Component identification and analysis in vivo of Sanhan Huashi formula / 中国中药杂志

Sanhan Huashi formula(SHF) is the intermediate of a newly approved traditional Chinese medicine(TCM) Sanhan Huashi Granules for the treatment of COVID-19 infection. The chemical composition of SHF is complex since it contains 20 single herbal medicines. In this study, UHPLC-Orbitrap Exploris 240 was used to identify the chemical components in SHF and in rat plasma, lung and feces after oral administration of SHF, and heat map was plotted for characterizing the distribution of the chemical components. Chromatographic separation was conducted on a Waters ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 μm) using 0.1% formic acid(A)-acetonitrile(B) as mobile phases in a gradient elution. Electrospray ionization(ESI) source was used to acquire data in positive and negative mode. By reference to quasi-molecular ions and MS/MS fragment ions and in combination with MS spectra of reference substances and compound information in literature reports, 80 components were identified in SHF, including 14 flavonoids, 13 coumarins, 5 lignans, 12 amino-compounds, 6 terpenes and 30 other compounds; 40 chemical components were identified in rat plasma, 27 in lung and 56 in feces. Component identification and characterization of SHF in vitro and in vivo lay foundations for disclosure of its pharmacodynamic substances and elucidation of the scientific connotation.

Anti-inflammatory material basis and mechanism of Artemisia stolonifera based on UPLC-Q-TOF-MS combined with network pharmacology and molecular docking / 中国中药杂志

This study aimed to explore the anti-inflammatory material basis and molecular mechanism of Artemisia stolonifera based on the analysis of the chemical components in different extracted fractions of A. stolonifera and their antioxidant and anti-inflammatory effects in combination with network pharmacology and molecular docking. Thirty-two chemical components were identified from A. stolonifera by ultra-performance liquid chromatography coupled to tandem quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Among them, there were 7, 21 and 22 compounds in water, n-butanol and ethyl acetate fractions, respectively. The antio-xidant capacity of different extracted fractions was evaluated by measuring their scavenging ability against 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl(DPPH) and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonic acid)(ABTS) free radicals and total antioxidant capacity [ferric reducing antioxidant power(FRAP) assay]. The inflammatory model of RAW264.7 cells was induced by lipopolysaccharide(LPS), and the levels of nitrite oxide(NO), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) in the supernatant and the mRNA expression of related inflammatory factors in cells were used to evaluate the anti-inflammatory effects. The results revealed that ethyl acetate fraction of A. stolonifera was the optimal antioxidant and anti-inflammatory fraction. By network pharmacology, it was found that flavonoids such as rhamnazin, eupatilin, jaceosidin, luteolin and nepetin could act on key targets such as TNF, serine/threonine protein kinase 1(AKT1), tumor protein p53(TP53), caspase-3(CASP3) and epidermal growth factor receptor(EGFR), and regulate the phosphatidylinositol-3-kinase-protein kinase B(PI3K-AKT) and mitogen-activated protein kinase(MAPK) signaling pathways to exert the anti-inflammatory effects. Molecular docking further indicated excellent binding properties between the above core components and core targets. This study preliminarily clarified the anti-inflammatory material basis and mechanism of ethyl acetate fraction of A. stolonifera, providing a basis for the follow-up clinical application of A. stolonifera and drug development.

Effect and mechanism of baicalin on the proliferation and migration of human periodontal ligament stem cells induced by lipopolysaccharide / 中国药房

