The potential mechanism of ursolic acid in the treatment of bladder cancer based on network pharmacology and molecular docking.

OBJECTIVE: This study explored the potential molecular mechanisms of ursolic acid (UA) in bladder cancer treatment using network pharmacology and molecular docking. METHODS: The Traditional Chinese Medicine Systems Pharmacology and UniProt databases were used to screen potential targets of UA. Relevant bladder cancer target genes were extracted using the GeneCards database. All data were pooled and intercrossed to obtain common target genes of UA and bladder cancer. Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. Molecular docking was conducted to verify the possible binding conformation between UA and bladder cancer cells. Then, in vitro experiments were performed to further validate the predicted results. RESULTS: UA exerts anti-tumor effects on bladder cancer through multiple targets and pathways. Molecular docking indicated that UA undergoes stable binding with the proteins encoded by the top six core genes (STAT3, VEGFA, CASP3, TP53, IL1B, and CCND1). The in vitro experiments verified that UA can induce bladder cancer cell apoptosis by regulating the PI3K/Akt signaling pathway. CONCLUSIONS: Our study illustrated the potential mechanism of UA in bladder cancer based on network pharmacology and molecular docking. The results will provide scientific references for follow-up studies and clinical treatment.

Mechanism of Shengmaisan Regulating Cardiac Remodeling of Arrhythmias with Deficiency of Qi and Yin / 中国实验方剂学杂志

Arrhythmia is an important disease among cardiovascular diseases. Malignant arrhythmias often occur clinically and are induced by abnormal ion channels， electrical activity disorders， myocardial fibrosis， inflammation， dysfunctional mitochondrial biogenesis， mitochondrial calcium overload， out-of-balance energy metabolism， oxidative stress， sympathetic hyperactivity， and other pathological cardiac remodeling， and they are the main causes of sudden cardiac death. In traditional Chinese medicine， arrhythmias are considered to be palpitations， which are commonly caused by deficiency of Qi and Yin. It is often manifested as a deficiency of the spleen and stomach， resulting in malfunction of the Qi mechanism， followed by a particularly severe decline in cardiac function. Shengmaisan is a representative formula for nourishing Qi and Yin， consisting of Ginseng Radix et Rhizoma， Ophiopogonis Radix， and Schisandrae Chinensis Fructus. In recent years， clinical studies have shown that Shengmaisan and its additions and subtractions are commonly used in the treatment of arrhythmias. In this article， the mechanisms of the active ingredients of Shengmaisan in the electrophysiology， biochemistry， structure， autonomic nervous system， and subcellular fraction of the heart are reviewed， and the multi-target， multi-system， and integrality of Shengmaisan in the treatment of arrhythmias of Qi and Yin deficiency are described. In addition， energy metabolism disorder is tightly juxtaposed with Qi and Yin deficiency syndrome. Mitochondria， as the center of myocardial energy metabolism， play a paramount role in cardiac remodeling， indicating that Shengmaisan will be a salient part of future research to ameliorate cardiac pathologic remodeling through energy metabolism of mitochondria， so as to provide a theoretical basis for the clinical treatment of these arrhythmias.

Targeted metabolomics reveals PFKFB3 as a key target for elemene-mediated inhibition of glycolysis in prostate cancer cells.

BACKGROUND: Elemene, an active anticancer extract derived from Curcuma wenyujin, has well-documented anticarcinogenic properties. Nevertheless, the role of elemene in prostate cancer (PCa) and its underlying molecular mechanism remain elusive. PURPOSE: This study focuses on investigating the anti-PCa effects of elemene and its underlying mechanisms. METHODS: Cell-based assays, including CCK-8, scratch, colony formation, cell cycle, and apoptosis experiments, to comprehensively assess the impact of elemene on PCa cells (LNCaP and PC3) in vitro. Additionally, we used a xenograft model with PC3 cells in nude mice to evaluate elemene in vivo efficacy. Targeted metabolomics analysis via HILIC-MS/MS was performed to investigate elemene potential target pathways, validated through molecular biology experiments, including western blotting and gene manipulation studies. RESULTS: In this study, we discovered that elemene has remarkable anti-PCa activity in both in vitro and in vivo settings, comparable to clinical chemotherapeutic drugs but with fewer side effects. Using our established targeted metabolomics approach, we demonstrated that ß-elemene, elemene's primary component, effectively inhibits glycolysis in PCa cells by downregulating 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) expression. Furthermore, we found that ß-elemene accomplishes this downregulation by upregulating p53 and FZR1. Knockdown and overexpression experiments conclusively confirmed the pivotal role of PFKFB3 in mediating ß-elemene's anti-PCa activity. CONCLUSION: This finding presents compelling evidence that elemene exerts its anti-PCa effect by suppressing glycolysis through the downregulation of PFKFB3. This study not only improves our understanding of elemene in PCa treatment but also provides valuable insights for developing more effective and safer therapies for PCa.

