In vitro inhibition of carnosic acid against influenza A virus infections / 药学学报

Carnosic acid (CA) is the main phenolic diterpenoid active ingredient in plants such as rosemary and sage, and has antiviral, antioxidant, anti-inflammatory effects and so on, however, its antiviral activity against influenza virus infections was not reported. In this study, antiviral activities against influenza A virus infections of three main bioactive ingredients from rosemary, including rosmarinic acid, CA and ursolic acid, were evaluated using virus titer titration assay, and CA showed remarkable inhibition on influenza H5N1 replication in A549 cells. The antiviral activity of CA was further confirmed and its mechanism of action was investigated using the indirect immunofluorescence assay (IFA), Western blot and real-time fluorescence quantification polymerase chain reaction (qRT-PCR). The results showed that the 50% effective concentration (EC50) of CA against influenza H5N1 in A549 cells and MDCK cells were 4.30 and 3.64 μmol·L-1, respectively. Meanwhile, CA also showed inhibition on influenza virus 2009panH1N1 (EC50: 10.1 μmol·L-1) and H3N2 (EC50: 12.8 μmol·L-1) replications in A549 cells. Mechanistic studies showed that antiviral activity of CA is related to its induction of heme oxygenase-1 (HO-1) in A549 cells and suppression on production of reactive oxygen in H5N1-infected cells.

Genetic analysis of 387 cases of fetal sex chromosome abnormalities detected from amniotic fluid samples / 中华围产医学杂志

Objective:To analyze fetal sex chromosome abnormalities in prenatal diagnosis based on amniotic fluid cell culture.Methods:Clinical data of 12 164 pregnant women who underwent amniocentesis in Maternal and Child Health Hospital of Hunan Province from January 2017 to December 2020 were retrospectively analyzed. For those diagnosed with fetal sex chromosome abnormalities, the results of karyotyping and chromosome microarray analysis (CMA) were analyzed and described.Results:(1) Among the 12 164 cases, fetal sex chromosome abnormalities were detected in 387 cases (3.2%), including 351 cases with abnormal sex chromosome karyotype and 36 with sex chromosome microdeletion/microduplication. (2) High-risk patients indicated by non-invasive prenatal test (NIPT) had the highest proportion of sex chromosomes abnormalities (74.2%, 287/387), followed by those with other ultrasound abnormalities (8.5%, 33/387), high risk of Down syndrome screening (7.0%, 27/387), advanced maternal age (4.7%, 18/387), history of adverse pregnant or delivery (3.3%, 13/387), and nuchal translucency thickening or cervical lymphatic hygroma (2.3%, 9/387). (3) Detected chromosome karyotype abnormalities included numerical abnormalities [73.2%(257/351)], mosaicism [18.8(66/351)], and structural abnormalities [8.0%(28/351)], among which, 47,XXY [46.7%(120/257)], 45,X/46,XX[48.5%(32/66)], and X chromosome deletion [39.3%(11/28)] were the most common, respectively. Among 36 sex chromosome microdeletions/microduplications cases, 15(41.7%) were with pathogenic copy number variation (CNV), including 14 cases of X chromosome microdeletion/microduplication; 7(19.4%) with benign CNV, and 14(38.9%) with CNV of unknown clinical significance. The fragment size [ M (min-max)] of the 15 pathogenic CNV was 1.68 Mb(0.37-9.20 Mb). Of the nine cases with microdeletions, seven were found with deletion in the Xp22.31 region. Conclusions:Numerical abnormalities are the most common fetal sex chromosome abnormalities detected from amniotic fluid samples. Others included mosaicism and chromosome structure abnormalities.

