ObjectiveTo explore the hub genes of acute-on-chronic liver failure （ACLF） using bioinformatics methods， predict the potential traditional Chinese medicines （TCMs） against ACLF， and verify the treatment mechanism based on experiments. MethodPerl and R were used to analyze the GSE142255 dataset to obtain the differentially expressed genes （DEGs）， from which the hub genes in the protein-protein interaction of DEGs were identified by five algorithms of the CytoHubba plug-in. The receiver operating characteristic （ROC） curve and GSE168048 dataset were then used to verify the hub genes. Coremine Medical was employed to map the TCMs corresponding to the hub genes and then the natures， tastes， and meridian tropism of the TCMs were analyzed. The TCM systems pharmacology database and analysis platform （TCMSP） and DEGs were used to obtain the common targets shared by high-frequency TCMs and ACLF， and Cytoscape was used to establish the "hub gene-high-frequency TCM-active ingredient-common target" network. Furthermore， gene ontology （GO） annotation， Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis， and in vitro experiments were performed. ResultA total of 388 DEGs were obtained， in which the 7 hub genes encoded CD4 integrin subunit alpha M （ITGAM）， CD2， lymphocyte-specific protein tyrosine kinase （LCK） proto-oncogene， C-C motif chemokine ligand 5 （CCL5）， matrix metallopeptidase-9 （MMP-9）， and Fc epsilon receptor IG （FCER1G）. The TCM candidates for treating ACLF were mainly cold， bitter， and had tropism to the liver meridian， among which the high-frequency TCMs （Hedyotis Diffusae Herba， Ganoderma， and Astragali Radix） and the active ingredients （quercetin， kaempferol， and beta-sitosterol） had significant therapeutic potential. The enrichment analysis results showed that TCMs acted on multiple targets and pathways such as autophagy， oxidative stress， and inflammatory cytokines in addition to regulating hub genes. L02 cell experiments showed that the quercetin group had lower levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and malondialdehyde （MDA）， lower protein levels of ubiquitin-binding protein p62 and MMP-9， and higher levels of superoxide dismutase （SOD）， glutathione （GSH）， and microtubule-associated protein 1 light chain 3 Ⅱ/Ⅰ （LC3 Ⅱ/Ⅰ） than the D-galactosamine （D-GaLN） group （P<0.05， P<0.01）. In addition， the pretreatment with 3-methyladenine （3-MA） inhibited the activating effect of quercetin on the autophagy of L02 cells. ConclusionThe potential TCMs and active ingredients predicted based on the hub genes of ACLF have a great research value. Quercetin has the potential to treat ACLF by inhibiting the D-GaLN-induced oxidative stress and inflammatory response in L02 cells and regulating the expression of MMP-9， which may be associated with the activation of autophagy.

Objective To investigate the correlation between MEX3A and differentiation characteristics of gastric cancer and intestinal metaplasia,and its combination with caudal-related homeobox transcription factor 2(CDX2)and mucin 2(MUC2)and mucin 5AC(MUC5AC)to determine the role of carcinogenic intestinal metaplasia.Methods From January 2010 to December 2014,a total of 410 cases of gastric cancer and paracarcinoma paraffin-embedded tissue samples were selected from the Central Hospital Affiliated to Shenyang Medical College and the Second Hospital Affiliated to Shenyang Medical College.According to pathological diagnosis,they were divided into control group(mild superficial gastritis,79 cases),intestinal metaplasia group(149 cases)and gastric cancer group(182 cases).The expressions of MEX3A,CDX2,MUC2 and MUC5AC were detected by immunohistochemistry.Results MEX3A was highly expressed in gastric cancer group and intestinal metaplasia group,especially diffuse gastric cancer,poorly differentiated gastric cancer and type Ⅲ intestinal metaplasia(P<0.05).CDX2 and MUC2 were highly expressed in gastric cancer group and intestinal metaplasia group,especially intestinal type gastric cancer,highly and moderately differentiated gastric cancer,type Ⅰ and type Ⅱ intestinal metaplasia(P<0.05).The expression of MUC5AC was high in control group and low in gastric cancer group and intestinal metaplasia group,especially in intestinal type gastric cancer,type Ⅰ and type Ⅲ intestinal metaplasia(P<0.05).Gastric cancer and intestinal metaplasia differentiation were negatively correlated with MEX3A and MUC5AC expression,but positively correlated with CDX2 and MUC2 expression(P<0.05).MEX3A was negatively correlated with the expression of CDX2 and MUC2,and positively correlated with the expression of MUC5AC in gastric cancer(P<0.05).MEX3A was negatively correlated with the expression of CDX2 and MUC2 in intestinal metaplasia(P<0.05),while CDX2 was positively correlated with the expression of MUC2(P<0.05).Conclusion MEX3A is negatively correlated with gastric cancer and intestinal metaplasia differentiation.Gastric cancer is characterized by high MEX3A expression and low CDX2 and MUC2 expression.

