Responsive regularity of neurons in the hindlimb region of primary somatosensory cortex to different temperature thermal needle stimulation of "Zusanli"(ST36) in mice. / å°é¼ åˆçº§ä½“æ„Ÿçš®å±‚åŽè‚¢åŒºç¥žç»å ƒå¯¹"足三里"不同温度热刺激的响应规律.

OBJECTIVES: To study the regularity of central response to thermal needle stimulation of "Zusanli" (ST36) at different temperature, and to analyze the temperature difference of central responses. METHODS: Six male C57BL/6j adult mice were used in the present study. For observing activities of neurons in the hindlimb region of left primary somatosensory cortex (S1HL, A/P=0.46 mm, M/L=1.32 mm, D/V=-0.14 mm) by using a fast high-resolution miniature two-photon microscopy (FHIRM-TPM), the mice were anesthetized with 3% isoflurane (inhalation), with its head fixed in a stereotaxic apparatus, then, adeno-associated virus (AAV-hSyn-GCaMP6f-WPRE-hGHpA, for showing intracellular calcium transients in neurons transfected) was injected into the left S1HL region using a micro-syringe after scalp surgical operation. The mice's right ST36 were stimulated using internal thermal needles with the temperature being 43 ℃, or 45 ℃, or 47 ℃, separately. Image J software and MATLAB 2020b software were used to process the image data of neuronal calcium activity (Ca2+ signaling) in the left S1HL region, including the instant maximum calcium peak value (ΔF/F) in 2 s, instant calcium spike frequency in 2 s, short-term calcium peak value (ΔF/F) in 3.5 min, short-term calcium spike frequency in 3.5 min, calcium peak duration in 3.5 min, maximum calcium peak value (ΔF/F) at the 1st , 2nd and 3rd min, and calcium spike frequency at the 1st, 2nd and 3rd min after thermal needle stimulation. RESULTS: In comparison with the normal temperature needle stimulation, the instant intracellular maximum calcium peak value, instant calcium spike frequency, short-term maximum calcium peak value, short-term calcium spike frequency, and calcium peak duration of S1HL neurons in response to 43 ℃, 45 ℃ and 47 ℃ internal thermal needle stimulation of ST36 were significantly increased (P<0.001, P<0.01). Comparison among the 43 ℃, 45 ℃ and 47 ℃ thermal needle stimulation showed that the 45 ℃ thermal needle stimulation was obviously superior to 43 ℃ and 47 ℃ thermal needle stimulation in increasing instant calcium spike frequency, short-term calcium spike frequency and calcium peak duration of S1HL neurons (P<0.001, P<0.01). The 47 ℃ thermal needle stimulation was stronger than 43 ℃ and 45 ℃ thermal needle stimulation in increasing the instant maximum calcium peak value (P<0.001). The maximum calcium peak value was apparently higher (P<0.001) at the 2nd min than that at the 1st and 3rd min after 43 ℃, 45 ℃ and 47 ℃ thermal needle stimulation. No significant differences were found in the short-term maximum calcium peak value among the 3 thermal needle stimulation and in the calcium spike frequency among the 3 time points after 43 ℃, 45 ℃ and 47 ℃ thermal needle stimulation. CONCLUSIONS: S1HL neurons respond to all 43 ℃, 45 ℃ and 47 ℃ thermal needle stimulation of ST36 in mice, while more actively to 45 ℃ thermal needle stimulation.

Clinical effects and mechanisms of a Chinese patent medicine, Tongxinluo capsule, as an adjuvant treatment in coronary heart disease.

Coronary heart disease (CHD) is the leading cause of death globally, posing a serious threat to human health. However, the current treatment approaches available for CHD fall short of the ideal results. Tongxinluo (TXL) is a traditional Chinese medicine (TCM) that has been employed in the clinical treatment of cardiovascular and cerebrovascular diseases (such as angina pectoris, stroke, etc.) in China for many years and holds great potential as a prospective treatment. TXL either as a standalone treatment or in combination with interventions recommended in CHD guidelines has been shown to be effective and well tolerated in clinical trials for CHD. Drawing on the evidence from clinical trials and experimental studies, this review will focus on the cardiovascular protective properties and related mechanisms of TXL. By searching 8 Chinese and English databases, more than 4000 articles were retrieved. These articles were categorized, then read, and finally written into this review. In this review, the pharmacological properties of TXL include regulation of blood lipids, improvement of endothelial function, anti-inflammatory, antioxidant, inhibition of apoptosis and regulation of autophagy, anti-fibrosis, promotion of angiogenesis, and modulation of exosome communication. The information provided in this review will help the reader to comprehend better the insights that TCM has developed over time in practice and provide new perspectives for the treatment of CHD.

Activity-guided isolation and identification of antiherpesvirus and antineuroinflammatory active terpenoids from Artemisia vulgaris L. based on the LC-MS/MS molecular network.

