Supercritical CO2 fluid extract from Stellariae Radix ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis by inhibit M1 macrophages polarization via AMPK activation.

Yin chai hu (Radix Stellariae) is a root medicine that is frequently used in Chinese traditional medicine to treat fever and malnutrition. In modern medicine, it has been discovered to have anti-inflammatory, anti-allergic, and anticancer properties. In a previous study, we were able to extract lipids from Stellariae Radix using supercritical CO2 extraction (SRE), and these sterol lipids accounted for up to 88.29% of the extract. However, the impact of SRE on the development of atopic dermatitis (AD) has not yet been investigated. This study investigates the inhibitory effects of SRE on AD development using a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model. Treatment with SRE significantly reduced the dermatitis score and histopathological changes compared with the DNCB group. The study found that treatment with SRE resulted in a decrease of pro-inflammatory cytokines TNF-α, CXC-10, IL-12, and IL-1ß in skin lesions. Additionally, immunohistochemical analysis revealed that SRE effectively suppressed M1 macrophage infiltration into the AD lesion. Furthermore, the anti-inflammatory effect of SRE was evaluated in LPS + INF-γ induced bone marrow-derived macrophages (BMDMs) M1 polarization, SRE inhibited the production of TNF-α, CXC-10, IL-12, and IL-1ß and decreased the expression of NLRP3. Additionally, SRE was found to increase p-AMPKT172, but had no effect on total AMPK expression, after administration of the AMPK inhibitor Compound C, the inhibitory effect of SRE on M1 macrophages was partially reversed. The results indicate that SRE has an inhibitory effect on AD, making it a potential therapeutic agent for this atopic disorder.

[Comprehensive identification of metabolites and metabolic characteristics of luteolin and kaempferol in Simiao Yong'an Decoction in rats by UHPLC-LTQ-Orbitrap MS/MS].

Simiao Yong'an Decoction is a classic prescription for treating gangrene. Modern medical evidence has proven that Si-miao Yong'an Decoction has therapeutic effects on atherosclerosis(AS), vascular occlusion angeitides, and hypertension, while its pharmacodynamic mechanism remains unclear. The evidence of network pharmacology, molecular docking, literature review, and our previous study suggests that luteolin and kaempferol are two major flavonoids in Simiao Yong'an Decoction and can inhibit macrophage inflammation and exert anti-AS effects. However, due to lack of the metabolism studies in vivo, little is known about the metabolic characteristics of luteolin and kaempferol. This study employed ultra-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS/MS) and relevant software to identify the metabolites and metabolic pathways of luteolin and kaempferol in rat plasma, urine, and feces, after oral administration of luteolin and kaempferol, respectively. After the administration of luteolin, 10, 11, and 3 metabolites of luteolin were detected in the plasma, urine, and feces, respectively. After the administration of kaempferol, 9, 3, and 1 metabolites of kaempferol were detected in the plasma, urine, and feces, respectively. The metabolic pathways mainly involved methylation, glucuronidation, and sulfation. This study enriches the knowledge about the pharmacological mechanism of luteolin and kaempferol and supplies a reference for revealing the metabolic process of other flavonoids in Simiao Yong'an Decoction, which is of great significance for elucidating the pharmacological effects and effective substances of this decoction in vivo.

Machine learning classification of polycystic ovary syndrome based on radial pulse wave analysis.