OBJECTIVE To explore the regulatory effects of baicalin on the proliferation and migration of human periodontal ligament stem cells （hPDLSCs） induced by lipopolysaccharide （LPS） and Janus protein tyrosine kinase 2 （JAK2）/signal transduction and transcription activator 3 （STAT3） signaling pathways. METHODS hPDLSCs were divided into control group， LPS group， different concentration baicalin groups （0.1， 1 and 10 mg/L）. ELISA method and CCK-8 assay were used to determine the contents of cell inflammatory factors [interleukin 6 （IL-6）， IL-1β and tumor necrosis factor-α （TNF-α）] and cell viability， so as to screen the optimal concentration of baicalin for follow-up pathway validation experiments. The cells were then divided into control group， LPS group， optimal baicalin concentration group and inhibitor group （10 μg/mL LPS+1 mg/L baicalin +3 μmol/L JAK2/STAT3 pathway inhibitor AG490）. After treated for 24 h， the proliferation rate of hPDLSCs， apoptosis rate， migration rate， invasion cell number， mRNA and protein expressions of Cyclin D1 and caspase-3， the expression of JAK2/STAT3 pathway-related proteins were all detected. RESULTS According to cell inflammatory factors and cell viability， 1 mg/L was selected as the optimal concentration of baicalin. Compared with control group， cell proliferation rate， migration rate， invasion cell number， Cyclin D1 mRNA and protein expression were significantly decreased in LPS group， while cell apoptosis rate， caspase-3 mRNA and protein expression， p-JAK2 and p-STAT3 protein expression were significantly increased （P＜0.05）. After treated with 1 mg/L baicalin， the above indexes were reversed significantly （P＜0.05）. The improvement of above indexes in the inhibitor group was more obvious （P＜0.05）. CONCLUSIONS Baicalin can promote the proliferation， migration and invasion of LPS-induced hPDLSCs and inhibit their apoptosis and inflammation by blocking the JAK2/STAT3 pathway.

Synchronous tele-ultrasonography is helpful for a naive operator to perform high-quality thyroid ultrasound examinations

Purpose@#This study investigated the value of synchronous tele-ultrasonography (TUS) for naive operators in thyroid ultrasonography (US) examinations. @*Methods@#Ninety-seven patients were included in this prospective, parallel-controlled trial. Thyroid scanning and diagnosis were completed by resident A independently, resident B with guidance from a US expert through synchronous TUS, and an on-site US expert. The on-site expert’s findings constituted the reference standard. Two other off-site US experts analyzed all data in a blind manner. Inter-operator consistency between the two residents and the on-site US expert for thyroid size measurements, nodule measurements, nodule features, American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) categories, and image quality was compared. Two questionnaires were completed to evaluate the clinical benefit. @*Results@#Resident B detected more nodules consistent with the on-site expert than resident A did (89.4% vs. 56.5%, P0.75), while resident A achieved lower consistency in ACR TI-RADS categories, composition, echogenicity, margin, echogenic foci, and vascularity (all ICCs 0.40-0.75). Residents A and B had excellent consistency in target nodule measurements (all ICCs >0.75). Resident B achieved better performance than resident A for gray values, time gain compensation, depth, color Doppler adjustment, and the visibility of key information (all P<0.05). Furthermore, 61.9% (60/97) of patients accepted synchronous TUS, and 59.8% (58/97) patients were willing to pay for it. @*Conclusion@#Synchronous TUS can help inexperienced residents achieve comparable thyroid diagnostic capability to a US expert.

Effect and Involved Mechanism of RSL3-induced Ferroptosis in Acute Leukemia Cells MOLM13 and Drug-resistant Cell Lines / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect and involved mechanism of RSL3 on ferroptosis action in acute leukemia cells MOLM13 and its drug-resistant cells.@*METHODS@#After MOLM13 treated with RSL3, CCK-8 assay was performed to detect cell viability, flow cytometry was used to detect the reactive oxygen species (ROS) level of the cells, RT-qPCR and Western blot were used to detect the expression of glutathione peroxidase 4 (GPX4). After MOLM13/IDA and MOLM13/Ara-C, the drug-resistant cell lines were constructed, the ferroptosis induced by RSL3 was observed. Bone marrow samples were collected from patients with acute monocytic leukemia. RT-qPCR and Western blot were performed to detect the expression of related genes and proteins involved in ferroptosis pathway.@*RESULTS@#RSL3 significantly inhibited the cell viability of MOLM13 and increased the intracellular ROS level, which were partially reversed by ferrostatin-1. The mRNA and protein expression of GPX4 decreased in MOLM13 treated with RSL3. RSL3 inhibited the viability of MOLM13/IDA and MOLM13/Ara-C cells more strongly than that of non-drug resistant cells, also increased the intracellular ROS level . The cytotoxic effects were partially reversed by ferrostatin-1. The mRNA and protein expressions of GPX4 in MOLM13/IDA and MOLM13/Ara-C cells were higher than those in non-drug resistant cells. The mRNA and protein levels of GPX4 in bone marrow of relapsed/refractory acute mononuclear leukemia patients were higher than those of ordinary acute mononuclear leukemia patients.@*CONCLUSION@#RSL3 can induce non-drug resistant cells MOLM13 ferroptosis by inhibiting GPX4 activity. MOLM13/IDA and MOLM13/Ara-C are more sensitive to RSL3 compared with non-drug resistant cells MOLM13, which may be caused by the differences in GPX4 expression. The expressions of GPX4 mRNA and protein in relapsed/refractory acute mononuclear leukemia are higher than those in ordinary acute mononuclear leukemia.

