[Electroacupuncture at acupoints of yangming meridians for sarcopenia: a randomized controlled trial].

OBJECTIVE: To observe the clinical effect of electroacupuncture at acupoints of yangming meridians for sarcopenia. METHODS: A total of 60 patients with sarcopenia were randomized into an observation group and a control group, 30 cases in each group. In the control group, conventional nutrition intervention for sarcopenia was adopted. In the observation group, on the basis of the treatment in the control group, acupuncture was applied at bilateral Binao (LI 14), Quchi (LI 11), Zusanli (ST 36), Yanglingquan (GB 34), etc.,ipsilateral Quchi (LI 11) and Zusanli (ST 36) were connected to electroacupuncture, with discontinuous wave, 2 Hz in frequency, 1-10 mA in intensity, 2 times a week, with a interval of 3 days. A total of 12-week treatment was required in the two groups. Before and after treatment, the appendicular skeletal muscle mass index (ASMI), grip strength, 6 m-walking time, body fat percentage and body moisture percentage were observed in the two groups. RESULTS: Compared with those before treatment, after treatment, ASMI and grip strength were increased while 6 m-walking time was shortened in the two groups (P<0.05); body fat percentage was decreased while body moisture percentage was increased in the observation group (P<0.05). After treatment, in the observation group, ASMI, grip strength and body moisture percentage were increased (P<0.05), 6 m-walking time was shortened and body fat percentage was decreased (P<0.05) compared with those in the control group. CONCLUSION: Electroacupuncture at acupoints of yangming meridians can effectively improve the skeletal muscle mass, muscle function, body fat percentage and body moisture percentage in patients with sarcopenia, and make the distribution of muscle and fat more reasonable.

Design, Synthesis and Antitumor Activity of Novel Selenium-Containing Tepotinib Derivatives as Dual Inhibitors of c-Met and TrxR.

Cellular mesenchymal-epithelial transition factor (c-Met), an oncogenic transmembrane receptor tyrosine kinase (RTK), plays an essential role in cell proliferation during embryo development and liver regeneration. Thioredoxin reductase (TrxR) is overexpressed and constitutively active in most tumors closely related to cancer recurrence. Multi-target-directed ligands (MTDLs) strategy provides a logical approach to drug combinations and would adequately address the pathological complexity of cancer. In this work, we designed and synthesized a series of selenium-containing tepotinib derivatives by means of selenium-based bioisosteric modifications and evaluated their antiproliferative activity. Most of these selenium-containing hybrids exhibited potent dual inhibitory activity toward c-Met and TrxR. Among them, compound 8b was the most active, with an IC50 value of 10 nM against MHCC97H cells. Studies on the mechanism of action revealed that compound 8b triggered cell cycle arrest at the G1 phase and caused ROS accumulations by targeting TrxR, and these effects eventually led to cell apoptosis. These findings strongly suggest that compound 8b serves as a dual inhibitor of c-Met and TrxR, warranting further exploitation for cancer therapy.

Clinical study of Yiqi-Tongmai Decoction on qi deficiency and blood stasis syndrome of isolated coronary artery muscle bridge angina pectoris / 国际中医中药杂志

