Objective To report the diagnosis of a canine distemper virus outbreak among a colony of cynomolgus monkeys at an experimental monkey farm in 2019. MethodsA total of 46 samples were collected from 21 diseased cynomolgus monkeys (exhibiting symptoms such as facial rash, skin scurf, runny nose, and diarrhea) and from one deceased monkey at an experimental monkey breeding farm in South China in late 2019, including serum, skin rash swabs, and anticoagulated whole blood, liver, lung, and skin tissues were submitted for testing. All submitted samples were tested for canine distemper virus gene fragments using real-time quantitative PCR, while immunohistochemical staining was performed to detect canine distemper virus nucleoprotein in lung tissues. The skin tissue of the deceased monkey was ground and sieved. The filtrate was inoculated into a monolayer MDCK cell line for virus isolation. Then, whole-genome sequencing was performed to identify the isolated virus. The Clustal Omega tool was used to align and analyze the homology of different Asian canine distemper virus isolates. A phylogenetic tree was constructed, followed by genetic evolutionary analysis. ResultsClinical retrospective analysis revealed that the diseased cynomolgus monkeys exhibited symptoms similar to those observed in cynomolgus monkeys infected with measles virus. Necropsy findings showed red lesions in the lungs and significant hemorrhage in the colonic mucosa. Real-time quantitative PCR detected canine distemper virus nucleic acid in the serum, skin rash swabs of the infected monkeys, and various tissue samples of the deceased monkey, all of which tested positive. Calculation based on the standard curve formula indicated the viral load was highest in the skin tissue. Immunohistochemical staining of the deceased monkey's lung tissue demonstrated aggregation of CDV nucleoprotein in alveolar epithelial cells, bronchi, and bronchioles. A CDV strain was isolated from the skin tissue of the deceased monkey. Phylogenetic analysis indicated that this strain shares the closest relationship (98.86%) with the Asian-1 type canine distemper virus strain CDV/dog/HCM/33/140816, previously identified in dogs in Vietnam. ConclusionBased on comprehensive analysis of clinical symptoms, nucleic acid detection, viral protein immunohistochemistry, and whole-genome sequencing results, the diagnosis confirms that the cynomolgus monkeys in this facility are infected with canine distemper virus. It is recommended to include canine distemper virus as a routine surveillance target in captive monkey populations. Additionally, this study provides a foundation for further research on the molecular biological characteristics of canine distemper virus.

Objective To report the diagnosis of a canine distemper virus outbreak among a colony of cynomolgus monkeys at an experimental monkey farm in 2019. MethodsA total of 46 samples were collected from 21 diseased cynomolgus monkeys (exhibiting symptoms such as facial rash, skin scurf, runny nose, and diarrhea) and from one deceased monkey at an experimental monkey breeding farm in South China in late 2019, including serum, skin rash swabs, and anticoagulated whole blood, liver, lung, and skin tissues were submitted for testing. All submitted samples were tested for canine distemper virus gene fragments using real-time quantitative PCR, while immunohistochemical staining was performed to detect canine distemper virus nucleoprotein in lung tissues. The skin tissue of the deceased monkey was ground and sieved. The filtrate was inoculated into a monolayer MDCK cell line for virus isolation. Then, whole-genome sequencing was performed to identify the isolated virus. The Clustal Omega tool was used to align and analyze the homology of different Asian canine distemper virus isolates. A phylogenetic tree was constructed, followed by genetic evolutionary analysis. ResultsClinical retrospective analysis revealed that the diseased cynomolgus monkeys exhibited symptoms similar to those observed in cynomolgus monkeys infected with measles virus. Necropsy findings showed red lesions in the lungs and significant hemorrhage in the colonic mucosa. Real-time quantitative PCR detected canine distemper virus nucleic acid in the serum, skin rash swabs of the infected monkeys, and various tissue samples of the deceased monkey, all of which tested positive. Calculation based on the standard curve formula indicated the viral load was highest in the skin tissue. Immunohistochemical staining of the deceased monkey's lung tissue demonstrated aggregation of CDV nucleoprotein in alveolar epithelial cells, bronchi, and bronchioles. A CDV strain was isolated from the skin tissue of the deceased monkey. Phylogenetic analysis indicated that this strain shares the closest relationship (98.86%) with the Asian-1 type canine distemper virus strain CDV/dog/HCM/33/140816, previously identified in dogs in Vietnam. ConclusionBased on comprehensive analysis of clinical symptoms, nucleic acid detection, viral protein immunohistochemistry, and whole-genome sequencing results, the diagnosis confirms that the cynomolgus monkeys in this facility are infected with canine distemper virus. It is recommended to include canine distemper virus as a routine surveillance target in captive monkey populations. Additionally, this study provides a foundation for further research on the molecular biological characteristics of canine distemper virus.

