Multi-omics and chemical profiling approaches to understand the material foundation and pharmacological mechanism of sophorae tonkinensis radix et rhizome-induced liver injury in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophorae tonkinensis Radix et Rhizoma (STR) is an extensively applied traditional Chinese medicine (TCM) in southwest China. However, its clinical application is relatively limited due to its hepatotoxicity effects. AIM OF THE STUDY: To understand the material foundation and liver injury mechanism of STR. MATERIALS AND METHODS: Chemical compositions in STR and its prototypes in mice were profiled by ultra-performance liquid chromatography coupled quadrupole-time of flight mass spectrometry (UPLC-Q/TOF MS). STR-induced liver injury (SILI) was comprehensively evaluated by STR-treated mice mode. The histopathologic and biochemical analyses were performed to evaluate liver injury levels. Subsequently, network pharmacology and multi-omics were used to analyze the potential mechanism of SILI in vivo. And the target genes were further verified by Western blot. RESULTS: A total of 152 compounds were identified or tentatively characterized in STR, including 29 alkaloids, 21 organic acids, 75 flavonoids, 1 quinone, and 26 other types. Among them, 19 components were presented in STR-medicated serum. The histopathologic and biochemical analysis revealed that hepatic injury occurred after 4 weeks of intragastric administration of STR. Network pharmacology analysis revealed that IL6, TNF, STAT3, etc. were the main core targets, and the bile secretion might play a key role in SILI. The metabolic pathways such as taurine and hypotaurine metabolism, purine metabolism, and vitamin B6 metabolism were identified in the STR exposed groups. Among them, taurine, hypotaurine, hypoxanthine, pyridoxal, and 4-pyridoxate were selected based on their high impact value and potential biological function in the process of liver injury post STR treatment. CONCLUSIONS: The mechanism and material foundation of SILI were revealed and profiled by a multi-omics strategy combined with network pharmacology and chemical profiling. Meanwhile, new insights were taken into understand the pathological mechanism of SILI.

The phytochemistry, pharmacology, pharmacokinetics, quality control, and toxicity of Forsythiae Fructus: An updated systematic review.

Forsythiae Fructus (FF), the dried fruit of F. suspensa, is commonly used to treat fever, inflammation, etc in China or other Asian countries. FF is usually used as the core herb in traditional Chinese medicine preparations for the treatment of influenza, such as Shuang-huang-lian oral liquid and Yin-qiao powder, etc. Since the wide application and core role of FF, its research progress was summarized in terms of traditional uses, phytochemistry, pharmacology, pharmacokinetics, quality control, and toxicity. Meanwhile, the anti-influenza substances and mechanism of FF were emphasized. Till now, a total of 290 chemical components are identified in F. suspensa, and among them, 248 components were isolated and identified from FF, including 42 phenylethanoid glycosides, 48 lignans, 59 terpenoids, 14 flavonoids, 3 steroids, 24 cyclohexyl ethanol derivatives, 14 alkaloids, 26 organic acids, and 18 other types. FF and their pure compounds have the pharmacological activities of anti-virus, anti-inflammation, anti-oxidant, anti-bacteria, anti-tumor, neuroprotection, hepatoprotection, etc. Inhibition of TLR7, RIG-I, MAVS, NF-κB, MyD88 signaling pathway were the reported anti-influenza mechanisms of FF and phenylethanoid glycosides and lignans are the main active groups. However, the bioavailability of phenylethanoid glycosides and lignans of FF in vivo was low, which needed to be improved. Simultaneously, the un-elucidated compounds and anti-influenza substances of FF strongly needed to be explored. The current quality control of FF was only about forsythoside A and phillyrin, more active components should be taken into consideration. Moreover, there are no reports of toxicity of FF yet, but the toxicity of FF should be not neglected in clinical applications.

Comparative Analysis of Characteristic Volatile Compounds in Five Types of Infant Nutrition Powders by HS-GC-IMS and GC-MS.

This study employed the headspace-gas chromatography-ion migration spectrum (HS-GC-IMS) in conjunction with the gas chromatography-mass spectrometer (GC-MS) technique for the assessment of the flavor quality of complementary food powder intended for infants and young children. A total of 62 volatile compounds were identified, including aldehydes, esters, alcohols, ketones, pyrazines, and furans, among which aldehydes were the most abundant compounds. Based on the principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) models, infant nutritional powder (YYB) from different manufacturers could be clearly distinguished. Among them, 2-hydroxybenzaldehyde, 1, 2-dimethoxyethane, 2-isobutyl-3-methoxypyrazine, and methyl butyrate were the four most critical differential volatiles. In addition, these differences were also manifested in changes in fatty acids. The reason for this phenomenon can be attributed to the difference in the proportion of raw materials used in nutrition powder, micronutrient content, and the packaging process. In conclusion, this study provides comprehensive information on the flavor quality of YYB, which can be used as a basis for quality control of YYB.