Objective:To evaluate the clinical efficacy of Yiqi-Tongmai Decoction on isolated coronary muscle bridge angina patients with qi deficiency and blood stasis syndrome. Methods:A total of 64 patients with isolated coronary artery muscular bridge angina pectoris with qi deficiency and blood stasis syndrome in Beijing Hospital of Traditional Chinese Medicine affiliated to Capital Medical University from April 2016 to January 2020 who met the inclusion criteria were divided into 2 groups by random number table method, with 32 patients in each group. The control group took diltiazem hydrochloride tablets orally, and the treatment group took Yiqi-Tongmai Decoction on the basis of the control group. Both groups were treated for 8 weeks. The TCM syndrome scores were observed before and after treatment, and Seattle Angina Questionnaire was assessed for patient's quality of life and functional status. The exercise ECG test was observed before and after treatment, and the cause of angina pectoris need to be recorded, including the movement time and plate movement caused by time of ST segment in electrocardiogram (ecg) and dynamic evolution. Results:The total effective rate of angina pectoris was 84.38% (27/32) in the treatment group, and 53.13% (17/32) in the control group, and the difference between the two groups was statistically significant ( χ2=8.09, P<0.05). After treatment, the degree of physical activity limitation (69.24 ± 14.21 vs. 59.42 ± 11.71, Z=-2.61), stable state of angina (82.25 ± 21.24 vs. 69.11 ± 19.52, Z=2.64), angina (80.24 ± 18.31 vs. 69.11 ± 15.54, Z=2.63), treatment satisfaction (86.16 ± 19.23 vs. 61.19 ± 17.35, Z=2.22), degree of disease cognition (74.41 ± 21.13 vs. 60.43 ± 19.42, Z=2.40) scores in the treatment group were significantly higher than those in the control group ( P<0.05). In the treatment group, the time of exercise-induced angina pectoris [(476.15 ± 62.15)s vs. (399.38 ± 78.42)s, Z=-2.08], the time of ST segment descending 1 mm after exercise [(394.54 ± 75.61)s vs. (309.64 ± 81.62)s, Z=-2.40] in the treatment group were significantly longer than those in the control group ( P<0.05). The total effective rate of TCM syndrome was 93.8% (30/32) in the treatment group and 65.6% (21/32) in the control group, and the difference was statistically significant ( χ2=7.96, P<0.05). The TCM syndrome scores of the treatment group (25.15 ± 6.15 vs. 36.38 ± 10.42, Z=-2.56) in the treatment group were significantly lower than that of the control group ( P<0.05). There were no obvious adverse reactions in both groups during treatment. Conclusion:Yiqi-Tongmai Decoction can improve the clinical symptoms of isolated coronary artery muscle bridge angina pectoris with qi deficiency and blood stasis syndrome, reduce the onset of angina pectoris, delay the time of exercise induced angina pectoris, and improve the clinical efficacy.

Effect and Safety of Tongyan Spray () on Hyoid Motion in Patients with Dysphagia after Ischemic Stroke.

OBJECTIVE: To observe the effects and safety of Tongyan Spray () on the range and time of hyoid motion in patients with ischemic post-stroke dysphagia. METHODS: Seventy-two patients with ischemic post-stroke dysphagia were selected and randomly assigned to a treatment group (36 cases) and a control group (36 cases) by a random number table from January 2013 to October 2014. All patients swallowed 4 kinds of barium meals with different traits respectively, and each patient underwent video fluoroscopy (VF) examination twice. In the treatment group, Tongyan Spray was sprayed to the pharynx on both sides and the middle part once respectively. The spray was applied 30 min before the second examination. Purified water at room temperature was used as placebo in the control group. The changes in the range and time of hyoid motion in both groups were observed before and after treatment. RESULTS: Six patients dropped out in each group, and 60 patients completed the study and were included in the final analysis. Significant improvement was observed in the range of superior hyoid excursion distance and the time of hyoid motion in the treatment group compared with the control group (P<0.05). There were no obvious adverse reactions observed in oral mucosa in both groups during the whole study. CONCLUSION: Tongyan Spray was an effective and safe medicine for improving swallowing function in patients with ischemic post-stroke dysphagia.

Effect of Oral Chinese Medicine Combined with Western Medicine on Cancer Pain: A Meta-Analysis.

