The chemical constituents and hypoglycemic activity of alcoholic extract of sea buckthorn leaves / 药学学报

The purpose of this research is to identify the chemical constituents of sea buckthorn leaves extract (SBLE) and explore its hypoglycemic biological activity. SBLE was prepared by hot reflux extraction with 65% ethanol, and its chemical composition was analyzed by ultra-high-performance liquid chromatography-photodiode array-mass spectrometry/mass spectrometry (UHPLC-PDA-MS/MS) system. The animal experiments were compliant with ethical principles for animal use and had been approved by the Animal Experiment Ethics Committee of Jinan University. Mice were injected with streptozocin (STZ) to establish a hyperglycemic animal model, and SBLE (1.5 g·kg-1) was administered by gavage for 5 weeks. The fasting blood glucose (FBG) and oral glucose tolerance were detected. Normal mice were given SBLE (1.5 g·kg-1) by intragastric administration for 10 days, and blood was collected from the tail vein to detect the changes in blood glucose within 120 min after sucrose or starch loading. The mucous membrane of the small intestine of mice was taken to detect the activity of α-glucosidase (AG), and the activity of yeast-derived AG incubated with SBLE was evaluated. The glucose uptake by Caco-2 cells treated with SBLE was detected by fluorescence microscopy and cytometry, and the gene expression of sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2) in Caco-2 cells were detected by real-time quantitative PCR (qPCR). A total of 18 compounds were identified, mainly including tannins and flavonoids. SBLE reduced FBG and increased oral glucose tolerance in STZ hyperglycemic mice. SBLE effectively inhibited the increase of blood glucose caused by starch intake in normal mice. SBLE exerted good inhibitory activity on yeast-derived AG (IC50 = 16.94 μg·mL-1) and small intestinal mucosa AG with an inhibition rate of 15.48%. SBLE (25-100 μg·mL-1) dose-dependently inhibited glucose uptake by Caco-2 cells, and SBLE significantly reduced the mRNA level of SGLT1 without changing the expression of GLUT2. In conclusion, the UHPLC characteristic fingerprint of SBLE is established with 18 chemical components identified by mass spectrometry, and SBLE exerts hypoglycemic effect by inhibiting the activity of AG and the absorption of glucose by intestinal epithelial cells.

Study on the toxic mechanism of Mahuang xixin fuzi decoction based on fecal metabolomics / 中国药房

OBJECTIVE To study the toxic mechanism of Mahuang xixin fuzi decoction （MXF） on normal mice. METHODS Totally 48 SPF grade BABL/C mice were randomly divided into blank group， MXF low-dose， medium-dose and high-dose groups， with 12 mice in each group. MXF low-dose， medium-dose and high-dose groups were given drug intragastrically at the dose of 11.262， 33.786， 45.050 g/kg， respectively. Blank group was administered with equal volume of normal saline， once a day， for consecutive 7 d. The body weight， anal temperature and survival rate were recorded， organ index and serum biochemical factors were detected. After the last administration， fecal samples of mice were collected and detected by UHPLC-QE/MS. RESULTS Compared with blank group， the body weight was decreased significantly from the 3rd to the 5th day after administration in MXF medium-dose group， and from the 2nd to the 7th day after administration in MXF high-dose group significantly （P＜0.05）. There was no significant difference in anal temperature among the treatment groups； the average survival rates of MXF medium-dose and high-dose groups were 58.33% and 50.00%， respectively. Compared with blank group， there were significant difference in the indexes of spleen， lung， thymus， adrenal gland and creatine kinase in MXF low-dose， medium-dose and high-dose groups， the testis index in MXF low-dose and high-dose groups， the creatine kinase isoenzyme/creatine kinase ratio in MXF low-dose group， the α-hydroxybutyrate dehydrogenase， lactate dehydrogenase and alkaline phosphatase in MXF medium-dose group， the urine and cystatin C in MXF medium-dose and high-dose groups （P＜0.05）. The fecal metabonomic analysis showed that 19 biomarkers such as phenylpyruvate， L-tyrosine， phosphatidylcholine， glycerol 3-phosphate in MXF low-dose， medium-dose and high-dose groups were significantly different from those in the blank group. CONCLUSIONS When MXF reaches a certain dose， it will have adverse effects on the body weight， multiple organs and serum biochemical indicators of mice， thus showing a certain toxic effect. Its mechanism may be related to disrupting the intestinal flora metabolism， causing inflammatory reaction and immune disorders.