Analysis of initial sandplay characteristics among university students with different levels of loneliness.

BACKGROUND AND OBJECTIVE: Loneliness is detrimental to mental health, with university students at higher risk of feeling lonely than other population groups. The mental health of college students is a hot topic at present. Despite numerous studies exploring interventions for loneliness among university students. However, little research has explored early psychological manifestations of university students with different levels of loneliness. Despite numerous studies exploring interventions for loneliness among university students, little research has explored early psychological manifestations of university students with different levels of loneliness. Initial sandplay is a good tool to reveal psychological activity. Therefore, our study aims to explore the characteristics of initial sandplay application among university students with different levels of loneliness. METHODS: We recruited 60 volunteers from a university to perform a sandplay experiment from January to April 2021. The UCLA Loneliness Scale measured the levels of loneliness. These 60 participants were divided into the experimental group (n = 30) and control group (n = 30) according to their levels of loneliness. The experimental group included participants with a scale score of more than 44. Other participants with a scale score of less than 44 belong to the control group. We recorded their sandplay artwork and statistically analyzed it by the Sandplay Process Record Form. Group comparisons were performed using the t-test or Wilcoxon rank-sum test for continuous variables, and the chi-square test or Fisher's exact test for categorical variables. The logistic regression analysis by forward stepwise method was conducted to analyze the sandplay theme features for loneliness. RESULTS: Regarding the sandplay tools, the experimental group used fewer transportation tools (t=-3.608, p < 0.01) and more natural elements (t = 2.176, p < 0.05) than the control group. Moreover, the experimental group created more natural scenes (χ2 = 4.310, p < 0.05) and used less of the lower left (χ2 = 4.593, p < 0.05) and lower right (χ2 = 5.934, p < 0.05) spaces. With regards to sand changes, the experimental group was less likely than the control group to make substantial changes (χ2 = 5.711, p < 0.05) and more likely to make almost no changes (χ2 = 4.022, p < 0.05). In terms of the themes, the experimental group was more likely to exhibit sandplay artwork themes of emptiness (χ2 = 8.864, p < 0.05) and neglect (χ2 = 6.667, p < 0.05), and less likely to show themes of energy (χ2 = 5.079, p < 0.05). In the logistic regression analysis of the sandplay themes, emptiness (OR = 5.714, 95%CI: 1.724-18.944, p = 0.003) and neglect (OR = 7.000, 95%CI: 1.381-35.479, p = 0.010) were demonstrated a nominal association with high levels of loneliness among both groups (F = 16.091, p < 0.01, ΔR2 = 0.193), but failed to pass the Bonferroni testing correction (p threshold < 0.0025). CONCLUSION: University students with higher degree of loneliness do not like to drastic changes and prefer to use natural elements in element selection, while the control group likes to drastic changes and prefers to use transportation tools in element selection. Regression analysis of sandplay theme features revealed emptines and neglect may as significant associated factors for loneliness. We propose sandplay characteristics can help identify university students with different levels of loneliness during psychological evaluations. Therefore, it is important that the school and healthcare systems assist college students in identifying the loneliness through initial sandplay and carrying on the necessary psychological counseling to the lonely student population.

Preparation, Characterization, and Antioxidant Properties of Selenium-Enriched Tea Peptides.

The research on the activity of selenium (Se)-enriched agricultural products is receiving increasing attention since Se was recognized for its antioxidant activities and for its enhancement of immunity in trace elements. In this study, antioxidant Se-containing peptides, namely, Se-TAPepI-1 and Se-TAPepI-2, were optimally separated and prepared from Se-enriched tea protein hydrolysates by ultrafiltration and Sephadex G-25 purification, and subsequently, their physicochemical properties, oligopeptide sequence, and potential antioxidant mechanism were analyzed. Through the optimization of enzymatic hydrolysis conditions, the Se-enriched tea protein hydrolyzed by papain exhibited a better free radical scavenging activity. After separation and purification of hydrolysates, the two peptide fractions obtained showed significant differences in selenium content, amino acid composition, apparent morphology, peptide sequence, and free radical scavenging activity. Therein, two peptides from Se-TAPepI-1 included LPMFG (563.27 Da) and YPQSFIR (909.47 Da), and three peptides from Se-TAPepI-2 included GVNVPYK (775.42 Da), KGGPGG (552.24 Da), and GDEPPIVK (853.45 Da). Se-TAPepI-1 and Se-TAPepI-2 could ameliorate the cell peroxidation damage and inflammation by regulating NRF2/ARE pathway expression. Comparably, Se-TAPepI-1 showed a better regulatory effect than Se-TAPepI-2 due to their higher Se content, typical amino acid composition and sequence, higher surface roughness, and a looser arrangement in their apparent morphology. These results expanded the functional activities of tea peptide and provided the theoretical basis for the development of Se-containing peptides from Se-enriched tea as a potential natural source of antioxidant dietary supplements.

