Mechanism of Liuwei Dihuang Pills in treatment of mice with diminished ovarian reserve based on proteomics / 中国中药杂志

This study aims to investigate the efficacy and possible mechanism of Liuwei Dihuang Pills in the treatment of diminished ovarian reserve(DOR) by using proteomic techniques. Firstly, cyclophosphamide(60 mg·kg~(-1)) combined with busulfan(6 mg·kg~(-1)) was injected intraperitoneally to establish the mouse model of DOR. After drug injection, the mice were continuously observed and the success of modeling was evaluated by the disturbance of the estrous cycle. After successful modeling, the mice were administrated with the suspension of Liuwei Dihuang Pills by gavage for 28 days. At the end of the gavage, four female mice were selected and caged together with males at a ratio of 2∶1 for the determination of the pregnancy rate. Blood and ovary samples were collected from the remaining mice on the next day after the end of gavage. Hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM) were then employed to observe the morphological and ultrastructural changes in the ovaries. The serum levels of hormones and oxidation indicators were measured by enzyme-linked immunosorbent assay. Quantitative proteomics techniques were used to compare the ovarian protein expression before and after modeling and before and after the intervention with Liuwei Dihuang Pills. The results showed that Liuwei Dihuang Pills regulated the estrous cycle of DOR mice, elevated the serum levels of hormones and anti-oxidation indicators, promoted follicle development, protected the mitochondrial morphology of ovarian granulosa cells, and increased the litter size and survival of DOR mice. Furthermore, Liuwei Dihuang Pills negatively regulated the expression of 12 differentially expressed proteins associated with DOR, which were mainly involved in lipid catabolism, inflammatory response, immune regulation, and coenzyme biosynthesis. These differentially expressed proteins were significantly enriched in sphingolipid metabolism, arachidonic acid metabolism, ribosomes, ferroptosis, and cGMP-PKG signaling pathway. In summary, the occurrence of DOR and the treatment of DOR with Liuwei Dihuang Pills are associated with multiple biological pathways, mainly including oxidative stress response, inflammatory response, and immune regulation. "Mitochondria-oxidative stress-apoptosis" is the key to the treatment of DOR by Liuwei Dihuang Pills. YY1 and CYP4F3 may be the key upstream targets that trigger mitochondrial dysfunction and ROS accumulation, and the metabolism of arachidonic acid is the main signaling pathway of drug action.

Efficacy and Safety of Linezolid Combined with Routine Anti-tuberculosis Drugs for Tuberculous Meningitis ： A Meta-analysis / 中国药房

OBJECTIVE：To systematically evaluate the efficacy and safety of linezolid （LZD）combined with routine anti- tuberculosis drugs in the treatment of tuberculous meningitis （TBM），so as to provide evidence-based reference for clinical medi- cation. METHODS ：Retireved from PubMed ，Cochrane Library ，Embase，CNKI and Wanfang database ，randomized controlled trials（RCT）of LZD combined with routine anti-tuberculosis drugs （trial group ）versus routine anti-tuberculosis drugs （control group）were collected from the inception to Jan. 2020. After literature screening and data extraction ， the quality of the included literature were evaluated with bias risk assessment tool recommended by Cochrane system evaluator handbook 5.2. Meta-analysis was conducted by using Rev Man 5.3 software，and sensitivity analysis and publication bias analysis were performed. RESULTS ： Totally 9 RCTs involving 602 patients were included. Meta-analysis showed that total response rate [OR ＝4.05，95％CI（2.26，7.26）， P＜0.000 01]， changes of protein content of cerebrospinal fluid [MD ＝0.48，95％CI（0.20，0.77），P＝0.000 8]，changes of white blood cells count of cerebrospinal fluid [MD ＝44.43，95％CI（20.06，68.81），P＝0.000 4]，changes of cerebrospinal fluid glucose/ synchronous blood glucose [MD ＝0.09，95％CI（0.05，0.14），P＜0.000 1] of trial group were significantly higher than those of control group. There was no statistical significance in the changes of chloride content of cerebrospinal fluid [MD ＝8.08，95％CI（－0.64， 16.80），P＝0.07] and the incidence of ADR [OR ＝1.34，95％CI（0.57，3.11），P＝0.50] between 2 groups. The results of sensitivity analysis showed that there were significant differences comparison with before exclusion when the change of protein content in cerebrospinal fluid and the change of glucose/synchronous blood glucose in cerebrospinal fluid were taken as indexes ，and there was no significant difference comparison with before exclusion when the changes of white blood cell count and chloride content in cerebrospinal fluid were taken as indexes. The results of publication bias analysis showed that there was a certain publication bias in this study. CONCLUSIONS ：LZD combined with conventional anti-tuber culosis drugs is effective and safe for TBM. Because the inconsistent results of sensitivity analysis and publication bias exists in publication bias analysis ，the conclusions need to be further confirmed by more large sample and multi-center studies.