Efficacy of combined local flaps in repair of larger defects in the nasal and perinasal region after Mohs micrographic surgery in 11 cases / 中华皮肤科杂志

Objective:To investigate efficacy and advantages of combined local flaps in repairing large defects in patients with nasal and perinasal non-melanoma skin cancers after Mohs micrographic surgery.Methods:From March 2018 to November 2020, 11 patients with nasal and perinasal non-melanoma skin cancers, who underwent Mohs micrographic surgery followed by repair with combined local flaps, were collected from Department of Dermatology, the Second Hospital of Hebei Medical University. According to the location and size of postoperative defects, flaps were designed based on the nasal aesthetic subunit principle. For large defects that could not be directly sutured or covered by a single local flap, 2 or 3 kinds of flaps were applied in combination, such as kite flap, modified diamond flap, nasolabial skin flap, bilobed skin flap, etc.Results:Among the 11 patients, 10 were diagnosed with basal cell carcinoma and 1 with squamous cell carcinoma, and the area of defects ranged from 2.0 cm × 2.3 cm to 2.7 cm × 3.6 cm. After Mohs micrographic surgery combined with local skin flap repair, all skin flaps survived well without blood supply obstruction, the texture, color and contour of the skin flaps were similar to those of the surrounding normal skin, and no obvious scars were formed. During the postoperative follow-up of 4 to 32 months, no recurrence of the tumors occurred, and the patients was satisfied with the appearance.Conclusion:To repair large defects using combined skin flaps of 2 or 3 kinds after Mohs micrographic surgery in patients with nasal and perinasal non-melanoma skin cancers can maintain the normal nasal or perinasal morphological structure and aesthetic appearance, and yield a satisfactory cosmetic effect.

Novel assays for quality evaluation of XueBiJing:Quality variability of a Chinese herbal injection for sepsis management / 药物分析学报

XueBiJing is an intravenous five-herb injection used to treat sepsis in China.The study aimed to develop a liquid chromatography-tandem mass spectrometry(LC-MS/MS)-or liquid chromatography-ultraviolet(LC-UV)-based assay for quality evaluation of XueBiJing.Assay development involved identifying marker constituents to make the assay therapeutically relevant and building a reliable one-point cali-brator for monitoring the various analytes in parallel.Nine marker constituents from the five herbs were selected based on XueBiJing's chemical composition,pharmacokinetics,and pharmacodynamics.A selectivity test(for"similarity of response")was developed to identify and minimize interference by non-target constituents.Then,an intercept test was developed to fulfill"linearity through zero"for each analyte(absolute ratio of intercept to C response,＜2％).Using the newly developed assays,we analyzed samples from 33 batches of XueBiJing,manufactured over three years,and found small batch-to-batch variability in contents of the marker constituents(4.1％-14.8％),except for senkyunolide I(26.5％).

The disbalance of LRP1 and SIRPα by psychological stress dampens the clearance of tumor cells by macrophages

The relationship between chronic psychological stress and tumorigenesis has been well defined in epidemiological studies; however, the underlying mechanism remains underexplored. In this study, we discovered that impaired macrophage phagocytosis contributed to the psychological stress-evoked tumor susceptibility, and the stress hormone glucocorticoid (GC) was identified as a principal detrimental factor. Mechanistically, GC disturbed the balance of the "eat me" signal receptor (low-density lipoprotein receptor-related protein-1, LRP1) and the "don't eat me" signal receptor (signal regulatory protein alpha, SIRPα). Further analysis revealed that GC led to a direct, glucocorticoid receptor (GR)-dependent trans-repression of LRP1 expression, and the repressed LRP1, in turn, resulted in the elevated gene level of SIRPα by down-regulating miRNA-4695-3p. These data collectively demonstrate that stress induces the imbalance of the LRP1/SIRPα axis and entails the disturbance of tumor cell clearance by macrophages. Our findings provide the mechanistic insight into psychological stress-evoked tumor susceptibility and indicate that the balance of LRP1/SIRPα axis may serve as a potential therapeutic strategy for tumor treatment.