Effect of rTMS combined with CBT on alcohol craving and cognitive function in patients with alcohol dependence / 中华行为医学与脑科学杂志

Objective:To explore the effect of repetitive transcranial magnetic stimulation (rTMS) combined with cognitive behavioral therapies (CBT) on the cognitive function and alcohol craving in patients with alcohol dependence.Methods:From March 2019 to September 2021, a total of 150 patients with alcohol dependence were enrolled and randomly divided into rTMS treatment group (rTMS+ sham CBT, n=41), CBT treatment group (CBT+ sham rTMS, n=34), rTMS+ CBT treatment group( n=36) and control group (sham rTMS+ sham CBT, n=39). At baseline (before treatment), 2nd week, 8th week, 12th week and 24th week, alcohol dependence scale (ADS) was used to evaluate the degree of alcohol dependence, the obsessive compulsive drinking scale (OCDS) was used to assess patients' drinking craving, and Montreal cognitive assessment scale (MoCA) was used to assess the overall cognitive level of patients.SPSS 23.0 statistical software was used to compare the differences of ADS, OCDS and MoCA scale scores of the four groups by repeated measure ANOVA and simple effect analysis. Results:(1)The patients in the four groups were evaluated with ADS scale at baseline, 12th week and 24th week respectively.The interaction of group×time( F=1.279, P=0.279) and the main effect of group were not significant ( F=0.882, P=0.454), and the main effect of time was significant ( F=12.925, P<0.001) .Further simple effect analysis showed that the ADS score of rTMS+ CBT group was lower than that of baseline(14.48±5.70, 10.00±6.51) ( P=0.01) at 24th week.(2)Patients in the four groups were assessed with OCDs scale at baseline, 2nd week, 8th week, 12th week and 24th week, and the interaction of group×time was significant ( F=2.015, P=0.042). Further simple effect analysis showed that the OCDs scores of rTMS group and rTMS+ CBT group at each follow-up time node were lower than those at baseline period (all P<0.05). (3)Patients in the four groups were assessed with MoCA scale at baseline, 8th week, 12th week and 24th week, and the interaction of group×time was not significant ( F=1.660, P=0.106), and the main effect of group and the main effect of time were significant ( F=2.964, P=0.038; F=14.239, P<0.001). Further simple effect analysis showed that the score of MoCA scale in CBT group at the 24th week was higher than that at baseline (21.73±5.81, 24.60±3.98)( P=0.029), the score of MoCA scale in rTMS+ CBT group at the 24th week was higher than that at the 8th week (23.50±6.01, 25.95±2.87) ( P=0.006), and the score of MoCA scale in rTMS group at the 12th week was higher than that in control group (22.08±6.64, 26.64±2.46)( P=0.009). Conclusion:rTMS combined with CBT can be effective in improving alcohol craving and cognitive function in patients with alcohol dependence, and has a good long-term effect.

Study on integrated technology of producing area processing and decoction pieces processing of Curcuma longa / 中国药房

OBJECTIVE To op timize the i ntegrated technology of producing area processing and decoction pieces processing of Curcuma longa （hereinafter refer to “integrated technology ”）. METHODS The content of ethanol-soluble extract in C. longa was determined by hot leaching method ；the contents of curcumin ，demethoxycurcumin and bisdemethoxycurcumin were determined by high performance liquid chromatography. On the basis of identification of producing area processing technology ， Using overall desirability （OD） value of the contents of ethanol-soluble extract ， curcumin， demethoxycurcumin and bisdemethoxycurcumin as evaluation indexes ，moisture content ，slice thickness and drying temperature as factors ，the integrated technology of C. longa was optimized by single factor tests combined with central composite design-response surface method ，and the validation tests were conducted. At the same time ，prepared product was compared with traditional decoction pieces prepared according to 2020 edition of Chinese Pharmacopoeia （part Ⅰ）. RESULTS The best integrated technology was that the fresh C. longa was boiled in boiling water for 5 min，dried at 50 ℃ to 40％ water content ，cut into 2 mm thin slices ，and dried at 50 ℃ until moisture content not exceeding 15.0％. After validation ，The deviation between the average OD value （0.811 3，RSD＝2.13％） and the predicted value （0.848 1）of the contents of ethanol-soluble extract ，curcumin，demethoxycurcumin and bisdemethoxycurcumin was 4.34％. OD value of the contents of ethanol-soluble extract ，curcumin，demethoxycurcumin and bisdemethoxycurcumin in decoction pieces prepared by integrated technology were all higher than those prepared by traditional technology. CONCLUSIONS The process optimized in this study is simple ，stable and feasible.