Amelioration Effects and Regulatory Mechanisms of Different Tea Active Ingredients on DSS-Induced Colitis.

The potential biological function of tea and its active components on colitis has attracted wide attention. In this study, different tea active ingredients including tea polyphenols (TPPs), tea polysaccharides (TPSs), theabrownin (TB), and theanine (TA) have been compared in the intervention of dextran sulfate sodium (DSS)-induced colitis in mice. Specifically, TPP showed the greatest effect on colitis since it reduced 60.87% of disease activity index (DAI) compared to that of the DSS-induced colitis group, followed by the reduction of 39.13% of TPS and 28.26% of TB on DAI, whereas there was no obvious alleviative effect of TA on colitis. TPP, TPS, and TB could regulate the composition and abundance of gut microbiota to increase the content of short-chain fatty acids (SCFAs) and enhance intestinal barrier function. Further evidence was observed that TPP and TPS regulated the activation of Nrf2/ARE and the TLR4/MyD88/NF-κB P65 pathway to alleviate the colitis. Results of cell experiments demonstrated that TPP showed the greatest antiapoptosis and mitochondrial function protective capability among the tea ingredients via inhibiting the Cytc/Cleaved-caspase-3 signaling pathway. In summary, the superior anticolitis activity of TPP compared to TPS and TB is primarily attributed to its unique upregulation of the abundance of Akkermansia and its ability to regulate the mitochondrial function.

Early intervention improves clinical responses to seasonal allergic rhinitis by stimulation in sphenopalatine ganglion (Xinwu acupoint).

OBJECTIVE: To examine the efficacy of early intervention (4 weeks before pollen dispersal) with sphenopalatine ganglion (Xinwu acupoint) stimulation in patients with allergies after the onset of seasonal allergic rhinitis (SAR). METHODS: This is a prospective, randomized and unblinded half-open study. Forty-one SAR volunteers were randomly assigned to either the sphenopalatine ganglion (SPG) acupuncture plus supplementary acupuncture (SPG group) or the sham-SPG acupuncture plus supplementary acupuncture (SA group) stimulation 4 weeks before the onset of allergy season. The changes of the total nasal symptom score (TNSS) and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores were measured on the first week in the onset of allergy season. RESULTS: Four patients dropped out due to local hematoma and pain in the SPG and SA groups. The remaining 37 patients continued through to the end of the trial. After early intervention 4 weeks before the onset of allergy season, the sneezing, nasal congestion and itchiness scores in the first week of onset time were significantly lower in the SPG group than in the SA group patients ( 0.001). The RQLQ score obtained at the onset of symptoms indicated that symptoms were more significantly ameliorated in the SPG group than in the SA group (0.001). CONCLUSIONS: The results of this study confirmed that early intervention by sphenopalatine ganglion (Xinwu acupoint) stimulation can effectively improve the symptoms and the quality of SAR patients' daily lives.

Detection methods, migration patterns, and health effects of pesticide residues in tea.

Due to its rich health benefits and unique cultural charm, tea drinking is increasingly popular with the public in modern society. The safety of tea is the top priority that affects the development of tea industry and the health of consumers. During the process of tea growth, pesticides are used to prevent the invasion of pests and diseases with maintaining high quality and stable yield. Because hot water brewing is the traditional way of tea consumption, water is the main carrier for pesticide residues in tea into human body accompanied by potential risks. In this review, pesticides used in tea gardens are divided into two categories according to their solubility, among which water-soluble pesticides pose a greater risk. We summarized the methods of the sample pretreatment and detection of pesticide residues and expounded the migration patterns and influencing factors of tea throughout the process of growth, processing, storage, and consumption. Moreover, the toxicity and safety of pesticide residues and diseases caused by human intake were analyzed. The risk assessment and traceability of pesticide residues in tea were carried out, and potential eco-friendly improvement strategies were proposed. The review is expected to provide a valuable reference for reducing risks of pesticide residues in tea and ensuring the safety of tea consumption.