A review of the ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and toxicology of Abri Herba (Ji-Gu-Cao).

Abri Herba (AH, known as 'Ji-Gu-Cao' in China) has a long-term medicinal history of treating cholecystitis, acute and chronic hepatitis and non-alcoholic fatty liver (NAFL) in China or other Asian countries. This review aimed to provide a comprehensive analysis of AH in terms of ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and toxicology. The information involved in the study was collected from a variety of electronic resources, and >100 scientific studies have been used since 1962. Until now, 95 chemical compounds have been isolated and identified from AH and the seeds of Abrus cantoniensis Hance (ACH), including 47 terpenoids, 26 flavonoids and 4 alkaloids. The pharmacological activities of AH extracts and their pure compounds have been explored in the aspects of anti-hyperlipidaemia, hepatoprotection, anti-tumour, anti-viral, anti-bacterial, anti-inflammatory and analgesic, immunomodulation, antioxidant and others. The pharmacokinetics and excretion kinetics of AH in vivo and 15 traditional and clinical prescriptions containing AH have been sorted out, and the potential therapeutic mechanism and drug metabolism pattern were also summarised. The pods of ACH are toxic, with a median lethal dose (LD50) of 10.01 ± 2.90 g/kg (i.g.) in mice. Interestingly, the toxicity of ACH's pods and seeds decreased after boiling. However, the toxicity mechanism of pods of ACH is unclear, limiting its clinical application. Clinical trials in the future should be used to explore its safety. Meanwhile, as one of the relevant pharmacological activities, the effects and mechanism of AH on anti-hyperlipidaemia and hepatoprotection should be further studied, which is of great significance for understanding its mechanism of action in the treatment of NAFL disease and improving its clinical application.

The comparative analysis of Lonicerae Japonicae Flos and Lonicerae Flos: A systematical review.

ETHNOPHARMACOLOGICAL RELEVANCE: Lonicerae Japonicae Flos (LJF) and Lonicerae Flos (LF) were once used as the same herb in China, but they were distinguished by Chinese Pharmacopoeia in 2005 in terms of their medicinal history, plant morphology, medicinal properties and chemical constituents. However, their functions, flavor, and meridian tropism are the same according to the Chinese pharmacopoeia 2020 edition, making researchers and customers confused. AIM OF THE REVIEW: This review aimed to provide a comparative analysis of LJF and LF in order to provide a rational application in future research. MATERIALS AND METHODS: The information was gathered from China National Knowledge Infrastructure (CNKI), SciFinder, Google Scholar, PubMed, Web of Science, and Chinese Masters and Doctoral Dissertations (all chosen articles were reviewed attentively from 1980.1 to 2023.8). RESULTS: Till now, 507 chemical compounds have been isolated and identified in LJF, while 223 ones (79 overlapped compounds) are found in LF, including organic acids and derivatives, flavonoids, triterpenoids, iridoids, and essential oil components, etc. In addition, the pharmacological activities of LJF and LF, especially for their anti-influenza efficacy and mechanism, and their difference in terms of pharmacokinetic parameters, toxicology, and clinical applications were also summarized. CONCLUSION: The current work offers comparative information between LJF and LF in terms of botany, traditional uses, phytochemistry, ethnopharmacology, pharmacokinetics, toxicology, and pharmacology, especially their anti-influenza activities. Despite the same clinical applications and similar chemical components in LJF and LF, differentiated components were still existed, resulting in differentiated pharmacological activities and pharmacokinetics parameters. Moreover, the research about anti-influenza mechanism and functional substances of LJF and LF is dramatically limited, restricting their clinical applications. In addition, few studies have investigated the metabolism feature of LF in vivo, which is one of the important bases for revealing the pharmacological mechanism of LF. At the same time, the toxicity of LJF and LF is not fully studied, and the toxic compounds of LJF and LF need to be screened out in order to standardize the drug use and improve their rational applications.