Superiority of motor imagery acupuncture in improving muscle tension for patients with upper limb hemiplegia of stroke in early stage / 中国针灸

OBJECTIVE@#To verify the superiority of motor imagery acupuncture in improving muscle tension for patients with upper limb hemiplegia in early stroke.@*METHODS@#A total of 64 patients of stroke hemiplegia with upper limb flaccid paralysis were randomly divided into an observation group (32 cases, 1 case dropped off ) and a control group (32 cases, 4 cases dropped off ). The observation group was treated with motor imagery acupuncture (both acupuncture and motor imagery therapy at affected upper limb were performed).The control group was treated with acupuncture plus motor imagery therapy at affected lower limb, 2 h later after acupuncture, motor imagery therapy was applied to upper limb. Baihui (GV 20) to Taiyang (EX-HN 5) of healthy side, Fengchi (GB 20) and Jianyu (LI 15), Jianjing (GB 21), Quchi (LI 11), Waiguan (TE 5) on the affected side, ect. were selected in both groups, once a day, 5 times a week for 4 weeks. Before and after treatment, 4, 8 weeks after treatment, the modified Ashworth scale (MAS) grade and Brunnstrom stage were compared in the two groups.@*RESULTS@#Compared before treatment, the muscle tension of shoulder, elbow and wrist each time point after treatment was increased in the two groups (@*CONCLUSION@#Motor imagery acupuncture could promote hemiplegia upper limb muscle tension recovery in patients of stroke hemiplegia with upper limb flaccid paralysis, make the patients gradually shift to the separate fine movement mode, inhibit and relieve the appearance and development of spasm.

Soil Physical and Chemical Properties， Microorganisms and Metabolites in Different Culture Environments of Gastrodia elata / 中国实验方剂学杂志

Objective:To study the soil physical and chemical properties， microorganisms， and metabolites in different culture environments of <italic>Gastrodia elata</italic>， so as to provide scientific basis for subsequent cultivation of <italic>G. elata</italic> in multiple environments. Method:The tubersphere soil of <italic>G. elata</italic> cultured in different environments was collected for analyzing the soil nutrients， microbial numbers， and metabolite differences using the agrochemical method， plate-count method， and gas chromatography-time-of-flight mass spectrometry （GC-TOF-MS）-based non-targeted metabonomic approach. Result:The analysis of soil physical and chemical properties revealed the highest soil moisture， pH， available potassium， and available phosphorus in the spinney and the highest electrical conductivity， total nitrogen， alkali-hydrolyzable nitrogen， and organic matter in the pinewood. As demonstrated by the quantitative analysis of soil microorganisms， the cultivable microorganisms were bacteria， actinomycetes， and fungi， with the bacterial population and total microbial biomass in the spinney and the number of fungi and actinomycetes in the barren slope detected to be the largest. The ratio of bacteria to fungi （B/F value） in the pinewood was the highest， while that in the barren slope was the lowest. The results of metabonomic research demonstrated that the compositions and quantities of soil metabolites in the spinney （Z group）， pinewood （S group）， and barren slope （HD group） varied. Through comparisons between S and Z groups， between HD and Z groups， as well as between HD and S groups by orthogonal partial least squares discriminant analysis （OPLS-DA）， 18， 35， and 24 differential metabolites were separately screened out， and the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis yielded 5， 9， and 13 metabolic pathways. There existed a significant causal relationship of the soil physical and chemical properties and microbial numbers with the metabolites. Conclusion:The soil physical and chemical properties， microbial numbers， and metabolite changes differed significantly in different culture environments of <italic>G. elata</italic>， which were sorted by the suitability in a descending order as follows： spinney > pinewood >barren slope. The soil physical and chemical properties and microbial numbers are the crucial factors driving changes in soil metabolites， suggesting that regulating the soil physical and chemical characteristics and microbial characteristics in the culture environment is an important mechanism for maintaining the <italic>G. elata</italic>-soil-microbial symbiotic system.