Cognitive impairment caused by chronic cerebral hypoperfusion (CCH) is associated with white matter injury (WMI), possibly through the alteration of autophagy. Here, the autophagy-lysosomal pathway (ALP) dysfunction in white matter (WM) and its relationship with cognitive impairment were investigated in rats subjected to two vessel occlusion (2VO). The results showed that cognitive impairment occurred by the 28th day after 2VO. Injury and autophagy activation of mature oligodendrocytes and neuronal axons sequentially occurred in WM by the 3rd day. By the 14th day, abnormal accumulation of autophagy substrate, lysosomal dysfunction, and the activation of mechanistic target of rapamycin (MTOR) pathway were observed in WM, paralleled with mature oligodendrocyte death. This indicates autophagy activation was followed by ALP dysfunction caused by autophagy inhibition or lysosomal dysfunction. To target the ALP dysfunction, enhanced autophagy by systemic rapamycin treatment or overexpression of Beclin1 (BECN1) in oligodendrocytes reduced mature oligodendrocyte death, and subsequently alleviated the WMI and cognitive impairment after CCH. These results reveal that early autophagy activation was followed by ALP dysfunction in WM after 2VO, which was associated with the aggravation of WMI and cognitive impairment. This study highlights that alleviating ALP dysfunction by enhancing oligodendrocyte autophagy has benefits for cognitive recovery after CCH.

Recently, the incidence and mortality of cancer has raised. More and more cytotoxic drugs and molecular targeted medicines have been used in clinic. However, most drugs just display a short-term anti-tumor effect. If patients received treatment for a long time, it would arise resistance to chemotherapy frequently. One of its important reasons is the accumulation of drug induced cancer cells. Thus, this paper emphasizes on biological character of drug induced cells, including cell biological phenotype, the change of gene and protein, variation of metabolism, dynamic change of signal transduction pathway and so on. Meanwhile, according to the characteristics of drug induced cells, we propose some strategies to inhibit drug induced cells, which would provide the foundation of clinical therapy and novel anti-tumor drug research and development.

OBJECTIVE：To provide reference for optimizing resource allocation and precise investment of China ’s pharma- ceutical industry. METHODS ：The number of invention patent applications in China ’s pharmaceutical industry was searched from China Intellectual Property Netwerk ，and the status quo and structure of patent applications in China ’s pharmaceutical industry were analyzed. SPSS 23.0 software was used to analyze the input-output correlation of the number of invention patent applications with R&D investment and main business income of pharmaceutical enterprises in China. RESULTS ：The number of invention patent applications in China ’s pharmaceutical industry increased year by year. From 2000 to 2015，225 861 invention patents had been applied by domestic applicants and 43 149 invention patents had been applied by foreign applicants in China ；only 49.94％ domestic applicants applied for professional invention ，while 96.79％ of foreign applicants applied for professional invention. There was a positive correlation between the R&D expenditure of pharmaceutical enterprises and the number of invention patent applications，which indicated that the R&D investment of pharmaceutical industry in China was beneficial to the invention patent applications. The number of invention patent applications of pharmaceutical enterprises was also positively correlated with the main business income ，indicating that the increase of invention patent applications of pharmaceutical enterprises also effectively expanded the economic scale of pharmaceutical industry. CONCLUSIONS ：Compared with foreign countries ，the structure of patent applicants in domestic pharmaceutical industry needs to be adjusted urgently. Pharmaceutical enterprises have not yet become the main applicants. The continuous R&D investment of pharmaceutical enterprises effectively promotes the application of invention patent，expanded the economic scale of the pharmaceutical industry.