[Bushen Anshen acupuncture for perimenopausal insomnia of kidney-yin deficiency: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of Bushen Anshen acupuncture (acupuncture for tonifying kidney and calming spirit ) in treating perimenopausal insomnia (PMI) of kidney-yin deficiency. METHODS: A total of 72 patients with PMI of kidney-yin deficiency were randomized into an observation group (36 cases, 1 case dropped off) and a control group (36 cases, 1 case dropped off). Acupuncture was applied at Baihui (GV 20) and bilateral Shenshu (BL 23), Taixi (KI 3), Anmian (Extra) in the observation group, while sham acupuncture of shallow needling at non-acupoints was applied in the control group. The treatment was required once every other day, 3 times a week for 10 times in the two groups. Before and after treatment, Pittsburgh sleep quality index (PSQI) was used to evaluate the subjective sleep quality, and polysomnography (PSG) was used to monitor the objective sleep quality in the two groups. RESULTS: After treatment, the scores of sleep quality, sleep latency, sleep duration, sleep efficiency, hypnotic, daytime dysfunction and total score of PSQI were decreased compared with those before treatment in the observation group (P<0.01), the scores of sleep duration, sleep efficiency and total score of PSQI were decreased compared with those before treatment in the control group (P<0.05); the scores of sleep quality, sleep latency, sleep efficiency, hypnotic and total score of PSQI in the observation group were lower than those in the control group (P<0.05). After treatment, the sleep time was prolonged, the sleep efficiency was improved, the sleep latency and the awake time after falling asleep were shortened, the arousal awake index was reduced (P<0.01) when PSG indexes were monitored, and the percentage of non-rapid eye movement sleep period 1 (N1%) was decreased while the percentage of non-rapid eye movement sleep period 3 (N3%) was increased (P<0.05) compared with those before treatment in the observation group; there was no statistical difference in the PSG indexes compared with those before treatment in the control group (P>0.05). After treatment, compared with the control group, the sleep time was prolonged, the sleep efficiency was improved, the sleep latency and the awake time after falling asleep were shortened, the arousal awake index and N1% were decreased in the observation group (P<0.01). CONCLUSION: Bushen Anshen acupuncture can effectively improve the subjective and objective sleep quality in PMI patients of kidney-yin deficiency.

Pickering emulsions synergistically stabilized by sugar beet pectin and montmorillonite exhibit enhanced storage stability and viscoelasticity.

Sugar beet pectin (SBP) is a naturally occurring emulsifying type of pectin fabricated into nanocomposites with montmorillonite (MMT) and then introduced as a stabilizer for high internal phase emulsions (HIPEs). SBP-MMT composites performed well in emulsifying medium-chain triglyceride with an oil volume fraction (φ) of 0.1-0.85 and SBP/MMT mass ratios of 1:0.1-1:0.75. The two representative high internal phase emulsions stabilized by SBP-MMT composites at different SBP/MMT mass ratios exhibited good stability against creaming and coalescence. In these emulsion systems, SBP and MMT formed a network in the continuous phase that markedly improved the rheological properties, including the storage modulus (by 3 orders of magnitude). Confocal light scattering microscopy analysis indicated that a fraction of MMT could work synergistically with SBP in adsorbing on oil droplet surfaces, enhancing stability. SBP-MMT composites stabilized high internal phase emulsions destabilized after the freeze-thaw treatment (-40 °C for 20 h and 25 °C for 4 h) but could be facilely re-emulsified via high-speed shearing. The gastrointestinal digestion behaviors were also modified by stabilizing SBP and MMT. Overall, this work reveals a hitherto undocumented strategy for fabricating highly stable emulsions based on SBP-MMT composites which have huge prospects for application in the food and related industries.

Selenized glucose improves rat semen quality by improving the gut microbiota and serum metabolome.