Effects of Proprioceptive Neuromuscular Facilitation on Balance, Motor and Activities of Daily Living for Stroke Patients: A Meta-analysis / 中国康复理论与实践

Objective:To analyze the effects of proprioceptive neuromuscular facilitation (PNF) on balance, motor and activities of daily living (ADL) for stroke patients. Methods:The randomized controlled trials about the effects of PNF on motor, balance and ADL in stroke patients were retrieved from PubMed, Embase, CNKI, Wanfang data, and VIP, since establishment to December, 2019. The primary outcome measures were Berg Balance Scale (BBS), Fugl-Meyer Assessment (FMA) and modified Bathel Index (MBI). The secondary outcome measures were Functional Reach Test (FRT), Trunk Impairment Scale (TIS), and Timed 'Up and Go' Test (TUGT). The literatures were independently screened by two investigators, and the quality of the articles was evaluated using the Cochrane Library systematic review criteria, and meta-analysis was performed using RevMan 5.3. Results:A total of 13 articles were included with 786 stroke patients. PNF increased the score of BBS for sequelae patients (MD = 3.31, 95%CI 2.58 to 4.04, P < 0.001), FMA for recovery patients (MD = 8.31, 95%CI 5.68 to 10.97, P < 0.001); as well as MBI score (MD = 6.84, 95%CI 5.20 to 8.48, P < 0.001), FRT distance (MD = 1.11, 95%CI 0.39 to 1.84, P = 0.003) and TIS score (MD = 1.75, 95%CI 1.19 to 2.31, P < 0.001) for all the patients, and decreased TUGT time for sequelae patients (MD = -1.86, 95%CI -2.62 to -1.10, P < 0.001). Conclusion:PNF can significantly improve balance, motor and ADL for stroke patients. The effectiveness is various with the course of disease. More high-quality researches are needed.

Effect of Forsythionin A on Gastrointestinal Motility Disorders in Mice Treated with Chemotherapy / 中国实验方剂学杂志

Objective:To observe the effect of forsythiaside A on gastrointestinal motility disorder induced by chemotherapy in mice， and explore the mechanism of forsythiaside A regulating gastrointestinal motility. Method:The 60 KM mice were randomly divided into normal group， model group， metoclopramide group （5 mg·kg-1） and forsythiaside A low， medium and high-dose groups （30， 60， 120 mg·kg-1）， 10 for each group， which include half male and half female. The above dose was given once a day for 4 consecutive days， which the intragastric volume was 10 mL·kg-1. One hour after 1rd day administration， equal volume of saline was intraperitoneally injected to the normal group， 2 mg·kg-1 cisplatin was intraperitoneally injected to the other groups with daily for 4 consecutive days. Observing the effects of forsythiaside A on gastric emptying and small intestinal propulsion on mice models， serum gastrin （GAS） and somatostatin （SS）， motilin （MTL）， vasoactive intestinal peptide （VIP） levels were examined by enzyme-linked immunosorbent assay （ELISA）. Activities of acetylcholinesterase （AChE） and total nitric oxide synthase （tNOS） in gastric antrum and ileum were detected by ELISA. The expression of AChE and inducible nitric oxide synthase （iNOS） in gastric antrum and ileum were detected by Western blot. Result:Compared with normal group， the gastric retention rate and small intestinal propulsion rate of the model group were significantly increased （P<0.01）， serum levels of MTL， GAS， SS and VIP， the AChE activity in the homogenate of ileum in the model group were significantly reduced （P<0.05，P<0.01）， while the tNOS activities in gastric antrum and ileum were significantly increased （P<0.05，P<0.01）. Protein expression of AChE in gastric antrum and ileum were significantly decreased （P<0.05）， and the expression level of iNOS protein was significantly increased in the model group （P<0.05）. Compared with model group， different doses of forsythiaside A can reduce the gastric residual rate and small intestinal propulsion rate of mice to varying degrees. Meanwhile forsythiaside A can increase the serum levels of MTL， GAS， SS， and VIP， and the AChE activity and protein expression levels in gastric antrum and ileum tissues were also increased， while tNOS activity and iNOS protein expression were decreased in gastric antrum and ileum （P<0.05，P<0.01）. Conclusion:Forsythiaside A can significantly ameliorate the delayed gastric emptying and small intestine hyperfunction induced by cisplatin in mice. Its mechanism to ameliorate gastrointestinal dysfunction caused by chemotherapy is related to the regulation of gastrointestinal AChE and NOS activity in gastric antrum and ileum and the regulation of gastrointestinal hormone levels.

