[Role of lymphatic system in coronary heart disease based on theory of combined phlegm and stasis].

According to the traditional Chinese medicine(TCM) theory, coronary heart disease(CHD) is mainly caused by heart vessel obstruction due to Qi stagnation, blood stasis, and phlegm turbidity. Chest impediment with combined phlegm and stasis is a common syndrome of CHD, with the manifestations of chest tightness, chest pain, and asthma. Lymphatic system is one of the important immune systems in the human body and has a close relationship with the Qi and blood movement in TCM. The dysfunction of the lymphatic system may lead to metabolism disorders, the generation of dampness pathogen which turns into sticky and difficult-to-dissolve phlegm turbidity. Moreover, it can affect blood circulation and coagulation, causing slow blood flow, increased blood viscosity, and microcirculation disorders. Alterations in lymphatic hydrodynamics may affect the interaction between blood circulation and the lymphatic system. A variety of small molecule drugs and TCM can treat cardiovascular diseases by targeting the lymphatic system. This review discusses the role of the lymphatic system in CHD based on the theory of combined phlegm and stasis, involving the influences of mechanical factors on lymphatic function and the effects and pharmacological mechanisms of TCM and chemicals that target lymphocyte function and lymphatic circulation. By expounding the development process of combined phlegm and stasis in CHD from the lymphatic system, this paper aims to provide new ideas for deciphering pharmacological mechanisms of TCM for resolving phlegm and stasis.

Kidney Yang Deficiency Syndrome Exacerbates Aß25-35-Induced Pathological Changes, and Ginsenoside Re Ameliorates Synapse Lesions in Aß25-35- Injected Rats with Kidney Yang Deficiency Syndrome.

BACKGROUND: Traditional Chinese medicine (TCM) indicates that Alzheimer's disease (AD) is considered the consequence produced by Kidney Yang Deficiency Syndrome (KDS-Yang), which has similar clinical characteristics to glucocorticoid withdrawal syndrome. Ginsenoside Re (G-Re) has been found to ameliorate the symptoms and pathological impairments of AD. However, it's not clear whether G-Re could protect memory and synapse lesions against kidney deficiency dementia. METHODS: Subcutaneous injection of hydrocortisone for 14 days was used to produce KDS-Yang. On the 15th day, Aß25-35 peptide was injected into the intracerebroventricular (icv) of KDS-Yang rats. Spine density was analyzed by Golgi staining and the ultrastructural morphology of the synapse was detected using Transmission Electron Microscopy (TEM). Western blot was used to examine the expression of pS396, pS404, Tau-5, tGSK-3ß, pS9GSK-3ß, Syt, Syn I, GluA1, GluN2B, PSD93, PSD95, ß2-AR and pS346-b2-AR. RESULTS: Hyperphosphorylation of tau in Aß25-35-injected rats with KDS-Yang was stronger than in Aß25-35-injected rats at the sites of Ser396 and Ser404. G-Re improved spatial memory damage detected by Morris water-maze (MWM), enhanced spines density, the thickness of postsynaptic density (PSD) and increased the expression of Syt, Syn I, GluA1, GluN2B, PSD93 and PSD95. Moreover, GRe decreased the hyperphosphorylation of ß2-AR at serine 346 in Aß25-35-injected rats with KDS-Yang. CONCLUSION: KDS-Yang might exacerbate AD pathological lesions. Importantly, G-Re is a potential ingredient for protecting against memory and synapse deficits in kidney deficiency dementia.

Jasminoidin and ursodeoxycholic acid exert synergistic effect against cerebral ischemia-reperfusion injury via Dectin-1-induced NF-κB activation pathway.