Research advances on the biomechanical micro- environment facilitated wound repair through the regulation of cell migration / 中华烧伤杂志

Biomechanical microenvironment refers to a variety of mechanical signals in the extracellular mechanical microenvironment, which will change correspondingly with time and space. It plays an important role in histological changes such as cell migration, proliferation, and differentiation, and can further affect wound healing. Wound healing is a complex pathophysiological process, and one of the important factors that affects wound healing is whether the cells can efficiently and quickly migrate to the wound center or not. Previous studies have shown that biomechanical microenvironment can not only induce the directional migration of cells, but also improve the migration rate of cells. In the complex natural environment, cells adopt various migration patterns and are dominated by special patterns such as local myosin contractility and extracellular microenvironment. In addition to overcoming the extracellular barrier, cells also need to interact with neighboring cells and tissue through local physical and mechanical forces and signals to complete migration and thus accelerate wound healing. Therefore, in recent years, scholars at home and abroad have been actively developing biological materials based on improving biomechanical microenvironment in order to further promote cell migration and thus accelerate wound healing. This paper reviews the recent research advances on the role of biomechanical environment in wound healing promotion via the regulating of cell migration and the development of related biomaterials.

Pharmacokinetic study of Erlong Zuoci Pill in rats / 中国药科大学学报

@#To establish a quantitative LC-MS/MS method for the simultaneous detection of components of Erlong Zuoci Pill in rat plasma: verbascoside, oxypaeoniflorin, echinacoside and benzoylpaeoniflorin, and to evaluate the pharmacokinetic characteristics of Erlong Zuoci Pill in rats, plasma samples were purified by protein precipitation using methanol as a protein precipitant.Methanol was used as the organic phase and aqueous solution containing 0.1% formic acid was used as the water phase.The quantitative analysis method of verbascoside, oxypaeoniflorin, echinacoside and benzoylpaeoniflorin was established in negative ion mode, and the validation of bioanalytical method was carried out.Healthy SD rats were selected, and 20 mL/kg (equivalent to the original drug 10 g/kg dose) of Erlong Zuoci Pill extract was administered by intragastric administration.The plasma concentration of the target compounds at different time intervals after administration was determined using the established method, and the pharmacokinetic parameters was calculated by the Phoenix WinNonlin8.3 software using the non-compartmental model.The method validation results showed that verbascoside (r = 0.993 7) and oxypaeoniflorin (r = 0.994 6) had good linear relationship in the concentration range of 0.5-50 ng/mL, echinacoside (r = 0.993 6) and benzoylpaeoniflorin (r = 0.992 6) had good linear relationship in the concentration range of 1-100 ng/mL.The relative standard deviations of the inter- and intra- batch precision of the four compounds were all less than 15%, and the inter- batch and intra- accuracies were between 85% and 115%.Extraction recovery, matrix effect and stability met the relevant requirements.After a single gavage of Erlong Zuoci Pill extract in rats, all the four compounds were rapidly absorbed and eliminated.Oxypaeoniflorin, echinacoside, and benzoylpaeoniflorin showed two peaks in their drug concentration-time curves.Compared with the other three compounds, oxypaeoniflorin has the highest concentration in rat plasma with cmax1 of (24.40 ± 4.78) ng/mL and cmax2 of (22.50 ± 2.70) ng/mL. The results show that the validation results of this method are in line with the guiding principles of biological sample analysis methods, and it can be used to evaluate the pharmacokinetic characteristics of Erlong Zuoci Pill extract in rats.

Research status of related factors affecting the prognosis of central retinal vein occlusion / 国际眼科杂志(Guoji Yanke Zazhi)

Central retinal vein occlusion(CRVO)is a common retinal vascular disease that severely affects visual acuity. Currently, ranibizumab, aflibercept and dexamethasone implant have been successful in treating macular edema associated with CRVO. However, there were still 1/3 patients with no significant improvement in vision after treatment, 30.7% patients with macular edema subsiding after treatment but recurring, and 28.1% patients with macular edema persisting after treatment. How to determine the prognosis of patients by their different clinical manifestations at the early stage of disease onset can help clinicians to better select treatment options for patients according to their specific disease conditions. Recent studies on the prognosis of CRVO treatment have focused on imaging markers including disorganization of retinal inner layers, retinal hyperreflective foci, subretinal fluid, ischemic index, leakage index, and biomarkers including VEGF, interleukin(IL)-6, IL-8, etc. This article reviews the progress of research on factors related to the prognosis of CRVO, with the aim of treating, managing and monitoring patients with CRVO more precisely and effectively.