Natural Products and Gastric Cancer: Cellular Mechanisms and Effects to Change Cancer Progression.

Gastric cancer is a severe malignant tumor with high morbidity and mortality, which seriously affects people's health. At present, the most common treatment for gastric cancer is chemotherapy. However, chemotherapy is very harmful to the human body, and some of the injuries caused by chemotherapy are irreversible. Natural products have low toxicity and anti-cancer activity, so they are currently widely studied at present. Natural products are a large variety of compounds naturally found in fruits, vegetables, spices, and medicinal plants. It is reported that natural products have different anti-cancer properties. This review has summarized the study of natural products in inducing gastric cancer cell apoptosis, inhibiting gastric cancer cell metastasis, and inhibiting gastric cancer cell proliferation. The relevant references on gastric cancer and natural products were obtained from scientific databases, including Pub- Med, Web of Science, and Science Direct. This paper records dozens of natural products with anti-gastric tumor activity and describes the potential living anti-cancer chemical compounds, their element targets, and their underlying mechanism. This review may lay the foundation for future researchers to treat gastric cancer.

Elemene induces cell apoptosis via inhibiting glutathione synthesis in lung adenocarcinoma.

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizome of Curcuma wenyujin Y.H. Chen & C. Ling, also known as Wen-E-Zhu, has been used for cancer treatment since ancient times, with roots dating back to the Song Dynasty. Elemene (EE), a sesquiterpene extract with potent anticancer properties, is extracted from Wen-E-Zhu, with ß-elemene (BE) being its main active compound, along with trace amounts of ß-caryophyllene (BC), γ-elemene and δ-elemene isomers. EE has demonstrated broad-spectrum anti-cancer effects and is commonly used in clinical treatments for various types of malignant cancers, including lung cancer. Studies have shown that EE can arrest the cell cycle, inhibit cancer cell proliferation, and induce apoptosis and autophagy. However, the exact mechanism of its anti-lung cancer activity remains unclear and requires further research and investigation. AIM OF THE STUDY: In this study, the possible mechanism of EE and its main active components, BE and BC, against lung adenocarcinoma was investigated by using A549 and PC9 cell lines. MATERIALS AND METHODS: The subcutaneous tumor model of nude mice was constructed to evaluate the efficacy of EE in vivo, then the in vitro half-inhibitory concentration (IC50) of EE and its main active components, BE and BC, on A549 and PC9 cells at different concentrations were determined by CCK-8. Flow cytometry was used to detect the apoptosis and cycle of A549 and PC9 cells treated with different concentrations of BE and BC for 24 h. Non-targeted metabolomics analysis was performed on A549 cells to explore potential target pathways, which were subsequently verified through kit detection and western blot analysis. RESULTS: Injection of EE in A549 tumor-bearing mice effectively suppressed cancer growth in vivo. The IC50 of EE and its main active components, BE and BC, was around 60 µg/mL. Flow cytometry analysis showed that BE and BC blocked the G2/M and S phases of lung adenocarcinoma cells and induced apoptosis, leading to a significant reduction in mitochondrial membrane potential (MMP). Results from non-targeted metabolomics analysis indicated that the glutathione metabolism pathway in A549 cells was altered after treatment with the active components. Kit detection revealed a decrease in glutathione (GSH) levels and an increase in the levels of oxidized glutathione (GSSG) and reactive oxygen (ROS). Supplementation of GSH reduced the inhibitory activity of the active components on lung cancer and also decreased the ROS content of cells. Analysis of glutathione synthesis-related proteins showed a decrease in the expression of glutaminase, cystine/glutamate reverse transporter (SLC7A11), and glutathione synthase (GS), while the expression of glutamate cysteine ligase modified subunit (GCLM) was increased. In the apoptosis-related pathway, Bax protein and cleaved caspase-9/caspase-9 ratio were up-regulated and Bcl-2 protein was down-regulated. CONCLUSIONS: EE, BE, and BC showed significant inhibitory effects on the growth of lung adenocarcinoma cells, and the mechanism of action was linked to the glutathione system. By down-regulating the expression of proteins related to GSH synthesis, EE and its main active components BE and BC disrupted the cellular redox system and thereby promoted cell apoptosis.

Recent advances in the utilization of tea active ingredients to regulate sleep through neuroendocrine pathway, immune system and intestinal microbiota.