Discussion on the principle of protein restriction in the acute stage of hereditary metabolic diseases from the perspective of acrodermatitis with metabolic disorders / 中华实用儿科临床杂志

With the popularization of tandem mass spectrometry and gene detection technology, more and more attention has been paid to hereditary metabolic diseases.The overall incidence rate of hereditary metabolic diseases is 1∶1 000, and the number of patients is huge.The disability and mortality of hereditary metabolic diseases in the acute decompensated period are high.The acute treatment is critical for the prognosis of patients.Limiting the intake of protein is an effective treatment for many patients with amino acid and organic acid hereditary metabolic diseases.However, the lack of standard for protein restriction in the acute decompensation period may lead to " over treatment" in clinical practice and the occurrence of acrodermatitis with hereditary metabolic disorders.In order to standardize and improve the application of dietary therapy in acute treatment, the main points of acute dietary treatment for some common amino acid and organic acid hereditary metabolic diseases were summarized in this paper, and the general protein restriction principle in the acute stage of hereditary metabolic diseases was further explored, so as to provide reference for clinical doctors.

Hydrogen agronomy: research progress and prospects / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Agriculture is the foundation of social development. Under the pressure of population growth, natural disasters, environmental pollution, climate change, and food safety, the interdisciplinary “new agriculture” is becoming an important trend of modern agriculture. In fact, new agriculture is not only the foundation of great health and new energy sources, but is also the cornerstone of national food security, energy security, and biosafety. Hydrogen agronomy focuses mainly on the mechanism of hydrogen gas (H2) biology effects in agriculture, and provides a theoretical foundation for the practice of hydrogen agriculture, a component of the new agriculture. Previous research on the biological effects of H2 focused chiefly on medicine. The mechanism of selective antioxidant is the main theoretical basis of hydrogen medicine. Subsequent experiments have demonstrated that H2 can regulate the growth and development of plant crops, edible fungus, and livestock, and enhance the tolerance of these agriculturally important organisms against abiotic and biotic stresses. Even more importantly, H2 can regulate the growth and development of crops by changing the soil microbial community composition and structure. Use of H2 can also improve the nutritional value and postharvest quality of agricultural products. Researchers have also shown that the biological functions of molecular hydrogen are mediated by modulating reactive oxygen species (ROS), nitric oxide (NO), and carbon monoxide (CO) signaling cascades in plants and microbes. This review summarizes and clarifies the history of hydrogen agronomy and describes recent progress in the field. We also argue that emerging hydrogen agriculture will be an important direction in the new agriculture. Further, we discuss several scientific problems in hydrogen agronomy, and suggest that the future of hydrogen agronomy depends on contributions by multiple disciplines. Important future research directions of hydrogen agronomy include hydrogen agriculture in special environments, such as islands, reefs, aircraft, and outer space.

Microdialysis sampling and HPLC-MS/MS quantification of sinomenine, ligustrazine, gabapentin, paracetamol, pregabalin and amitriptyline in rat blood and brain extracellular fluid / 药学学报

The treatment plan for chronic pain often proceeds from a single drug to drug combination therapy. Sinomenine and ligustrazine, natural alkaline substances derived from traditional Chinese medicines, are expected to provide a new choice for combination analgesic therapy strategies. Here we establish a microdialysis sampling and HPLC-MS/MS quantification method for sinomenine, ligustrazine, gabapentin, paracetamol, pregabalin and amitriptyline in rat blood and brain extracellular fluid. Blood and brain microdialysis probes were implanted in the jugular vein toward the right atrium and left corpus striatum zone (AP +0.2 mm, ML 3.0 mm, DV 3.5 mm) in rats. The blood and brain microdialysis probes were perfused with citric acid buffer solution and Ringer's solution, respectively. Blood and brain extracellular fluid microdialysate were collected at intervals of 20 min at a perfusion rate of 1.5 μL·min-1, and continuously collected for 24 h after administration. The liquid chromatographic separation used a C18-reversed phase chromatographic column (HSS T3 2.5 μm, 2.1 mm×50 mm), the mobile phase was methanol/water (containing 0.05‰ formic acid), and gradient elution was carried out at a flow rate of 0.3 mL·min-1. Mass spectrometric detection used an electrospray ion source, positive ion mode and multi-reaction monitoring method. The selected quantitative ions for sinomenine, ligustrazine, gabapentin, paracetamol, pregabalin, amitriptyline and internal standard naloxone were 330/181, 137/80, 172/154, 152/110, 160/142, 278/233 and 328/310 respectively. The specificity, linear range, matrix effect, accuracy, precision, stability and probe recovery were investigated and confirmed to be suitable for the determination of the above drugs in rat blood and brain extracellular fluid microdialysate. The calculated in vivo recovery of microdialysis probes ranged from 19.38% to 25.88%. After intravenous administration of sinomenine (50 mg·kg-1), ligustrazine (50 mg·kg-1), gabapentin (50 mg·kg-1), paracetamol (50 mg·kg-1), pregabalin (50 mg·kg-1) and amitriptyline (40 mg·kg-1) to rats, the peak concentration in the blood microdialysate was in the range of 0.2-10 μg·mL-1. Drug concentrations could also be detected in brain extracellular fluid microdialysate, however with lower levels (peak concentration: 0.1-6 μg·mL-1) than those of blood microdialysates at each time point. In conclusion, this method can be applied to microdialysis sampling and quantification of sinomenine, ligustrazine, gabapentin, paracetamol, pregabalin and amitriptyline in rats. The method will promote research in identifying herb-drug pharmacokinetic interactions, as well as safety concerns in combination-therapy strategies.