Two cardenolide glycosides from the seed fairs of Asclepias curassavica and their cytotoxic activities / 中国天然药物

Two cardenolide glycosides, corotoxigenin 3-O-[β-D-glucopyranosyl-(1→4)-6-deoxy-β-D-glucopyranoside] (1) and coroglaucigenin 3-O-[β-D-glucopyranosyl-(1→4)-6-deoxy-β-D-glucopyranoside] (2), were isolated from the seed fairs of Asclepias curassavica. The structures of 1-2 were determined based on the combination of the analysis of their MS, NMR spectroscopic data and acid hydrolysis. The inhibitory effects of compounds 1 and 2 on human colorectal carcinoma cells (HCT116), non-small cell lung carcinoma cells (A549) and hepatic cancer cells (SMMC-7721) were evaluated. The results showed that both compounds 1 and 2 significantly inhibited the viability, proliferation, and migration of A549, HCT116 and SMMC-7721 cells, suggesting that compounds 1 and 2 can be applied in the treatment of lung, colon and liver cancers in clinical practice. This study may not only provide a scientific basis for clarifying the active ingredients in A. curassavica, but also help to understand its antitumor activity, which can promote the application of A. curassavica in clinical treatment of various cancers.

Ventromedial Thalamus-Projecting DCN Neurons Modulate Associative Sensorimotor Responses in Mice / 神经科学通报·英文版

The deep cerebellar nuclei (DCN) integrate various inputs to the cerebellum and form the final cerebellar outputs critical for associative sensorimotor learning. However, the functional relevance of distinct neuronal subpopulations within the DCN remains poorly understood. Here, we examined a subpopulation of mouse DCN neurons whose axons specifically project to the ventromedial (Vm) thalamus (DCNVm neurons), and found that these neurons represent a specific subset of DCN units whose activity varies with trace eyeblink conditioning (tEBC), a classical associative sensorimotor learning task. Upon conditioning, the activity of DCNVm neurons signaled the performance of conditioned eyeblink responses (CRs). Optogenetic activation and inhibition of the DCNVm neurons in well-trained mice amplified and diminished the CRs, respectively. Chemogenetic manipulation of the DCNVm neurons had no effects on non-associative motor coordination. Furthermore, optogenetic activation of the DCNVm neurons caused rapid elevated firing activity in the cingulate cortex, a brain area critical for bridging the time gap between sensory stimuli and motor execution during tEBC. Together, our data highlights DCNVm neurons' function and delineates their kinematic parameters that modulate the strength of associative sensorimotor responses.

The Effects of Decitabine Combined with All-Trans Retinoic Acid on the Number of Immune Cells in Myeloid Neoplasms / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of decitabine (DEC) combined with all-trans retinoic acid (ATRA) on the number of immune cells, efficacy and adverse reactions in the treatment of myeloid neoplasms patients.@*METHODS@#Eighty-four patients with myeloid tumors, including AML, MDS-EB-1 or MDS-EB-2 treated by the regimen containing decitabine in our hospital from January 2009 to October 2019 were enrolled and retrospectively analyzed, among the patients, 21 patients treated with DEC alone, 24 patients treated with DEC combined with ATRA (DEC/ATRA) and 39 patients treated with DEC combined with G-CSF priming regimen (DEC/priming). The changes of peripheral blood immune cell levels before and after treatment of the patients between the three groups were compared, and the differences in clinical efficacy and adverse reactions of the patients between the three groups were also compared.@*RESULTS@#There was no statistical differences in the number of immune cells among the patients in the three groups before treatment (P>0.05). NK cell levels decreased significantly in the patients in DEC and DEC/ATRA group after treatment (P<0.05); After treatment, the levels of CD8+ and CD3+T cells in the patients treated by DEC /priming regimen significantly increased (P<0.05), while the levels of CD3-HLA-DR+ B cells significantly decreased (P<0.05). The overall response rate (ORR) of the patients in DEC/ATRA group (75%) and DEC/priming group (74.36%) was significantly higher than 42.86% in DEC monotherapy group, and the differences showed statistically significant (P<0.05), while the ORR between the patients in DEC/ATRA and DEC/priming group showed no statistic differences (P>0.05). There were no statistical differences in overall survival (OS) and incidence of bleeding between the patients in the three groups (P>0.05). The incidences of grade 3 to 4 bone marrow suppression and the infection rate of the patients in DEC monotherapy and DEC/ATRA group were significantly lower than that in DEC/priming regimen group after treatment (all P<0.05), however, there was no statistical difference between DEC monotherapy and the DEC/ATRA group.@*CONCLUSION@#The efficacy of DEC/ATRA on myeloid neoplasms is comparable to that of DEC/priming regimen, and the anti-myeloid tumor effect of DEC/ATRA regimen may be related to the regulation of NK cells and T cells.