BACKGROUND: Patients with Polycystic ovary syndrome (PCOS) experienced endocrine disorders that may present vascular function changes. This study aimed to classify and predict PCOS by radial pulse wave parameters using machine learning (ML) methods and to provide evidence for objectifying pulse diagnosis in traditional Chinese medicine (TCM). METHODS: A case-control study with 459 subjects divided into a PCOS group and a healthy (non-PCOS) group. The pulse wave parameters were measured and analyzed between the two groups. Seven supervised ML classification models were applied, including K-Nearest Neighbors (KNN), Support Vector Machine (SVM), Decision Trees, Random Forest, Logistic Regression, Voting, and Long Short Term Memory networks (LSTM). Parameters that were significantly different were selected as input features and stratified k-fold cross-validations training was applied to the models. RESULTS: There were 316 subjects in the PCOS group and 143 subjects in the healthy group. Compared to the healthy group, the pulse wave parameters h3/h1 and w/t from both left and right sides were increased while h4, t4, t, As, h4/h1 from both sides and right t1 were decreased in the PCOS group (P < 0.01). Among the ML models evaluated, both the Voting and LSTM with ensemble learning capabilities, demonstrated competitive performance. These models achieved the highest results across all evaluation metrics. Specifically, they both attained a testing accuracy of 72.174% and an F1 score of 0.818, their respective AUC values were 0.715 for the Voting and 0.722 for the LSTM. CONCLUSION: Radial pulse wave signal could identify most PCOS patients accurately (with a good F1 score) and is valuable for early detection and monitoring of PCOS with acceptable overall accuracy. This technique can stimulate the development of individualized PCOS risk assessment using mobile detection technology, furthermore, gives physicians an intuitive understanding of the objective pulse diagnosis of TCM. TRIAL REGISTRATION: Not applicable.

Single-Atom Nanoenzyme-Based Autoluminescence System for Cancer Cell Imaging and Mitochondrial-Targeted Therapy.

The autoluminescence nanoplatform based on a single-atom catalyst has the potential to achieve accurate tumor diagnosis and treatment. Taking advantage of this, glycyrrhetinic acid (GA) and chitosan-modified single Fe-N-C atom catalysts (SAF NPs) loaded with luminol-curcumin (Cur) were fabricated (SAF-LCCG). Once delivered to the tumor, this autoluminescence SAF-LCCG could target the mitochondria to restrain tumor metastasis and promote the production of hydrogen peroxide (H2O2). Then, SAF NPs with Fenton-like properties could actively utilize intracellular H2O2 to produce ·OH for chemodynamic therapy. After that, excess ·OH and H2O2 were transmitted to luminol to emit blue-violet chemiluminescence (CL) for cancer cell imaging. Synchronously, light was transferred to Cur to produce reactive oxygen species (ROS) which realized photodynamic therapy. Besides, Cur could be served as a chemotherapeutic drug to enhance intracellular ROS for penetrating therapy. More importantly, the massive accumulation of ROS in cancer cells can promote the CL intensity of luminol, which realized the cyclic ROS amplification. This autoluminescence nanoplatform was developed for accurate cancer cell imaging, effective inhibition of tumor metastasis, and synergistic and penetrated treatment of tumors.

Metabolomic Analysis Reveals the Metabolic Diversity of Wild and Cultivated Stellaria Radix (Stellaria dichotoma L. var. lanceolata Bge.).

Stellaria Radix, called Yinchaihu in Chinese, is a traditional Chinese medicine, which is obtained from the dried roots of Stellaria dichotoma L. var. lanceolata Bge. Cultivated yinchaihu (YCH) has become a main source of production to alleviate the shortage of wild plant resources, but it is not clear whether the metabolites of YCH change with the mode of production. In this study, the contents of methanol extracts, total sterols and total flavonoids in wild and cultivated YCH are compared. The metabolites were analyzed by ultra-high performance liquid chromatography-tandem time-of-flight mass spectrometry. The content of methanol extracts of the wild and cultivated YCH all exceeded the standard content of the Chinese Pharmacopoeia. However, the contents of total sterols and total flavonoids in the wild YCH were significantly higher than those in the cultivated YCH. In total, 1586 metabolites were identified by mass spectrometry, and 97 were significantly different between the wild and cultivated sources, including ß-sitosterol, quercetin derivatives as well as many newly discovered potential active components, such as trigonelline, arctiin and loganic acid. The results confirm that there is a rich diversity of metabolites in the wild and cultivated YCH, and provide a useful theoretical guidance for the evaluation of quality in the production of YCH.

Flavonoids from the roots and rhizomes of Sophoratonkinensis and their in vitro anti-SARS-CoV-2 activity.

Acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had caused a global pandemic since 2019, and posed a serious threat to global health security. Traditional Chinese medicine (TCM) has played an indispensable role in the battle against the epidemic. Many components originated from TCMs were found to inhibit the production of SARS-CoV-2 3C-like protease (3CLpro) and papain-like protease (PLpro), which are two promising therapeutic targets to inhibit SARS-CoV-2. This study describes a systematic investigation of the roots and rhizomes of Sophora tonkinensis, which results in the characterization of 12 new flavonoids, including seven prenylated flavanones (1-7), one prenylated flavonol (8), two prenylated chalcones (9-10), one isoflavanone (11), and one isoflavan dimer (12), together with 43 known compounds (13-55). Their structures including the absolute configurations were elucidated by comprehensive analysis of MS, 1D and 2D NMR data, and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations. Compounds 12 and 51 exhibited inhibitory effects against SARS-CoV-2 3CLpro with IC50 values of 34.89 and 19.88 µmol·L-1, repectively while compounds 9, 43 and 47 exhibited inhibitory effects against PLpro with IC50 values of 32.67, 79.38, and 16.74 µmol·L-1, respectively.

Comparative metabolomics provides novel insights into correlation between dominant habitat factors and constituents of Stellaria Radix (Stellaria dichotoma L. var. lanceolata Bge.).

Stellaria dichotoma L. var. lanceolata Bge. (SDL) is the original plant of the traditional Chinese medicine Yinchaihu (Stellaria Radix). It is mainly distributed in the arid desert areas of northwest China, which is the genuine medicinal material and characteristic cultivated crop in Ningxia. This study aims to analyze the effects of different origins on SDL metabolites and quality, as well as to screen the dominant habitat factors affecting SDL in different origins. In this study, metabolites of SDL from nine different production areas were analyzed by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF MS) based metabolomics. And field investigations were conducted to record thirteen habitat-related indicators. Results showed that 1586 metabolites were identified in different origins, which were classified as thirteen categories including lipids, organic acids and organic heterocyclic compounds derivatives. Multivariate statistical analysis showed that the metabonomic spectra of SDL from different origins had various characteristics. What's more, co-expression network correlation analysis revealed that three metabolites modules (MEturquoise, MEbrown and MEblue) were more closely with the habitat factors and 104 hub metabolites were further screened out as the habitat-induced metabolite indicators. Besides, soil texture, soil pH value and soil total salt content were found as the dominant habitat factors which affect SDL metabolites. In conclusion, the study showed different habitat factors had various effects on SDL's quality and established relationship between them, which provide reference for revealing SDL's genuineness formation mechanism and guiding industrial crops practical production by habitat factors selection.

Qingfei oral liquid alleviates RSV-induced lung inflammation by promoting fatty-acid-dependent M1/M2 macrophage polarization via the Akt signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Respiratory syncytial virus (RSV) is a common pathogen that causes lower respiratory tract disease in infants and the elderly, and no vaccination is presently available. Qingfei oral liquid (QF), a traditional Chinese medicine formula, has been shown in clinic to have anti-inflammatory properties. AIM OF THE STUDY: The present study investigated whether QF can suppress RSV-induced lung inflammation in mice models via fatty acid-dependent macrophage polarization. MATERIAL AND METHODS: BALB/c mice were given a low, medium, or high dose of QF intragastrically for four consecutive days following RSV infection. The lung inflammatory status was assessed using H&E staining and cytokine assays. The active components of QF and fatty acid metabolism were analyzed using ultra-high-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). A lipid metabolism-related pathway was found through network pharmacology and molecular docking investigations. Western blotting assays were used to determine the levels of ATP-citrate lyase (ACLY), peroxisome proliferation-activated receptor alpha (PPAR), Akt protein kinase B and its phosphorylated form in Akt signaling. Flow cytometry was used to quantify the number of macrophage subtypes (M1/M2), and immunohistochemistry was used to examine the expression of inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1). RESULTS: In the lung tissues of RSV-infected mice, QF suppressed the transcription of pro-inflammatory proteins such as interleukin-1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6), while increasing the level of anti-inflammatory factors such as interleukin-10 (IL-10). The alterations in metabolic enzyme activity mediated by Akt signaling were linked to QF's significant reduction in lung fatty acid accumulation. Lower ACLY expression and higher PPAR expression were found after QF treatment, showing that these two enzymes were downstream targets of Akt signaling, controlling fatty acid synthesis (FAS) and fatty acid oxidation (FAO), respectively. The reprogramming of fatty acid metabolism resulted in the polarization of macrophages from M1 to M2, with lower expression of iNOS and higher expression of Arg-1. Additionally, application of an Akt agonist (SC-79) reduced QF's anti-inflammatory effects by increasing FAS and decreasing macrophage polarization. CONCLUSIONS: QF inhibited Akt-mediated FAS and polarized M1 to M2 macrophages, resulting in an anti-inflammatory impact.