Effects of Comamonas testosteroni on PAHs degradation and bacterial community structure in Leymus chinensis rhizosphere soil / 生物工程学报

To investigate the degradation of polycyclic aromatic hydrocarbons (PAHs) and the changes of rhizosphere microorganisms in the rhizosphere soil of Leymus chinensis during the remediation of PAHs contaminated soil by Comamonas testosteroni (C.t)-assisted Leymus chinensis, we evaluated the removal of PAHs in the rhizosphere of Leymus chinensis using gas chromatography-mass spectrometry (GC-MS), analyzed the bacterial community and the diversity in Leymus chinensis rhizosphere soil by high-throughput sequencing technology, characterized the correlation among PAHs degradation and bacterial community components performing redundancy analysis (RDA) and network analysis, and predicted PAHs degradation potential via PICRUSt software in this paper. The degradation of PAHs in the rhizosphere of Leymus chinensis was promoted, the abundance and diversity of bacteria and the correlation among bacteria and PAHs were changed, and the degradation potential of PAHs in Leymus chinensis rhizosphere soil was enhanced in the later stage of phytoremediation (60-120 d) due to the incorporation of C.t. The accelerated degradation of three PAHs (Nap, Phe, BaP) was accompanied by the differ abundance and correlation of Proteobacteria (Sphingomonas, MND1, Nordella), Actinomycetes (Rubrobacter, Gaiella), Acidobacteria (RB41) and Bacteroides (Flavobacterium) affected by C.t. The results provide new insight into the microorganism choices for microbial assisted plant remediation of soil PAHs and the mechanisms of enhanced PAHs degradation via the combination of Comamonas testosteroni engineering bacteria and plants.

Effect of Adjuvant Therapy of Huayu Pills on Neurological Recovery of Patients with Acute Cerebral Infarction / 中国实验方剂学杂志

Objective:To observe the effects of adjuvant therapy of Huayu pills on neurological recovery of patients with acute cerebral infarction (ACI) and syndrome of Qi deficiency and blood stasis, and to investigate its mechanism of action for antioxidation, anti-inflammation and improvement of microcirculation. Method:One hundred and forty patients were randomly divided into control group (70 cases) and observation group (70 cases) by random number table. During the study period, there were 3 drop-out cases, 2 excluded cases, and 65 completed cases in the control group. There were 1 drop-out cases, 4 excluded case, and 65 completed cases in the observation group. Western medicine was given in both groups. Patients in control group additionally got oral administration of Xiaoshuang Tongluo tablets, 6 tablets/time, 3 times/day. The patients in observation group got oral administration of Huayu pills, 5 g/time, 2 times/days. The treatment course was 4 weeks in both groups. Before the treatment, and at the second and fourth week after treatment, scores of national institute of health stroke scale (NIHSS) were graded. Before and after treatment, scores of functional independent measures (FIM) scale, fugl-meyer assessment of motor function (FMA), Qi deficiency and blood stasis syndrome were graded. Disability/mortality and safety were discussed after treatment. Levels of the whole blood viscosity (BV), plasma viscosity (PV), platelet aggregation rate (PAG), fibrinogen (FIB), P-selectin (CD62p), D-dimer (D-D), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), lipid peroxide (PLO), homocysteine (Hcy), tumor necrosis factor -α (TNF-α), serum cystatin C (Cys-C) and hypersensitive C-reactive protein (hs-CRP) were detected both before and after treatment. Result:In the analysis of rank sum test, clinical efficacy in observation group was better than that in control group (Z=2.131, P<0.05). At the second and fourth week after treatment, scores of NIHSS, Qi deficiency and blood stasis, as well as levels of NO, PLO, MDA, Hcy, Cys-C, hs-CRP, TNF-α, BV, PV, PAG, FIB, CD62 p and D-D in observation group were lower than those in control group (P<0.01), while levels of FIM, FMA and SOD were all higher than those in control group (P<0.01). Conclusion:Based on the comprehensive treatment of Western medicine, adjuvant therapy of Huayu pills can improve the degree of nerve function defect, improve the ability of exercise and daily life, reduce the degree of disability, improve the microcirculation and hemorheology, reduce the inflammatory reaction, eliminate oxygen free radicals, and relieve the oxidative stress injury in patients with ACI and Qi deficiency and blood stasis syndrome, and the clinical efficacy is better than that of Western medicine alone.