Meta-analysis and GRADE evaluation of Shuxuetong Injection in treatment of stroke in progressive / 中国中药杂志

This study aims to systematically evaluate the efficacy and safety of Shuxuetong Injection in the treatment of stroke in progressive. Randomized controlled trials of Shuxuetong Injection in the treatment of stroke in progressive were searched from CNKI, Wanfang, VIP, CMB, PubMed and EMbase. After strict literature screening, data extraction and quality evaluation, a total of 22 articles were included for analysis by RevMan 5.3. The Meta-analysis showed that Shuxuetong Injection combined with conventional treatment was superior to the conventional treatment alone in the major outcome indicators including effective rate(RR=1.27, 95%CI[1.20, 1.33], Z=9.18, P<0.000 01), deterioration rate(RR=0.38, 95%CI[0.22, 0.68], Z=3.31, P=0.000 9), NIHSS scores(MD=-3.89, 95%CI[-4.34,-3.43], Z=16.83, P<0.000 01), CSS scores(MD=-5.59, 95%CI[-6.42,-4.76], Z=13.20, P<0.000 01) and activity of daily living scores(MD=12.02, 95%CI[10.31, 13.72], Z=13.83, P<0.000 01), mortality during treatment was not increased(RR=0.40, 95%CI[0.13, 1.26], Z=1.56, P=0.12). Moreover, Shuxuetong Injection combined with conventional treatment further reduced the secondary outcome indicators including fibrinogen(MD=-0.35, 95%CI[-0.58,-0.13], Z=3.09, P=0.002), triglyceride(MD=-0.38, 95%CI[-0.67,-0.10], Z=2.65, P=0.008), low density lipoprotein cholesterol(MD=-0.72, 95%CI[-0.83,-0.61], Z=12.64, P<0.000 01), serum hypersensitive C-reactive protein(MD=-4.41, 95%CI[-6.96,-1.86], Z=3.38, P=0.000 7), and interleukin-6(MD=-5.43, 95%CI[-6.91,-3.96], Z=7.22, P<0.000 01). GRADE evaluation results showed that the major outcome indicators had low quality of evidence. Shuxuetong Injection in the treatment of stroke in progressive can improve the clinical effective rate, reduce the deterioration rate, improve the neurological function and activity of daily living, down-regulate the levels of fibrinogen, triglyceride, low density lipoprotein cholesterol and alleviate the inflammatory response. Although most studies have reported no adverse reactions, there are selective reports. The safety of Shuxuetong Injection needs to be further verified by more high-quality randomized controlled trial.

A monoclonal antibody-based icELISA for puerarin / 中国中药杂志

Puerarin was conjugated with bovine serum albumin(BSA) and ovalbumin(OVA) by periodate oxidation to serve as the immunogen and coating antigen, respectively. BALB/c mice were immunized with puerarin-BSA according to the routine immunization procedure, and the titer and specificity of serum were detected after three immunization. After booster immunization, mouse spleen lymphocytes were fused with mouse myeloma cells, and 24 hybridoma cell lines of the monoclonal antibodies against puerarin were screened by monoclonal antibody screening technique. Ascites was prepared and purified. The cross-reactivity of monoclonal antibody(mAb) M1 with 4'-methoxy puerarin, daidzin, puerarin-6″-O-xyloside, daidzein, mirificin, 3'-methoxy puerarin, and 3'-hydroxy puerarin was 239.84%, 112.18%, 67.89%, 58.28%, 22.37%, 0.40%, and 0.20%, respectively, and those with other analogs such as baicalein and baicalin were all less than 0.10%. The IC_(50) and the working range of the indirect competitive enzyme-linked immunosorbent assay(icELISA) for puerarin were 44.80 ng·mL~(-1) and 8.20-292.30 ng·mL~(-1), respectively. The average recovery was 91.95%-98.20% with an RSD in the range of 0.70%-2.60%. The content of puerarin in different Puerariae Lobatae Radix samples was determined with icELISA and validated by UPLC-MS. The correlation between data obtained from icELISA and UPLC-MS was 0.999 0, indicating that icELISA is suitable for the rapid detection of puerarin in Puerariae Lobatae Radix samples.

Overwork Affects Extracellular Matrix of Arterial Vessel Wall in Rats / 中国医学科学院学报