Sleep disorders have received widespread attention nowadays, which have been promoted by the accelerated pace of life, unhealthy diets and lack of exercise in modern society. The chemical medications to improve sleep has shown serious side effects and risks with high costs. Therefore, it is urgent to develop efficient nutraceuticals from natural sources to ensure sleep quality as a sustainable strategy. As the second most consumed beverage worldwide, the health-promoting effects of tea have long been widely recognized. However, the modulatory effect of teas on sleep disorders has received much less attention. Tea contains various natural sleep-modulating active ingredients such as L-theanine (LTA), caffeine, tea polyphenols (TPP), tea pigments, tea polysaccharides (TPS) and γ-aminobutyric acid (GABA). This review focuses on the potential influence and main regulating mechanisms of different tea active ingredients on sleep, including being absorbed by the small intestine and then cross the blood-brain barrier to act on neurons in the brain as neurotransmitters, manipulating the immune system and further affect sleep-wake cycle by regulating the levels of cytokines, and controlling the gut microbes to maintain the homeostasis of circadian rhythm. Current research progress and limitations are summarized and several future development directions are also proposed. This review hopes to provide new insights into the future elucidation of the sleep-regulating mechanisms of different teas and their natural active ingredients and the development of tea-based functional foods for alleviating sleep disorders. HighlightsNatural sleep-modulating active ingredients in tea have been summarized.Influences of drinking tea or tea active ingredients on sleep are reviewed.Three main regulating mechanisms of tea active ingredients on sleep are explained.The associations among nervous system, immune system and intestinal microbiota are investigated.The potential of developing delivery carriers for tea active ingredients is proposed.

A comprehensive review on the prevention and regulation of Alzheimer's disease by tea and its active ingredients.

Alzheimer's disease (AD) has brought a heavy burden to society as a representative neurodegenerative disease. The etiology of AD combines multiple factors, concluding family, gender, head trauma, diseases and social psychology. There are multiple hypotheses explaining the pathogenesis of AD such as ß-amyloid (Aß) deposition and tau hyperphosphorylation, which lead to extracellular amyloid plaques and neurofibrillary tangles in neurons. The existing therapeutic drugs have several disadvantages including single target, poor curative effect, and obvious side effects. Tea contains many bioactive components, such as tea polyphenols (TPP), L-theanine (L-TH), tea pigment, tea polysaccharides and caffeine. The epidemiological investigations have shown that drinking tea can reduce the risk of AD. The mechanisms of tea active ingredients in the prevention and regulation of AD includes reducing the generation and aggregation of Aß; inhibiting tau aggregation and hyperphosphorylation; inhibiting neuronal apoptosis and regulate neurotransmitters; relieving oxidative stress and neuroinflammation as well as the regulation of intestinal flora. This review summarizes the different signaling pathways that tea active ingredients regulate AD. Furthermore, we propose the main limitations of current research and future research directions, hoping to contribute to the development of natural functional foods based on tea active ingredients in the prevention and treatment of AD.

Natural AD-modulating active ingredients in tea have been summarized.Influences of drinking tea or tea active ingredients on AD are reviewed.Main regulating mechanisms of tea active ingredients on AD are explained.The main limitations of current research and future directions are proposed.

Identification of Kidney-Yang Deficiency Syndrome in Osteoporosis Patients Based on Rule Ensemble Method of Bagging Combining LASSO Regression / 中国实验方剂学杂志

ObjectiveTo investigate the identification of kidney Yang deficiency syndrome of patients with osteoporosis（OP）， and to form the clinical syndrome identification rules of traditional Chinese medicine（TCM）. MethodBasic information， etiology， clinical symptoms and other characteristics of 982 OP patients were included， and statistical tests were used to screen the variables associated with kidney Yang deficiency syndrome. Taking the decision tree as the base model， bootstrap aggregation algorithm（Bagging algorithm） was utilized to establish the classification model of kidney Yang deficiency syndrome in OP， generating numerous rules and removing redundancy. Combining least absolute shrinkage and selection operator（LASSO） regression to screen key rules and integrate them to construct an identification model， achieving the identification of kidney Yang deficiency syndrome in OP patients. ResultEighteen key identification rules were screened out， and of these， where 11 rules with regression coefficients>0 correlated positively with the kidney Yang deficiency syndrome， the rule with the highest coefficient was chilliness（present）&feverish sensation over the palm and sole（absent）. The other 7 rules with regression coefficients<0 correlated negatively with the syndrome， the rule with the lowest coefficient was reddish tongue（present）&diarrhea（absent）&deficiency of endowment（absent）. According to the regression coefficients of each key rule， variables with importance>0.2 were ranked as chilliness， reddish tongue， feverish sensation over the palm and sole， cold limbs， clear urine， diarrhea， deficiency of endowment， prolonged illness. The results of the partial dependence analysis of the identification model showed that compared to OP patients without chilliness， those with chilliness（present） had a 0.266 8 higher probability of being identified as having kidney Yang deficiency syndrome， indicating that this variable had the highest impact on identification of the syndrome. Similarly， compared to OP patients without reddish tongue， those with reddish tongue had a 0.141 9 lower probability of being identified as having kidney Yang deficiency syndrome， indicating that this variable had the highest impact on identifying non-kidney Yang deficiency syndrome. The accuracy， sensitivity， specificity and area under receiver operating characteristic curve（AUC） of the established kidney Yang deficiency syndrome identification model in the test set were 0.865 9， 0.853 7， 0.872 0 and 0.931 5， respectively. ConclusionA precise identification model of OP kidney Yang deficiency syndrome is conducted basing on the rule ensemble method of Bagging combining LASSO regression， and the screened key rules can explain the identification process of kidney Yang deficiency syndrome. In this research， according to the regression coefficients of rules， the importance and partial dependence of variables， combined with the thinking of TCM， the influence of patient characteristics on the identification of syndromes is described， so as to reveal the primary and secondary syndromes of identification and assist the clinical identification of kidney Yang deficiency syndrome.