Polymorphism and Forensic Application of 11 Y-SNP in Guizhou Shui Ethnic Group / 法医学杂志

Objective To investigate the frequency distribution features of 11 Y-SNP of Guizhou Shui ethnic group, explore its genetic relationship with other ethnic groups and evaluate its forensic application value. Methods Multiplex amplification of the 11 Y-SNP of samples of 180 unrelated male individuals from Guizhou Shui ethnic group was performed with microsequencing technique. The frequency of haplogroup was calculated by direct counting method, and principal component analysis （PCA） of Guizhou Shui ethnic group and reference ethnic groups was performed by using Multi-variate statistical package （MVSP）. The Fst genetic distance between Guizhou Shui ethnic group and other ethnic groups was calculated with Arlequin v3.5. The phylogenetic tree was established with MEGA 4.0 software according to the Fst value. Results Six types of Y chromosome haplogroups were observed in total. Among which, the distribution frequency of O-M175 haplogroup was the highest （71.11%）, followed by C-M130 （25.00%）, and D-M174 （3.89%）. O1b-M268 （31.11%） and O2a2-IMS-JST021354 （28.33%） had a relatively high distribution frequency in O haplogroup. The paternal relationship between Guizhou Shui ethnic group and Guizhou Gelao ethnic group in the same language group was the closest. Conclusion The distribution of Y-SNP haplogroup of the Shui ethnic group in Guizhou has certain specificity, which can provide basic data for forensic biogeographic inference.

Research progress of Cre/LoxP system in the eyes of animal model / 中华实验眼科杂志

Cre/LoxP system has been widely used as new type of gene targeting, which can transform genes in specific tissues and organs, remove specific gene fragments, and help to study the effects of specific genes on growth and development.Cre/LoxP system is the core technology of conditional gene targeting, which induces gene targeting, and spatiotemporal specific gene targeting.The resource about the mechanism of the Cre/LoxP system is helpful to obtain the Cre transgenic mouse model on different cell types of the retina.The Cre transgenic mice with specific expression in retinal bipolar cells and ganglion cells can provide the experimental basis for the absence of specific tissue single genes during growth and development.This review focused on the Cre/LoxP system and specific Cre recombinase mouse model in eyes.

Expressions of Sry-related High Mobility Group Box 9 and Gastrokine-1 in Gastric Cancer and Their Relationships with Prognosis / 中国医学科学院学报