Selenium (Se), a well-known antioxidant, is important for male fertility and sperm quality. The gut microbiota is involved in vital activities and cross-talk between reproduction and the gut axis. It is still unclear whether the gut microbiota mediates the impact of selenium on semen quality, and what the underlying mechanisms may be. A selenized glucose (SeGlu) derivative is a novel organic Se compound. After 7 days of acclimation, the Sprague-Dawley (SD) male rats (230 g, 6 weeks) were divided into three drinking groups: deionized water group (CK), SeGlu 0.15 group (0.15 mg Se per L), and SeGlu 0.4 group (0.4 mg Se per L). All animals were euthanized 30 days post-treatment. Serum and intratesticular testosterone and semen parameters were measured. Metagenomic and non-targeted metabolomic approaches were used to study the effects of SeGlu on the gut microbiota and serum metabolites of rats. In both the SeGlu 0.15 Group and the SeGlu 0.4 Group, we found a significant increase in seminiferous epithelium thickness. While the SeGlu 0.4 Group had a tendency to increase with insignificant difference, the SeGlu 0.15 Group significantly improved the sperm viability, survival rate, and seminal plasma fructose. SeGlu had no effect on intratesticular testosterone levels, or abnormal sperm counts. Measured serum testosterone levels using ELISA and LC-MS, which showed a decreasing trend. ELISA did not reveal significant differences, but LC-MS indicated a significant decrease in SeGlu 0.4 group. Meanwhile, the SeGlu 0.15 Group reduced the abundance of harmful bacteria such as Rikenella, Barnesiella, Tenacibaculum, and Aeromonas while increasing the abundance of beneficial microbiota such as Intestinimonas, Christensenella, Coprococcus, and Butyrivibrio. Linear discriminant analysis Effect Size (LEfSe) identified the SeGlu 0.15 group's feature genera as Roseburia, Clostridium, Ruminococcus, and Eubacterium. Serum metabolites showed that the SeGlu 0.15 Group increased 5 beta-androstane-3,17-dione while decreasing estrone and 2-methoxyestradiol (2-MeOE2). In conclusion, the SeGlu 0.15 Group can significantly alter the levels of several sex hormones in serum, improve the quality of rats' sperm, and reduce harmful bacterial colonization. SeGlu 0.15 may be used as an effective dietary supplement.

Hyperbaric oxygen enhanced the chemotherapy of mitochondrial targeting molecule IR-780 in bladder cancer.

BACKGROUND: Bladder cancer has a high rate of recurrence and drug resistance due to the lack of effective therapies. IR-780 iodide, a near-infrared (NIR) mitochondria-targeting fluorescent agent, has been demonstrated to achieve higher selectivity than other drugs in different tumor types and exhibited tumor-killing effects in some cancers. However, this therapeutic strategy is rarely studied in bladder cancer. MATERIAL AND METHODS: The accumulation of IR-780 in bladder cancer was measured by NIR imaging. Human bladder cell lines (T24, 5637, and TCCSUP) were treated with IR-780 or combined IR-780 and hyperbaric oxygen (HBO). Cell viability, cell apoptosis, cellular ATP production, mitochondrial reactive oxygen species (ROS), and plasma membrane potential were detected. Mitochondrial complex I protein NDUFS1 was measured by western blot. To confirm the anti-tumor efficacy of IR-780 + HBO, mouse bladder cell line (MB49) tumor-bearing mice were established and tumor size and weight were recorded. Besides, cell apoptosis and tumor size were assessed in drug-resistant bladder cancer cells (T24/DDP) and xenografts to evaluate the effect of IR-780 + HBO on drug-resistant bladder cancer. RESULTS: IR-780 selectively accumulated in bladder cancer (bladder cancer cells, transplanted tumors, and bladder cancer tissue from patients) and could induce cancer cell apoptosis by targeting the mitochondrial complex I protein NDUFS1. The combination with HBO could significantly enhance the anti-tumor effect of IR-780 in vitro by promoting cancer cell uptake and inducing excessive mitochondrial ROS production, while suppressing tumor growth and recurrence in animal models without causing apparent toxicity. Moreover, this combination antitumor strategy was also demonstrated in drug-resistant bladder cancer cells (T24/DDP) and xenografts. CONCLUSION: We identified for the first time a combination of IR-780 and HBO (IR-780 + HBO), which exhibits mitochondria-targeting and therapeutic capabilities, as a novel treatment paradigm for bladder cancer.

Complete chloroplast genome sequence and phylogenetic analysis of Ilex pernyi Franch.

Ilex pernyi Franch. is a Chinese unique medicinal plant with high value for decoration, human consumption, and as a medicine. In this study, we sequenced the complete chloroplast (cp) genome of I. pernyi Franch. and established its phylogenetic relationship in the Aquifoliaceae family. The total length of the chloroplast genome of I. pernyi Franch. was found to be 157,220 bp, with an overall GC content of 37.7% and a typical quadripartite structure with a pair of inverted repeats (IRs, 29,092 bp), which was separated by a small single-copy (SSC) region of 18,427 bp and a large single-copy (LSC) region of 89,609 bp. The cp genome contained 132 genes: 87 protein-coding, 37 tRNA, and 8 rRNA genes. The phylogenetic analysis indicated that I. pernyi Franch. was closely related to Ilex cornuta.

