) months vs. 10 (6-14) months, P < 0.001), later introduction of complementary foods (P < 0.001), and poorer acceptance of complementary foods (P < 0.001) than TD children. Total ABC and CARS scores were lower in the group of children with ASD who had been breastfed for 12 months or more than in the group who had been breastfed for less than 6 months. Children with ASD who were given complementary food after 6 months had lower general quotient (GQ), adaptive ability, fine motor and language scores than those who were given complementary food within 4-6 months. Children with ASD with poor acceptance of complementary foods had higher ABC and SRS scores and lower gross motor scores than those who had good acceptance. CONCLUSIONS: Children with ASD have a shorter duration of breastfeeding, a later introduction of complementary foods, and poorer acceptance of complementary foods than TD children. These feeding patterns may be related to the symptoms and growth of children with ASD. The research suggests that continued breastfeeding for longer than 12 months may be beneficial in reducing ASD symptoms and that infants who have difficulty introducing complementary foods should be followed up for neurodevelopment. TRIAL REGISTRATION: The ethics committee of the Children's Hospital of Chongqing Medical University approved the study. Approval Number: (2018) IRB (STUDY) NO. 121, and registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2000031194, registered on 23/03/2020).

Removal efficacy and mechanism of nitrogen and phosphorus by biological aluminum-based P-inactivation agent (BA-PIA).

In this study, aluminum-based P-inactivation agent (Al-PIA) was used as a high-efficiency microbial carrier, and the biological Al-PIA (BA-PIA) was prepared by artificial aeration. Laboratory static experiments were conducted to study the effect of BA-PIA on reducing nitrogen and phosphorus contents in water. Physicochemical characterization and isotope tracing method were applied to analyze the removal mechanism of nitrogen and phosphorus. High-throughput techniques were used to analyze the characteristic bacterial genus in the BA-PIA system. The nitrogen and phosphorus removal experiment was conducted for 30 days, and the removal rates of NH4+-N, TN and TP by BA-PIA were 81.87%, 66.08% and 87.97%, respectively. The nitrogen removal pathways of BA-PIA were as follows: the nitrification reaction accounted for 59.0% (of which denitrification reaction accounted for 56.4%), microbial assimilation accounted for 18.1%, and the unreacted part accounted for 22.9%. The characteristic bacteria in the BA-PIA system were Streptomyces, Nocardioides, Saccharopolyspora, Nitrosomonas, and Marinobacter. The loading of microorganisms only changed the surface physical properties of Al-PIA (such as specific surface area, pore volume and pore size), without changing its surface chemical properties. The removal mechanism of nitrogen by BA-PIA is the conversion of NH4+-N into NO2--N and NO3--N by nitrifying bacteria, which are then reduced to nitrogen-containing gas by aerobic denitrifying bacteria. The phosphorus removal mechanism is that metal compounds (such as Al) on the surface of BA-PIA fix phosphorus through chemisorption processes, such as ligand exchange. Therefore, BA-PIA overcomes the deficiency of Al-PIA with only phosphorus removal ability, and has better application prospects.

Evaluation of the potential of ultrasound-mediated drug delivery for the treatment of ovarian cancer through preclinical studies.

Ovarian cancer (OC) has the greatest mortality rate among gynecological cancers, with a five-year survival rate of <50%. Contemporary adjuvant chemotherapy mostly fails in the case of OCs that are refractory, metastatic, recurrent, and drug-resistant. Emerging ultrasound (US)-mediated technologies show remarkable promise in overcoming these challenges. Absorption of US waves by the tissue results in the generation of heat due to its thermal effect causing increased diffusion of drugs from the carriers and triggering sonoporation by increasing the permeability of the cancer cells. Certain frequencies of US waves could also produce a cavitation effect on drug-filled microbubbles (MBs, phospholipid bilayers) thereby generating shear force and acoustic streaming that could assist drug release from the MBs, and promote the permeability of the cell membrane. A new class of nanoparticles that carry therapeutic agents and are guided by US contrast agents for precision delivery to the site of the ovarian tumor has been developed. Phase-shifting of nanoparticles by US sonication has also been engineered to enhance the drug delivery to the ovarian tumor site. These technologies have been used for targeting the ovarian cancer stem cells and protein moieties that are particularly elevated in OCs including luteinizing hormone-releasing hormone, folic acid receptor, and vascular endothelial growth factor. When compared to healthy ovarian tissue, the homeostatic parameters at the tissue microenvironment including pH, oxygen levels, and glucose metabolism differ significantly in ovarian tumors. US-based technologies have been developed to take advantage of these tumor-specific alterations for precision drug delivery. Preclinical efficacy of US-based targeting of currently used clinical chemotherapies presented in this review has the potential for rapid human translation, especially for formulations that use all substances that are deemed to be generally safe by the U.S. Food and Drug Administration.

