Effects of Wenyang jieyu decoction on PI3K/Akt signaling pathway and neurotransmitters in kidney-yang deficiency depressed rats / 中国药房

OBJECTIVE To investigate the effects of Wenyang jieyu decoction on phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway and neurotransmitters in rats with kidney-yang deficiency depression. METHODS The SD rats were divided into blank group， model group， fluoxetine group （positive control of western medicine， 4.17 mg/kg）， Xiaoyao powder group （positive control of TCM， 1.88 g/kg） and Wenyang jieyu decoction low-dose， medium-dose and high-dose groups （1.25， 2.50， 5.00 g/kg）， with 15 rats in each group. Except for blank group， the other groups were treated with corticosterone 20 mg/kg subcutaneously to induce kidney-yang deficiency depressed model， meanwhile the mice were given relevant medicine intragastrically， once a day， for 28 consecutive days. The general conditions of rats were observed. The sucrose preference rate and the static time of forced swimming were detected， and organ indexes of rats were calculated. The levels/contents of neurotransmitters in serum were detected， the expressions of PI3K/Akt pathway-related proteins in hippocampus were detected， and the number of dendritic spines was determined. RESULTS Compared with blank group， model group suffered from the symptoms such as hair loss， fear of cold， curling up； sucrose preference rate， indexes of adrenal gland， thymus gland and spleen，serum levels of cyclic adenosine phosphate （cAMP）， brain-derived neurotrophic factor and gamma-aminobutyric acid， the ratio of cAMP to cyclic guanosine monophosphate， the contents of norepinephrine， dopamine and 5-hydroxy-tryptamine， the expressions of PI3K， Akt， mammalian target of rapamycin， and the number of dendritic spines in the hippocampus were significantly decreased （P＜0.01）. The time of immobility， level of glutamic acid and protein expression of glycogen synthetase kinase-3β were prolonged and increased （P＜0.01）. Compared with model group， depression symptoms of rats in each administration group were improved， and the above indexes were mostly reversed （P＜0.05 or P＜0.01）. CONCLUSIONS Wenyang jieyu decoction can improve depression-like behavior and the deficiency of kidney-yang， regulate the secretion of neurotransmitters， and activate PI3K/Akt signaling pathway， thus playing a role in protecting hippocampal neurons.

Clinical significance of high-risk HPV-DNA detection combined with TCT in screening and follow-up of cervical lesions / 上海预防医学

ObjectiveTo explore the application value of high-risk HPV-DNA detection combined with TCT in cervical lesion screening and follow-up. MethodsThis study was conducted from February 2019 to February 2021. During this period， 241 subjects who were the patients referred from the primary community hospitals to the center for re-examination of cervical lesions. Of which 80 were patients with cervical intraepithelial neoplasia. Liquid-based cytology （TCT） technology was used to examine the cervical cytological morphology. The second-generation high-throughput sequencing technology and time-of-flight mass spectrometry technology， independently developed by BGI， were used to screen for HPV-DNA typing. At the same time， biopsy sampling was carried out， and the final pathological diagnosis was made. TCT detection and combined HPV-DNA detection were performed on 80 patients to compare the relationship between TCT alone and TCT/HPV-DNA combined test for the diagnosis and prognosis of CIN Ⅱ and CIN Ⅲ. Follow-up was conducted， and the HPV infection and TCT were re-tested. ResultsAmong the 80 cases of cervical intraepithelial neoplasia， 41 cases （51.25%） were between 35 and 44 years old， higher than the other age groups （P<0.001）. Compared with either TCT or HPV-DNA， TCT combined with HPV-DNA had obvious advantages in sensitivity， specificity， positive predictive value， and negative predictive value （P<0.05）. The recurrence rate in CIN Ⅱ and CIN Ⅲ groups was 9.52% and 16.67% respectively after 18 months of the follow-up. ConclusionTCT detection plays a positive role in cervical pre-cancer screening. By combining high-risk HPV-DNA typing and TCT detection， the detection values of sensitivity and specificity are significantly higher， which can improve the accuracy of cervical lesion screening and is of great significance for the follow-up work.