Objective To explore the effect of overwork (OW) on extracellular matrix of arterial vessel wall in rats. Methods Random number grouping method was employed to assign 18 Sprague-Dawley rats into three groups(n=6):the control group(no special treatment),group OW(forced swimming twice a day for 15 days),and sleep deficiency(SD)+OW group(in addition to forced swimming twice a day,the rats were put on the platforms in water to limit sleep for 15 days).On the 16th day,the abdominal aorta and common carotid artery were collected after blood sampling from heart under deep anesthesia.A part of the abdominal aorta sample was taken for Masson staining of collagen fiber,and Verhoeff-Van Gieson staining was carried out for the elastic fiber of common carotid artery.Image J was employed for the quantitative analysis of collagen fiber and elastic fiber content.The expression of collagen 1(Col-1) protein was quantified by immunohistochemistry and the ultrastructure of vascular matrix was examined by transmission electron microscopy.The other part of the abdominal aorta sample was used to determine the mRNA levels of matrix metalloproteinase(MMP)-1,MMP-2,MMP-9,tissue inhibitor of metalloproteinases-1(TIMP-1),and Col-1 by quantitative real-time polymerase chain reaction. Results Compared with that in control group,the content of collagen fiber in groups OW and SD+OW had no significant change(all P>0.05);the content of elastic fiber in groups OW and SD+OW decreased(all P<0.001) and had no significant difference between each other(P>0.05).The vascular vessel wall of group OW showed slight fiber breakage,while that of group SD+OW presented wormhole-like or spongy fiber fragmentation.The mRNA levels of MMP-1 and MMP-2 in groups OW and SD+OW had no significant difference between each other(P>0.05) but were higher than that in control group(all P<0.001).The mRNA levels of MMP-9 and TIMP-1 had no significant difference among the three groups(all P>0.05).Groups OW and SD+OW had lower mRNA level(all P<0.001) and protein level(all P<0.001) of Col-1 than control group,while the mRNA and protein levels of Col-1 had no significant difference between groups OW and SD+OW(P>0.05). Conclusion OW can reduce the content of Col-1 and elastic fibers in the extracellular matrix of arterial vessels,destroy the elastic lamina of vascular wall,up-regulate the expression of MMP-1 and MMP-2,thereby injuring arterial vessels.

Metabolomics-based comparative analysis of the effects of host and environment on Viscum coloratum metabolites and antioxidative activities / 药物分析学报

Viscum coloratum(Komn.)Nakai is a well-known medicinal hemiparasite widely distributed in Asia.The synthesis and accumulation of its metabolites are affected by both environmental factors and the host plants,while the latter of which is usually overlooked.The purpose of this study was to comprehensively evaluate the effects of host and habitat on the metabolites in V.coloratum through multiple chemical and biological approaches.The metabolite profile of V.coloratum harvested from three different host plants in two habitats were determined by multiple chemical methods including high-performance liquid chromatography-ultraviolet(HPLC-UV),gas chromatography-flame ionization detector(GC-FID)and ultra-performance liquid chromatography quadrupole time of flight mass spectrometry(UPLC-QTOF/MS).The differences in antioxidant efficacy of V.coloratum were determined based on multiple in vitro models.The multivariate statistical analysis and data fusion strategy were applied to analyze the dif-ferences in metabolite profile and antioxidant activity of V.coloratum.Results indicated that the metabolite profile obtained by various chemical approaches was simultaneously affected by host and environment factors,and the environment plays a key role.Meanwhile,three main differential metab-olites between two environment groups were identified.The results of antioxidant assay indicated that the environment has greater effects on the biological activity of V.coloratum than the host.Therefore,we conclude that the integration of various chemical and biological approaches combined with multivariate statistical and data fusion analysis,which can determine the influences of host plant and habitat on the metabolites,is a powerful strategy to control the quality of semi-parasitic herbal medicine.

Mechanism of omege-6 PUFA increasing the susceptibility to acute myocardial ischemia injury / 药学学报

The abnormal lipids metabolism is a critical pathological feature of coronary heart disease (CHD). Additional supplemental intake of polyunsaturated fatty acid (PUFA) has long been considered to be an effective strategy for preventing CHD, but more and more clinical trials have denied this view. Still, it is ambiguity for the specific mechanism of PUFA in CHD. The experimental programs are compliant with ethical principles for animal use and have been approved by the Animal Experiment Ethics Committee of Jinan University. In the present study, we established an animal model by intake of omega-6 PUFA combined acute myocardial ischemia to explore the mechanism of CHD. Intragastric administration of linoleic acid (LA) for 14 days, intraperitoneal injection of isoprenaline (ISO) was applied to induce acute myocardial ischemia for the animal model establishment. The animal ultrasound imaging system was used to detect cardiac function in vivo after ISO injection for 24 h. Serum and heart tissue samples were collected for the myocardial enzyme, phospholipidomics analysis and molecular biological detection. Compared to the LA group, the cardiac function showed that the left ventricular ejection fraction (EF%) and the left ventricular shortening fraction (FS%) decreased, aspaetate aminotransferase (AST), creatine kinase isoenzyme (CK-MB), and lactate dehydrogenase (LDH) increased in the LA + ISO mice. Compared to the ISO group, the phospholipidomics analysis showed that the PUFAs significantly were raised in the LA + ISO myocardium, and the content of oxidized phosphatidylethanolamine (ox-PE) changed most remarkable. Compared with the ISO group, the molecular biology detection showed that glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH) were depleted, the end-products of ox-PE were increased, and the level of arachidonic acid 12/15-lipoxygenase (ALOX15) protein expression increased obviously. We suggest that ALOX15 mediated phospholipid peroxidation might be the critical mechanism of LA increased the susceptibility of myocardial ischemia injury. This study provides an experimental basis for whether PUFA could be used as an alternative treatment strategy for CHD prevention and provides a new intervention target for the early prevention strategy of CHD.