Somatostatin plus Gastroscopic Administration of Omeprazole for the Treatment of Acute Upper Gastrointestinal Bleeding: An Exploration of a Promising Alternative.

Objective: To analyze the efficacy and safety of somatostatin combined with gastroscopic administration of omeprazole in the treatment of acute upper gastrointestinal bleeding. Methods: Eligible 112 patients with acute upper gastrointestinal bleeding treated in our hospital from May 2019 to July 2020 were randomized at a ratio of 1 : 1 either to the control group (somatostatin) or observation group (somatostatin combined with omeprazole gastroscope administration). The treatment efficacy, the average hemostasis time, rebleeding rate, average length of hospital stay, and the incidence of adverse reactions were compared. Results: The study group demonstrated significantly higher total effective rate than the control group (96.45% vs. 80.36%, <0.05). The study group demonstrated superior performances compared to the control group with respect to the average hemostasis time ((14.17 ± 2.53 h) vs. (28.84 ± 4.07 h)), rebleeding rate (3.57% vs. 14.28%), and average length of hospital stay ((5.86 ± 1.26 d) vs. (9.74 ± 1.07 d)) (all p < 0.05). The chi-square test revealed a remarkably lower total incidence of adverse reactions in the study group vs. control group which was (4 (7.14%) vs. 12 (21.43%)) (p < 0.05). Conclusion: The combination of somatostatin and gastroscopic administration of omeprazole might be a promising alternative for the treatment of acute upper gastrointestinal bleeding. It improves the clinical treatment effect and controls the symptoms of patients, with a good safety profile.

Characteristics of Pulse Parameters in Patients with Polycystic Ovary Syndrome Varied at Different Body Mass Index Levels.

Objective: To analyze the characteristics of pulse graph parameters in patients with polycystic ovary syndrome (PCOS) varied at different body mass index (BMI) levels and to provide pulse diagnosis basis for syndrome differentiation and treatment of PCOS. Methods: Pulse graph parameters of 152 patients with PCOS (26 lean patients, 63 patients with moderate weight, and 63 overweight patients) were measured by a Z-BOX pulse meter, and the pulse graph parameters of patients with PCOS varied at different BMI levels were analyzed. Results: Fine pulse, slippery pulse, and string-like pulse were the most common pulse conditions in patients with PCOS. The common pulse conditions of patients with PCOS varied at different BMI levels. The order of pulse conditions was as follows: lean group: fine pulse > string-like pulse > slippery pulse; moderate group: fine pulse > slippery pulse > string-like pulse; and overweight group: slippery pulse > fine pulse > sunken pulse. Compared to the overweight group, the pulse graph parameters h1, h3, h4, h5, h4/h1, As, and Ad increased in the moderate group (P < 0.05), and the parameters h1, h3, and Ad increased (P < 0.05) and the parameter t1 decreased (P < 0.05) in the lean group. Conclusion: Pulse graph parameters among patients with PCOS varied at different BMI levels, which can probably provide pulse diagnosis basis for syndrome differentiation and treatment of PCOS by traditional Chinese medicine (TCM).

Ten undescribed cadinane-type sesquiterpenoids from Eupatorium chinense.

Ten undescribed cadinane-type sesquiterpenes (1-10) were isolated from the whole plant of Eupatorium chinense. Their planar structures were mainly elucidated by extensive analysis of spectroscopic data and DFT NMR calculations. The absolute configurations of 1, 2, and 3 were determined by TDDFT ECD calculations while those of compounds 4-7 and 9 were confirmed by single crystal X-ray diffraction experiments. Compounds 2 and 3 are a pair of C-10 epimers, compounds 4 and 5 a pair of C-1 epimers, and compounds 9 and 10 a pair of compounds isomerized at both C-1 and C-10. A possible biosynthetic pathway for these new sesquiterpenes was proposed.

Clinical practice guidelines for the treatment of allergic rhinitis in children with traditional Chinese medicine.