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.

Genetic Analysis of Thalassemia in 22 940 Pregnant Women in Xiangxi Tujia and Miao Autonomous Prefecture / 中国实验血液学杂志

OBJECTIVE@#To investigate the incidence and types of thalassemia in Xiangxi Tujia and Miao Autonomous Prefecture.@*METHODS@#Automatic capillary electrophoresis was used to screen the thalassemia phenotypes of 22 940 blood samples of pregnant women and puerperants collected in our hospital and some other medical institutions in the prefecture during 2017-2019, among which there were 3 356 cases of Tujia ethnicity, 2 821 cases of Miao ethnicity, and 2 233 cases of Han ethnicity included, whose ethnicity were indicated. The samples with positive result would undergo further genetic testing.@*RESULTS@#There were 2 314 cases of suspicious thalassemia were screened from 22 940 cases by the electrophoresis, thus the positive rate was 10.1% (hematological phenotypes from some other institutions were not included). Specifically, there were 1 706 cases with HBA2 less than 2.5%, 255 cases with HBA2 ranged from 2.5% to 3.5%, which displayed abnormal hematology (MCV or/and MCH) or other abnormal bands, and 353 cases with HBA2>3.5%. There were 436 suspected positive patients in 2 314 suspicious samples received further thalassemia gene testing in our hospital, among them 48 cases were diagnosed with α-thalassemia, 85 cases with β-thalassemia, and 2 cases as compound type. The positive diagnosis rate of α-thalassemia gene test was 11.0%, β-thalassemia was 19.4%, and positive pregnant women was 31.0%.@*CONCLUSION@#The positive rate of thalassemia screening in Xiangxi Autonomous Prefecture is roughly the same as that in other regions of Hunan. The positive predictive value of β-thalassemia screening is as high as 86%. Compared with the missed screening data, it is recommended to use hematology (MCV, MCH) method combined with capillary hemoglobin electrophoresis for thalassemia screening.

Sagittaria sagittifolia polysaccharides regulates Nrf2/HO-1 to relieve liver injury caused by multiple heavy metals in vivo and in vitro / 中国中药杂志

This study explored whether Sagittaria sagittifolia polysaccharides(SSP) activates the nuclear factor erythroid-2-related factor2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway to protect against liver damage jointly induced by multiple heavy metals. First, based on the proportion of dietary intake of six heavy metals in rice available in Beijing market, a heavy metal mixture was prepared for inducing mouse liver injury and HepG2 cell injury. Forty male Kunming mice were divided into five groups: control group, model group, glutathione positive control group, and low-and high-dose SSP groups, with eight mice in each group. After 30 days of intragastric administration, the liver injury in mice was observed by HE staining. In the in vitro experiment, MTT assay was conducted to detect the effects of SSP at 0.25, 0.5, 1, and 2 mg·mL~(-1) on HepG2 cell survival at different time points. The content of alanine transaminase(ALT) and aspartate aminotransferase(AST) in the 48-h cell culture fluid was measured using micro-plate cultivation method, followed by the detection of the change in reactive oxygen species(ROS) content by flow cytometry. The mRNA expression levels of Nrf2 and HO-1 in cells were determined by RT-PCR, and their protein expression by Western blot. HE staining results showed that compared with the model group, the SSP administration groups exhibited significantly alleviated inflammatory cell infiltration and fatty infiltration in the liver, with better outcomes observed in the high-dose SSP group. In the in vitro MTT assay, compared with the model group, SSP at four concentrations all significantly increased the cell survival rate, decreased the ALT, AST, and ROS content(P<0.05), and down-regulated Nrf2 and HO-1 mRNA and protein expression(P<0.05). SSP significantly improves inflammatory infiltration in the liver tissue of mice exposed to a variety of heavy metals and corrects the liver fat degeneration, which may be related to its regulation of the Nrf2/HO-1 signaling pathway, reduction of ROS, and alleviation of oxidative damage.