BACKGROUND: Jasminoidin (JA) and ursodeoxycholic acid (UA) were shown to act synergistically against ischemic stroke (IS) in our previous studies. PURPOSE: To investigate the holistic synergistic mechanism of JA and UA on cerebral ischemia. METHODS: Middle cerebral artery obstruction reperfusion (MCAO/R) mice were used to evaluate the efficacy of JA, UA, and JA combined with UA (JU) using neurological function testing and infarct volume examination. High-throughput RNA-seq combined with computational prediction and function-integrated analysis was conducted to gain insight into the comprehensive mechanism of synergy. The core mechanism was validated using western blotting. RESULTS: JA and UA synergistically reduced cerebral infarct volume and alleviated neurological deficits and pathological changes in MCAO/R mice. A total of 1437, 396, 1080, and 987 differentially expressed genes were identified in the vehicle, JA, UA, and JU groups, respectively. A strong synergistic effect between JA and UA was predicted using chemical similarity analysis, target profile comparison, and semantic similarity analysis. As the 'long-tail' drugs, the top 20 gene ontology (GO) biological processes of JA, UA, and JU groups primarily reflected inflammatory response and regulation of cytokine production, with specific GO terms of JU revealing enhanced regulation on immune response and tumor necrosis factor superfamily cytokine production. Comparably, the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling of common targets of JA, UA, and JU focused on extracellular matrix organization and signaling by interleukins, immune system, phagosomes, and lysosomes, which interlock and interweave to produce the synergistic effects of JU. The characteristic signaling pathway identified for JU highlighted the crosstalk between autophagy activation and inflammatory pathways, especially the Dectin-1-induced NF-κB activation pathway, which was validated by in vivo experiments. CONCLUSIONS: JA and UA can synergistically protect cerebral ischemia-reperfusion injury by attenuating Dectin-1-induced NF-κB activation. The strategy integrating high throughput data with computational models enables ever-finer mapping of 'long-tail' drugs to dynamic variations in condition-specific omics to clarify synergistic mechanisms.

The role of traditional herbal medicine for ischemic stroke: from bench to clinic-A critical review.

BACKGROUND: Ischemic stroke (IS) is a leading cause of death and severe long-term disability worldwide. Over the past few decades, considerable progress has been made in anti-ischemic therapies. However, IS remains a tremendous challenge, with favourable clinical outcomes being generally difficult to achieve from candidate drugs in preclinical phase testing. Traditional herbal medicine (THM) has been used to treat stroke for over 2,000 years in China. In modern times, THM as an alternative and complementary therapy have been prescribed in other Asian countries and have gained increasing attention for their therapeutic effects. These millennia of clinical experience allow THM to be a promising avenue for improving clinical efficacy and accelerating drug discovery. PURPOSE: To summarise the clinical evidence and potential mechanisms of THMs in IS. METHODS: A comprehensive literature search was conducted in seven electronic databases, including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, the Chinese National Knowledge Infrastructure, the VIP Information Database, the Chinese Biomedical Literature Database, and the Wanfang Database, from inception to 17 June 2022 to examine the efficacy and safety of THM for IS, and to investigate experimental studies regarding potential mechanisms. RESULTS: THM is widely prescribed for IS alone or as adjuvant therapy. In clinical trials, THM is generally administered within 72 h of stroke onset and are continuously prescribed for over 3 months. Compared with Western medicine (WM), THM combined with routine WM can significantly improve neurological function defect scores, promote clinical total effective rate, and accelerate the recovery time of stroke with fewer adverse effects (AEs). These effects can be attributed to multiple mechanisms, mainly anti-inflammation, antioxidative stress, anti-apoptosis, brain blood barrier (BBB) modulation, inhibition of platelet activation and thrombus formation, and promotion of neurogenesis and angiogenesis. CONCLUSIONS: THM may be a promising candidate for IS management to guide clinical applications and as a reference for drug development.

Traditional Chinese medicine for transformation of gastric precancerous lesions to gastric cancer: A critical review.

Gastric cancer (GC) is a common gastrointestinal tumor. Gastric precancerous lesions (GPL) are the last pathological stage before normal gastric mucosa transforms into GC. However, preventing the transformation from GPL to GC remains a challenge. Traditional Chinese medicine (TCM) has been used to treat gastric disease for millennia. A series of TCM formulas and active compounds have shown therapeutic effects in both GC and GPL. This article reviews recent progress on the herbal drugs and pharmacological mechanisms of TCM in preventing the transformation from GPL to GC, especially focusing on anti-inflammatory, anti-angiogenesis, proliferation, and apoptosis. This review may provide a meaningful reference for the prevention of the transformation from GPL to GC using TCM.