It is a difficult problem of forensic medicine to accurately estimate the post-mortem interval. Entomological approach has been regarded as an effective way to estimate the post-mortem interval. The developmental biology of carrion-breeding flies has an important position at the post-mortem interval estimation. Phorid flies are tiny and occur as the main or even the only insect evidence in relatively enclosed environments. This paper reviews the research progress of carrion-breeding phorid flies for estimating post-mortem interval in forensic medicine which includes their roles, species identification and age determination of immatures.
Animals ; Autopsy ; Diptera ; Entomology ; Environment ; Forensic Medicine ; Humans ; Postmortem Changes

AIMTo explore the cerebral cortex mechanism of visceral nociceptive sensation and its characteristics on the cell level, we investigated the membrane electrical properties of 176 stimulus-relative neurons of greater splanchnic nerve (GSN) in anterior cingulate gyrus (ACG) of 20 adult healthy cats.

METHODSWe used intracellular recording techniques of glass microelectrode and injected polarizing current into the neurons in ACG.

RESULTSAmong 176 neurons, 148 were visceral nociceptive neurons (VNNs) and 28 non-visceral nociceptive neurons (NVNNs). The membrane resistance (Rm), time constant (tau), membrane capacity (Cm), and the I-V curve of both VNNs and NVNNs in ACG were significantly different. The discharge frequency and amplitude of both VNNs and NVNNs produced by injecting depolarized current were different, too.

CONCLUSIONThe results suggest that structure of cell membrane, volume of the soma, and other aspects of morphology between VNNs and NVNNs in ACG may have significant differences. The results also might provide progressively experimental evidence for specific theory of pain sensation.

Animals ; Cats ; Gyrus Cinguli ; cytology ; physiology ; Membrane Potentials ; Nociceptors ; physiology ; Splanchnic Nerves ; physiology ; Visceral Afferents ; physiology

OBJECTIVETo introduce the establishment of food pharmacy research progress.

METHODTo overview research situations of food pharmacy development according to edible product.

RESULTFood pharmacy development in China has been set up preliminarily, and needs to be developed further.

CONCLUSIONThe trend of the functional food will be safe, effective and its quality will be control.

Food Analysis ; Food Technology ; Pharmacy

Objective: To identify the latent classes of cyberbullying in college students, and to analyze its relationship with depressive symptoms and suicidal ideation, so as to provide a theoretical reference for effectively intervention of cyberbullying. Methods: Cluster random sampling was used to select 1 094 college students from Liaoning Province and Jilin Province from April to May, 2021. The Cyberbullying Victims Behaviors Scale, the Center for Epidemiological Studies Depression Scale and BSI CV were used in this study and data was analyzed by using latent class analysis, one way analysis of variance and Logistic regression to analyze the data. Results: Cyberbullying of college students could be divided into three latent classes: low incidence group ( 72.40 %), general incidence group (20.20%) and high incidence group (7.40%). There were significant differences in depressive symptoms and suicidal ideation among different classes of cyberbullying ( P <0.01). Logistic regression analysis showed that after controlling for demographic variables, general incidence group and high incidence group significantly and positively predicted depressive symptoms ( β general incidence group =0.88, β high incidence group =2.44, P <0.01) and suicidal ideation ( β general incidence group =0.50, β high incidence group =1.20, P <0.01). Conclusion Families, schools and society should conduct different interventions for college students who suffer from different classes of cyberbullying to reduce depressive symptoms and suicidal ideation and promote mental health of college students.

Objective: To identify potential categories of problematic social networks use for college students and further analyze the association of different categories with online social anxiety and depressive symptoms, and to provide reference for formulating preventive measures to promote college students rational use of social networks. Methods: From May to June 2021, 1 082 college students from 3 universities in Shenyang, Liaoning Province were selected by convenient sampling. Students completed the Problematic Mobile Social Media Usage Assessment Questionnaire(PMSMUAQ), the Social Anxiety Scale for Social Media Users (SAS SMU) and Center for Epidemiologic Studies Depression Scale (CES D), the latent profile analysis (LPA) and R3STEP were used to analyze the data. Results: College students problematic social network use was divided into three potential categories: moderate use group (31.98%, 346), mild dependence group (49.26%, 533), and deep addiction group (18.76%, 203). Logistic regression analysis showed that urban students had a greater proportion in the deeply addicted group ( OR =1.62, P <0.05). The incidence ratios of the mildly dependent and deeply addicted groups gradually increased as daily time spent online increased ( OR =1.11，1.20， P < 0.01). There were significant differences in online social anxiety and depressive symptoms among college students with different problematic social network use types( χ 2=188.70, 62.60, P <0.01), and the deeply addicted group scored higher on online social anxiety and depressive symptoms. Conclusion There is heterogeneity in problematic social network use among college students. And to reduce the emergence of online social anxiety and depressive symptoms, college educators and parents should pay more attention to students with higher levels of problematic social network use.