In order to solve the problems in traditional health management experimental teaching, such as high cost, safety and difficult repeatability, a virtual simulation experimental teaching platform for health management combined with Traditional Chinese Medicine (TCM) characteristics has been constructed by using virtual simulation, multimedia, and human-computer interaction technologies, which comprises TCM constitution identification, TCM health management and health management service process. Through the combination of virtual simulation and reality situation, the platform has formed an online and offline model of experimental teaching, which has improved the innovation and practice ability of students and enhanced the teaching quality.

This study explores the potential antiepileptic mechanism of ursolic acid(UA)and its improvement of GABAergic interneuron damage induced by epilepsy based on transcriptome analysis.Hippocampal tissues from rats in the control group(NC group),epilepsy group(SE group),and epilepsy UA treatment group(UA group)were subjected to full-length transcriptome sequencing.The obtained sequencing data were analyzed,using gene ontology(GO),the Kyoto Encyclopedia of Genes and Genomes(KEGG),and protein-protein interaction(PPI)to perform the analysis of differential genes(DEGs).The expression levels of key differential genes were verified using RT-qPCR in hippocampal tissue.Finally,an epilepsy in vitro model was constructed on primary neurons,RT-qPCR was used to verify the expression levels of key differential genes,and the expression level of GABAA receptor γ2 subunit(GABRG2)on neurons was further examined using immunofluorescence and Western blot.The heatmap of pairwise sample expression correlation and the clustering analysis of differentially expressed genes showed that the SE group was farthest from the NC group,and that after UA treatment,the overall trend shifted towards the normal group.Compared with the SE group,a total of 220 differential genes were screened in the UA group,including 143 upregulated genes and 77 downregulated genes.GO enrichment analysis showed that it involved three processes in the primary classification:biological processes,cellular components,and molecular functions.KEGG pathway enrichment analysis showed that DEGs were involved in 36 biological pathways,including cAMP signaling pathway and calcium signaling pathway.PPI analysis showed that DEGs were closely related to GABA and inflammation.RT-qPCR results showed that UA treatment increased the expression levels of GABA receptor-related gene(Gng4),GABA synthesis-related gene(Camk2a,Vgf,and Npy)and inflammation-related gene(Timp1 and Spp1)in hippocampal tissue,and decreased the expression levels of GABA synthesis-related gene(Nptx2)and cAMP-related pathway gene(Gnas).It further confirmed that UA treatment increased the expression levels of Gng4 and Camk2a on neurons and decreased the expression level of Gnas.Immunofluorescence and Western blot results showed that,compared with the SE group,the expression level of GABRG2 on primary neurons increased after UA treatment.This study enriched the transcriptome data of UA's antiepileptic effect and laid a theoretical foundation for further research on UA's antiepileptic and neuroprotective effects.

【Objective】 To understand the epidemiological characteristics of COVID-19 in Shaanxi Province from December 9, 2021 to January 20, 2022, and analyze the factors influencing the interval from isolation to diagnosis. 【Methods】 We collected the data of local COVID-19 cases from December 9, 2021 to January 20, 2022 published on the official website of Health Commission of Shaanxi Province. Descriptive statistical method was used to analyze the epidemiological characteristics of COVID-19 in Shaanxi Province. Mann-Whitney U test and Kruskal-Wallis H test were used to compare the differences between groups. The unconditional Logistic regression model was applied to analyze the factors influencing the interval between isolation and diagnosis. 【Results】 The outbreak of COVID-19 in Shaanxi Province started on December 9, 2021 and ended on January 20, 2022. The overall change trend of the outbreak showed an "inverted V" shape. A total of 2,080 confirmed local cases were reported, and the main type of disease was mild, with an incidence rate of 5.26/100,000. Xi’an had the most cases, accounting for 98.69% of the total. The reported cases were mainly concentrated in people aged 21 to 55 years old, with a male-to-female sex ratio of 1.19∶1. The median interval from isolation to diagnosis was 3 days, the shortest interval being 0 day and the longest interval being 21 days. Unconditional Logistic regression model analysis showed that the way of finding cases was the factor influencing the interval from isolation to diagnosis. Compared with the way of isolation of the key population, the way of the nucleic acid screening could reduce the risk of late detection of confirmed cases by 89% (OR=0.11, 95% CI: 0.07-0.16). 【Conclusion】 The way of finding cases is the factor influencing the interval from isolation to diagnosis. In the face of the recent intensification of the spread of Omicron variant in mainland China, accurate and rapid identification and detection of confirmed cases can not only reduce the risk of the spread of the epidemic, but also endeavor more time and initiative for the treatment of patients, which is the key to curbing the spread of the epidemic.