Class-imbalance Prediction and High-dimensional Risk Factor Identification of Adverse Reactions of Traditional Chinese Medicine with Centralized Monitoring in Real-world Hospitals / 中国实验方剂学杂志

ObjectiveTo achieve high-dimensional prediction of class imbalanced of adverse drug reaction（ADR） of traditional Chinese medicine（TCM） and to classify and identify risk factors affecting the occurrence of ADR based on the post-marketing safety data of TCM monitored centrally in real world hospitals. MethodThe ensemble clustering resampling combined with regularized Group Lasso regression was used to perform high-dimensional balancing of ADR class-imbalanced data， and then to integrate the balanced datasets to achieve ADR prediction and the risk factor identification by category. ResultA practical example study of the proposed method on a monitoring data of TCM injection performed that the accuracy of the ADR prediction， the prediction sensitivity， the prediction specificity and the area under receiver operating characteristic curve（AUC） were all above 0.8 on the test set. Meanwhile， 40 risk factors affecting the occurrence of ADR were screened out from total 600 high-dimensional variables. And the effect of risk factors on the occurrence of ADR was identified by classification weighting. The important risk factors were classified as follows：past history， medication information， name of combined drugs， disease status， number of combined drugs and personal data. ConclusionIn the real world data of rare ADR with a large amount of clinical variables， this paper realized accurate ADR prediction on high-dimensional and class imbalanced condition， and classified and identified the key risk factors and their clinical significance of categories， so as to provide risk early warning for clinical rational drug use and combined drug use， as well as scientific basis for reevaluation of safety of post-marketing TCM.

Constructing a Syndrome Differentiation Model by Combining Latent Structure Analysis of Association Rules： An Example of Kidney Yang Deficiency Syndrome in Primary Osteoporosis / 中医杂志

ObjectiveTo construct a quantitative differentiation model of traditional Chinese medicine （TCM） syndromes by taking primary osteoporosis （POP） with kidney yang deficiency syndrome as an example， and to provide methodological reference for the standardization of syndrome differentiation. MethodsHigh-frequency clinical features of POP were screened by descriptive statistical analysis， and strong association features of POP were obtained by association rule algorithm. On this basis， a latent structure （latent tree） model was established through latent structure analysis， and the implicit and explicit variables （features） related to POP with kidney yang deficiency syndrome were comprehensively clustered， and the clustering results were interpreted by the indexes of mutual information and cumulative information coverage， to explore the primary and secondary symptoms， and to deduce the categories of POP with kidney yang deficiency syndrome based on the probability of the features appearing in the various latent categories. Based on the categories， the clinical feature scores and identification thresholds were calculated， and the syndrome differentiation model of POP with kidney yang deficiency was initially constructed by combining the comprehensive judgment rules. Finally， the results of TCM professionals' judgment were used as the gold standard to further evaluate the effectiveness of the model in assisting the syndrome differentiation. ResultsThe 32 features strongly associated with POP were obtained， and the Bayes information critedon score of the further constructed latent tree model was -15291.93. Based on the mutual information and the cumulative information coverage， the main symptoms of POP with kidney yang deficiency syndrome were bone weakness， fatigue， pale tongue， clear urine， frequent nocturnal urination， cold limbs， thin pulse， white coating， and secondary symptoms were weakness， loss of libido， loose stool， frequent urination， lumbar and knee weakness， and fear of cold. From the probability of the occurrence of each clinical feature in different latent categories of POP with kidney yang deficiency syndrome， the state was introduced as S0 category （none/mild kidney yang syndrome）/ S1 category （moderate kidney yang syndrome）/ S2 category （severe kidney yang syndrome）. Optimizing the preliminary rules of state identification and refining the state of S1 category， the results showed that among 970 patients with POP， there were 520 patients having no/mild kidney yang deficiency syndrome， 224 patients with moderate to mild kidney yang deficiency syndrome， 81 patients with moderate to severe kidney yang deficiency syndrome， and 145 patients with severe kidney yang deficiency syndrome. During the evaluation and validation process， the correct rate of the model assessment index was 0.8835， while the sensitivity was 0.7181， and the specificity was 0.9437. ConclusionCombined with the latent structure analysis of the association rule， the syndrome differentiation model for POP with kidney yang deficiency could be constructed， and the model shows a good quantitative identification effect， which can provide methodological supports for clinicians to improve the efficiency and accuracy of TCM diagnosis.