Seven undescribed terpenoids, comprising two guaiane-type sesquiterpene lactones (1-2), one eucalyptol-type sesquiterpene (3), one monolactone (4), and three triterpenoids (5-7), along with 35 known analogues, were isolated from the leaves of Artemisia vulgaris L. Their structures and configurations were analysed by extensive spectroscopy. Compounds 1, 2, 8-10, 13, 17, 19, and 28 showed antineuroinflammatory activity, and compounds 1 and 2 revealed remarkable antineuroinflammatory effects, with an IC50 value of 2.2 ± 0.1 and 1.6 ± 0.1 µM, more potent than the positive control drug dexamethasone. Furthermore, compounds 1 and 2 could inhibit the expression of BV-2 inflammatory genes (IL-6, TNF-α, IL-1ß) induced by LPS, downregulate the critical inflammatory protein production of iNOS and COX-2. The anti-HSV-1 activity screening revealed that compounds 28, 29 and 38 exhibited inhibitory activity against HSV-1 proliferation. Particularly, compound 28 exhibited a significant anti-HSV-1 effect, inhibiting the proliferation of HSV-1 and acyclovir-resistant strains of HSV-1/153 and HSV-1/Blue. Our research identified compounds 1, 2, and 28 from A. vulgaris., which could potentially serve as lead compounds for antineuroinflammatory and anti-HSV-1 activities.

[Effect of mild moxibustion at 45 ℃ with different durations at "Zusanli" （ST36） on the inflammatory factors in the abdominal aorta of hyperlipidemia rats].

OBJECTIVE: To investigate the effects of mild moxibustion at 45°C on the chronic inflammatory response of the abdominal aorta in rats with hyperlipidemia and the effects of different moxibustion durations. METHODS: Thirty-six SD rats were randomly divided into the following groups： blank control group (2 weeks), model group (2 weeks), moxibustion group (2 weeks), blank group (4 weeks), model group (4 weeks), and moxibustion group (4 weeks). A model of hyperlipidemia with chronic inflammation was established through high-fat diet feeding for 8 weeks. Rats in the moxibustion groups received mild moxibustion treatment at bilateral "Zusanli"(ST36) at 45 °C, 10 min every time, once a day, for consecutive 2 or 4 weeks. The morphology of the abdominal aorta in each group was observed by using HE staining. Contents of serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), oxidized low-density lipoprotein (ox-LDL), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), endothelin-1 (ET-1) and the contents of nitric oxide (NO), ox-LDL, and ET-1 in the abdominal aorta were measured by using ELISA. Protein and mRNA expressions of IL-6 and TNF-α in the abdominal aorta of rats in each group were detected by using Western blot and real-time fluorescence quantitative PCR respectively. The positive expression of IL-6 in the abdominal aorta of rats was detected by Immunofluorescence. RESULTS: Compared to the blank control group, rats in the model group had increased contents of LDL, TC, TG, ox-LDL, VCAM-1, ICAM-1, IL-6, TNF-α, and ET-1 in the serum, increased contents of ox-LDL and ET-1 in the abdominal aorta, increased protein and mRNA expressions of IL-6 and TNF-α in the abdominal aorta(P<0.01, P<0.05, P<0.001), with decreased HDL content in the serum, decreased NO content in the abdominal aorta (P<0.01, P<0.05), as well as dark pink abdominal aorta, rough textures in the adventitia, media, and intima, and rough endothelial layer. Compared to the model group(2 weeks), LDL, ICAM-1, ET-1 contents in the serum, ox-LDL content in the abdominal aorta were decreased(P<0.05), while serum IL-6 and TNF-α contents, and NO content in the abdominal aorta were significantly increased(P<0.01, P<0.05), with smoother vascular walls, and relatively clear nucleus and surrounding tissue structures of abdominal aorta in the moxibustion group(2 weeks). Compared to the model group(4 weeks), contents of LDL, TC, TG, VCAM-1, ICAM-1, IL-6, TNF-α, ox-LDL, and ET-1 in the serum, ox-LDL and ET-1 contents in abdominal aorta, protein and mRNA expressions of IL-6 and TNF-α in the abdominal aorta were significantly decreased(P<0.05, P<0.01), while HDL content in the serum and NO content in the abdominal aorta were significantly increased(P<0.05, P<0.01), with smoother vascular walls, and relatively clear nucleus and surrounding tissue structures of abdominal aorta in the moxibustion group(4 weeks). In addition, content of HDL in the serum were significantly increased(P<0.05), while TNF-α content in the serum, protein expression of IL-6 in the abdominal aorta were significantly decreased (P<0.001, P<0.05), with smoother vascular walls, and clearer nucleus and surrounding tissue structures of abdominal aorta in the moxibustion group(4 weeks), in comparison with the moxibustion group(2 weeks). CONCLUSION: Mild moxibustion of 45 °C at ST36 can improve vascular endothelial damage and inflammatory response induced by high-fat diet by regulating serum lipids, vascular tone, adhesion molecules, and inflammatory factors, of which the effect of moxibustion intervention for 4 weeks is more significant.