Since December 2019,severe acute respiratory syndrome coronavirus 2 has been found to be the culprit in the coronavirus disease 2019 (COVID-19),causing a global pandemic.Despite the existence of many vaccine programs,the number of confirmed cases and fatalities due to COVID-19 is still increasing.Furthermore,a number of variants have been reported.Because of the absence of approved anti-coronavirus drugs,the treatment and management of COVID-19 has become a global challenge.Under these circumstances,drug repurposing is an effective method to identify candidate drugs with a shorter cycle of clinical trials.Here,we summarize the current status of the application of drug repurposing in COVID-19,including drug repurposing based on virtual computer screening,network pharmacology,and bioactivity,which may be a beneficial COVID-19 treatment.

Objective:To assess the change rules of fetal cervical, thoracic and lumbar spinal volume and centrum volume with gestational ages.Methods:The 3.0 T MRI was performed on 55 fetal specimens ranging from 17 to 42 gestational weeks with sequence of three dimensional T 2WI. Among 55 samples, 20 samples were obtained from spontaneous abortion of pregnant women and 35 samples were obtained from induced labor of mothers due to serious diseases. The fetal specimen was derived from sectional imaging anatomy research institute of the medical school of Shandong University. No spinal abnormalities were found on CT scans. The cervical, thoracic and lumbar spinal volume was obtained by delineating the vertebral body contour on the reconstructed cross-sectional image with the OsiriX software (www.osirix-viewer.com). And the volume of the cervical, thoracic and lumbar spine was divided by the number of the vertebral bodies to obtain the centrum unit volume. Five lumbar vertebral bodies were measured one by one. Regression analysis was made between the volume of cervical, thoracic and lumbar spine and gestational weeks, and between the volume of lumbar vertebral bodies and gestational weeks to analyze the growth rule of spine. Results:(1) The cervical, thoracic and lumbar spine volume increased linearly with gestational ages, and the linear regression equation was as follows: cervical spine volume (mm 3) =-1 260.937+81.235×gestational week ( R2=0.974, P<0.05), thoracic spine volume (mm 3) =-5 933.521+347.503×gestational week ( R2=0.972, P<0.05), lumbar spine volume (mm 3) =-5 130.912+294.473×gestational week ( R2=0.976, P<0.05). (2) The order from large to small of fetal spinal growth rate was thoracic, lumbar and cervical segment. Within the same gestational age, the order from large to small of spinal volume was thoracic, lumbar and cervical segment. The order from large to small of centrum unit volume growth rate was lumbar, thoracic and cervical vertebrae. (3) The volume of each lumbar vertebral body also increased linearly with gestational age. Conclusion:The cervical, thoracic and lumbar volume show a good correlation with the gestational weeks in the second and third trimester fatal specimens, and the growth rate of different segments is different.