Regulation of fungal community and the quality formation and safety control of Pu-erh tea.

Pu-erh tea belongs to dark tea among six major teas in China. As an important kind of post-fermented tea with complex microbial composition, Pu-erh tea is highly praised by many consumers owing to its unique and rich flavor and taste. In recent years, Pu-erh tea has exhibited various physiological activities to prevent and treat metabolic diseases. This review focuses on the fungi in Pu-erh tea and introduces the sources, types, and functions of fungi in Pu-erh tea, as well as the influence on the quality of Pu-erh tea and potential safety risks. During the process of fermentation and aging of Pu-erh tea, fungi contribute to complex chemical changes in bioactive components of tea. Therefore, we examine the important role that fungi play in the quality formation of Pu-erh tea. The associations among the microbial composition, chemicals excreted, and potential food hazards are discussed during the pile-fermentation of Pu-erh tea. The quality of Pu-erh tea has exhibited profound changes during the process of pile-fermentation, including color, aroma, taste, and the bottom of the leaves, which are inseparable from the fungus in the pile-fermentation of Pu-erh tea. Specifically, the application prospects of various detection methods of mycotoxins in assessing the safety of Pu-erh tea are proposed. This review aims to fully understand the importance of fungi in the production of Pu-erh tea and further provides new insights into subtly regulating the piling process to improve the nutritional properties and guarantee the safety of Pu-erh tea.

A comprehensive review on bioavailability, safety and antidepressant potential of natural bioactive components from tea.

Depression is a global public health issue with high morbidity and mortality, which tends to cause fatigue, inability to concentrate, insomnia, and loss of appetite, especially represented by major depressive disorder (MDD). Pathologically, depression is associated with hyperactivity of hypothalamic-pituitaryadrenal (HPA) axis, inflammation, loss of monoaminergic system, and disturbance of gut microbiota. Epidemiological studies have shown that regular tea drinking can reduce the risk of depression. Tea bioactive compounds (L-theanine, catechin, tea pigment and GABA) can regulate depression by inhibiting hyperactive HPA axis, reducing the inflammatory response, restoring the monoaminergic system, inhibiting monoamine oxidase levels, increasing the enrichment of intestinal flora and promoting microbial-gut-brain axis activity. This review discusses the composition, structure, bioavailability and safety of bioactive components from tea, and focuses on exploring the possible pathways of tea bioactive compounds in the regulation of depression. In addition, the low bioavailability of natural bioactive compounds from tea limits the efficacy on depression. Emerging technologies (such as metabolomics, proteomics, and genomics) and nano-encapsulation can be utilized to improve the stability and bioavailability of tea active ingredients, and reduce the potential biotoxicity. The review provides a theoretical basis of utilization of tea active compounds for formulating the prevention and treatment of depression.

Current understanding and future perspectives on the extraction, structures, and regulation of muscle function of tea pigments.