Impact of Acupuncture on Sleep and Comorbid Symptoms for Chronic Insomnia: A Randomized Clinical Trial.

STUDY OBJECTIVES: To evaluate the efficacy and safety of acupuncture at HT 7 (Shenmen) and KI 7 (Fuliu) on sleep and comorbid symptoms for chronic insomnia. METHODS AND DESIGN: A randomized, single-blind, parallel and sham-controlled trial consisted of an acupuncture group (n = 41) and a sham acupuncture group (n = 41). Setting: a tertiary hospital of integrated Chinese and Western medicine. Participants: 82 subjects with chronic insomnia based on the International Classification of Sleep Disorders, Third Edition (ICSD-3). Interventions: a 10-session acupuncture treatment at bilateral HT 7 and KI 7 or sham acupoints with shallow needling was performed over 3 weeks. Measurements: the Pittsburgh sleep quality index (PSQI) and insomnia severity index (ISI) were evaluated at baseline, posttreatment, and at two follow-ups as the primary outcome measures. Polysomnography (PSG) on two consecutive nights, the Beck anxiety inventory (BAI), the Beck depression inventory (BDI) fatigue severity scale (FSS) and the Epworth sleepiness scale (ESS) were evaluated at baseline and posttreatment as the secondary outcome measures. RESULTS: After the treatments, PSQI scores decreased by 5.04 in the acupuncture group and 2.92 in the sham acupuncture group. ISI scores decreased by 7.65 in the acupuncture group and 5.05 in the sham acupuncture group. The between-group differences in the primary outcome measures posttreatment were statistically significant. However, no differences were found between the two groups during the two follow-ups. Regarding the PSG data, there were significantly lower levels of sleep onset latency (SOL), a lower percentage of sleep stage N1 and a higher percentage of sleep stage N3 in the acupuncture group than in the sham acupuncture group. After treatment, there were lower levels of comorbid symptoms (BAI, BDI, FSS and ESS) in both groups. However, no significant differences were observed between the groups. CONCLUSION: Acupuncture at HT 7 and KI 7 is an effective and safe nonpharmacologic intervention option for chronic insomnia. CLINICAL TRIAL REGISTRATION: The study was registered at the Chinese Clinical Trial Registry, registration ID: ChiCTR1900023787, China.

Near-infrared light-responsive hybrid hydrogels for the synergistic chemo-photothermal therapy of oral cancer.

Light-stimulus-responsive therapies have been recognized as a promising strategy for the efficient and safe treatment of oral squamous cell carcinoma (OSCC). Hydrogels have emerged as a promising multifunctional platform combining localized drug delivery and sustained drug release with multimodal properties for combined OSCC therapy. However, inaccurate drug release and limited light-absorption efficiency have hindered their on-demand chemo-photothermal applications. To tackle these problems, an injectable and near-infrared (NIR) light-responsive hybrid system was developed by incorporating light-responsive mesoporous silica nanoparticles (MSNs) as doxorubicin (DOX) carriers into the IR820/methylcellulose hydrogel networks for chemophotothermal therapy. Under NIR radiation, the incorporated IR820, a new green cyanine dye, was excited to induce photothermal effects against tumor cells. Meanwhile, MSNs achieved self-degradation-controlled DOX release via the cleavage of diselenide bonds induced by reactive oxygen species. Through the combination of chemotherapy and phototherapy, a long-lasting synergistic anti-tumor effect was achieved in vitro and in vivo with less toxicity. These findings demonstrate the potential of light-responsive hydrogels as a multifunctional platform for accurate synergistic chemophotothermal treatment of OSCC.

Acupuncture for insomnia with short sleep duration: protocol for a randomised controlled trial.