Objective To explore the expressions of Sry-related high mobility group box 9(SOX9)and gastrokine-1(GKN1) in gastric cancer tissues and their relationships with clinicopathologic features and prognosis of patients.Methods Immunohistochemistry was used to detect the expressions of SOX9 and GKN1 in 70 cases of gastric cancer tissues and corresponding paracancerous tissues including 27 cases of intestinal metaplasia and 43 cases of normal gastric mucosa. The relationships of SOX9 and GKN1 expressions with clinicopathological features and prognosis were analyzed in gastric cancer tissues.Results The high expression rates of SOX9 in gastric cancer tissues,intestinal metaplasia,and normal gastric mucosa were 92.9%(65/70),77.8%(21/27),and 55.8%(24/43),respectively(=21.722,<0.001). Positive nuclear and cytoplasmic staining was observed. The high nuclear expression rate of SOX9 in gastric cancer tissues was 67.1%,which was significantly higher than those of intestinal metaplasia(37.0%,=0.007)and normal gastric mucosa(23.3%,<0.001). The high cytoplasmic expression rate of GKN1 in normal gastric mucosa was 76.7%,which was significantly higher than those of intestinal metaplasia(44.4%,=0.006)and gastric cancer tissues(37.1%,<0.001). Univariate analysis demonstrated that the nuclear expression of SOX9 in gastric cancer was associated with the degree of tissue differentiation(=0.007),while the cytoplasmic expression of GKN1 was associated with both the degree of tissue differentiation(=0.002)and whether the pathological type was a signet-ring cell carcinoma(=0.009). Furthermore,the nuclear expression of SOX9 was negatively correlated with the expression of GKN1 in gastric cancer(=15.424,<0.001). The 5-year survival rates of patients with high or low nuclear expression of SOX9 were 33.8% and 67.5%,respectively(=0.016).The 5-year survival rates of patients with high or low expression of GKN1 were 60.0% and 35.6%,respectively(=0.044). Further research indicated that 5-year survival rate of patients with high nuclear expression of SOX9 and low expression of GKN1 was 28.8%. Cox multivariate regression analysis showed that TNM stage(stage Ⅱ:=7.435,95%:1.313-42.096,=0.023;stage Ⅲ:=12.214,95%:2.677-55.721,=0.001)and nuclear expression level of SOX9(=3.297,95%:1.199-9.065,=0.021)were independent risk factors for the prognosis of gastric cancer patients.Conclusions Changes in the expressions of SOX9 and GKN1 may be associated with the malignant biological behavior of gastric cancer. SOX9 may be a potential prognostic factor. The combined detection of SOX9 and GKN1 expression and the further study of their molecular mechanism may provide new clues for early diagnosis,targeted therapy,and prognostic prediction of gastric cancer.

Whole-process Management and Application of Digital Medical Records / 医学信息学杂志

The paper conducts whole-process management of digital medical records after visualized traditional paper medical records are stored in the database,and introduces the framework,application and its realization of the digital medical record information system which is able to change the management mode of traditional medical records,optimize the working process,achieve the integration of medical records information resources,and improve comprehensively the medical records management level.

Applied value of susceptibility-weighted imaging in acute ischemic stroke / 医疗卫生装备

Objective To evaluate the applied values of susceptibility weighted imaging (SWI) in acute ischemic stroke.Methods Totally 40 patients with acute ischemic stroke were included within 72 hours after symptom onset.They adopted multimodal magnetic resonance imaging examination,including regular magnetic resonance imaging sequence (T1WI,T2WI),time of flight MR angiography (TOF-MRA),diffusion weighted imaging (DWI) and susceptibility weighted imaging (SWI).Furthermore,12 of the 40 patients received dynamic susceptibility contrast enhanced perfusion weighted imaging (DSCPWI) examination.Results Of the 40 patients,12 ones had positive results for multiple lesions of cerebral microbleeds (CMBs) by SWI,and the detection rate was 30％.There were 24 patients showed susceptibility vessel sign (SVS) in SWI,and the susceptibility rate was 60％.In the 12 patients received DSC-PWI examination simultaneously,there were 7 cases had the anomaly range by SWI larger than that by DWI while similar to that by DSC-PWI.Conclusion SWI can show SVS and CMBs clearly,estimate ischemic penumbra,know intracranial conditions completely and supply reliable basis for individualized treatment.

Effect of osthole on apoptosis of human cervical carcinoma Hela cells / 重庆医学

Objective To investigate the effect and the possible mechanism of osthole on proliferation and apopotosis of human cervical carcinoma Hela cells and its passible mechanism.Methods After cervical carcinoma Hela cells were incubated with different concentrations osthole,the cell proliferation activity was examined by MTT assay.The apoptosis rate and cellular ROS level were measured by flow cytometry.The Bcl-2 and Bax mRNA expression was determined by semi-quantitative RT-PCR.Results In comparison with the control group,osthole with different concentrations could obviously inhibit the Hela cells proliferation and accelerated the cellular apoptosis,lowered the expression rate of Bcl-2/Bax,raise the cellular ROS level in a osthole dose-dependent manner.Conclusion Osthole may inhibit Hela cell proliferation and accelerates the cells apoptosis,which might be associated with the increasing the cellular ROS level,promoting Bax expression and inhibiting Bcl-2 expression.