OBJECTIVE: To assess the effect of oral Chinese medicine (OCM) combined with Western medicine (WM) on cancer pain. METHODS: PubMed, Embase, Cochrane Library, Clinical Trials Registry Platform, Chinese National Knowledge Infrastructure (CNKI), Wanfang and VIP databases were searched from their inception to September {dy2019}. Randomized controlled trials (RCTs) treating cancer pain by Chinese medicine (CM) combined with WM were included. The primary outcome were total pain relief rate and the quality of life (QOL), and the other outcomes were the average daily dosage of analgesics, the primary time of pain, the analgesic duration time, and adverse events. The methodological quality of RCTs was assessed in accordance with Cochrane 5.1.0 handbook of systematic reviews of interventions. Evidence level was assessed by the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. RESULTS: There were 1,087 patients in the 14 studies, with 544 in the experiment group and 543 in the control group. These studies were all conducted in China, and published between 2006 and {dy2019}. Compared with the WM, OCM combined with WM could significantly relieve the cancer pain [risk ratio (RR)=1.43, 95% confidence interval (CI): 1.32, 1.56), improve QOL (RR=8.57, 95% CI: 4.25, 12.89), decrease the primary time of pain (RR=-0.20, 95% CI: -0.24, -0.16], prolong the analgesic duration time (RR=3.47, 95% CI: 2.09, 4.85), reduce the dosage of analgesics (RR=-19.52, 95% CI: -36.32, -2.72), and reduce side events (RR=0.49, 95% CI: 0.37, 0.65). Evidence levels for total pain relief rate, primary time of pain and side events were low, evidence level for QOL, analgesic duration time and average daily dosage of analgesics were very low. CONCLUSIONS: Compared with the WM, OCM combined with WM could significantly relieve the cancer pain, improve the QOL, decrease the primary time of pain, prolong the analgesic duration time, reduce the dosage of analgesics and side events. The evidence levels were low or very low.

Clinical Effect of Tiaomai Mixture on Premature Ventricular Contraction in Coronary Heart Disease Due to Qi-Yin Deficiency and Stagnated Heat in Blood Vessel / 中国实验方剂学杂志

Objective:To investigate the clinical effect of Tiaomai mixture combined with metoprolol tartrate on premature ventricular contraction in coronary heart disease （CHD） due to Qi-Yin deficiency and stagnated heat in blood vessel. Method:A total of 95 patients with CHD complicated with premature ventricular contraction were randomized into a treatment group and a control group. Four cases dropped out， leaving 91 cases （45 in the treatment group and 46 in the control group） included in the follow-up. On the basis of routine treatments for CHD， patients in the control group were further treated with metoprolol tartrate， while those in the treatment group received metoprolol tartrate plus Tiaomai mixture. Such curative effect and safety indexes as traditional Chinese medicine （TCM） syndrome score， electrocardiogram （ECG）， and 24 h dynamic ECG were observed before and after four-week treatment. Result:After treatment， the therapeutic effect on arrhythmia in the treatment group was better than that in the control group（<italic>P</italic><0.05）. The treatment group was superior to the control group in reducing the frequency of premature ventricular contraction （<italic>P</italic><0.05）， improving the Lown grade （<italic>P</italic><0.01）， increasing the heart rate variability index （<italic>P</italic><0.05）， and ameliorating the QT dispersion in ECG （<italic>P</italic><0.05）， hypersensitive C-reactive protein， and homocysteine（<italic>P</italic><0.05）. As revealed by comparison with those before treatment， both interventions improved TCM syndrome， with better outcomes observed in the treatment group （<italic>P</italic><0.01）， manifested as the alleviation of shortness of breath， fatigue， dry mouth with desire to drink， and tongue and pulse manifestations （<italic>P</italic><0.01）. Conclusion:Tiaomai mixture improves the clinical efficacy against arrhythmia in CHD patients by regulating the heart rate variability index， inhibiting inflammatory cytokines， lowering homocysteine， and relieving clinical symptoms， which is worthy of clinical promotion and application.

Chronic inflammatory pain decreases the glutamate vesicles in presynaptic terminals of the nucleus accumbens.