INTRODUCTION: Insomnia with short sleep duration has a more serious negative impact on patient health. The existing literature suggests that medication therapy is more effective for this phenotype of insomnia compared with cognitive-behavioural therapy. However, the potential side effects of hypnotic medications hinder their clinical application. Acupuncture has been widely used in the treatment of insomnia, but it remains unclear whether it has therapeutic efficacy for insomnia with short sleep duration. The purpose of this trial is to evaluate the efficacy and safety of acupuncture for insomnia with short sleep duration. METHODS AND ANALYSIS: This study is designed as a randomised, single-centre, single-blinded, placebo acupuncture controlled trial involving 152 participants. Eligible patients will be divided into two groups according to the objective total sleep time: insomnia with normal sleep duration group and insomnia with short sleep duration group. Then, patients in each group will be randomly assigned to two subgroups, the treatment group (acupuncture) and the control group (placebo acupuncture), in a 1:1 ratio with 38 subjects in each subgroup. The primary outcome is the Pittsburgh Sleep Quality Index and the Insomnia Severity Index. Secondary outcomes are actigraphy, the Beck Anxiety Inventory, the Beck Depression Inventory and the Fatigue Severity Scale. All adverse effects will be assessed by the Treatment Emergent Symptom Scale. Outcomes will be evaluated at baseline, post treatment, as well as at 1-week and 1-month follow-up. ETHICS AND DISSEMINATION: This protocol has been approved by the ethics committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine (no. 2019-17). Written informed consent will be obtained from all participants. The results will be disseminated through peer-reviewed journals for publications. TRIAL REGISTRATION NUMBER: ChiCTR1900023473; Pre-results.

Defense of pyrethrum flowers: repelling herbivores and recruiting carnivores by producing aphid alarm pheromone.

(E)-ß-Farnesene (EßF) is the predominant constituent of the alarm pheromone of most aphid pest species. Moreover, natural enemies of aphids use EßF to locate their aphid prey. Some plant species emit EßF, potentially as a defense against aphids, but field demonstrations are lacking. Here, we present field and laboratory studies of flower defense showing that ladybird beetles are predominantly attracted to young stage-2 pyrethrum flowers that emitted the highest and purest levels of EßF. By contrast, aphids were repelled by EßF emitted by S2 pyrethrum flowers. Although peach aphids can adapt to pyrethrum plants in the laboratory, aphids were not recorded in the field. Pyrethrum's (E)-ß-farnesene synthase (EbFS) gene is strongly expressed in inner cortex tissue surrounding the vascular system of the aphid-preferred flower receptacle and peduncle, leading to elongated cells filled with EßF. Aphids that probe these tissues during settlement encounter and ingest plant EßF, as evidenced by the release in honeydew. These EßF concentrations in honeydew induce aphid alarm responses, suggesting an extra layer of this defense. Collectively, our data elucidate a defensive mimicry in pyrethrum flowers: the developmentally regulated and tissue-specific EßF accumulation and emission both prevents attack by aphids and recruits aphid predators as bodyguards.

Rational design of a triple-type human papillomavirus vaccine by compromising viral-type specificity.

Sequence variability in surface-antigenic sites of pathogenic proteins is an important obstacle in vaccine development. Over 200 distinct genomic sequences have been identified for human papillomavirus (HPV), of which more than 18 are associated with cervical cancer. Here, based on the high structural similarity of L1 surface loops within a group of phylogenetically close HPV types, we design a triple-type chimera of HPV33/58/52 using loop swapping. The chimeric VLPs elicit neutralization titers comparable with a mix of the three wild-type VLPs both in mice and non-human primates. This engineered region of the chimeric protein recapitulates the conformational contours of the antigenic surfaces of the parental-type proteins, offering a basis for this high immunity. Our stratagem is equally successful in developing other triplet-type chimeras (HPV16/35/31, HPV56/66/53, HPV39/68/70, HPV18/45/59), paving the way for the development of an improved HPV prophylactic vaccine against all carcinogenic HPV strains. This technique may also be extrapolated to other microbes.

[Regularity of Acupoint Selection in Treatment of Insomnia by Catgut Embedding Therapy].