Trichosanates A-G and cucurbitacins W-Y, anticomplement monoterpenoids and cucurbitane-type triterpenoids from the pericarps of Trichosanthes kirilowii.

The pericarps of Trichosanthes kirilowii are often used to treat cough in traditional Chinese medicine, and its ethanol extract exhibited effective therapeutic effects on acute lung injury (ALI) in vivo caused by H1N1. An anticomplement activity-guided fractionation on the extract resulted in the isolation of ten new terpenoids, including seven monoterpenoids, trichosanates A-G (1-7), and three cucurbitane-type triterpenoids, cucurbitacins W-Y (8-10), as well as eleven known terpenoids (11-21). The new terpenoids' structures were determined by spectroscopic analysis, X-ray crystallographic analysis (1), electronic circular dichroism (ECD) analysis and calculations (2-10). Twelve monoterpenoids (1-7 and 11-15) and five cucurbitane-type triterpenoids (8-10, 18, and 20) exhibited anticomplement activity in vitro. For the monoterpenoids, the long aliphatic chain substituents might enhance their anticomplement activity. Additionally, two representative anticomplement terpenoids, 8 and 11, obviously attenuated H1N1-induced ALI in vivo by inhibiting complement overactivation and reducing inflammatory responses.

Shenqi formula delayed Alzheimer's disease-like symptoms by skn-1 pathway in Caernorhabditis elegans.

ETHNOPHARMACOLOGICAL RELEVANCE: Shenqi formula is composed of Codonopsis pilosula (Cp) and Lycium barbarum (Lb), and it is traditionally used for promoting qi and nourishing the spleen, liver and kidney. Cp and Lb have been reported to improve cognitive performance in APP/PS1 mice, prevent the accumulation of Aß, and reduce the neurotoxicity of Aß to achieve the anti-Alzheimer's disease (AD) effect. AIM OF THE STUDY: Shenqi formula was explored the therapeutic effect on Caenorhabditis elegans AD pathological model and the underlying mechanism of action. MATERIALS AND METHODS: Paralysis assay and serotonin sensitivity assay was used to detect whether Shenqi formula can alleviate AD paralysis phenotype, and then DPPH, ABTS, NBT and Fenton methods were applied to investigate the scavenging capacity to free radical, ROS, ·O2- and ·OH of Shenqi formula in vitro. H2DCF-DA and MitoSOX™ Red were employed to measure ROS and .O2- accumulation, respectively. RNAi was used to knock down the expression of skn-1 and daf-16 related to oxidative stress resistance signalling pathway. Fluorescence microscopy was used to record the expression of SOD-3::GFP, GST-4::GFP, SOD-1::YFP, and the nuclear translocation of SKN-1 and DAF-16. Western blot assay was carried out to test Aß monomers and oligomers. RESULTS: Shenqi formula delayed the AD-like pathological characteristics in C. elegans, and the complete Shenqi formula was more effective than Cp or Lb alone. The effect of Shenqi formula on delaying worm paralysis was partially eliminated by skn-1 RNAi, but not daf-16 RNAi. Shenqi formula significantly inhibited the abnormal deposition of Aß protein, decreased Aß protein monomers and oligomers. It increased the expressions of gst-4, sod-1, and sod-3 similar to paraquat, companied by rise then fall of ROS and .O2- in AD worms. CONCLUSIONS: Shenqi formula at least partially depended on SKN-1 signalling pathway to exert its anti-AD effect, and it is potential to be used as a kind of health food to prevent the progress of AD.

[Moxibustion of 45 ℃ at "Zusanli" (ST36) improves vascular endothelial oxidative stress in hyperlipidemia rats].