Effect of tea polyphenols on sturgeon myofibrillar protein structure in the in vitro anti-glycation model mediated by low temperature vacuum heating.

The binding mechanism between tea polyphenols and sturgeon myofibrillar protein (SMP) in the early stage (0, 2, 4 min), middle stage (6, 10 min) and late stage (15 min) of low temperature vacuum heating (LTVH) in an in vitro anti-glycation model was investigated. The result indicated that the protein cross-linking during LTVH treatment were mainly induced by tea polyphenols. The loss rate of free arginine (Arg) and free lysine (Lys) of SMP at the late stage of LTVH treatment (15 min) was 73.95 % and 83.16 %, respectively. The hydrophobic force and disulfide bond were the main force between tea polyphenols and SMP in the middle and late stage of LTVH treatment. The benzene ring and phenolic hydroxyl group of tea polyphenols can interact with the amino acid residues of SMP, which was exothermic and entropy-increasing. This study provides new insights in the interaction mechanisms between tea polyphenols-protein during heat treatment process.

Recommendations for diagnosis and treatment of SARS-CoV-2 infection in children / 西安交通大学学报(医学版)

Children are also at high risk of novel coronavirus infection. However, as children are in the developmental stage and their phylogeny is not yet complete, adult guidelines cannot be directly copied in the diagnosis and treatment of SARS-CoV-2 infection in children. Therefore, The Second Affiliated Hospital of Xi’an Jiaotong University organized relevant professionals of Children’s Hospital. Based on the "Diagnosis and Treatment Plan for SARS-CoV-2 Infection (Trial 10th Edition)" issued by the General Office of the National Health Commission of the State Administration of Traditional Chinese Medicine, the diagnosis and treatment plan suggestions for children with novel coronavirus infection in The Second Affiliated Hospital of Xi’an Jiaotong University were formulated by referring to several instructive diagnosis and treatment plans and combining our hospital’s experience in treating children with SARS-CoV-2 infection. This recommendation makes a concise and practical description from the perspectives of epidemiology, clinical manifestations, clinical typing, treatment and nursing of children infected with SARS-CoV-2, and also makes recommendations for the diagnosis and treatment of high-risk factors and complications for the reference of front-line clinical pediatricians so as to achieve timely and reasonable diagnosis and treatment of children infected with SARS-CoV-2. Early identification and active treatment of high-risk and critically patients can minimize the harm caused by complications.

Effects of electroacupuncture preconditioning of "Neiguan"(PC 6) on myocardial ischemia reperfusion injury via Akt/mTOR pathway / 国际中医中药杂志