Objective: To observe the expressional changes in Notch signaling pathway and toll-like receptor 4 (TLR4) and their interactions on the functions of CD14⁺ monocytes in chronic hepatitis C patients. Methods: A total of 24 treatment-naïve chronic hepatitis C cases and 10 healthy individuals, who visited Shaanxi Provincial People's Hospital from August to October 2017, were enrolled. Selected CD14⁺ monocytes were stimulated by the Notch signaling pathway inhibitor DAPT or transfected with TLR4 siRNA, and the levels of Notch1, Notch2, Hes1 and Hes5 mRNA were detected by real-time quantitative PCR. TLR4 protein levels and phosphorylation of NF-κB was detected by Western blot. ELISA was used to detect the level of cytokines secreted from CD14⁺ monocytes. A t-test or paired t-test was used for comparison between groups. Results: The relative expression of Notch1 mRNA (3.97 ± 2.03 vs. 0.91 ± 0.76, P < 0.01) and downstream of Notch signaling pathway (5.96 ± 2.31 vs. 0.99 ± 0.45, P < 0.01), Hes1 mRNA and Hes5 mRNA (4.31 ± 1.05 vs. 0.84 ± 0.20, P < 0.01) in CD14+ monocytes of chronic hepatitis C patients was significantly higher than that of healthy individuals. The relative expression of TLR4 mRNA (5.14 ± 1.09 vs. 1.27 ± 0.39) and protein level in CD14⁺ monocytes of chronic hepatitis C patients were significantly higher than those of healthy individuals (P < 0.01). An inhibition of Notch signaling pathway with DAPT had reduced the relative expression level of TLR4 mRNA (2.58 ± 1.36 vs. 4.34 ± 1.88, P < 0.05), protein expression and phosphorylation of NF-B in CD14⁺ monocytes of chronic hepatitis C patients. Furthermore, the secretion level of MCP-1 [(94.32 ± 23.59) pg/ml vs. (64.07 ± 9.39) pg/ml, P < 0.01] and IL-8 [(12.54 ± 4.89) pg/ml vs. (7.92 ± 3.01) pg/ml, P < 0.05] was significantly reduced. TLR4 siRNA transfection reduced the expressions of Notch1 mRNA (2.09 ± 1.72 vs. 3.73 ± 1.75, P < 0.05), Hes1 (2.87 ± 0.84 vs. 5.54 ± 0.97, P < 0.01), and Hes5 (2.89 ± 0.93 vs. 4.51 ± 1.54, P < 0.01) in CD14⁺ monocytes of chronic hepatitis C patients. Conclusion Interaction of Notch signaling pathway with TLR4 can promote the function of CD14⁺ monocytes in chronic hepatitis C patients.

Objective To study the effect of deep brain stimulation of subthalamic nucleus (STN-DBS) on non-motor symptoms (NMSs) in patients with Parkinson's disease (PD).Methods Seventeen PD patients,admitted to and accepted bilateral STN-DBS in our hospital from 2012 to 2018,were chosen in our study.Unified Parkinson's Rating Scale (UPDRS) Ⅲ and Non-motor Symptoms Scale (NMSS) were used to evaluate the motor symptoms and non-motor symptoms one week before and 12 months after surgery.The correlations of motor symptoms and non-motor symptoms with age and gender were analyzed.Results The UPDRS Ⅲ total scores of 17 patients were 33.48+10.00 one week before DBS and 10.59±6.70 one year after DBS,with statistically significant difference (P＜0.05).The NMSS total scores were 144.47±51.31 one week before DBS and 86.35±40.23 one year after DBS,with statistically significant difference (P＜0.05).There were statistically significant differences in scores of sleep and fatigue,mental and behavioral abnormalities,sensory abnormality,cognitive impairment and constipation between one week before and one year after surgery (P＜0.05).NMSS scores showed no significant correlation with gender,but showed significant correlations with age,course of disease and Hoehn-Yahr grading (P＜0.05).Conclusion Bilateral STN-DBS can significantly improve some non-motor symptoms to a certain degree.

Objective To investigate the clinical effectiveness of treatment combining Honghe lotion and clotrimazole in patients with colpitis mycotica in pregnancy. Methods 200 patients with colpitis mycotica in pregnancy in our hospital from January, to September, 2017 were randomized into observation and control group with 100 patients in each. Patients in control group were treated with clotrimazole while patients in observation group were treated with additional Honghe lotion. Effectiveness at the end of course of treatment, the time of symptom disappearance, satisfactory rate of treatment, adverse effect and recurrence during 6-month follow-up in two groups were compared. Results Total effective rate at the end of course of treatment in observation group was significantly higher than that in control group and the rate of recurrence after 6-month follow-up was significantly lower than that in control group(P＜0. 05). Time of symptom disappearance in observation group was significantly shorter and the satisfactory rate of treatment in observation group was significantly higher than those in control group respectively (P＜0. 05). There was no adverse effects observed in two groups during treatment. Conclusion Treatment combining Honghe lotion and clotrimazole in patients with colpitis mycotica in pregnancy was effective with low rate of recurrence and good safety. It was worth clinical promotion.