Allergic rhinitis (AR) is one of the most common allergic diseases in children and it can lead to physical and mental health problems. Traditional Chinese medicine (TCM) plays an important role in understanding the phenotypes and treatment of AR. However, there are currently no normative clinical practice guidelines (CPGs) for the treatment of AR in children. The study aimed to develop an evidence-based CPG for the treatment of AR in children with TCM. Systematic literature research, expert questionnaire, and clinical evaluation after three rounds of surveys were adopted to form recommendations for treating children with AR using the Delphi method. Depending on the clinical manifestations, we finally recommended two decoctions with two Chinese patent medicines for an acute attack of AR and two decoctions for a chronic period of AR. For the acute attack of AR in children, Xinyi Qingfei decoction, Wenfei Zhiliu decoction, Xinqin granules, and Xinyi Biyan pills were suggested, whereas for the chronic period of AR, Buzhong Yiqi and Jingui Shenqi decoctions were recommended. The four external treatment methods suggested for the prevention and care of AR were body acupuncture, moxibustion, auricular point pressing, and acupoint application. The recommended levels of the suggested TCM strategies ranged from Grade B to D, indicating the weakness of the recommendations. TCM has the potential to offer new insights into phenotypes and the management of AR worldwide; however, more high-quality clinical studies are needed to improve the quality of evidence.

Polyisoprenylated benzophenone derivatives from Garcinia cambogia and their anti-inflammatory activities.

Ten new polyisoprenylated benzophenone derivatives, 4,8-epi-uralione F (1), 4,8-epi-uralione G (2), uralione S (3), coccinone J (4), 6-epi-coccinone C (5), coccinone I (6), 36-hydroxy-guttiferone J (7), multiflorone I (8), garciniagifolone F (9) and 36-hydroxy-garciniagifolone F (10), were isolated from the fruits of Garcinia cambogia, along with seven known analogues. The structures of the new compounds were established based on the detailed analysis of 1D and 2D nuclear magnetic resonance (NMR) spectra and high resolution electrospray ionization mass spectrometra (HRESIMS), and their absolute configurations were determined from the electronic circular dichroism (ECD) spectra. All the isolates were tested for their inhibitory effects against nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The results indicated that compound 1 displayed a potent NO inhibitory effect with an IC50 value of 41.60 ± 0.17 µM. Furthermore, compound 1 suppressed inducible NO synthase (iNOS) expression in a dose-dependent manner through inhibiting the activation of nuclear factor-κB (NF-κB).

Chinese Herbal Medicine Xingnaojing Injection for Acute Ischemic Stroke: An Overview of Systematic Reviews and Meta-Analyses.

Background: Xingnaojing injection (XNJ) is the only Chinese herbal injection approved for both intracerebral hemorrhage and ischemic stroke (IS) first-aid on ambulances in China; many systematic reviews (SRs) and meta-analyses (MAs) of XNJ on stroke have been published. The purpose of this research was to evaluate and summarize the current evidence on XNJ for IS. Methods: A comprehensive search was conducted for SRs and MAs of XNJ on IS in seven databases up to January 1, 2021. Two authors independently identified SRs and MAs, extracted data, assessed the quality of the included SRs and MAs using the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2), and assessed quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Results: A total of 10 SRs met the inclusion criteria. The quality of included SRs using AMSTAR 2 was critically low as the critical items were poorly reported. Only 10% of SRs reported 50% of the 16 items, while the remaining 90% SRs reported just less than half of the items on AMSTAR 2. For GRADE, 7 (35%) of outcomes had low-quality evidence, 10 (50%) with very low, and 3 (15%) with moderate quality evidence. Very low to low quality of evidence indicated XNJ plus conventional therapy (CT) alleviated the neurological deficits of acute IS. Moderate-quality evidence showed XNJ plus CT reduced mortality when compared to Danshen injection plus CT, and very low-quality evidence showed XNJ plus CT could not improve the degree of coma, while low-quality evidence indicated the opposite. Mild adverse events in the CT group were less than those in the XNJ plus CT group, and there were no serious adverse events, but there was no statistical difference between the two groups. The included 10 SRs indicated that XNJ was used for acute IS, but only four SRs (40%) reported the course of disease. Conclusion: XNJ appears to be effective and safe for acute IS in improving the neurological deficits, but the evidence is not robust enough. However, whether administering XNJ immediately after or within 24 h of IS is best remains unknown due to the lack of data. Well-designed large-scale randomized controlled trials with measurable outcomes are required in future studies.