Effect of Wenyang Jieyu Decoction on Hippocampal Neuroplasticity in Depressed Rats Induced by Corticosterone / 中国实验方剂学杂志

ObjectiveTo observe the effect of Wenyang Jieyu decoction （WYJY） on the hippocampal structure of depressed rats with kidney-yang deficiency. MethodThe 105 SD rats were randomly divided into normal group， model group， fluoxetine group （4.17 mg·kg-1）， Xiaoyaosan group （1.88 g·kg-1）， and low-， medium- and high-dose （1.25，2.50，5.00 g·kg-1） WYJY groups，15 in each group. The depression model was induced by subcutaneous injection of corticosterone in rats except for those in the normal group and the rats were orally administered once a day for 28 days. The depression-like behaviors of rats were observed by sucrose preference test， novelty-suppressed feeding test， forced swimming test， and open field test. The morphology of hippocampal neurons was observed by hematoxylin-eosin（HE） staining， and the density of hippocampal neurons was detected by Nissl staining. The ultrastructure of hippocampal synapses was observed by transmission electron microscopy （TEM）. The expression of synaptophysin （SYP）， postsynaptic density-95 （PSD95）， and apoptosis-related protein Caspase-3 in hippocampal neurons was observed by immunohistochemistry， and bromodeoxyuridine （BrdU） and doublecortin （DCX） were used to observe the apoptosis and regeneration of hippocampal neurons. ResultWYJY could improve weight loss in depressed rats. As revealed by the behavioral tests， the model group showed depression-like behaviors， which were relieved in the WYJY groups and the positive drug groups. HE staining showed that the nuclei of hippocampal neurons in the model group were constricted， deeply stained， and sparsely arranged， while the neurons in the WYJY groups and the positive drug groups were significantly improved. Nissl staining demonstrated that the cell density of the model group was lower than that of the normal group （P<0.05）. Compared with model group， the groups with drug intervention showed increased cell density （P<0.05） and compact arrangement. According to the results in TEM， compared with normal group， the model group showed shortened synaptic active zone （P<0.05）， widened synaptic cleft （P<0.05）， and thinned tight zone （P<0.05）. Compared with model group， the groups with drug intervention showed shortened synaptic active zone （P<0.05）， narrowed synaptic cleft （P<0.05）， and thickened tight zone （P<0.05）. As displayed by the results of immunocytochemistry and immunofluorescence， compared with the normal group， the model group showed decreased protein expression of SYP， PSD95， BrdU， and DCX in the hippocampus （P<0.05） and increased protein expression of Caspase-3 （P<0.05）. Compared with the model group， the groups with drug intervention showed increased protein expression of SYP， PSD95， BrdU， and DCX in the hippocampus （P<0.05） and decreased protein expression of Caspase-3 （P<0.05）. ConclusionWYJY can promote the regeneration of hippocampal neurons in rats and improve the depression of rats.

Establishment of HPLC Fingerprint of Wine-processed Schisandra chinensis and Analysis of Chemical Pattern Recognition / 中国药房

OBJECTIVE：To establish the fingerprint of wine-processed Schisandra chinensis ，and to conduct cluster analysis and principal component analysis. METHODS ：HPLC method was adopted. The determination was performed on Diamonsil C 18（2） column with mobile phased consisted of methanol-water （gradient elution ）at the flow rate of 1 mL/min. The detection wavelength was set at 250 nm，and the column temperature was 30 ℃；the injection volume was 10 μL. With schisandrol A as the reference peak，HPLC fingerprints of 15 batches of samples were drawn and their similarity were evaluated with Similarity Evaluation System of TCM Chromatographic Fingerprint （2012 edition）. The common peaks were determined. Cluster analysis and principal component analysis were performed by using SPSS 22.0 statistical software. RESULTS ：There were 20 common peaks in 15 batches of samples ，and the similarities were 0.983-0.999；a total of 8 common peaks were identified ，namely 5-hydroxymethyl furfural，schisandrol A ，schisandrol B ，schisantherin A ，schisantherin B ，deoxyschizandrin，γ-schizandrin，pseudo-γ-schizandrin. The results of cluster analysis showed that 15 batches of wine-processed S. chinensis could be clustered into 4 categories. Among them，S1-S4 and S 14 were clustered into one category ，S9-S11 were clustered into one category ，S5，S7-S8，S12-S13 were clustered into one category ，and S 6 and S 15 were clustered into one category. The results of principal component analysis showed that the cumulative variance contribution rate of first four principal component s was 85.381％；the classification results were basically consistent with the results of cluster analysis. Compared with S. chinensis ，5-hydroxymethyl furfural was newly found in S. chinensis after wine-processing ，with high content ；but there was no significant difference in the other chromatographic peaks. CONCLUSIONS：The established HPLC fingerprint is simple and easy to operate ，combined with cluster analysis and principal component analysis ，can be used for quality control of wine-processed S. chinensis decoction pieces.