OBJECTIVE: To explore the antioxidant effect of moxibustion on vascular endothelial function and the under-lying mechanism. METHODS: Forty male SD rats were randomly divided into blank, model, moxibustion and endothelial nitric oxide synthase (eNOS) inhibitor groups, with 10 rats in each group. Hyperlipidemia rat model was established by high fat diet for 8 weeks. Rats in the moxibustion group received 45 ℃ moxibustion at "Zusanli" (ST36) for 10 min once daily for consecutive 4 weeks. Rats in the eNOS inhibitor group received intraperitoneal injection of eNOS inhibitor L-NAME (1 mg/100 g) at the same time of moxibustion intervention. The morphology of abdominal aorta endothelium was observed by HE staining. Lipid deposition in abdominal aorta was observed by oil red O staining. The contents of total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) in serum and reactive oxygen species (ROS), nitric oxide (NO), superoxide dismutase (SOD), oxidized LDL lipoprotein (ox-LDL), endothelin-1 (ET-1), eNOS, malondialdehyde (MDA) in serum and abdominal aorta were determined by ELISA. The expression of eNOS in abdominal aorta was detected by immunofluorescence. RESULTS: HE staining of the abdominal aorta showed no significant pathological abnormality in the blank group; the endovascular cortex was rough, and the inner, media and outer membrane were rough in the model group; the nucleus and surrounding tissue structure were clear and the vascular wall was smooth in the moxibustion group; abdominal aorta texture was rough in the eNOS inhibitor group. Compared with the blank group, the area of oil red O staining in abdominal aorta increased (P<0.05); the contents of serum TC, TG and LDL-C increased (P<0.01, P<0.05) while HDL-C decreased (P<0.05); the contents of ET-1 in serum and abdominal aorta were increased (P<0.01, P<0.05) while the contents of NO and eNOS were decreased (P<0.05, P<0.001); the contents of ROS, ox-LDL and MDA in serum and abdominal aorta were increased (P<0.001, P<0.01, P<0.000 1) while the content of SOD in abdominal aorta was decreased (P<0.000 1); the expression level of eNOS in abdominal aorta was decreased (P<0.05) in the model group. Compared with the model group, the area of oil red O staining in abdominal aorta decreased (P<0.05); the contents of TC, TG and LDL-C in serum decreased (P<0.05) while HDL-C increased (P<0.05); the contents of ET-1 in serum and abdominal aorta were decreased (P<0.01, P<0.05) while the contents of NO and eNOS in abdominal aorta were increased (P<0.001, P<0.01); the contents of ROS and MDA in serum and abdominal aorta were decreased (P<0.001, P<0.01, P<0.05), the content of ox-LDL was decreased (P<0.01) and the content of SOD was increased (P<0.000 1) in abdominal aorta; the expression level of eNOS in abdominal aorta was increased (P<0.05) in the moxibustion group. Compared with the moxibustion group, the contents of serum TC, LDL-C and MDA in the eNOS inhibitor group were increased (P<0.05); the contents of ET-1, ROS, ox-LDL and MDA in abdominal aorta were increased (P<0.05), the contents of NO, eNOS and SOD were decreased (P<0.05); the expression level of eNOS in abdominal aorta was decreased (P<0.05). CONCLUSION: 45 ℃ moxibustion at ST36 can protect and repair vascular endothelial injury in abdominal aorta of hyperlipidemia rats and improve the oxidative stress of vascular endothelium.

Electroacupuncture Zusanli (ST36) Relieves Somatic Pain in Colitis Rats by Inhibiting Dorsal Root Ganglion Sympathetic-Sensory Coupling and Neurogenic Inflammation.

Referred somatic pain triggered by hyperalgesia is common in patients with inflammatory bowel disease (IBD). It was reported that sprouting of sympathetic nerve fibers into the dorsal root ganglion (DGR) and neurogenic inflammation were related to neuropathic pain, the excitability of neurons, and afferents. The purpose of the study was to explore the potential and mechanism of electroacupuncture (EA) at Zusanli (ST36) for the intervention of colon inflammation and hyperalgesia. Sprague-Dawley (SD) was randomly divided into four groups, including control, model, EA, and sham-EA. Our results showed EA treatment significantly attenuated dextran sulfate sodium- (DSS-) induced colorectal lesions and inflammatory cytokine secretion, such as TNF-α, IL-1ß, PGE2, and IL-6. EA also inhibited mechanical and thermal pain hypersensitivities of colitis rats. Importantly, EA effectively abrogated the promotion effect of DSS on ipsilateral lumbar 6 (L6) DRG sympathetic-sensory coupling, manifested as the sprouting of tyrosine hydroxylase- (TH-) positive sympathetic fibers into sensory neurons and colocalization of and calcitonin gene-related peptide (CGRP). Furthermore, EA at Zusanli (ST36) activated neurogenic inflammation, characterized by decreased expression of substance P (SP), hyaluronic acid (HA), bradykinin (BK), and prostacyclin (PGI2) in colitis rat skin tissues corresponding to the L6 DRG. Mechanically, EA treatment reduced the activation of the TRPV1/CGRP, ERK, and TLR4 signaling pathways in L6 DRG of colitis rats. Taken together, we presumed that EA treatment improved colon inflammation and hyperalgesia, potentially by suppressing the sprouting of sympathetic nerve fibers into the L6 DGR and neurogenic inflammation via deactivating the TRPV1/CGRP, ERK, and TLR4 signaling pathways.

To Explore the Mechanism of "Fuzi-Guizhi" for the Treatment of Osteoarthritis on the Basis of Network Pharmacology and Molecular Docking.