Objective:To observe the effects of electroacupuncture preconditioning on the autophagy-related pathway protein kinase B (Akt)/mammalian target of rapamycin (mTOR) in myocardial tissue of rats with myocardial ischemia reperfusion injury (MIRI); To investigate the protective mechanism of "Neiguan"(PC 6) on myocardial injury.Methods:Totally 48 SD rats were randomly divided into blank group, sham-operation group, model group and Neiguan group ( n=12 in each group). The Neiguan group was applied to bilateral "Neiguan"(PC 6) by electroacupuncture for 30 min, once daily for consecutive 7 days before model replication. Except in the blank group, the MIRI model was established by ligation of the descending anterior branch of the left coronary artery in the rest groups after the intervention. The histomorphological changes in the myocardium of the rats were observed by HE staining, and the expression levels of Akt, phosphorylated Akt (p-Akt), mTOR and phosphorylated mTOR (p-mTOR) in the myocardium were measured by protein immunoblotting. The ratio of p-Akt/Akt and p-mTOR/mTOR was calculated. Results:In the blank group, the myocardial fibres were arranged regularly and neatly, and no inflammatory cell infiltration or haemorrhage was seen in the interstitium; in the sham-operation group, the arrangement of myocardial fibers was slightly irregular, no rupture was found, and a small amount of myocardial fiber gap was slightly enlarged; in the model group, the distribution of myocardial fibers was disordered, hypertrophic cardiomyocytes increased, some mitochondria were red and swollen or the outer membrane was ruptured, and inflammatory infiltration and hemorrhage were seen in the interstitium; the extent of myocardial lesions in the Neiguan group was less than that in the model group, with a small amount of interstitial hemorrhage and inflammatory cell infiltration. There was no statistical significance in the levels of Akt and mTOR in the myocardial tissues of the rats in each group ( P>0.05); compared with the sham-operation group, the levels of p-Akt, p-mTOR and p-Akt/Akt, p-mTOR/mTOR in the model group decreased ( P<0.01); compared with the model group, the levels of p-Akt, p-mTOR and p-Akt/Akt, p-mTOR/mTOR in the Neiguan group increased ( P<0.01). Conclusion:Electroacupuncture preconditioning may inhibit excessive autophagy by activating the Akt/mTOR pathway in cardiomyocytes of MIRI rats, thereby exerting a protective effect on the myocardium.

Icariside II Attenuates Vascular Remodeling Via Wnt7b/CCND1 Axis.

ABSTRACT: Angioplasty often fails due to the abnormal proliferation of vascular smooth muscle cells (VSMCs). Success rates of angioplasty may increase following the administration of an agent that effectively ameliorates aberrant vascular remodeling. Icariside II (ICS-II) is a natural flavonol glycoside extract from the Chinese herbal medicine Epimedii that possesses several medicinal qualities that are beneficial in humans. Nevertheless, the role of ICS-II in addressing aberrant vascular remodeling have yet to be clarified. The current investigation studies the molecular effects of ICS-Ⅱ on balloon-inflicted neointimal hyperplasia in rats in vivo and on platelet-derived growth factor-induced vascular proliferation in primary rat aortic smooth muscle cells (VSMCs) in vitro. ICS-II was found to be as effective as rapamycin, the positive control used in this study. ICS-II inhibited neointimal formation in injured rat carotid arteries and notably reduced the expression of Wnt7b. ICS-Ⅱ significantly counteracted platelet-derived growth factor-induced VSMCs proliferation. Cell cycle analysis showed that ICS-II triggered cell cycle arrest during the G1/S transition. Western blot analysis further indicated that this cell cycle arrest was likely through Wnt7b suppression that led to CCND1 inhibition. In conclusion, our findings demonstrate that ICS-II possesses significant antiproliferative qualities that counteracts aberrant vascular neointimal hyperplasia. This phenomenon most likely occurs due to the suppression of the Wnt7b/CCND1 axis.

[A mini-review on anti-tumor effect of cannabidiol].

Cannabidiol is the main non-psychoactive component of Cannabis sativa, which has multiple medicinal activities, such as antiepileptic, immunomodulation, analgesic, antioxidant, anticonvulsant, anti-anxiety and other functions. In recent years, it has been found that cannabidiol can inhibit the proliferation of various tumor cells, induce apoptosis and autophagy of tumor cells, arrest cell cycle, interrupt invasion and metastasis of tumor cells, regulate tumor microenvironment, exert synergistic therapy with other chemotherapeutic drugs, and reduce the toxicity of chemotherapeutic drugs. However, its anti-tumor effect remains controversial and its application is limited. The study of microspheres, nano liposomes and other new drug delivery systems can improve the anti-tumor effect of cannabidiol. In this study, the anti-tumor mechanism and application of cannabidiol were summarized and discussed in order to provide inspirations for its further investigation and application.