Comparative Study of the Genetic Diversity, Antimicrobial Resistance, and Pathogenicity of / 生物医学与环境科学（英文）

Objective@#This study was performed to compare the genetic diversity, virulence, and antimicrobial resistance of @*Methods@#A total of 38 clinical strains and 19 strains from healthy individuals were isolated from the samples collected in Ma'anshan City, Anhui Province. Their taxonomy was investigated using concatenated @*Results@#The 57 @*Conclusions@#The taxonomy, virulence properties, and antibiotic resistance of

MicroRNA-135a in ABCA1-labeled Exosome is a Serum Biomarker Candidate for Alzheimer's Disease / 生物医学与环境科学（英文）

Objective@#In the present study, the ABCA1 was used as a label to capture specific exosomes, the level of ABCA1-labeled exosomal microRNA-135a (miR-135a) was evaluated for the diagnosis of Alzheimer's disease (AD), especially in patients with early stages of AD.@*Methods@#This is a preliminary research focused on the levels of ABCA1 in WBCs, RBCs, HT-22 cells, and neuron cells. The diagnostic value of ABCA1-labeled exosomal miR-135a was examined using the CSF and serum of APP/PS1 double transgenic mice, and 152 patients with SCD, 131 patients with MCI, 198 patients with DAT, and 30 control subjects.@*Results@#The level of ABCA1 exosomes harvested from HT-22 cells and neuron culture medium was significantly higher compared to that of RBCs and WBCs ( @*Conclusion@#This study outlines a method to capture specific exosomes and detect them using immunological methods, which is more efficient for early diagnosis of AD.

Genetic Diversity, Antimicrobial Resistance, and Virulence Genes of Isolates from Clinical Patients, Tap Water Systems, and Food / 生物医学与环境科学（英文）

Objective@#This study aimed to evaluate the genetic diversity, virulence, and antimicrobial resistance of isolates from clinical patients, tap water systems, and food.@*Methods@#Ninety isolates were obtained from Ma'anshan, Anhui province, China, and subjected to multi-locus sequence typing (MLST) with six housekeeping genes. Their taxonomy was investigated using concatenated sequences, while their resistance to 12 antibiotics was evaluated. Ten putative virulence factors and several resistance genes were identified by PCR and sequencing.@*Results@#The 90 isolates were divided into 84 sequence types, 80 of which were novel, indicating high genetic diversity. The isolates were classified into eight different species. PCR assays identified virulence genes in the isolates, with the enterotoxin and hemolysin genes , , , and found in 47 (52.2%), 13 (14.4%), 22 (24.4%), and 12 (13.3%) of the isolates, respectively. The majority of the isolates (≥ 90%) were susceptible to aztreonam, imipenem, cefepime, chloramphenicol, gentamicin, tetracycline, and ciprofloxacin. However, several resistance genes were detected in the isolates, as well as a new variant.@*Conclusions@#Sequence type, virulence properties, and antibiotic resistance vary in isolates from clinical patients, tap water systems, and food.

Study on the Effect and Its Mechanism of Pseudostrychnine on Human Colon Cancer HT- 29 Cells / 中国药房

OBJECTIVE：To investigate the effects and its mechanism of pseudostrychnine on the apoptosis of human colon can - cer HT- 29 cells. METHODS ：Human colon cancer HT- 29 cells were randomly divided into blank group ，pseudostrychnine low-dose，medium-dose and high-dose groups （125，250，500 μmol/L）. They were cultured with culture medium without medicine or relevant concentration of pseudostrychnine for 48 h. The cell apoptosis and mitochondrial transmembrane potential were detected by flow cytometry. Western blotting assay was employed to detect the protein expression of P 53，Caspase-3，Caspase-9，DNA re - pair enzyme from rabbit （c-PARP）and Bcl- 2. RESULTS ：Compared with blank group ，apoptotic rate of cells was increased signifi - cantly in pseudostrychnine low-dose ，medium-dose and high-dose groups ，while mitochondrial transmembrane potential was de - creased significantly （P＜0.01），in concentration-dependent manner. The protein expression levels of P 53，Caspase-3，Caspase-9 and c-PARP were increased in pseudostrychnine medium-dose and high-dose groups ，compared with blank group ；while those of Bcl-2 were decreased significantly in pseudostrychnine low-dose ，medium-dose and high-dose groups （P＜0.05 or P＜0.01）. CON - CLUSIONS：Pseudostrychnine may change mitochondrial membrane potential by up-regulating the protein expression of P 53 and down-regulating the protein expression of Bcl- 2，and activate the expression of Caspase- 3，c-PARP and Caspase- 9，so as to acti - vate endogenous mitochondrial pathway and promote the apoptosis of HT- 29 cells.