Tumor-Homing and Immune-Reprogramming Cellular Nanovesicles for Photoacoustic Imaging-Guided Phototriggered Precise Chemoimmunotherapy.

Many studies have focused on developing effective therapeutic strategies to selectively destroy primary tumors, eliminate metastatic lesions, and prevent tumor recurrence with minimal side effects on normal tissues. In this work, we synthesized engineered cellular nanovesicles (ECNVs) with tumor-homing and immune-reprogramming functions for photoacoustic (PA) imaging-guided precision chemoimmunotherapy. M1-macrophage-derived cellular nanovesicles (CNVs) were loaded with gold nanorods (GNRs), gemcitabine (GEM), CpG ODN, and PD-L1 aptamer. The good histocompatibility and tumor-homing effect of CNVs improved drug retention in the bloodstream and led to their enrichment in tumor tissues. Furthermore, the photothermal ability of GNRs enabled PA imaging-guided drug release. GEM induced tumor immunogenic cell death (ICD), and CpG ODN promoted an immune response to the antigens released by ICD, leading to long-term specific antitumor immunity. In addition, the PD-L1 aptamer relieved the inhibitory effect of the PD1/PD-L1 checkpoint on CD8+ T-cells and augmented the immunotherapeutic effect. The synergistic innate and adaptive immune responses enhanced the antitumor effect of ECNVs. In summary, this nanoplatform integrates local targeted photothermal therapy with extensive progressive chemotherapy and uses ICD to reshape the immune microenvironment for tumor ablation.

Vitamin D status is primarily associated with core symptoms in children with autism spectrum disorder: A multicenter study in China.

OBJECTIVE: We aimed to investigate the relationship between vitamin D status and core symptoms and neurodevelopmental levels in children with ASD with a multicenter survey. METHODS: We enrolled 1321 ASD children and 1279 typically developing (TD) children aged 2-7 years from 13 cities in China. ASD symptoms were assessed with the Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS) and Childhood Autism Rating Scale (CARS), and neurodevelopmental levels were evaluated with the Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016). RESULTS: Children with ASD had lower serum 25(OH)D levels than TD children. Serum 25(OH)D levels were negatively associated with CARS and communication warning behavior of CNBS-R2016 scores, and were not associated with the development quotients of ASD children. ASD Children were grouped based on the quartiles for 25(OH)D levels in the controls, and children in the first to third quartiles had higher SRS social communication and/or CARS and communication warning behavior of CNBS-R2016 scores than those in the fourth quartile. CONCLUSIONS: Serum 25(OH)D levels were primarily associated with core symptoms in children with ASD, and individuals with relatively lower 25(OH)D levels displayed worse autistic symptomatology. More research is needed to determine whether vitamin D supplements would be a useful treatment for ASD.

Three kinds of active thin-layer capping materials for reducing the phosphorus load in eutrophic water body: comparison in dynamic experiment.