OBJECTIVE: The objective of this study is to analyze and verify the main drug components and targets of "Fuzi-Guizhi" in the treatment of osteoarthritis by using the network pharmacology platform. METHODS: The integrated pharmacology of "Fuzi-Guizhi" was analyzed by using the platform of integrated pharmacology of traditional Chinese medicine to explore its mechanism in the treatment of osteoarthritis. By establishing an arthritis model in vitro, the pharmacological effect of "aconitecassia twigs" on articular cartilage was evaluated and conducted for molecular docking. RESULTS: 28 candidate active components, 37 compound targets, and 583 osteoarthritis-related potential targets were screened, and 10 key target processes were screened in the protein interaction network model. Enrichment analysis showed that the 10 core targets involved 958 GO biologic function items and 76 KEGG signal pathways, which were mainly related to apoptosis and mitochondrial functional metabolism and "Fuzi-Guizhi" drug-containing serum inhibited the expression of Caspase-3 mRNA and protein in chondrocytes and promoted the synthesis of ATP. CONCLUSION: Our research is preliminary that the mechanism of action of "Fuzi-Guizhi" may inhibit chondrocyte degeneration by resisting mitochondrial apoptosis, and further experimental research is required to determine.

Emodin alleviates arthritis pain through reducing spinal inflammation and oxidative stress.

Chronic pain is the predominant problem for rheumatoid arthritis patients, and negatively affects quality of life. Arthritis pain management remains largely inadequate, and developing new treatment strategies are urgently needed. Spinal inflammation and oxidative stress contribute to arthritis pain and represent ideal targets for the treatment of arthritis pain. In the present study, collagen-induced arthritis (CIA) mouse model was established by intradermally injection of type II collagen (CII) in complete Freund's adjuvant (CFA) solution, and exhibited as paw and ankle swelling, pain hypersensitivity and motor disability. In spinal cord, CIA inducement triggered spinal inflammatory reaction presenting with inflammatory cells infiltration, increased Interleukin-1ß (IL-1ß) expression, and up-regulated NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and cleaved caspase-1 levels, elevated spinal oxidative level presenting as decreased nuclear factor E2-related factor 2 (Nrf2) expression and Superoxide dismutase (SOD) activity. To explore potential therapeutic options for arthritis pain, emodin was intraperitoneally injected for 3 days on CIA mice. Emodin treatment statistically elevated mechanical pain sensitivity, suppressed spontaneous pain, recovered motor coordination, decreased spinal inflammation score and IL-1ß expression, increased spinal Nrf2 expression and SOD activity. Further, AutoDock data showed that emodin bind to Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) through two electrovalent bonds. And emodin treatment increased the phosphorylated AMPK at threonine 172. In summary, emodin treatment activates AMPK, suppresses NLRP3 inflammasome response, elevates antioxidant response, inhibits spinal inflammatory reaction and alleviates arthritis pain.

In situ assembled titanium carbide-based heterojunctions for the synergistic enhancement of NIR-II photothermal/photodynamic therapy against breast cancer.

The combined use of photothermal therapy (PTT) and photodynamic therapy (PDT) could circumvent the drawbacks of each individual therapeutic strategy, resulting in an enhanced antitumor effect. However, the lack of highly effective photo-agents that are irradiation-safe in the biologically transparent window hinder the advancement of phototherapy clinically. Hence, in this study, a charge separation engineering strategy was adopted to fabricate a nanoplatform with heterojunctions, namely, in situ TiO2-loaded MXene (Ti3C2/TiO2 heterojunctions). This nanoplatform exhibited reduced bandgap (1.68 eV), enhanced NIR-II photothermal conversion efficiency (44.98%), and extended absorption edge compared to pristine TiO2 for enhanced photodynamic effect. More importantly, the proliferation of tumor cells could be efficiently inhibited at a 5 mm chicken breast depth after 1064 nm laser irradiation, and the intracellular ROS production significantly increased under 660 nm or even 1064 nm laser irradiation with heterojunctions (HJs) compared with that of TiO2. Moreover, the in vivo data further confirmed that the as-prepared heterojunctions could efficiently eradicate tumors efficiently via improved photothermal effect with NIR-II laser irradiation and upregulated ROS production. Collectively, the reported HJs strategy provides an opportunity for the success of combinational PTT and PDT therapy in tumor treatment.

[Characteristics of Soil Organic Carbon Components and Their Correlation with Other Soil Physical and Chemical Factors in Cotton Fields with Different Continuous Cropping Years in the Oasis on the Northern Edge of Tarim Basin].