Association of blood lead and blood selenium with serum high-sensitivity C-reactive protein among Chinese adults aged 19 to 79 years / 中华流行病学杂志

Objective: To investigate the association of blood lead and blood selenium with serum high-sensitivity C-reactive protein (hs-CRP) among Chinese adults aged 19 to 79 years. Methods: The participants were enrolled from the first wave of China National Human Biomonitoring (CNHBM) conducted from 2017 to 2018. 10 153 participants aged 19 to 79 years were included in this study. Fasting blood samples were obtained from participants. Lead and selenium in whole blood and hs-CRP in serum were measured. Individuals with hs-CRP levels above 3.0 mg/L were defined as elevated hs-CRP. Generalized linear mixed models and restricted cubic spline models were used to analyze the association of blood lead and blood selenium with elevated hs-CRP. Logistic regression models were used to analyze the multiplicative scale and additive scale interaction between blood lead and blood selenium on elevated hs-CRP. Results: The age of participants was (48.91±15.38) years, of which 5 054 (61.47%) were male. 1 181 (11.29%) participants were defined as elevated hs-CRP. After multivariable adjustment, results from generalized linear models showed that compared with participants with the lowest quartile of blood lead, the OR (95%CI) of elevated hs-CRP for participants with the second, third, and highest quartiles were 1.14 (0.94-1.37), 1.25 (1.04-1.52) and 1.38 (1.13-1.68), respectively. When compared with participants with the lowest quartile of blood selenium, the OR (95%CI) of elevated hs-CRP for participants with the second, third and highest quartiles were 0.86 (0.72-1.04), 0.91 (0.76-1.11), and 0.75 (0.61-0.92), respectively. Results from the interaction analysis showed no significant interaction between lead and selenium on elevated hs-CRP. Conclusion: Blood concentration of lead was positively associated with elevated serum hs-CRP, and blood concentration of selenium was inversely related to elevated hs-CRP, while blood lead and selenium did not present interaction on elevated hs-CRP.

Clinical Efficacy of Maxingshigantang Enema in Treating Infants with Pneumonia and Asthma and Intervention Mechanism of Lung-intestine Microenvironment / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of Maxingshigantang enema in the treatment of infant viral pneumonia by comparing related indicators， and comprehensively evaluate the effect of traditional Chinese medicine （TCM） enema on the intestinal microenvironment. MethodSixty infants with viral pneumonia were selected and randomly divided into 3 groups. The dosage of enema drugs in high- （0.117 g·mL-1） and low-concentration （0.07 g·mL-1） TCM enema groups was same （3.5 g per time）， and the control group received normal saline enema， once a day for 7 days. Finally， the curative effect， total symptom score， salivary secretory immunoglobulin A （sIgA）， human beta defensin 2 （hBD2） and fecal calprotectin （CALP） of each group were statistically analyzed by SPSS 21.0， and the clinical efficacy of TCM enema in treating children with pneumonia and asthma was comprehensively evaluated. ResultThe curative effect of high-concentration TCM enema group （total effective rate 100%， χ2=7.059） was equivalent to that of low-concentration TCM enema group （total effective rate 95%， χ2=4.329）， higher than that of control group （total effective rate 70%） （P<0.017）. After treatment， compared with control group and low-concentration TCM enema group， high-concentration TCM enema group had higher total symptom score of children （P<0.05， P<0.01）. The proportion of coccobacillus was reduced in three groups， with high- and low-concentration TCM enema groups lower than control group （P<0.05）. The salivary sIgA concentration was increased in three groups （P<0.05）， with high-concentration TCM enema group higher than the other groups （P<0.01）. The hBD2 concentration was decreased in three groups， with high- and low-concentration TCM enema groups lower than control group （P<0.05）. The three groups reduced the fecal CALP concentration， and high-concentration TCM enema group had the highest reduction， followed by low-concentration TCM enema group （P<0.01）. ConclusionTCM enema outweighs western medicine in improving clinical symptoms， intestinal flora， and mucosal immune function， and reducing inflammation in children， and the high-concentration TCM enema group has better curative effect. Therefore， with easiness to operate， high compliance， and significant therapeutic effect， TCM enema is worthy of clinical promotion.