OBJECTIVE: To analyze the regularity of acupoint selection in the treatment of insomnia by using catgut embedding so as to provide reference and evidence for clinical application. METHODS: Sixty-six studies about acupoint catgut embedding treatment of insomnia published from 1996 to 2017 were finally selected from the databases of China National Knowledge Infrastructure (CNKI), Chinese Journal of Science and Technology of VIP (VIP), and WanFang Database. The Excel 2016 software was used for data processing and analysis, SPSS 21.0 was employed for descriptive and cluster analyses, and the Clementine 12.0 software was employed to analyze the association regularities of the most frequently used acupoints or acupoint recipes. RESULTS: The most frequently selected main acupoints for insomnia by using catgut embedment are Xinshu (BL 15), Shenshu (BL 23), Sanyinjiao (SP 6), Pishu (BL 20), Ganshu (BL 18), combined with adjuvant acupoints Danshu (BL 19) and Fenglong (ST 40). The most frequently selected channels are the Bladder and Stomach Meridians, and the most frequently involved body positions are the back and lower limbs. Effective clusterings are BL 20-SP 6, Shenmen (HT 7)-Anmian, ST 40-Shenting (GV 24), Qihai (CV 6)-Jueyinshu (BL 14). Descriptive analysis indicated: ①The stronger correlation acupoint groups between back-shu points are BL 18-BL 23; BL 18，BL 15-BL 23; BL 18，BL 20，BL 15-BL 23. ②The stronger correlation acupoint groups between common acupoints are Neiguan (PC 6)，Zusanli (ST 36) -SP 6; PC 6, HT 7 - SP 6.③The stronger correlation acupoint groups between common acupoints and back-shu points are BL 18, SP 6-BL 23; PC 6, BL 23 - SP 6; ST 36, PC 6, BL 15 - SP 6; BL 18，BL 15，SP 6 - BL 23. CONCLUSION: Acupoint catgut embedding therapy is effective in the treatment of insomnia, being worthy of further popularization in clinical practice.

Intravenous Administration of Lycopene, a Tomato Extract, Protects against Myocardial Ischemia-Reperfusion Injury.

BACKGROUND: Oral uptake of lycopene has been shown to be beneficial for preventing myocardial ischemia-reperfusion (I/R) injury. However, the strong first-pass metabolism of lycopene influences its bioavailability and impedes its clinic application. In this study, we determined an intravenous (IV) administration dose of lycopene protects against myocardial infarction (MI) in a mouse model, and investigated the effects of acute lycopene administration on reactive oxygen species (ROS) production and related signaling pathways during myocardial I/R. METHODS: In this study, we established both in vitro hypoxia/reoxygenation (H/R) cell model and in vivo regional myocardial I/R mouse model by ligating left anterior artery descending. TTC dual staining was used to assess I/R induced MI in the absence and presence of acute lycopene administration via tail vein injection. RESULTS: Lycopene treatment (1 µM) before reoxygenation significantly reduced cardiomyocyte death induced by H/R. Intravenous administration of lycopene to achieve 1 µM concentration in circulating blood significantly suppressed MI, ROS production, and JNK phosphorylation in the cardiac tissue of mice during in vivo regional I/R. CONCLUSION: Elevating circulating lycopene to 1 µM via IV injection protects against myocardial I/R injury through inhibition of ROS accumulation and consequent inflammation in mice.

[Effect of Transcutaneous Electrical Acupoint Stimulation on Post-surgical Gastrointestinal Function, Autonomic Nerve Activities and Plasma Brain-gut Peptide Levels in Patients Undergoing Gastrointestinal Surgery].

OBJECTIVE: To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on ileus-postope-rative gastrointestinal functions and plasma ghrelin, motilin, and gastrin contents, and heart rate variability (HRV) in patients undergoing gastrointestinal surgery, so as to explore the interaction of vagus-brain-gut peptide. METHODS: A total of 58 patients undergoing elective gastrointestinal surgery were randomly assigned to TEAS (n=29) and sham-TEAS group (n=29, patients had no subjective sensation to 1 mA TEAS, thus, being considered to be sham-TEAS). TEAS (2 Hz/100 Hz, 6-8 mA for LI 4-PC 6, 12-18 mA for ST 36-SP 6) was applied to bilateral Hegu (LI 4)-Neiguan (PC 6) from 30 min pre-operation to the end of the operation and to bilateral LI 4-PC 6 and Zusanli (ST 36)-Sanyinjiao (SP 6) for 30 minutes twice daily in 3 consecutive post-operative days. ECGs of 12 leads were recorded to analyze different parameters of HRV from 2 days before and 4 days after surgery. Plasma ghrelin, motilin and gastrin contents were assayed by radioimmunoassay, and the patients' first bowel sound, first independent walk, first flatus, first solid food-intake and first defecation were recorded to evaluate the recovery state of gastrointestinal motility. RESULTS: Postoperative gastrointestinal motility:compared with the sham-TEAS group, the first bowel sound and the first defecation after surgery appeared apparently earlier in the TEAS group (P<0.05), but no significant differences were found between the two groups at the time of the first independent walk, first flatus and the first solid food-intake in patients undergoing gastrointestinal surgery. Plasma brain-gut peptides:the plasma ghrelin and motilin contents 4 days post-surgery were significant increased in the TEAS group than in the sham-TEAS group (P<0.05). No significant difference was found between the two groups in plasma gastrin contents (P>0.05). HRV domains:in comparison with pre-surgery, the levels of low frequency (LF) and high frequency (HF) of frequency domain (FD) and root mean square of successive differences (rMSSD) of the time domain (TD) of HRV 4 days after surgery were significantly decreased in the sham-TEAS group (P<0.05), but no significant changes were found in both FD and TD domains of the TEAS group 4 days after surgery (P>0.05). Compared with the sham-TEAS group, the HF and rMSSD levels were significantly increased in the TEAS group 4 days after the surgery (P<0.05). No significant differences were found between the two groups in the levels of very low frequency, LF and LF/HF levels of FD, and standard deviation of NN (beat-to-beat) intervals, the standard deviation of the average NN intervals and the proportion of NN 50 (the number of pairs of successive NNs that differ by more than 50 ms) divided by total number of NNs of TD. CONCLUSIONS: TEAS can promote gastrointestinal activities (i.e., reducing the time spending of first bowel sound and the first defecation) in gastrointestinal surgery patients, which may be related to its effects in up-regulating ghrelin and motilin contents and parasympathetic activity.