In this article, dynamic simulation experiments have studied the effects of three capping materials, quartz sand (QS), aluminum-based phosphorus-locking agent (Al-PIA), and lanthanum-modified bentonite (LMB) in reducing phosphorus load in eutrophic water bodies. The changes of various forms of phosphorus in Al-PIA and sediment before and after the test were analyzed, and the mechanism of phosphorus migration and transformation in different capping systems was described. The dynamic simulation test lasted 95 days. The results showed that when the initial concentration of total phosphorus (TP) was 3.55 mg/L, the capping strength was 2 kg/m2 and the hydraulic retention time of water circulation was 0.5 days, indicating that the average reduction rates of TP by LMB, Al-PIA and QS systems were 74.66%, 69.54%, and 3.64%, respectively, compared with the control system. The analysis of variance showed that there were significant differences (P < 0.05) in the TP concentration of the overlying water between the LMB, Al-PIA capping system, and the control system. Lanthanum ions in LMB can fix phosphorus. Al-PIA reduces the phosphorus concentration in water by means of ion exchange, adsorption, complexation, etc. LMB and Al-PIA promoted the migration of phosphorus in sediment. Among them, the phosphorus fixed by Al-PIA was mainly in the form of non-apatite inorganic phosphorus (NAIP) in inorganic phosphorus (IP), which can be seen; Al-PIA can effectively reduce the phosphorus load of eutrophic water.

[Blade acupuncture combined with functional exercise for chronic pain after non-small cell lung cancer surgery: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of blade acupuncture combined with functional exercise for chronic pain after non-small cell lung cancer surgery. METHODS: A total of 62 patients with chronic pain after surgery for non-small cell lung cancer were randomly divided into an observation group and a control group, 31 cases in each group. The patients in the control group were treated with functional exercise. On the base of the treatment in the control group, the patients in the observation group were treated with blade acupuncture at the tendon nodes or painful points, once a week for 4 weeks. The visual analogue scale (VAS) scores of pain before treatment and day 1, day 7, day 14, day 28 of treatment and day 90, day 180 when follow up were compared between the two groups; the brief pain inventory (BPI) scores before and after treatment were compared between the two groups. RESULTS: The VAS score in the observation group at each time point after treatment was lower than that before treatment (P<0.01), and lower than that in the control group (P<0.01). Compared before treatment, the daily life score, emotion score, walking ability score, sleep score and life enjoyment score and total score of BPI in the observation group were reduced after treatment (P<0.05), and the daily life score, emotion score, sleep score and total score of BPI in the observation group were lower than those in the control group (P<0.05). CONCLUSION: The blade acupuncture combined with functional exercise could effectively alleviate the chronic pain after non-small cell lung cancer surgery, improve the quality of life of patients, and the effect is lasting and stable.

Anticancer Action of Xiaoxianxiong Tang in Non-Small Cell Lung Cancer by Pharmacological Analysis and Experimental Validation.

Xiaoxianxiong Tang (XXXT) is a well-known traditional Chinese medicine formula. Evidence is emerging supporting the benefits of XXXT in ameliorating therapy for non-small cell lung cancer (NSCLC). The purpose of this study aimed to explore the effects and mechanisms of XXXT through network pharmacological analysis and biological validation. TCMSP database was used to identify potentially active compounds in XXXT with absorption, distribution, metabolism, excretion screening, and their potential targets. The disease targets related to NSCLC were predicted by searching for Therapeutic Target database, GeneCards database, DrugBank database, and DisGeNET database. Of the 4385 NSCLC-related targets, 156 targets were also the targets of compounds present in XXXT. Subsequently, GO function and KEGG pathway enrichment and PPI network analyses revealed that, of the 95 targets and 20 pathways influenced by 20 ingredients in XXXT, 20 targets were associated with patient survival, and XXXT could exert an inhibitory action on the PI3K-AKT signaling pathway. Moreover, XXXT restrained the proliferation of A549 and H460 cells in a concentration-dependent manner and suppressed the mRNA and protein levels of key targets CCNA2, FOSL2, and BIRC5 closely linked to the PI3K-AKT pathway. Hence, XXXT has the potential to improve therapy for NSCLC by targeting the PI3K-AKT signaling pathway.

Smoking behavior and circulating vitamin D levels in adults: A meta-analysis.