Phospholipid remodeling and Parkinson's disease / 药学学报

The remodeling of phospholipid includes two processes: deacylation and reacylation. It realizes the conversion of nascent phospholipids to mature phospholipids by changing the length and types of fatty acids at specific sites of phospholipids, which is a key step in phospholipid metabolism. Phospholipids are not only the basic components of biological membranes, but also participate in the transduction of many molecular signals in cells. Therefore, phospholipid remodeling disorders can affect the structure and function of cell membranes, as well as the activity of membrane proteins, causing a series of intricate signaling cascades, and finally lead to many pathological changes including neurodegeneration. This paper reviews the basic process of phospholipid remodeling and the involvement of its key enzymes, calcium independent group VIA phospholipase A2 (iPLA2β), peroxiredoxin 6 (PRDX6), calcium independent group VIB phospholipase A2 (iPLA2γ) as well as acyl-CoA lysocardiolipin acyltransferase 1 (ALCAT1) in the pathology of Parkinson's disease. The mutations in the gene encoding iPLA2β, PLA2G6, have been widely reported to be directly related to hereditary Parkinson disease-14 (PARK14). Here we focus on the molecular mechanism of iPLA2β in the development of Parkinson's disease, mainly involving phospholipid fatty acid metabolism disorders, mitochondrial physiology abnormalities and α-synuclein aggregate formation and other aspects, which will help to understand the role of phospholipid remodeling in Parkinson's disease, and provide new clues for the development of new Parkinson's disease diagnosis and treatment strategies.

Research progress on the detection methods and their application in ferroptosis / 药学学报

Ferroptosis is a novel type of cell death, which is distinguished from the traditional cell death pathways such as apoptosis, proptosis, necrosis and autophagy in terms of morphology, biochemistry and genetics. The main features of ferroptosis are the iron accumulation and lipid peroxidation. The regulation mechanism of ferroptosis involves glutathione metabolism, lipid peroxidation reactions and iron metabolism, which are closely related to the pathological process of tumor, aging, neurodegenerative diseases, ischemia reperfusion injury, cardiovascular and cerebrovascular diseases, kidney injury, hepatic fibrosis and so on. How to effectively study the role of ferroptosis regulation mechanism in the treatment of diseases becomes the hot spot and focus of the ferroptosis research. In recent years, with the in-depth study of ferroptosis, the identification, confirmation and the mechanism of ferroptosis have been developed significantly and have come forth continuously, in the meantime, techniques based on the morphology, biochemistry, molecular biology and genetics have been widely applied in the detection of ferroptosis. In order to deepen readers' understanding of ferroptosis and its detection methods, this paper will mainly review the current research progress on the detection methods and their application in ferroptosis, summarize and discuss their advantages and disadvantages in the detection of ferroptosis, this knowledge are crucial for better understanding and studying the biological function of ferroptosis.

Effect of Qinggan Xiefei Fang on increasing susceptibility of influenza virus caused by "liver fire invading lung" / 药学学报

In this study, chronic emotional stress-induced H1N1 influenza susceptibility model was employed to simulate the states of "emotional stagnation" and "liver fire invading lung", and the protective effect of Qinggan Xiefei Fang on viral pneumonia was investigated. Survival rate and morbidity rate of mice were observed within 21 days after H1N1 infection, the symptoms of viral pneumonia and the level of phospholipid peroxidation were detected in lungs of mice after 6-day infection. The experimental results showed that Qinggan Xiefei Fang could alleviate the decline of survival rate and morbidity rate of mice caused by chronic constraint stress loaded with H1N1, inhibit the replication of H1N1 and the production of inflammatory factors, reduce the level of phospholipid peroxidation, and improve the symptoms of pneumonia in mice. The results also showed that compound-target network of Qinggan Xiefei Fang contained 171 compounds and 260 corresponding targets involved in the signaling pathway of oxidative stress, inflammation and immunity. All the above results indicate that Qinggan Xiefei Fang protecting influenza virus pneumonia was related to the regulation of oxidative stress. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University, in compliance with the Institutional Animal Care Guidelines.