Mechanistic analysis for the origin of diverse diterpenes in Tripterygium wilfordii

Tripterygium wilfordii is a valuable medicinal plant rich in biologically active diterpenoids, but there are few studies on the origins of these diterpenoids in its secondary metabolism. Here, we identified three regions containing tandemly duplicated diterpene synthase genes on chromosomes (Chr) 17 and 21 of T. wilfordii and obtained 11 diterpene synthases with different functions. We further revealed that these diterpene synthases underwent duplication and rearrangement at approximately 2.3-23.7 million years ago (MYA) by whole-genome triplication (WGT), transposon mediation, and tandem duplication, followed by functional divergence. We first demonstrated that four key amino acids in the sequences of TwCPS3, TwCPS5, and TwCPS6 were altered during evolution, leading to their functional divergence and the formation of diterpene secondary metabolites. Then, we demonstrated that the functional divergence of three TwKSLs was driven by mutations in two key amino acids. Finally, we discovered the mechanisms of evolution and pseudogenization of miltiradiene synthases in T. wilfordii and elucidated that the new function in TwMS1/2 from the terpene synthase (TPS)-b subfamily was caused by progressive changes in multiple amino acids after the WGT event. Our results provide key evidence for the formation of diverse diterpenoids during the evolution of secondary metabolites in T. wilfordii.

[Nitrogen and phosphorus dynamics along the primary succession in the Hailuogou Glacier retreat area, eastern Tibetan Plateau, China.] / 青藏高原东缘海螺沟冰川退缩区植被原生演替的氮磷动态.

In this study, seven sampling sites (glaciers retreated for 0, 10, 30, 40, 50, 80 and 127 years) were chosen along a primary succession sequence in the Hailuogou glacial retreat area in the eastern margin of the Tibetan Plateau, China. The accumulation and cycling characteristics of N and P under different succession stages were analyzed by measuring biomass and N and P contents in surface soil and each vegetation layer. The N and P contents in leaves, branches and roots of tree layers decreased along the succession sequence, whereas the N and P contents in stems were higher in the late succession stage. The changes of N and P contents in litter and soil O layer were consis-tent with those in the leaves and branches of tree layers. Ecosystem N and P storage increased along the succession sequence. Ecosystem N accumulation was mainly dependent on the vegetation layer in the early succession stage. After the community reached the climax, soil became the main N pool of the ecosystem. Vegetation P storage was higher than that in the surface soil after 80 years of glacial retreat. The nutrient accumulation rate in each layer of the ecosystem was rapid in the middle succession stage, with an order of surface soil > tree layer > understory vegetation layer. The nutrient cycling coefficients of N and P in broadleaved forest in the middle stage were higher than those in coniferous forest in the late stage, whereas the N and P utilization efficiency was lower than that in coniferous forest. Therefore, the mechanism of low nutrient cycling and high utilization efficiency of coniferous trees was conducive to the their competition with other species, thus finally forming the climax community.

Effect of acupuncture on pain-emotion related brain regions in patients with cervical spondylosis of cervical type: a fMRI study / 中国针灸

OBJECTIVE@#To observe the changes of functional connectivity of brain pain-emotion regulation region in patients with cervical spondylosis of cervical type by functional magnetic resonance imaging (fMRI).@*METHODS@#Thirty-two subjects were selected. Of them, 16 patients with cervical spondylosis of cervical type were divided into an observation group and 16 healthy subjects into a control group. The patients in the observation group were treated with acupuncture at Tianzhu (BL 10), Jingbailao (EX-HN 15), Jianzhongshu (SI 15) and @*RESULTS@#In the observation group, the VAS score was (1.94±1.12) after the treatment, which was lower than (5.62±1.20) before treatment (@*CONCLUSION@#Pain involves the formation and expression of "pain-emotion-cognition". Acupuncture can systematically regulate the brain functional connections between cognitive regions such as dorsal prefrontal lobe and anterior cingulate gyrus and emotional regions such as insula and VTA in patients with cervical spondylosis of cervical type, suggesting that acupuncture has a multi-dimensional and comprehensive regulation effect on pain.