Hydrogen agronomy: research progress and prospects / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Agriculture is the foundation of social development. Under the pressure of population growth, natural disasters, environmental pollution, climate change, and food safety, the interdisciplinary "new agriculture" is becoming an important trend of modern agriculture. In fact, new agriculture is not only the foundation of great health and new energy sources, but is also the cornerstone of national food security, energy security, and biosafety. Hydrogen agronomy focuses mainly on the mechanism of hydrogen gas (H

Inhibitory effect of flavonoids from Scutellariae Radix on human cytochrome P450 1A / 中国中药杂志

This study investigated the inhibitory effect of eight natural flavonoids in Chinese herb Scutellariae Radix on huamn cytochrome P450 1 A(CYP1 A), a key cancer chemo-preventive target. In this study, phenacetin was used as a probe substrate for CYP1 A, while human liver microsomes and recombinant human CYP1 A enzymes were used as enzyme sources. Liquid chromatography-tandem mass spectrometry was used to monitor the formation rates of acetaminophen, the O-deethylated metabolite of phenacetin. The dose-dependent inhibition curves were depicted based on the changes of the formation rates of acetaminophen, while the IC_(50) were determined. Inhibition kinetic analyses and docking simulations were used to investigate the inhibition modes and mechanism of wogonin(the most potent CYP1 A inhibitor in this herb), while the inhibition constants(K_i) of wogonin against both CYP1 A1 and CYP1 A2 were determined. Among all tested flavonoids, wogonin, 7-methoxyflavanone and oroxylin A displayed a strong inhibitory effect on CYP1 A(IC_(50)100 μmol·L~(-1)). Further investigations demonstrated that wogonin had a weak inhibitory effect on other human CYP enzymes, suggesting that it could be used as a lead compound for the development of specific inhibitors of CYP1 A. Furthermore, the inhibition kinetic analyses clearly demonstrated that wogonin could strongly inhibit phenacetin O-deethylation in both CYP1 A1 and CYP1 A2 in a competitive manner, with K_i values at 0.118 and 0.262 μmol·L~(-1), respectively. Molecular docking demonstrated that wogonin could strongly interact with CYP1 A1 and CYP1 A2 via hydrophobic and π-π interactions, as well as Ser120 and Ser116 in CYP1 A1 via hydrogen-bonding. In conclusion, this study found that some flavonoids in Scutellariae Radix displayed a strong inhibitory effect on CYP1 A, while wogonin is the most potent CYP1 A inhibitor with a relatively high selectivity towards CYP1 A over other human CYPs.

UHPLC quantification and brain permeability study of sinomenine and ligustrazine in CQM after single intravenous administration / 药学学报