[Clinical observation on controlling antihypertension with the general anesthesia of TEAS and anesthetics in endoscopic endonasal surgery].

OBJECTIVE: To study whether the dose of controlling antihypertensive drug is reduced by transcutaneous electrical acupoint stimulation (TEAS) and the anesthetics, as well as the control of blood pressure (BP) and heart rate (HR) in endoscopic endonasal surgery with general anesthesia. METHODS: Sixty patients for selective endoscopic endonasal surgery with general anesthetics and controlling antihypertension involved were selected and randomized into a TEAS group, a sham-TEAS group, 30 cases in each one. The electric pads were attached to bilateral Hegu (LI 4), Zusanli (ST 36), Sanyinjiao (SP 6) and Quchi (LI 11), stimulated with Hans-200 apparatus, 3 to 5 mA, 2 Hz/100 Hz in the TEAS group based on the patients' response to comfort. No electric stimulation was applied to the sham-TEAS group. The general anesthesia started after 30 min intervention and lasted till the end of surgery. The BP and HR were observed and recorded at the end of monitoring in operation room, 10 min after tranquilization (T0), 30 min after intervention (Tj, after induction~of general anestiesa (T2), 30 min after surgery start (T3), 60 min after surgery start (T4) and 30 min after extubation (T5). The doses of vecuronium bromide, propofol and nitroglycerin were recorded statistically in surgery, as well as the operative bleeding volume, the operative time, the resuscitation time and the visual analogue scale (VAS) score after resuscitation. RESULTS: Compared with that at T0, the mean arterial pressure (MAP) at T2, T3, T4 and T5 in the TEAS group and at T3 and T4 in the sham-TEAS group was all reduced, indicating the significant difference (all P < 0.01). MAP at T2 and T5 in the TEAS group was lower than that in the sham-TEAS group (both P < 0.01). Compared, with that at T5, except at T2 in the TEAS group (P<0. 05), HR was not different significantly at the rest time points (all P > 0.05). HR was different at T2 to Ts in the sham-TEAS group statistically (all P < 0.01). The doses of vecuronium bromide, propofol and nitroglycerin, the operative bleeding volume, the operative time, the resuscitation time and VAS after resuscitation were not different significantly between the two groups (all P > 0.05). CONCLUSION: The general anesthesia with TEAS and anesthetics involved for controlling antihypertension contributes to the control of BP and HR in the patients in endoscopic endonasal surgery. The impacts are not obvious on the doses of antihypertensive drug, the general anesthetics, the operative bleeding volume, the time of resuscitation and the postoperative analgesia.

[Chemical constituents of Salix matsudana leaf].

OBJECTIVE: To study the chemical constituents of the leaf of Salix matsudana. METHODS: The chemical constituents were isolated by column chromatography on silica gel, Sephadex LH-20 and MPLC. Their structures were elucidated on the basis of spectral analysis. RESULTS: Eight compounds were isolated and their structures were identified as beta-Sitosterol(1),5,7-Dihydroxychromone-7-O-beta-D-glucopyranoside(2), (2S)-Helichrysin A(3), (2R)-Helichrysin A(4), Luteolin-7-O-beta-D-glucoside(5), Salicin(6), Apigenin-7-O-beta-D-glucopyranside(7), Lutelion-3'-methylether-7-O-f-D-glucopyranside(8). CONCLUSION: Compounds 1-4 are isolated from this plant for the first time.