Mindfulness-based online intervention on mental health and quality of life among COVID-19 patients in China: an intervention design.

BACKGROUND: COVID-19 can lead to increased psychological symptoms such as post-traumatic stress disorder (PTSD), depression, and anxiety among patients with COVID-19. Based on the previous mindfulness-based interventions proved to be effective, this protocol reports a design of a randomized controlled trial aiming to explore the efficacy and possible mechanism of a mindful living with challenge (MLWC) intervention developed for COVID-19 survivors in alleviating their psychological problems caused by both the disease and the pandemic. METHODS: In April 2021, more than 1600 eligible participants from Hubei Province of China will be assigned 1:1 to an online MLWC intervention group or a waitlist control group. All participants will be asked to complete online questionnaires at baseline, post-program, and 3-month follow-up. The differences of mental health status (e.g. PTSD) and physical symptoms including fatigue and sleeplessness between the COVID-19 survivors who receiving the online MLWC intervention and the control group will be assessed. In addition, the possible mediators and moderators of the link between the MLWC intervention and target outcomes will be evaluated by related verified scales, such as the Five Facets Mindfulness Questionnaire. Data will be analyzed based on an intention-to-treat approach, and SPSS software will be used to perform statistical analysis. DISCUSSION: The efficacy and potential mechanism of MLWC intervention in improving the quality of life and psychological status of COVID-19 survivors in China are expected to be reported. Findings from this study will shed light on a novel and feasible model in improving the psychological well-being of people during such public health emergencies. Trial registration Chinese Clinical Trial Registry (ChiCTR), ChiCTR2000037524; Registered on August 29, 2020, http://www.chictr.org.cn/showproj.aspx?proj=60034 .

Cytotoxic guaianolides and seco-guaianolides from Artemisia atrovirens.

A phytochemical investigation of a medicinal plant Artemisia atrovirens was carried out, resulting in the characterization of a novel bis-nor seco-guaianolide, seco-atrovirenolide A (1), a new 1,10-seco-guaianolide derivative, seco-atrovirenoic acid A (2), and a new artifact 10-methanoyloxy-seco-atrovirenoic acid A (3), together with eight known guaianolide and seco-guaianolide derivatives (4-11). The structures of new compounds were fully established by extensive analysis of MS, 1D and 2D NMR spectroscopic data. The absolute configurations of the isolated compounds were confirmed by TDDFT ECD calculation, Mosher's method, and X-ray crystal diffraction experiment. All the compounds were tested in vitro for their cytotoxicity against HL-60 and A549 cell lines. Some of them showed moderate inhibitory activity against HL-60 cell lines with IC50 values ranging from 5.99 to 11.74 µM.

Development of small-molecule tropomyosin receptor kinase (TRK) inhibitors for NTRK fusion cancers.

Tropomyosin receptor kinase A, B and C (TRKA, TRKB and TRKC), which are well-known members of the cell surface receptor tyrosine kinase (RTK) family, are encoded by the neurotrophic receptor tyrosine kinase 1, 2 and 3 (NTRK1, NTRK2 and NTRK3) genes, respectively. TRKs can regulate cell proliferation, differentiation and even apoptosis through the RAS/MAPKs, PI3K/AKT and PLCγ pathways. Gene fusions involving NTRK act as oncogenic drivers of a broad diversity of adult and pediatric tumors, and TRKs have become promising antitumor targets. Therefore, achieving a comprehensive understanding of TRKs and relevant TRK inhibitors should be urgently pursued for the further development of novel TRK inhibitors for potential clinical applications. This review focuses on summarizing the biological functions of TRKs and NTRK fusion proteins, the development of small-molecule TRK inhibitors with different chemotypes and their activity and selectivity, and the potential therapeutic applications of these inhibitors for future cancer drug discovery efforts.