Effects of Wenyang Jieyu Granules on the Behavior and Serum Level of Monoamine Neurotransmitter in Depression Model Rats / 中国药房

OBJECTIVE： To study the anti-depressive effects of Wenyang jieyu granules and its possible mechanism. METHODS： A total of 60 rats with similar behavior and body weight were randomly divided into blank control group （distilled water）， model group （distilled water）， fluoxetine positive control group （2.10 mg/kg） and Wenyang jieyu granules low-dose， medium-dose and high-dose groups （1.89， 3.78， 7.56 g/kg）， with 10 rats in each group. They were given relevant medicine intragastrically， once a day， for consecutive 28 d. Except for blank control group， other groups were given chronic unpredictable mild stress combined with feeding alone to establish depression model. On the 0， 7th， 14th， 21st and 28th day of administration， the changes of body weight were measured. The sucrose reference test and open-field test were adopted to determined the rate of sucrose reference， total distance and four corner distance within 4 min. 1 h after last administration， forced swimming test was used to measure struggling time and floating time within 4 min. The contents of 5-hydroxytryptamine （5-HT） and dopamine （DA） in serum were determined by HPLC. RESULTS： Compared with blank control group， body weight （7th， 14th， 21st and 28th day of administration） and the rate of sucrose reference （14th， 21st and 28th day of administration） were decreased significantly （P＜0.05 or P＜0.01）； total distance and four corner distance within 4 min （21st and 28th day of administration） were decreased significantly； struggling time within 4 min was shortened significantly and floating time within 4 min was prolonged significantly （P＜0.01）； serum contents of 5-HT and DA were decreased significantly （P＜0.01）. Compared with model group， body weight （28th day of administration in low-dose group， 21st and 28th day of administration in medium-dose group and high-dose group） and the rate of sucrose reference （28th day of administration） were increased significantly in Wenyang jieyu granules groups （P＜0.05 or P＜0.01）； total distance and four corner distance within 4 min （21st and 28th day of administration） were increased significantly （P＜0.01）； struggling time within 4 min was prolonged significantly and floating time within 4 min was shortened significantly （P＜0.01）. Serum contents of 5-HT and DA were increased significantly （P＜0.05 or P＜0.01）. Compared with fluoxetine positive control group， there was no statistical significance in above indexes among Wenyang jieyu granules groups （P＞0.05）. CONCLUSIONS： Wenyang jieyu granule has obvious anti-depression effect on depression model rats， which is similar to fluoxetine， and its mechanism may be related to the down-regulation of serum contents of 5-HT and DA.

Metabolic profiling analysis associated with acquired erlotinib resistance of lung adenocarcinoma cells based on liquid chromatography–high resolution mass spectrometry / 上海交通大学学报（医学版）

Objective · To explore the change of metabolomic profiling after erlotinib (anepithelial growth factor receptor tyrosine kinase inhibitor)resistance of lung adenocarcinoma cells (PC9-ER), and find the differential metabolome associated witherlotinib resistance. Methods · Metabolic profiling of PC9-ER cells and homologous parent PC9 cells was acquired by the ultraperformance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The data were analyzed by multi-dimensional statistical methods, such as partial least squares projection to latent structures-discriminant analysis (PLS-DA), to select and identify differential metabolites associated with erlotinib resistance. Results · A total of 14 differential metabolites were identified in PC9-ER cells. Seven up-regulated metabolites included N-acetylspermidine, phosphatidylethanolamine, AMP, pantothenic acid,proline, glutamate, and histidine, while seven down-regulated metabolites included citrulline, phosphorylcholine, glutathione, cysteinylglycine, glutathione oxidized, NAD, and S-adenosylmethionine, mainly participating in glutathione metabolism, glutamate metabolism, ammonia recycling, and protein biosynthesis. Conclusion · Metabolic profiling of erlotinib-resistant lung adenocarcinoma cells was changed. The information of differential metabolites associated with erlotinib resistance could provide clues for new resistance mechanisms and potential metabolism-related drug targets.