Brain gray matter changes in essential arm tremor patients:Voxel-based morphometry / 西安交通大学学报(医学版)

Objective To investigate the abnormalities of brain gray matter volume in patients with clinically-confirmed essential tremor (ET)of the hands only.Methods We analyzed brain gray matter voxel of 1 7 patients (younger than 55 years)with ET of the hands only and 1 7 healthy controls matched in age,gender and education by optimized voxel-based morphometry (VBM).Results VBM showed marked expansion of the bilateral cerebella, occipital fusiform cortices,and precentral lobes (P uncorrected < 0.005 )in ET patients compared with the controls. Atrophy was only detected in left parietal lobe.We also found volume enlargement in the thalamus,midbrain,and melluda of the left side by region of interest (ROI )analysis (P uncorrected <0.005).Conclusion Patients with arm tremor show expansion of gray matter,which might represent the adaptive reorganizational compensation through the increased demand on the visuospatial control of skilled movements in ET patients with early-stage arm tremor. These morphological changes may help to assess early stage and distinguish subtype of ET.

Mechanisms and Effect of Ginkgolide B on the Differentiation of Neuron Stem Cells / 中国康复理论与实践

@#Objective To observe the effect of Ginkgolide B of various consistency on the differentiation of neuron stem cells (NSCs).MethodsNSCs were cultured in differentiation medium containing Ginkgolide B of various consistency for 3 and 7 days, the neurites length and cell body area were measured by inverted phase-contrast micrograph, then neurofilament-200 (NF-200), glial fibrillary acidic protein (GFAP), adenomatus polyposis coli (CC-1) expression were detected and counted by fluorescence microscope. The suppressor of cytokine signaling-2 (SOCS2), inhibitor of DNA binding-2 (Id2) were alsoimmunostained. The percentage of positive cells were counted respectively.ResultsThe neurites length and cell body area in Ginkgolide B groups were obviously larger than that in the control group. The percentage of NF, GFAP positive cells in Ginkgolide B groups increased with dosage increasing of Ginkgolide B. Compared with the normal control group, the percentage of SOCS2 positive cells increased significantly ( P<0.01) and the percentage of Id2 positive cells decreased significantly ( P<0.01) in Ginkgolide B groups.ConclusionGinkgolide B can promote NSCs to differentiate into neuron and astrocyte, the percentage of astrocyte is increased with a dosage-dependent relationship with Ginkgolide B.

Expression of BAT2L protein in developmental brain of rats / 第三军医大学学报

Objective To detect the expression of BAT2L protein in developmental brain of rats.Methods Expression,distribution and location of BAT2L protein in developmental brain rats on embryonic day 18,postnatal days 1,7 and 15 and in adult at different time points were detected by Western blotting analysis,immunohistochemistry and immunofluorescence,respectively.Results Western blotting showed that the BAT2L protein expression level was higher in brain of rats on embryonic day 18,postnatal days 1 and 7 than on postnatal day 15 and in brain of adult rats.Immunohistochemistry and immunofluorescence showed that the BAT2L protein was distributed and located in cell membrane and cytoplasm of neurons but not in nuclei and extra-cellular space.Positive neurons were widely distributed in cerebral and cerebellar cortex,hippocampus and cerebral ganglion.The morphology of neurons was significantly different in newborn and adult rats.Positive prominences and branches of certain neurons were found in brain tissues of newborn rats but hardly in those of adult rats.Conclusion BAT2L protein is specifically expressed in cell body,membrane and prominence of neurons in brain of rats.

Cloning and high level expression of gene encoding human sCR1 binding domain in E.coli / 第三军医大学学报

Objective To clone and express the gene encoding the binding domain of human soluble complement receptor type 1 (sCR1). Methods sCR1-SCR15-18 cDNA was amplified using RT-PCR from human monocytes of peripheral blood and sequenced using vector pMD-18T. Recombinant pET32-sCR1-SCR15-18 was constructed using prokaryotic expression vector pET32 and transformed into bacterium BL21. IPTG was used to induce gene expression and the obtained expression product was identified by immunoblotting. Results The gene segment that specifically encodes sCR1 was synthesized, the sequence of which was consistent with that of sCR1-SCR15-18 cDNA as registered at GenBank. A prokaryotic expression recombinant pET32-sCR1-SCR15-18 was constructed. The amount of target protein accounted for 40% of the total bacterial proteins and inclusion bodies were present in the bacteria. Immunoblotting showed a single positive band at the site of 43?10~(3). Conclusion The gene encoding sCR1-SCR15-18 was cloned from human monocytes and efficiently expressed in E.coli.