Chuanxiong Qingfengteng mixture (CQM) is an analgesic developed based on clinical evidence and traditional Chinese medicine theory, which majorly consists of Ligusticum chuanxiong and Sinomenium acutum extracts. The current study aims to establish an UHPLC-UV method for the quantification of sinomenine and ligustrazine after CQM administration to rats, mice and cells, and to study the brain permeability of sinomenine and ligustrazine. The selectivity, linearity, accuracy, precision and stability of the established method demonstrated that it was suitable for the determination of sinomenine and ligustrazine in biological samples such as plasma, brain tissue and cellular fluid. After CQM was intravenously administered to rats and mice, both sinomenine and ligustrazine were detected in the brain from 5 min-2 h. The CSF/plasma partition coefficients (Kp, C/P) of each component were higher than those of brain tissue/plasma partition coefficient (Kp, B/P), the Kp, C/P and Kp, B/P of ligustrazine were higher than those of sinomenine. The concentrations between CSF and brain tissue were strongly correlated (Pearson's R>0.86, P<0.001). The unbound fraction in plasma of sinomenine and ligustrazine was 78.92% and 34.07%, respectively. The plasma protein binding rates displayed concentration-independent behavior within their respective in vivo concentration ranges. After CQM co-cultured with Caco-2 cell monolayers, the apparent permeability coefficient (Papp) of sinomenine and ligustrazine were 1.30×10-6 and 3.64×10-6 cm·s-1, respectively, following into the range of the intermediate and high permeability compounds. The efflux ratio (Papp(basolateral→apical)/Papp(apical→basolateral)) of sinomenine and ligustrazine were 0.67 and 0.85, respectively. When combined with P-glycoprotein inhibitor, the Papp of each component did not increase. In conclusion, the UHPLC-UV assay was successfully applied for the brain permeability study of CQM, the components of CQM can be quickly distributed to cerebrospinal fluid and pass through the blood-brain barrier. The brain permeability of ligustrazine is higher than that of sinomenine. The transmembrane transport of sinomenine and ligustrazine may not be affected by efflux transporters. All animal care and use complied with the Regulations for the Administration of Affairs Concerning Experimental Animals approved by the State Council of the People's Republic of China. All animal studies were implemented according to protocols, which were reviewed and approved by the Institutional Animal Care and Use Committee at Experimental Research Center, China Academy of Chinese Medical Sciences.

MiR-338-3p Enhances Ovarian Cancer Cell Sensitivity to Cisplatin by Downregulating WNT2B

PURPOSE: Chemoresistance is a concern in ovarian cancer patients, in whom survival remains. MicroRNA, a novel class of small RNAs, have frequently been found to be dysregulated in human malignancies and to act as negative regulators of gene expression. This study aimed to explore the function of miR-338-3p in cisplatin resistance in ovarian cancer and potential molecular mechanisms thereof. MATERIALS AND METHODS: The expression levels of miR-338-3p and WNT2B in ovarian cancer tissues and cells were estimated by real-time quantitative polymerase chain reaction (RT-qPCR). In addition, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide (MTT), transwell, and flow cytometry assays were used to assess biological role of miR-338-3p in vitro. Western blot assay was conducted to measure protein expression of WNT2B, epithelial-mesenchymal transition (EMT)-related proteins, and apoptosis-related proteins. The relationship between miR-338-3p and WNT2B was confirmed by dual-luciferase reporter. Finally, a xenograft tumor model was developed to explore the effects of overexpression of miR-338-3p on tumor growth in ovarian cancer in vivo. RESULTS: MiR-338-3p was downregulated in cisplatin resistant ovarian cancer tissues and cells. Mechanistically, high expression of miR-338-3p enhanced cell sensitivity to cisplatin by inhibiting proliferation, motility, and EMT and by promoting apoptosis via targeting WNT2B expression in vitro. Furthermore, overexpression of miR-338-3p increased cisplatin sensitivity among ovarian cancer in an in vivo xenograft tumor model. CONCLUSION: MiR-338-3p enhances the sensitivity of ovarian cancer cells to cisplatin by downregulating WNT2B.

Bobath Concept in the Process of Gait Rehabilitation for Post-stroke Patients with Hemiplegia (review) / 中国康复理论与实践

Bobath concept improves walking and motor function in stroke patients with hemiplegia by promoting posture control and establishing correct body mapping. The use of the Bobath concept alone or in combination with other treatments, such as knee stability training, Botulinum toxin injection, and Traditional Chinese Medicine, can effectively improve the walking ability of stroke patients. The Bobath concept has not been widely used, and its clinical effect is difficult to assess, which is the major problem at the current stage in China.

Advance in Neurodevelopmental Therapy for Balance Rehabilitation after Stroke (review) / 中国康复理论与实践

Recently, there are more and more new forms of neurodevelopmental therapy combination, such as combination with biofeedback, vibratory therapy, taping, and Traditional Chinese Medicine, etc., to improve static and dynamic balance of stroke patients.