Qingre Xiaoyanning inhibits emotional stress-induced reactivation of latent herpes simplex virus type 1 in mice / 药学学报

In this study, according to TCM theory of "liver qi stagnation forming fire", emotional stress mice model was employed to evaluate the protective effects of Qingre Xiaoyanning on herpes simplex virus type 1 (HSV-1) induced reactivation. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University, in compliance with the Institutional Animal Care Guidelines. BALB/c mice were divided into six groups, including mock group, HSV-1 latency group, HSV-1 reactivation group (HSV-1 latency + stress), low (0.658 g·kg-1·day-1) and high dose (1.316 g·kg-1·day-1) of Qingre Xiaoyanning groups and positive control group (acyclovir, 0.206 g·kg-1·day-1). Except for the normal group and HSV-1 latency group, all mice in other groups received a daily 12-h restraint stress for 4 days. After 7-day treatment of drugs, body weight and recurrent eye infections of mice were recorded. Brain tissues were harvested to monitor HSV-1 antigen distribution by immunohistochemical staining and detect virus titer by plaque assay. In the meantime, the mRNA and protein levels of infected cell polypeptide (ICP27) and glycoprotein B (gB) in the brain tissues were detected by RT-PCR and Western blot, respectively. The level of 4-hydroxynonenal (4-HNE) and expressions of ferroptosis-related proteins were measured by Western blot. The evaluation of malondialdehyde (MDA) content in the brain tissues was conducted by MDA assay commercial kit. The results showed that Qingre Xiaoyanning significantly retarded the decline of body weight of mice induced by HSV-1 reactivation, reduced the activation rate of HSV-1 and recurrent eye infections, declined virus titer of HSV-1, down-regulated gene and protein expressions of ICP27 and gB, and hindered the distribution of HSV-1 antigen in the brain of mice. Meanwhile, Qingre Xiaoyanning also decreased the protein expression of ferroptosis-related proteins, including DMT1, TFR1 and ALOX15 in the brain tissue of HSV-1 reactivated mice. The levels of lipid peroxidation products, 4-HNE and MDA, were also reduced by Qingre Xiaoyanning treatment. All the above results indicate that Qingre Xiaoyanning significantly inhibited HSV-1 reactivation by restraint stress, which might be related to the regulation of ferroptosis. Our findings provide a theoretical basis for the application of "clearing liver-fire" TCM on treatmenting HSV-1 reactivation-related symptoms.

GC-MS Analysis of Volatile Oil from Chaihu Guizhi Decoction and Study on Its Inhibitory Effects on in vitro Proliferation of Human Lung Adenocarcinoma A 549 Cells / 中国药房

OBJECTIVE：To study the compositi on of the volatile oil from Compound chaihu guizhi decoction ，and to evaluate its in vitro anti-proliferative activity on human lung adenocarcinoma A 549 cells. METHODS ：The volatile oil from Chaihu guizhi decoction was extracted according to the steam distillation method of general rules 2004 in the 2015 edition of Chinese Pharmacopoeia（part Ⅳ）. The volatile oil components were analyzed by GC-MS combined with Kováts index ，and the relative content of each component was calculated by peak area normalization method. Using different concentrations of cisplatin （4，8， 16，32，64 mg/L）as positive control ，MTT assay was used to detect the inhibitory effects of different concentrations of volatile oil from Chaihu guizhi decoction （25，50，100，200，400 mg/L）on in vitro proliferation of A 549 cell after 48 h of treatment. Negative control group （with cells but without drugs ）was set up. RESULTS ：A total of 71 chemical components were isolated from the volatile oil ，among which there were 59 compounds identified ，sum of peak areas accounting for 84.99％ of the total peak area. The compounds with relatively high content included ar-curcumene （17.65％），β-bisabolene（9.57％），β-ocimene（7.05％）， α-curcumene（5.35％），2，5-dimethylbenzaldehyde（4.24％），linalyl isobutyrate （2.70％），α-cedrene（2.48％），δ-cadinene （2.07％）. Compared with negative control group ，the proliferation rate of cells were decreased significantly in 4-64 mg/L cisplatin groups and 25-400 mg/L volatile oil from Chaihu guizhi decoction groups （P＜0.05）. IC 50 of cisplatin and volatile oil from Chaihu guizhi decoction to in vitro proliferation of A 549 cells were 10.150 and 73.526 mg/L. CONCLUSIONS ：The volatile oil from Chaihu guizhi decoction mainly includes ar-curcumene ，β-bisabolene，β-ocimene，α-curcumene，which shows certain inhibitory effect on in vitro proliferation of A 549 cells.