The mechanism of androgen independent signaling pathway in castration-resistant prostate cancer and the research progress on related drugs / 药学学报

Prostate cancer is one of the common malignant tumors of male urogenital system, and the incidence of prostate cancer in China has increased significantly in the past decade. At present, endocrine therapy based on androgen blockade is the main method of clinical treatment except radical surgery and radiotherapy/chemotherapy for prostate cancer. However, the clinical benefit can only be obtained in the early stage of treatment, and nearly 90% of patients will develop to the castration resistance, and among them, nearly 90% of patients will have bone metastasis. The quality of life decreases sharply with the progression of disease for patients. In addition to the androgen signal pathway, studies have shown that many other oncogenic signal pathways have involved in the development of castration resistance, including classic cancer signaling pathways, immune and inflammatory signaling pathways, etc. Understanding the mechanism of androgen independent signal pathway in the formation of castration resistance will help to understand the off-target effect of androgen blocking therapy and introduce new treatment targets or strategies to get rid of the "no drug available" dilemma for clinical treatment of castration resistance.

Research progress of maculopathy in pathological myopia / 国际眼科杂志(Guoji Yanke Zazhi)

@#A series of fundus changes caused by excessive axial elongation in pathological myopia, especially maculopathy, are the main factors causing vision loss or blindness. In recent years, with the increasing prevalence of high myopia and pathological myopia, people pay more and more attention to the fundus complications of pathological myopia. It has become a big difficult problem to prevent the irreversible vision impairment caused by pathological myopia. The purpose of this review is to discuss the latest progress of fundus characteristics, diagnosis and treatment of maculopathy in pathological myopia from three aspects based on the latest classification of myopic maculopathy, namely ATN classification system, which considers atrophic(A), tractional(T)and neovascular(N)components.

Cytogenetic and molecular genetic analysis of three fetuses at high risk of trisomy-16 detected by cell-free fetal DNA testing / 中华围产医学杂志

Objective:To investigate the power and prenatal diagnosis strategies of cell-free fetal DNA (cffDNA) testing for chromosomal aneuploidy screening apart from trisomy-13/18/21.Methods:This study collected the clinical data of three cases at high risk of trisomy-16 indicated by cffDNA testing in Hunan Provincial Maternal and Child Health Care Hospital from March 2019 to March 2020. Results of the conventional G-banding karyotype analysis of amniotic fluid, single nucleotide polymorphism array (SNP-array) and low-coverage massively parallel copy number variation sequencing (CNV-seq) of placenta/fetal skin samples were analyzed.Results:(1) cffDNA testing results suggested that case 1-3 were at high risk of trisomy-16 and the Z values of chromosome 16 were 20.57, 24.88 and 17.87, respectively. (2) Karyotype analysis of amniotic fluid samples did not identify any abnormalities in Case 1 and 2, while SNP-array revealed a 19.2 Mb and 23.0 Mb heterozygous deletion at 16p13.3p12.3 and 16q22.1q24.3 in Case 1, and a 16.0 Mb loss of heterozygosity at 16q22.3q24.3 in Case 2. Case 3 had a mosaicism karyotype of 47,XY,+16[3]/46,XY[97] and SNP-array analysis showed no heterozygous deletion greater than 5 Mb or copy number variation. (3) Ultrasonography indicated fetal growth restriction in Case 1 and 2 and fetal death in Case 3. All three pregnancies were terminated. CNV-seq analysis of placental tissue in the center of both fetal and maternal side revealed mosaic trisomy 16, with the copy numbers of chromosome 16 of 2.56/2.70, 2.73/2.82, 2.80/2.81, respectively. However, no copy number variation was detected in Case 1 or 2 by CNV-seq analysis of fetal skin tissues. Conclusions:cffDNA testing has a certain power in detecting trisomy-16 apart from trisomy-13/18/21. For high-risk cases of trisomy-16 indicated by cffDNA testing, SNP-array analysis combined with karyotype analysis is suggested to rule out low-level mosaicism and loss of heterozygosity.