With the aggravating aging of modern society, the sarcopenia-based aging syndrome poses a serious potential threat to the health of the elderly. Natural dietary supplements show great potential to reduce muscle wasting and enhance muscle performance. Tea has been widely recognized for its health-promoting effects. which contains active ingredients such as tea polyphenols, tea pigments, tea polysaccharides, theanine, caffeine, and vitamins. In different tea production processes, the oxidative condensation and microbial transformation of catechins and other natural substances from tea promotes the production of various tea pigments, including theaflavins (TFs), thearubigins (TRs), and theabrownins (TBs). Tea pigments have shown a positive effect on maintaining muscle health. Nevertheless, the relationship between tea pigments and skeletal muscle function has not been comprehensively elucidated. In addition, the numerous research on the extraction and purification of tea pigments is disordered with the limited recent progress due to the complexity of species and molecular structure. In this review, we sort out the strategies for the separation of tea pigments, and discuss the structures of tea pigments. On this basis, the regulation mechanisms of tea pigments on muscle functional were emphasized. This review highlights the current understanding on the extraction methods, molecular structures and regulation mechanisms of muscle function of tea pigments. Furthermore, main limitations and future perspectives are proposed to provide new insights into broadening theoretical research and industrial applications of tea pigments in the future.

The extraction and isolation methods of tea pigments are detailedly introduced.The structural research progress of tea pigments are summarized.The effects of tea pigments in the prevention of muscle diseases are introduced.The mechanism of tea pigments in enhancing skeletal muscle function are proposed.

Corn peptides improved obesity-induced non-alcoholic fatty liver disease through relieving lipid metabolism, insulin resistance and oxidative stress.

Non-alcoholic fatty liver disease (NAFLD) is increasingly threatening human health. The remarkable effects of corn peptides (CPs) as bioactive peptides on liver protection have attracted much attention. Nevertheless, the specific effect of CPs on NAFLD remains unclear. The present study was designed to investigate the efficacy of CPs in the prevention and auxiliary treatment of high-fat diet (HFD)-induced NAFLD in SD rats, and puerarin was used as the positive control. SD rats were fed a high-fat diet to establish the NAFLD rat model, and LO2 cells were treated with a high concentration of fructose to simulate the NAFLD cell model. NAFLD was comprehensively examined in terms of body weight, liver function markers, serum biochemistry and liver histology. Protein expression was determined using western blot analysis. The results of animal experiments showed that CPs could effectively inhibit the rate of weight gain, reduce the blood lipid level and liver index, and enhance glucose tolerance. The results of cell experiments showed that CPs could effectively reduce the accumulation of lipids in LO2 cells and inhibit the accumulation of reactive oxygen species (ROS). In addition, CPs could markedly reduce liver lipid accumulation in the liver cell and liver tissue, as further evidenced by the reduced expression of SREBP-1c in human non-tumour hepatic (LO2) cells. Meanwhile, the increased expression of SIRT1/PPAR-α and Nrf2/HO-1 pathways under the pretreatment of CPs in LO2 cells indicated that CPs could markedly relieve high fat-induced fatty liver injury, regulate insulin sensitivity, and reduce production of ROS. The results of in vivo and in vitro experiments demonstrated that CPs provided potential prevention and auxiliary treatment for NAFLD through reducing lipid accumulation, alleviating insulin resistance, and inhibiting oxidative stress. This study investigated the biological activity of CPs and laid the theoretical basis for the development of CP-based functional foods and dietary supplements.

Effect of Acupuncture on Outcomes of in vitro Fertilisation: A Scoping Review / 中国结合医学杂志

OBJECTIVES@#To identify, examine and summarize the available evidence on the effectiveness and safety of acupuncture for in vitro fertilisation (IVF) outcomes.@*METHODS@#Eight electronic databases, including PubMed, EMBASE, Cochrane Database of Systematic Review, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Database and VIP Database, were searched, supplemented by manual searches. Two researchers independently conducted the literature screening, data extraction, and methodological quality assessments. A narrative description was provided to show the general information and specific characteristics of the included studies. A bubble plot was used to visually display the overall effects of acupuncture on IVF outcomes.@*RESULTS@#Eighty-two studies were identified, including 64 primary studies and 18 systematic reviews. Transcutaneous electrical acupoint stimulation, electric acupuncture and manual acupuncture were applied in most studies and compared with no acupuncture, sham acupuncture and placebo acupuncture control groups. Sixty-three (98.4%) primary studies reported clinical pregnancy rate, and positive effects of acupuncture were found in 34 studies (54.0%). Live birth rate was reported in only 18 (28.1%) primary studies, of which 10 (55.6%) showed positive results. In addition, only 8 and 2 systematic reviews showed that acupuncture could increase clinical pregnancy events and live birth events, respectively. However, none of these reviews was of high methodological quality.@*CONCLUSIONS@#Available evidence suggests that acupuncture therapy could improve clinical pregnancy rates. However, whether acupuncture could increase live birth events was difficult to determine based on the few studies that have reported this outcome indicator. Furthermore, the methodological quality of most systematic reviews was assessed as critically low or low. Studies with a rigorous design and standardized implementation should be performed to refine the available evidence.