The study of soil organic carbon components in continuous cropping cotton fields in oases is helpful to reveal the change characteristics of the soil organic carbon stability mechanism in arid areas under the effects of man-land relationships. In this study, the contents of soil organic carbon, easily oxidized organic carbon, dissolved organic carbon, and microbial biomass carbon in cotton fields with different continuous cropping years (2 a, 5 a, 12 a, 20 a, and 35 a) were collected and analyzed by using space instead of the time series method. Through redundancy analysis, the relationship between soil organic carbon components and other soil physical and chemical factors was discussed. The results showed that:① continuous cropping for different years had a significant impact on the content of soil organic carbon components in the study area. The contents of soil organic carbon, easily oxidized organic carbon, dissolved organic carbon, and microbial biomass carbon in continuous cropping cotton fields for 12 a, 20 a, and 35 a were higher than those in continuous cropping cotton fields and wasteland for 2 a and 5 a. ω(soil organic carbon) reached the peak value (7.06 g·kg-1) in the cotton field in 20 a, which was 76.91% higher than that in the wasteland. The content of soil organic carbon decreased with the deepening of the soil layer. ② Based on the redundancy analysis of soil organic carbon content and soil environmental factors, the results showed that the content of soil organic carbon was positively correlated with total nitrogen, available phosphorus, and water content and negatively correlated with pH value and bulk density. The importance of soil environmental factors on the interpretation of soil organic carbon content was as follows:total N>available P>pH value>bulk density>water content>available K>total salt.

A comparative UHPLC-Q/TOF-MS-based metabolomics approach coupled with machine learning algorithms to differentiate Keemun black teas from narrow-geographic origins.

Geographic-label is a remarkable feature for Chinese tea products. In this study, the UHPLC-Q/TOF-MS-based metabolomics approach coupled with chemometrics was used to determine the five narrow-geographic origins of Keemun black tea. Thirty-nine differentiated compounds (VIP > 1) were identified, of which eight were quantified. Chemometric analysis revealed that the linear discriminant analysis (LDA) classification accuracy model is 91.7%, with 84.7% cross-validation accuracy. Three machine learning algorithms, namely feedforward neural network (FNN), random forest (RF) and support vector machine (SVM), were introduced to improve the recognition of narrow-geographic origins, the performances of the model were evaluated by confusion matrix, receiver operating characteristic curve (ROC) and area under the curve (AUC). The recognition of RF, SVM and FNN for Keemun black tea from five narrow-geographic origins were 87.5%, 94.44%, and 100%, respectively. Importantly, FNN exhibited an excellent classification effect with 100% accuracy. The results indicate that metabolomics fingerprints coupled with chemometrics can be used to authenticate the narrow-geographic origins of Keemun black teas.

Comparison Between Percutaneous Kyphoplasty and Percutaneous Vertebroplasty in Terms of Efficacy in Osteoporotic Vertebral Compression Fractures: A Meta-analysis.

Background and Aim: Osteoporotic vertebral compression fractures (OVCFs) are acknowledged to be common fractures, especially in the elderly population. Minimally invasive percutaneous methods of treatment for these fractures such as kyphoplasty (KP) and vertebroplasty (VP) have been valid and effective tools for decreasing clinical problems, which are associated with more beneficial effects compared with traditional methods such as open surgery or conservative treatment. Hence, we conducted the current meta-analysis in order to gather updated evidence for the systematic assessment of clinical and radiographic outcomes of KP compared with VP. Methods: We searched articles published based on the electronic databases, including PubMed, EMBASE, and Cochrane Library. Publications of studies comparing KP with VP in the treatment of OVCFs were collected. After rigorous and thorough review of study quality, we extracted the data on the basis of eligible trials, which analyzed the summary hazard ratios (HRs) of the end points of interest. Results: Our inclusion criteria involved a total of 6 studies. In total, data from 644 patients, 330 who received VP and 284 who received KP, were included in the review. There was no significant difference in either group in terms of visual analog scale (VAS) scores (MD = 0.17; 95% CI, -0.39 to 0.73; P = .56), risk of cement leakage (odds ratio [OR] = 1.31; 95% CI, 0.62 to 2.74; P = .47) or Oswestry Disability Index (ODI) scores (MD = 0.51; 95% CI, -1.87 to 2.88; P = .68). Nevertheless, the injected cement volume (MD = -0.52; 95% CI, -0.88 to -0.15; P = .005) in the VP group was linked to a markedly lower statistically significant trend compared with the KP group. Conclusion: This meta-analysis evaluated acceptable efficacy levels across the involved trials. VP injected cement volume had several advantages in this meta-analysis. Yet, no significant differences were observed in terms of VAS scores, ODI scores, or cement leakage when KP was compared to VP therapy. Given the combined results of our study, the optimal treatment for patients with OVCFs should be determined by further high-quality multicenter randomized controlled trials with longer follow-up and larger sample sizes.

Identification, potency evaluation, and mechanism clarification of α-glucosidase inhibitors from tender leaves of Lithocarpus polystachyus Rehd.