Polydatin Ameliorated Colonic Inflammation via Precluding Phosphorylation of PKCθ/STAT3 Pathway to Inhibit Th17 Cells in Mice with Ulcerative Colitis / 中国实验方剂学杂志

Objective:To investigate the therapeutic effect of polydatin on ulcerative colitis （UC） in mice and its regulation of protein kinase C<italic>θ</italic>（PKC<italic>θ</italic>）/signal transducer and activator of transcription 3（STAT3） signaling on T helper cell 17（Th17） and its mechanism in the treatment of UC. Method:The 32 male C57BL/6 mice were randomly divided into normal group， model group， polydatin group （0.045 g·kg^-1） and sulfasalazine group （0.5 g·kg^-1）. The UC model was established by giving 3% dextran sodium sulfate （DSS） solution to free drinking water in mice. Polydatin and sulfasalazine groups were given by gavage 0.5 h before modeling for 7 days. The normal group and model group were given the same amount of normal saline. After the last administration， the colonic tissue was taken and hematoxylin-eosin （HE） was used to observe the pathological changes of colonic tissue. Flow cytometry was used to detect the proportion of Th17 in the lamina propria of colonic mucosa. The expression of interleukin-17A （IL-17A） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Polydatin was added to CD4⁺T cells purified from spleen of C57BL/6 mice by magnetic-activated cell sorting （MACS） under the stimulation of cell stimulation cocktail <italic>in vitro </italic>in order to detect its impact on PKC<italic>θ</italic> and STAT3 phosphorylation. Result:Compared with normal group， the body weight was significantly decreased， and disease activity index （DAI） scores of the model group was significantly increased （<italic>P</italic><0.01）， the colonic mucosal epithelium was damaged and inflammatory cells infiltration in the mucosa and submucosa was obvious， the proportion of Th17 in the lamina propria of colonic mucosa was significantly increased （<italic>P</italic><0.01）， and the content of serum IL-17A was significantly increased （<italic>P</italic><0.01）. Compared with the model group， the weight and DAI score of polydatin and sulfasalazine groups were significantly improved （<italic>P</italic><0.01）， the degree of colon tissue damage was significantly improved， the proportion of Th17 in colon mucosa lamina propria was significantly decreased （<italic>P</italic><0.01）， and the content of IL-17A in serum was significantly decreased （<italic>P</italic><0.01）. <italic>In vitro</italic> experiments showed that polydatin could significantly inhibit the phosphorylation of PKC<italic>θ</italic> and STAT3 in Th17 （<italic>P</italic><0.01） as well as IL-17A secretion. Conclusion:Polydatin can improve the ulcerative colitis in mice via inhibiting the phosphorylation of PKC<italic>θ</italic> and STAT3 to preclude IL-17A secreting in Th17.

Gegen Qinliantang Regulates MMP-9/p38 MARK Pathway to Repair Intestinal Mucosal Barrier Function in Mice with Ulcerative Colitis / 中国实验方剂学杂志

Objective:To explore the protective effect of Gegen Qinliantang on the intestinal mucosal epithelial barrier function of ulcerative colitis （UC） mice， and to explore its mechanism of action in the treatment of ulcerative colitis via matrix metallopeptidase-9 （MMP-9）/p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway. Method:The 48 female C57BL/6 mice were randomly divided into normal group， model group， sulfasalazine group （0.3 g·kg^-1） and Gegen Qinliantang high， medium and low dose groups （2.84，1.42，0.71 g·kg^-1）. The UC murine model was established by 3% dextran sulfate sodium （DSS）. Gegen Qinliantang and sulfasalazine were intragastrically administered on the 8^th day after the model was established for 7 days， and the normal group was treated with the same amount of normal saline. Colon tissues were collected after the last administration， and the pathological changes of colon tissues were detected by hematoxylin-eosin （HE） staining. The expression of tight junction （TJ） proteins such as Occludin and zonula occludens-1（ZO-1） in colon tissues was detected by immunohistochemistry （IHC）， and the expression levels of tumor necrosis factor-alpha （TNF-<italic>α</italic>）， interleukin-1<italic>β</italic> （IL-1<italic>β</italic>）， and MMP-9 mRNA in colon tissues were detected by Real-time polymerase chain reaction （Real-time PCR）. The expression of phosphorylated p38 MAPK （p-p38 MAPK）， p38 MAPK and MMP-9 protein in colon tissues was detected by Western blot. Result:Compared with normal group， the body weight of mice decreased （<italic>P</italic><0.01） and disease activity index （DAI） score increased significantly （<italic>P</italic><0.01） in model group， the colon tissues of the model group were damaged more obviously， the expression of occludin and ZO-1 proteins in model group was significantly reduced （<italic>P</italic><0.01）， and the relative expression levels of TNF-<italic>α</italic>， IL-1<italic>β</italic>， and MMP-9 mRNA in model group were significantly increased （<italic>P</italic><0.01）， the expression of p-p38 MAPK and MMP-9 in model group was significantly increased （<italic>P</italic><0.01）. Compared with model group， the body mass and DAI score of the sulfasalazine group and Gegen Qinliantang group were significantly improved （<italic>P</italic><0.05，<italic>P</italic><0.01）， the colonic tissues damage were significantly improved， and the expression of Occludin and ZO-1 protein was significantly increased （<italic>P</italic><0.05，<italic>P</italic><0.01）， the relative expression levels of TNF-<italic>α</italic>， IL-1<italic>β</italic>， and MMP-9 mRNA were significantly decreased （<italic>P</italic><0.01）， and the expression of p-p38 MAPK and MMP-9 was significantly decreased （<italic>P</italic><0.01）. The changes in the middle dose group were the most obvious among the various dose groups of Gegen Qinliantang. Conclusion:Gegen Qinliantang repairs the intestinal mucosal barrier function by inhibiting the expressions of MMP-9 and inflammatory cytokines such as TNF-<italic>α</italic> and IL-1<italic>β</italic>， blocking the activation of the p38 MAPK signaling pathway， and increasing the expressions of tight junction protein.