Effect of Acupuncture on Ovary Morphology and Function in DHEA-Induced Polycystic Ovary Syndrome Model Rats / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of acupuncture on ovary morphology and function in dehydroepiandrosterone (DHEA)-induced polycystic ovary syndrome (PCOS) model rats.@*METHODS@#A total of 40 adult female Wistar rats were randomly allocated to 4 groups by a random number table, including control, model, metformin and acupuncture groups, 10 rats in each group. PCOS rat model was developed by injecting with DHEA (6 mg/100 g body weight) in 0.2 mL of oil subcutaneously. Electrical stimulation (2 Hz, 3 mA) was applied to Guanyuan (CV 4), Zigong (EX-CA1) and Qihai (CV 6) acupoints for 30 min daily in the acupuncture group, and metformin (200 mg/kg) was given to rats in the metformin group, both once per day for 21 consecutive days, and rats in the normal group was fed with normal saline and fed regularly. After 21 days of administration, the rat blood samples were collected for detecting the reproductive hormonal levels [luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E@*RESULTS@#Compared with the model group, rats in the acupuncture and metformin groups were significantly lower in weight gain, FSH, LH and T levels, and E@*CONCLUSION@#Acupuncture might improve ovary morphology and its function in DHEA-induced PCOS model rats.

Tongxinluo Ameliorates Myocardial Ischemia-Reperfusion Injury Mainly via Activating Parkin-Mediated Mitophagy and Downregulating Ubiquitin-Proteasome System / 中国结合医学杂志

OBJECTIVE@#To investigate the protective effects and mechanism of Chinese herbal compound Tongxinluo Capsule (, TXL) on the Parkin-mediated mitophagy and the ubiquitin-proteasome system in a rat model of myocardial ischemia-reperfusion injury (MIRI).@*METHODS@#Seventy adult male Sprague-Dawley rats were randomly divided into 7 groups: sham group, MIRI group, low- and high-dose TXL (0.5 and 1 g·kg@*RESULTS@#Compared with the sham group, the MIRI group exhibited a larger infarcted area (27.13%±0.01%, P<0.01), a higher apoptotic index (34.33%±2.03% vs.1.81%±0.03%, P<0.01), and higher cTnI expression (14.18±1.01 vs. 7.96±0.32, P<0.01). The mitochondrial integrity was damaged in the MIRI group, while TXL and ATV alleviated the damage of MIRI. More autophagosomes were observed in the high-dose TXL group than in the MIRI group (7.00±0.58 vs. 4.33±1.15, P<0.05). More amounts of PTEN-induced putative kinase protein 1 (PINK1) and Parkin translocated onto the mitochondria were detected in the high-dose TXL group than in the MIRI group (P<0.05). The ubiquitin response was signifificantly downregulated in the high-dose TXL group relative to the MIRI group (P<0.05). CQ administration abolished the activation of autophagy flux and the PINK1/ Parkin pathway induced by high-dose of TXL.@*CONCLUSIONS@#TXL ameliorates MIRI via activating Parkin-mediated mitophagy in rats. The downregulation of the ubiquitin-proteasome system is also involved.

Effects of Shuanghuanglian oral liquids on patients with COVID-19: a randomized, open-label, parallel-controlled, multicenter clinical trial / 医学前沿

We conducted a randomized, open-label, parallel-controlled, multicenter trial on the use of Shuanghuanglian (SHL), a traditional Chinese patent medicine, in treating cases of COVID-19. A total of 176 patients received SHL by three doses (56 in low dose, 61 in middle dose, and 59 in high dose) in addition to standard care. The control group was composed of 59 patients who received standard therapy alone. Treatment with SHL was not associated with a difference from standard care in the time to disease recovery. Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group (93.4% vs. 73.9%, P = 0.006). Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia, which was evaluated by density reduction of inflammatory focus from baseline, at day 7 (mean difference (95% CI), -46.39 (-86.83 to -5.94) HU; P = 0.025) and day 14 (mean difference (95% CI), -74.21 (-133.35 to -15.08) HU; P = 0.014). No serious adverse events occurred in the SHL groups. This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.