Lithocarpus polystachyus Rehd. known as Sweet Tea in China has attracted lots of interest for its good hypoglycemic effect and the potential as a hypoglycemic agent. Based on affinity separation-UPLC-Q-TOF-MS/MS, 54 potential α-glucosidase inhibitiors were identified and 44 were structurally determined. Out of them, 41 were identified for the first time from this plant including flavonoids, fatty acids, triterpenes, alkaloids, and coumarins. Enzyme assays revealed that flavonoids exhibited higher inhibitory activity against α-glucosidase than others with astilbin (IC50 = 6.14 µg·mL-1), morin (IC50 = 8.46 µg·mL-1), and naringenin (IC50 = 10.03 µg·mL-1) showing 2- to 4-fold higher potency than the positive control acarbose. They were proved as reversible inhibitors with mixed inhibition mechanism. Ki (Ki') values and molecular dockings strongly supported the potency order of astilbin, morin and naringenin that showed in the enzyme assays.

Efficacy of add-on Danhong injection in patients with unstable angina pectoris: A double-blind, randomized, placebo-controlled, multicenter clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Danhong injection (DHI)，which is extracted from Salviae miltiorrhizae and Flos carthami，has been widely prescribed to patients with unstable angina pectoris (UAP) in China. However, a high quality clinical trial is needed. AIM OF THE STUDY: To determine whether DHI can relieve symptoms of transient myocardial ischemia in patients with unstable angina pectoris. MATERIALS AND METHODS: A double-blind, placebo-controlled, randomized clinical trial was conducted in nine hospitals in China. Inpatients with UAP with blood stasis syndrome (BSS) were randomized 1:1 to receive DHI or placebo. The primary outcome was improvement rate in the quantification score of angina pectoris. Secondary outcomes included blood stasis syndrome scale, nitrates use, electrocardiogram recordings, PCI procedures, Seattle Angina Questionnaire (SAQ) and biochemical indexes. RESULTS: 160 participants were enrolled and 159 were analyzed. There was no significant difference in primary outcome as compared with control group at the end of 7-day treatment, but significant difference at 28-day follow up (70.53% [95% CI, 59.97-81.09%] and 54.34% [95% CI, 42.68-65.99%]; P = 0.0423). The BSS score was significantly lower in the DHI group than that in the control group at day 28 (6.49 [6.96] vs 10.53 [9.07], P = 0.0034). In addition, DHI was significantly superior to placebo in the angina stability score of SAQ (91.10 [17.37] versus 78.21 [22.08], P < 0.001). There were no significant differences in other secondary outcome measures. CONCLUSIONS: A small decrease in the total effective rate and an increase in the angina stability score were observed 28 days after implementation of DHI in UAP with a total blood stasis syndrome score decrease, but the efficacy was not observed at day 7. The findings support that DHI may potentially relieve clinical symptoms and can benefit angina stability. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02007187.

A NIR-triggered multifunctional nanoplatform mediated by Hsp70 siRNA for chemo-hypothermal photothermal synergistic therapy.

Recently, hypothermal photothermal therapy (HPTT) seemed essential for the future clinical transformation of cancer optical therapies. However, at a lower working temperature, heat shock proteins (HSPs) seriously affect the anti-tumor effect of HPTT. This work reports a reasonable design of a dual-responsive nanoplatform for the synergistic treatment of chemotherapy and HPTT. We adopted a one-step method to wrap indocyanine green (ICG) into imidazole skeleton-8 (ZIF-8) and further loaded it with the chemotherapy drug doxorubicin (DOX). Furthermore, we introduced Hsp-70 siRNA to block the affection of HSPs at an upstream node, thereby avoiding the side effects of traditional heat shock protein inhibitors. The prepared ZIF-8@ICG@DOX@siRNA nanoparticles (ZID-Si NPs) could significantly improve the stability of siRNA to effectively down-regulate the expression of HSP70 protein during the photothermal therapy, thus realizing the pH-controlled and NIR-triggered release of the chemotherapeutical drug DOX. Moreover, tumors were also imaged accurately by ICG wrapped in ZID-Si nanoparticles. After the evaluation of the in vitro and in vivo photothermal effect as well as the anti-tumor activity, we found that the added Hsp-70 siRNA enhanced the synergistic anti-cancer activity of HPTT and chemotherapy. In summary, this work holds great potential in cancer treatment, and suggests better efficacy of synergistic chemo/HPTT than the single-agent therapy.

Therapeutic effects of bone marrow mesenchymal stem cells-derived exosomes on osteoarthritis.