Mechanism of sodium salicylate-induced damage to HEI-OC1 cells based on metabonomics / 中国药科大学学报

@#The effect of sodium salicylate on the endogenous metabolism of hair cell-like cells (HEI-OC1).of mice was analyzed based on liquid chromatography-quadrupole time of flight mass spectrometry (LC-Q-TOF/MS).Firstly, HEI-OC1 cells were treated with different concentrations of sodium salicylate, and cell survival was examined by the CCK-8 method. Next, sodium salicylate was administered for different duration to observe the changes in cell morphology. Inter-group differential metabolites were screened out, and the associated metabolic pathways were analyzed based on metabonomic technology.Results showed that sodium salicylate could significantly inhibit the survival rate of HEI-OC1 cells, and that, as the concentration increased, the inhibitory effect became stronger. Also, the cell morphology could be elongated after administration and return to normal after withdrawal.Eighteen differential metabolites such as orotic acid, uridine and aspartic acid were screened out after treatment of sodium salicylate, which mainly involving two possible metabolic pathways, namely the metabolism of alanine, aspartic acid and glutamic acid, and that of pyrimidine.In summary, the application of metabolomics technology to evaluate the effect of sodium salicylate on hair cells from the microscopic perspective can provide new ideas for the study of sodium salicylate ototoxicity and development of tinnitus.

Evaluation of non-clinical anxiety disorder models / 药学学报

Anxiety disorders are one of the most common mental disorders in adults, the cause of which derives from a combination of genetics and environmental factors. A series of animal models have been established according to their pathogenesis to measure the level of anxiety or induce anxiety only, and these models have been widely applied in the non-clinical evaluation of anxiolytics. In this review, we present the current trends in the study of anxiety disorders and summarize typical non-clinical anxiety animal models, including models that both measure anxiety levels and induce anxiety, and models that induce anxiety only. This review summarizes the important issues in standardized non-clinical research of anxiety disorders and proposes criteria for the selection of an appropriate R&D model.

Allium tuberosum alleviates pulmonary inflammation by inhibiting activation of innate lymphoid cells and modulating intestinal microbiota in asthmatic mice / 中西医结合学报