Reward system has been proved to be important to nociceptive behavior, and the nucleus accumbens (NAc) is a key node in reward circuitry. It has been further revealed that dopamine system modulates the NAc to influence the pain sensation, whereas the role of glutamatergic projection in the NAc in the modulation of chronic pain is still elusive. In this study, we used a complete Freund's adjuvant-induced chronic inflammatory pain model to explore the changes of the glutamatergic terminals in the NAc, and we found that following the chronic inflammation, the protein level of vesicular glutamate transporter1 (VGLUT1) was significantly decreased in the NAc. Immunofluorescence staining further showed a reduced expression of VGLUT1-positive terminals in the dopamine receptor 2 (D2R) spiny projection neurons of NAc after chronic inflammatory pain. Furthermore, using a whole-cell recording in double transgenic mice, in which dopamine receptor 1- and D2R-expressing neurons can be visualized, we found that the frequency of spontaneous excitatory postsynaptic currents was significantly decreased and paired-pulse ratio of evoked excitatory postsynaptic currents was increased in D2R neurons, but not in dopamine receptor 1 neurons in NAc of complete Freund's adjuvant group. Moreover, the abnormal expression of soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex contributed to the reduced formation of glutamate vesicles. Hence, our results demonstrated that decreased glutamate release in the indirect pathway of the NAc may be a critical mechanism for chronic pain and provided a novel evidence for the presynaptic mechanisms in chronic pain regulation.

Arctigenin protects against steatosis in WRL68 hepatocytes through activation of phosphoinositide 3-kinase/protein kinase B and AMP-activated protein kinase pathways.

Arctigenin (ATG), a lignin extracted from Arctium lappa (L.), exerts antioxidant and anti-inflammatory effects. We hypothesized that ATG exerts a protective effect on hepatocytes by preventing nonalcoholic fatty liver disease (NAFLD) progression associated with lipid oxidation-associated lipotoxicity and inflammation. We established an in vitro NAFLD cell model by using normal WRL68 hepatocytes to investigate oleic acid (OA) accumulation and the potential bioactive role of ATG. The results revealed that ATG inhibited OA-induced lipid accumulation, lipid peroxidation, and inflammation in WRL68 hepatocytes, as determined using Oil Red O staining, thiobarbituric acid reactive substance assay, and inflammation antibody array assays. Quantitative RT-PCR analysis demonstrated that ATG significantly mitigated the expression of acetylcoenzyme A carboxylase 1 and sterol regulatory element-binding protein-1 and significantly increased the expression of carnitine palmitoyltransferase 1 and peroxisome proliferator-activated receptor alpha. The 40 targets of the Human Inflammation Antibody Array indicated that ATG significantly inhibited the elevation of the U937 lymphocyte chemoattractant, ICAM-1, IL-1ß, IL-6, IL-6sR, IL-7, and IL-8. ATG could activate the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and AMP-activated protein kinase (AMPK) pathways and could increase the phosphorylation levels of Akt and AMPK to mediate cell survival, lipid metabolism, oxidation stress, and inflammation. Thus, we demonstrated that ATG could inhibit NAFLD progression associated with lipid oxidation-associated lipotoxicity and inflammation, and we provided insights into the underlying mechanisms and revealed potential targets to enable a thorough understanding of NAFLD progression.

Chronic Inflammatory Pain Impairs mGluR5-Mediated Depolarization-Induced Suppression of Excitation in the Anterior Cingulate Cortex.

The anterior cingulate cortex (ACC) is a critical hub for nociceptive perception and pain-related anxiety. Long-term synaptic plasticity in ACC was found to be important for chronic inflammatory pain and pain-related anxiety. As short-term synaptic plasticity, depolarization-induced suppression of excitation (DSE) is involved in several conditions, such as chronic stress, epilepsy, and autism. However, it is still unknown whether DSE in the ACC is involved in the central sensitization of pain and anxiety. Using a whole-cell patch clamp, calcium imaging, western blot, and behavioral testing, we found that DSE was induced by a 2 s depolarization in postsynaptic pyramidal cells in ACC. DSE was mediated by endocannabinoid signaling and modulated by metabotropic glutamate receptor 5 (mGluR5). DSE was impaired by decreasing expression and dysfunction of mGluR5 in a mouse model of inflammatory pain induced by complete Freund's adjuvant. CDPPB, an mGluR5-positive allosteric modulator, could rescue hypersensitivity and anxiety-like behavior in this pain model. Our results demonstrated that mGluR5-mediated short-term plasticity in ACC may be a critical mechanism for chronic pain, and mGluR5 may potentially serve as a target of pain therapy, including treatments for hyperalgesia and anxiety.