To determine the effect of smoking on circulating vitamin D in adults, we performed a meta-analysis. Literature before 9 May 2021 was retrieved from electronic literature databases such as EMBASE, PubMed, and Cochrane. The quality of the included studies was assessed by two researchers against the Newcastle-Ottawa scale and JBI Evidence-based Health Care Centre criteria. All eligible studies and statistical analyses were performed using STATA 14. Twenty-four studies with 11,340 participants meeting the criteria were included in the meta-analysis. The results of meta-analysis showed that the level of circulating 25(OH)D in smokers was lower than that in nonsmokers. A subgroup analysis based on vitamin D supplement use showed that both smokers who used vitamin D supplements and smokers who did not use vitamin D supplements had lower blood 25(OH)D levels compared with the control group. In addition, subjects were divided into different subgroups according to age for meta-analysis, and the results showed that the serum 25(OH)D level in each subgroup of smokers was lower than that in the control group. This meta-analysis revealed differences in circulating vitamin D levels between smokers and nonsmokers, with smokers likely to have lower circulating vitamin D levels.

Quality evaluation of powdered poppy capsule extractive by systematic quantified fingerprint method combined with quantitative analysis of multi-components by single marker method.

Powdered Poppy Capsule Extractive (PPCE) is largely used as a raw material of Compound Liquorice Tablets, but there are few studies of its quality evaluation or control. In this paper, a novel strategy for quality assessment of PPCE, systematic quantified fingerprint method (SQFM) combined with quantitative analysis of multi-components by a single marker (QAMS) method, was developed and validated. According to the outcome of Pm and the content of codeine and morphine, 41 batches of PPCEs were classified into two classifications by hierarchical cluster analysis, and the samples in one of the categories were obviously inferior to normal in quality. The results demonstrated that the strategy developed in this paper could provide a new method for quality evaluation of PPCE or even other traditional Chinese medicine (TCM).

Metabolomic Study on the Preventive Effect of Patrinia scabiosaefolia Fisch on Multipathogen Induced Pelvic Inflammatory Disease in Rats.

Patrinia scabiosaefolia Fisch (PSF), a well-known traditional Chinese medicine (TCM), has been used as a "heat-clearing and detoxifying" agent. The present study was to illustrate the preventive effect of PSF on pelvic inflammatory disease (PID) in rats. The PID model was constructed by multipathogen infection of the upper genital tract with reference to the method previously reported. Urine metabolomic analysis was conducted with a GC-MS coupled with derivatization method. In this study, PID rats showed obvious infiltration of inflammatory cells and elevated expression of cytokines (IL-1ß and IL-6) in upper genital tract, compared with control rats. Sixteen differentiating metabolites contributed to the alteration of metabolic profile in PID rats, including two amino acids, three fat acids, nine organic acids, and two types of sugars. The rats, infected by multipathogen and administered with PSF, showed decreased infiltration of inflammatory cells and lowered expression of cytokines in upper genital tract, compared with PID rats. Meanwhile, PSF intervened in the PID-associated alterations in TCA cycle, sugar metabolism, amino acid metabolism, and other uncertain metabolic pathways. These results indicate that PSF has preventive effect on multipathogen induced PID and holistic interventional effect on disease-associated metabolomic change.

In vitro and in vivo anti-cancer activity of formononetin on human cervical cancer cell line HeLa.

Worldwide, cervical cancer (CC) is the third most common malignancy in women, and it remains a leading cause of cancer-related death of women. Genomic studies indicate that phosphoinositide 3-kinase (PI3K)/AKT signaling is one of the most frequently deregulated pathways in several human cancers, including CC. This signaling pathway has an important role in cancer cell proliferation, survival, motility, and metabolism, and therefore could be an attractive therapeutic target. In a previous study, we used a sensitive and high-speed homogeneous assay for the detection of kinase activity and for screening of PI3K/AKT signaling inhibitors in a high-throughput screening (HTS) format and then obtain formononetin, as an O-methylated isoflavone existed in a number of plants and herbs like Astragalus membranaceus. We showed that formononetin inhibited the phosphorylation of AKT and induced the apoptosis of CC cell line HeLa in a dose-dependent manner. Furthermore, formononetin suppressed xenograft tumor growth in nude mice. Our results indicated that formononetin may be used as an anti-cancer drug for cervical cancer in the future.