OBJECTIVE@#This study tests whether long-term intake of Allium tuberosum (AT) can alleviate pulmonary inflammation in ovalbumin (OVA)-induced asthmatic mice and evaluates its effect on the intestinal microbiota and innate lymphoid cells (ILCs).@*METHODS@#BALB/c mice were divided into three groups: phosphate buffer saline, OVA and OVA + AT. The asthmatic murine model was established by sensitization and challenge of OVA in the OVA and OVA + AT groups. AT was given to the OVA + AT group by oral gavage from day 0 to day 27. On day 28, mice were sacrificed. Histopathological evaluation of lung tissue was performed using hematoxylin and eosin, and periodic acid-Schiff staining. The levels of IgE in serum, interleukin-5 (IL-5) and IL-13 from bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay. The ILCs from the lung and gut were detected by flow cytometry. 16S ribosomal DNA sequencing was used to analyze the differences in colon microbiota among treatment groups.@*RESULTS@#We found that long-term intake of AT decreased the number of inflammatory cells from BALF, reduced the levels of IL-5 and IL-13 in BALF, and IgE level in serum, and rescued pulmonary histopathology with less mucus secretion in asthmatic mice. 16S ribosomal DNA sequencing results showed that AT strongly affected the colonic bacteria community structure in asthmatic mice, although it had no significant effect on the abundance and diversity of the microbiota. Ruminococcaceae and Desulfovibrionaceae were identified as two biomarkers of the treatment effect of AT. Moreover, AT decreased the numbers of ILCs in both the lung and gut of asthmatic mice.@*CONCLUSION@#The results indicate that AT inhibits pulmonary inflammation, possibly by impeding the activation of ILCs and adjusting the homeostasis of gut microbiota in asthmatic mice.

Qingre Xiaoyanning Capsules alleviate HSV-1 susceptibility induced by emotional stress / 中国中药杂志

In this study, emotional stress-induced herpes simplex virus type 1(HSV-1) susceptibility model was employed to simu-late the pathological state of " depression-induced liver fire", and the protection effect of Qingre Xiaoyanning(QX) in clearing liver fire was investigated. BALB/c mice were randomly divided into a normal group, a HSV-1 group, a restraint stress + HSV-1 group,low-(0. 658 g·kg~(-1)) and high-dose(1. 316 g·kg~(-1)) QX groups, and an acyclovir group. Except for the normal group and the HSV-1 group, the mice in other groups received daily restraint stress for 6 h from day 3 of medication. On day 9 of medication, mice were anesthetized by isoflurane and infected intranasally with HSV-1. Survival rate, weight change, encephalitis symptoms, and eye injury of mice were recorded for 14 d after virus infection. Hematoxylin-eosin(HE) staining and immunohistochemical staining were used to detect pathological changes and HSV-1 antigen distribution. Plaque assay was performed to detect the titer of HSV-1. The protein ex-pression of ICP27 in the mouse brain was detected by Western blot. The experimental results showed that QX could increase the survival rate of HSV-1-infected mice loaded with emotional stress(P<0. 001), reduce the titer of HSV-1 in the mouse brain(P<0. 01), relieve brain inflammation(P<0. 05) and eye injury(P<0. 05), down-regulate the expression of ICP27 related to HSV-1(P<0. 05), and decrease the distribution of HSV-1 antigen in the mouse brain. The results demonstrated that QX significantly reduced the susceptibility to HSV-1 induced by emotional stress, which is expected to provide a theoretical basis for the treatment and preven-tion of HSV-1 infection and promote the clinical development and application of Chinese medicine effective in clearing liver fire.

Heat-sensitive moxibustion of different suspension moxibustion methods and imitation moxibustion apparatus on moxibustion sensation and clinical efficacy in knee osteoarthritis / 中国针灸

OBJECTIVE@#To observe the moxibustion sensation and the clinical therapeutic effect of heat-sensitive moxibustion of two different suspension moxibustion methods and imitation moxibustion apparatus on mild to moderate knee osteoarthritis (KOA), and compare the therapeutic effect of different moxibustion methods.@*METHODS@#A total of 90 patients with mild to moderate KOA were randomized into a hand-held group (30 cases, 1 case dropped off), an imitation moxibustion apparatus group (30 cases) and a moxibustion shelf group (30 cases, 1 case dropped off). @*RESULTS@#The compositions of moxibustion sensation and numbers of moxibustion sensation types in individuals in the hand-held group and the moxibustion shelf group were richer, the moxibustion sensation intensity was higher than that in the imitation moxibustion apparatus group (@*CONCLUSION@#Heat-sensitive moxibustion can effectively treat knee osteoarthritis, while the different suspension moxibustion methods have an influence on clinical therapeutic effect, hand-held suspension moxibustion has the best efficacy.