Cognitive impairment in children with benign childhood epilepsy with centrotemporal spikes and attention deficit hyperactivity disorder: a prospective study / 中国当代儿科杂志

OBJECTIVES@#To study the difference in cognitive impairment between the children with benign childhood epilepsy with centrotemporal spikes (BECT) and attention deficit hyperactivity disorder (ADHD) and those with BECT or ADHD alone.@*METHODS@#A prospective study was performed on 80 children with BECT and ADHD, 91 children with BECT, and 70 children with ADHD , who were diagnosed with the diseases for the first time. Seventy children of the same age who underwent physical examination were enrolled as the healthy control group. Event-related potential P300, Wechsler Intelligence Scale for Children, and integrated visual and auditory continuous performance test were used to measure and compare each index between groups.@*RESULTS@#Compared with the healthy control group, the BECT+ADHD group, the BECT group, and the ADHD group had a significantly prolonged P300 latency, a significant reduction in the amplitude of P300, and significant reductions in the scores of verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), processing speed index (PSI), full scale intelligence quotient (FSIQ), auditory response control quotient (ARCQ), visual response control quotient, full response control quotient (FRCQ), auditory attention quotient (AAQ), visual attention quotient, and full attention quotient (@*CONCLUSIONS@#Compared with the children with BECT or ADHD alone, the children with both BECT and ADHD have basically the same fields of cognitive impairment but a higher degree of cognitive impairment in some fields.

Meta-analysis of Tanreqing Injection in adjuvant treatment of stroke-associated pneumonia / 中国中药杂志

To systematically evaluate the efficiency and safety of Tanreqing Injection in the treatment of stroke-associated pneumonia(SAP). Seven domestic and foreign databases(CNKI, Wanfang, VIP, CBM, PubMed, Cochrane Library, EMbase) were retrieved from the establishment to July 2020. According to the inclusion and exclusion criteria, randomized controlled trial of the effect of Tanreqing Injection in the treatment of SAP was selected. NoteExpress software was used to screen out literatures. RevMan 5.4 software was used for data analysis. GRADE system was used to evaluate the evidence quality of the outcome indicators. A total of 1 755 cases in 21 studies were retrieved, including 879 cases in experimental group and 876 cases in control group. In general, the quality of stu-dies received was not high. According to Meta-analysis,(1) in terms of shortening the length of hospital stay, Tanreqing Injection combined with conventional western medicine was better than conventional western medicine(MD=-4.04, 95%CI[-4.43,-3.65], P<0.000 01);(2) in terms of increasing effective rate, Tanreqing Injection combined with conventional western medicine was better than conventional western medicine(RR=1.22, 95%CI[1.17, 1.27], P<0.000 01);(3) in terms of reducing inflammation indicators, Tanreqing Injection combined with conventional western medicine was better than conventional western medicine(MD_(CRP)=-10.75, 95%CI[-15.61,-5.88], P<0.000 01; MD_(WBC count)=-1.62, 95%CI[-2.55,-0.69], P=0.000 6; MD_(PCT)=-0.58, 95%CI[-0.89,-0.26], P=0.000 3];(4) in terms of improving symptoms and signs, Tanreqing Injection combined with conventional wes-tern medicine was better than conventional western medicine(MD_(cough)=-2.73, 95%CI[-4.93,-0.53], P=0.02; MD_(antipyretic)=-1.07, 95%CI[-1.17,-0.98), P<0.000 01];(5) in terms of decreasing the NIHSS scores, Tanreqing Injection combined with conventional western medicine was better than conventional western medicine(MD=-3.02, 95%CI[-4.91,-1.13], P=0.002);(6) in terms of adverse reactions, there was no statistically significant difference between Tanreqing Injection combined with conventio-nal western medicine compared with conventional western medicine treatment(RR=1.19, 95%CI[0.61,2.29], P=0.61). GRADE system showed that the evidence levels of above outcome indicators were low and extremely low. The results proved that Tanreqing Injection combined with conventional western medicine had a good advantage in the treatment of SAP, with better observation indicators better than western medicine conventional treatment, and no increase in the incidence of adverse reactions. However, this study had certain limitations. The overall quality of the included studies was low, which affected the reliability of the results. Therefore, the conclusions of this study shall be used cautiously.