Effect ofFeng-Shi-NingCapsule on Balance of Peripheral Blood Th17/Treg Cells and Local Inflammatory Media of Rats with Rheumatoid Arthritis / 世界科学技术-中医药现代化

This study was aimed to observe the effects ofFeng-Shi-Ning (FSN) capsule on the balance of IL-17+CD4+T (Th17) / Foxp3+CD4+CD25+regulatory T (Treg) cells in peripheral blood and the inflammatory media in synovial fluid of rats with rheumatoid arthritis (RA), in order to further study the mechanism of FSN capsule in RA treatment. The collagen-induced arthritisⅡ (CIA) was used in the RA rat model establishment. The balance of Th17 and Treg cells in peripheral blood was analyzed by the flow cytometry method for effects of FSN capsule treatment. The levels of TNF-α, IL-6, IL-17A, IL-4 and IL-10 in synovial fluid were measured by cytometric bead array (CBA) method. The effects of the normal rats, CIA model rats and the rats treated by tripterygium wilfordii polyglycoside tablet (TPT) were compared. The results showed that compared with the model group, the percentage of Th17 cells in both the FSN capsule group and high-dose CIA group were obviously decreased (P 0.05). There was no significant difference on Th17 and Treg cells among each treatment group and TPT group (P > 0.05). Compared with the model group, the high-dose and middle dose FSN can obviously reduce the levels of TNF-α, IL-6 and IL-17A in synovial fluid of rats in each FSN group (P 0.05). Compared with the TPT group, there were no significant differences on IL-6, TNF-α, IL-17A, IL-4 and IL-10 in each treatment group (P > 0.05). It was concluded that FSN can obviously reduce the percentage of Th17, decrease the secretion of IL-6, TNF-α and IL-17A in synovial fluid. However, it had no obvious effects on the percentage of Treg cells, or the secretion of IL-4 and IL-10 in synovial fluid. The mechanism of FSN capsule in RA treatment may be through regulating Th17 cells, adjusting body immune imbalance, and inhibiting the excessive secretion of inflammatory media in synovial fluid.

Effects of modified Ganmai Dazao decoction on neuroendocrine system in patients with climacteric depression / 中国中药杂志

Clinical study of modified Ganmai Dazao decoction in the treatment of yang deficiency climacteric depression and observe the effects of modified Ganmai Dazao decoction on neuroendocrine system in patients with yang deficiency climacteric depression. 86 cases were randomly divided into treatment group treated with modified Ganmai Dazao decoction and control group treated with Deanxit. The curative effect was evaluated with Hamilton's depressive scale (HAMD) and pittsburgh sleep quality scale (PSQI) before and at the end of the two and four weeks of the treatment, the serum levels of serotonin (5-HT), norepinephrine (NE), estradiol (E2), follicle stimulating hormone (FSH), luteotropic hormone (LH) were detected before and after the four weeks of the treatment The results showed that the total effective power of treatment group was 88.4% and the total effective power of control group was 81.4% after four weeks interference, with insignificant difference between the two groups. After two and four weeks of the treatment, the score of HAMD decreased remarkably in both groups (P < 0.01), with insignificant difference between the two groups in same phase. After two and four weeks of the treatment, the total score of PSQI decreased remarkably in both groups (P < 0.05), with significant difference between the two groups after four weeks (P < 0.01). After four weeks of treatment, the serum levels of 5-HT and NE increased (P < 0.01), with insignificant difference between the groups. After four weeks of treatment, the serum levels of E2 increased obviously (P < 0.05), the levels of FSH decreased obviously (P < 0.05), the levels of LH decreased insignificant, with insignificant difference between two groups. This study indicates that modified Ganmai Dazao decoction has obvious therapeutic effects in the treatment of climacteric depression, and showed equivalent efficacy with Deanxit, and modified Ganmai Dazao decoction has better effect on improving the sleep quality in patients than Deanxit, the effect of improved clinical symptoms may be through adjusted levels of 5-HT, NE, E2, FSH and LH of climacteric depression.