Mesenchymal stem cells (MSCs) have shown chondroprotective effects in clinical models of osteoarthritis (OA). However, effects of MSC-derived exosomes on OA remain unclear. The study aimed to investigate the therapeutic potential of exosomes from human bone marrow MSCs (BM-MSCs) in alleviating OA. The anterior cruciate ligament transection (ACLT) and destabilization of the medial meniscus (DMM) surgery were performed on the knee joints of a rat OA model, followed by intra-articular injection of BM-MSCs or their exosomes. In addition, BM-MSC-derived exosomes were administrated to primary human chondrocytes to observe the functional and molecular alterations. Both of BM-MSCs and BM-MSC-derived exosomes alleviated cartilage destruction and subchondral bone remodelling in OA rat model. Administration of BM-MSCs and exosomes could reduce joint damage and restore the trabecular bone volume fraction, trabecular number and connectivity density of OA rats. In addition, in vitro assays showed that BM-MSCs-exosomes could maintain the chondrocyte phenotype by increasing collagen type II synthesis and inhibiting IL-1ß-induced senescence and apoptosis. Furthermore, exosomal lncRNA MEG-3 also reduced the senescence and apoptosis of chondrocytes induced by IL-1ß, indicating that lncRNA MEG-3 might partially account the anti-OA effects of BM-MSC exosomes. The exosomes from BM-MSCs exerted beneficial therapeutic effects on OA by reducing the senescence and apoptosis of chondrocytes, suggesting that MSC-derived exosomes might provide a candidate therapy for OA treatment.

Glycoproteins From Rabdosia japonica var. glaucocalyx Regulate Macrophage Polarization and Alleviate Lipopolysaccharide-Induced Acute Lung Injury in Mice via TLR4/NF-κB Pathway.

Background and Aims: Rabdosia japonica var. glaucocalyx is a traditional Chinese medicine (TCM) for various inflammatory diseases. This present work aimed to investigate the protective effects of R. japonica var. glaucocalyx glycoproteins on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the potential mechanism. Methods: Glycoproteins (XPS) were isolated from R. japonica var. glaucocalyx, and homogeneous glycoprotein (XPS5-1) was purified from XPS. ANA-1 cells were used to observe the effect of glycoproteins on the secretion of inflammatory mediators by enzyme-linked immunosorbent assay (ELISA). Flow cytometry assay, immunofluorescence assay, and Western blot analysis were performed to detect macrophage polarization in vitro. The ALI model was induced by LPS via intratracheal instillation, and XPS (20, 40, and 80 mg/kg) was administered intragastrically 2 h later. The mechanisms of XPS against ALI were investigated by Western blot, ELISA, and immunohistochemistry. Results: In vitro, XPS and XPS5-1 downregulated LPS-induced proinflammatory mediators production including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, and nitric oxide (NO) and upregulated LPS-induced IL-10 secretion. The LPS-stimulated macrophage polarization was also modulated from M1 to M2. In vivo, XPS maintained pulmonary histology with significantly reducing protein concentration and numbers of mononuclear cells in bronchoalveolar lavage fluid (BALF). The level of IL-10 in BALF was upregulated by XPS treatment. The level of cytokines including TNF-α, IL-1ß, and IL-6 was downregulated. XPS also decreased infiltration of macrophages and polymorphonuclear leukocytes (PMNs) in lung. XPS suppressed the expression of key proteins in the TLR4/NF-κB signal pathway. Conclusion: XPS was demonstrated to be a potential agent for treating ALI. Our findings might provide evidence supporting the traditional application of R. japonica var. glaucocalyx in inflammation-linked diseases.

Dietary calcium, magnesium, and phosphorus intakes and risk of stroke in Chinese adults.

Controversial results have been reported about the association of calcium, magnesium, and phosphorus and stroke risk, but none in China. To investigate the association between dietary calcium, magnesium, phosphorus, and stroke incidence in Chinese adults, we collected data from the China Health and Nutrition Survey (CHNS) from 2004 to 2011, including 6411 participants aged 45-79 years and free of stroke at baseline. Diet was assessed by interviews combining 3-d 24-h food recalls and household food inventory weighing at each survey round. The stroke incident was identified based on the validated self-report. Multivariate Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). For 32,024 person-years of follow-up, 179 stroke cases were documented. After adjustment for major lifestyle and dietary risk factors, calcium intake was positively associated with reduced stroke risk, and the HR of stroke comparing extreme quartiles was 0.53 (95% CI 0.29-0.96, Ptrend = 0.03). In further stratified analyses, significant heterogeneity across sex strata was found (Pinteraction = 0.03). Dietary calcium intake among men was more inversely related to stroke, with HRs being 0.33 (95% CI 0.15-0.76, P trend = 0.02), compared to 1.24 (95% CI 0.46-3.35, Ptrend = 0.89) among women. However, no significant association between stroke and magnesium or phosphorus was revealed. Our findings suggest that higher dietary calcium intake was associated with a lower risk of stroke in Chinese adults, particularly in men.