Persistency of Enlarged Autolysosomes Underscores Nanoparticle-Induced Autophagy in Hepatocytes.

The diverse biological effects of nanomaterials form the basis for their applications in biomedicine but also cause safety issues. Induction of autophagy is a cellular response after nanoparticles exposure. It may be beneficial in some circumstances, yet autophagy-mediated toxicity raises an alarming concern. Previously, it has been reported that upconversion nanoparticles (UCNs) elicit liver damage, with autophagy contributing most of this toxicity. However, the detailed mechanism is unclear. This study reveals persistent presence of enlarged autolysosomes in hepatocytes after exposure to UCNs and SiO2 nanoparticles both in vitro and in vivo. This phenomenon is due to anomaly in the autophagy termination process named autophagic lysosome reformation (ALR). Phosphatidylinositol 4-phosphate (PI(4)P) relocates onto autolysosome membrane, which is a key event of ALR. PI(4)P is then converted into phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2 ) by phosphatidylinositol-4-phosphate 5-kinase. Clathrin is subsequently recruited by PI(4,5)P2 and leads to tubule budding of ALR. Yet it is observed that PI(4)P cannot be converted in nanoparticle-treated hepatocytes cells. Exogenous supplement of PI(4,5)P2 suppresses the enlarged autolysosomes in vitro. Abolishment of these enlarged autolysosomes by autophagy inhibitor relieves the hepatotoxicity of UCNs in vivo. The results provide evidence for disrupted ALR in nanoparticle-treated hepatocytes, suggesting that the termination of nanoparticle-induced autophagy is of equal importance as the initiation.

Clinical observation of Tiaomai-Yinon the treatment of tachyarrhythmia with the TCM patterns of deficiency of Qi and Yin, and heat of blood stasis / 国际中医中药杂志

Objective To study the effect ofTiaomai-Yin with the therapy method of clearing heat and cooling blood to treat the tachyarrhythmia with the TCM patterns of deficiency of Qi and Yin, and heat of blood stasis.MethodsA total of 60 patients with tachyarrhythmia were randomly recruited into a control group and a treatment group, 30 patients in each. The treatment group was treated withTiaomai-Yin, while the control group was treated with Metoprolol. After both groups were treated for one month, the changes of TCM symptoms, ECG and 24 h DCG were observed.Results The total effective rate of the treatment groups was significantly better than the control group(86.67%vs. 56.67%;χ2=7.957,P<0.05).Tiaomai-Yin significantly improve the symptoms of shortness of breath (1.40 ± 2.11vs. 2.10 ± 1.87;t=-3.341,P<0.01), tiredness (1.30 ± 2.33vs. 2.10 ± 1.84;t=-3.262,P<0.01), dry mouth (0.09 ± 1.34vs. 2.50 ± 2.41;t=-3.194,P<0.01), and tongue (1.90 ± 1.65vs. 3.90 ± 1.81;t=-3.217,P<0.01) and pulse (2.60 ± 1.71vs. 5.10 ± 2.55;t=-3.283,P<0.01).ConclusionTiaomai-Yin had effects in treating tachyarrhythmia with the TCM patterns of deficiency of Qi and Yin, and heat of blood stasis with improvement of symptoms and fewer side effects.

An analysis for affecting factors to dosage of Chinese medicine during Jin and Yuan dynasty / 中国中药杂志

For studying medical works during the Jin and Yuan dynasty, author discussed the factors affect the dosage of medicine that doctors in that period believed to affect the dosage of medicine. Author found that doctors in that period developed the dosage theory in terms of compatibility of medicines, onset time, and onset region of a disease.