Acupoint selection rules of neurogenic dysphagia treated with acupuncture and moxibustion in ancient times / 中国针灸

Acupoint selection rules of neurogenic dysphagia treated with acupuncture and moxibustion from pre-Qin to late Qing Dynasty in were analyzed based on data mining. The literature regarding acupuncture and moxibustion for neurogenic dysphagia was searched and screened according to the inclusion and exclusion criteria in (5th Edition), the prescriptions were extracted according to the principle of acupoint extraction.The SPSS 21.0 and Clementine 12.0 were used to perform the cluster analysis and association rule analysis.A total of 191 acupuncture and moxibustion prescriptions were screened and extracted，including 45 acupoints. The top 5 acupoints of acupuncture and moxibustion for neurogenic dysphagia in frequency were Jiache (ST 6), Dicang (ST 4), Lieque (LU 7), Lianquan (CV 23), Shuigou (GV 26). The most involved meridians were the stomach meridian, the governor vessel and the conception vessel. The main acupoints were distributed in the scalp face neck and upper limbs. The most frequently used specific acupoints was crossing points,next was eight confluence points. There were 11 acupoint combinations with strong association according to the association rule analysis, and the top one acupoint combination was Hegu (LI 4)-Jiache (ST 6). There were 9 acupoint cluster groups according to the cluster analysis. Hegu (LI 4), Jiache (ST 6), Dicang (ST 4), Shuigou (GV 26) and Chengjiang (CV 24) were core acupoints for neurogenic dysphagia treated with acupuncture and moxibustion in ancient times, besides，selecting proximal and distal acupoints and selecting acupoints according to symptoms were emphasized.

Analysis on Mechanisms of Modified Guipitang in Treatment of Yin-Fire Insomnia with Anxiety Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To explore the mechanism of modified Guipitang in the treatment of Yin-Fire insomnia with anxiety with the help of network pharmacological analysis technology. Method:Traditional Chinese Medicine Systems Pharmacology (TCMSP) was used to screen the main components and target genes of modified Guipitang. GeneCards and Online Mendelian Inheritance in Man (OMIM) were used to establish the target gene sets of insomnia and anxiety. STRING 11.0 software was used to analyze the interaction between the overlapping genes, and Cytoscape_3.6.1 software analysis and Matthews correlation coefficient (MCC) algorithm were used to screen the core genes. Based on the results of network analysis, 48 SD female rats were randomly divided into blank control group, model group, eszopiclone tablets group (0.2 mg·kg-1·d-1), modified Guipitang low，medium，and high-dose groups (0.31，1.25，5 g·kg-1·d-1). The model of insomnia with anxiety was established by intraperitoneal injection of Para-chlorophenylalanine (PCPA) and these rats were treated with corresponding drugs for 7 days. Then the frequency, time and distance of the activities were observed in the experiment of autonomic activity. Real-time quantitative polymerase chain reaction (PCR) was used to detect the mRNA expressions of proactivated protein kinase 8 (MAPK8), RAC-alpha serine/threonine protein kinase (Akt1), mitogen-activated protein kinase 3 (MAPK3) and interleukin-6 (IL-6) in rat hippocampus. Result:A total of 228 active compounds were screened from TCMSP database and 181 intersecting genes of diseases and drugs were obtained by comparing with GeneCards and OMIM comprehensive database. 9 core genes, including MAPK3, MAPK8, Akt1 and IL-6 were identified by STRING software and MCC algorithm. Animal experiments showed that the number of activity times, time and distance of modified Guipitang in high and medium dose groups were significantly lower than those in the model group. The high and middle dose groups of modified Guipitang could significantly inhibit the mRNA expression of MAPK3, MAPK8, Akt1 and IL-6 in hippocampus（P<0.01）, while the low dose group had no significant effect. Conclusion:The mechanism of modified Guipitang in treating Yin-fire insomnia with anxiety may be related to the regulation of MAPK3, MAPK8, Akt1 and IL-6 genes.