Effect of electroacupuncture on expression of IL-23/IL-17 axis and TLR4 in infarcted tissue in rats with myocardial infarction / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) on expression of interleukin (IL) -23/IL-17 axis and Toll-like receptor 4 (TLR4) in the infarcted tissue in rats with myocardial infarction (MI), and to explore the mechanism of EA on alleviating MI injury.@*METHODS@#Forty male SD rats were randomly divided into a sham-operation group, a sham-operation plus EA group, a model group and an EA group, 10 rats in each group. The MI models were established by ligation of left anterior descending coronary artery in the model group and EA group, while only threading was performed in the sham-operation group and sham-operation plus EA group. The rats in the sham-operation plus EA group and EA group were treated with EA at "Neiguan" (PC 6), disperse-dense wave, 2 Hz/100 Hz, 2 mA, once a day, 20 min each time, for 3 days. After the intervention, the ejection fraction (EF) was measured by echocardiography to evaluate the cardiac function; the infarct area was measured by TTC staining; the HE staining was used to observe the morphological changes of myocardial tissue; the levels of IL-23 and IL-17 in infarcted tissue were detected by ELISA; the protein expression of TLR4 in infarcted tissue was detected by Western blot.@*RESULTS@#Compared with the sham-operation group, the EF was decreased (@*CONCLUSION@#EA may alleviate the excessive inflammatory response after MI by inhibiting the expression of IL-23/IL-17 axis in MI rats, and TLR4 may be involved during the process.

Effect of electroacupuncture at "Neiguan" (PC 6) on cardiac function and inflammatory factors of acupoint area in rats with acute myocardial ischemia / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on cardiac function and cardiomyocyte apoptosis in rats with acute myocardial ischemia (AMI), and to explore the correlation between myocardial protective effect of EA and inflammatory factors i.e. interleukin-1β (IL-1β) and interleukin-17 (IL-17) of "Neiguan" (PC 6) area.@*METHODS@#A total of 40 male SD rats with normal ultrasonic cardiogram were randomized into a sham-operation group, a sham-operation plus EA group, a model group and an EA group, 10 rats in each group. The AMI model was established by ligating the left anterior descending (LAD) branch of the coronary artery in the model group and the EA group, while the threading without ligating was adopted in the sham-operation group and the sham-operation plus EA group. In the sham-operation plus EA group and the EA group, EA at bilateral "Neiguan" (PC 6) was applied, with disperse-dense wave, 2 Hz/100 Hz in frequency and 2 mA in density, once a day, 20 min a time for 3 days. The cardiac ejection fraction (EF) and fractional shortening (FS) were measured by ultrasonic cardiogram to evaluate the cardiac function, the cardiomyocyte apoptosis was detected by TUNEL staining, the infiltration of inflammatory factors of "Neiguan" (PC 6) area was observed by H.E. staining, the expression of inflammatory factors IL-1β and IL-17 of "Neiguan" (PC 6) area was detected by immunofluorescence staining.@*RESULTS@#Compared with the sham-operation group, EF and FS were decreased (@*CONCLUSION@#Electroacupuncture at "Neiguan" (PC 6) can improve the cardiac function and reduce the apoptosis of cardiomyocyte in rats with acute myocardial ischemia, its mechanism may be related to the regulation of the inflammatory factors of "Neiguan" (PC 6) area.

Bibliometric analysis on the clinical researches of tumor treated with acupuncture-moxibustion on the base of PubMed database / 中国针灸

OBJECTIVE@#To analyze the literature characteristics of the clinical researches on tumor treatment with acupuncture-moxibustion in PubMed database so as to provide the references for the study of acupuncture-moxibusion in intervention of tumor.@*METHODS@#The articles on the clinical researches of acupuncture-moxibusion in treatment of tumor were retrieved from PubMed database listed till December 31, 2018. Using bibliometric methodology, the analysis was conducted on publication year, publication journal, author, country or region, research institution, disease spectrum and therapeutic regimen.@*RESULTS@#A total of 143 articles are included. The publications are increased steadily since 2004. The articles are published in 64 international journals, of which, @*CONCLUSION@#Acupuncture-moxibustion is quite extensively involved in the treatment of tumor in the field of nervous (mental) system and digestive system. But the regimen of acupuncture- moxibustion needs to be further optimized and promoted.