Outbreak of piglet diarrhea associated with a new reassortant porcine rotavirus B.

Rotavirus B (RVB) is a causative agent leading to acute viral gastroenteritis diarrhea in both children and young animals, and has been commonly detected in piglets. In order to determine the causative agent of diarrheal outbreak occurring in December 2022 in piglets from a pig herd in Luoyang, Henan province of China, four common viral pathogens causing piglet diarrhea-three coronaviruses and rotavirus A (RVA) were first tested and found negative, therefore metagenomic sequencing was performed to explore other potential pathogens in the diarrheal samples. Unexpectedly, the most abundant viral reads mapped to RVB, and were de novo assembled to complete 11 viral gene segments. Sequence comparisons revealed that 5 gene segments encoding VP1, VP2, VP3, NSP3 and NSP4 of RVB strain designated as HNLY-2022 are most closely related to RVB strains derived from herbivores with low nucleotide similarities of 65.7-75.3%, and the remaining segments were relatively close to porcine RVB strains with the VP4 gene segment showing very low nucleotide identity (65.0%) with reference strains, indicating HNLY-2022 is a new reassortant RVB strain. Based on the previously proposed genotype classification criterion, the genotype constellation of RVB strain HNLY-2022 is G6-P[6]-I4-R6-C6-M6-A7-N5-T7-E5-H4 with more than half of the genotypes (P[6], R6, C6, M6, T7 and E5) newly reported. Therefore, the new reassortant RVB strain is the likely causative agent for the diarrheal outbreak of piglets occurred in China and more epidemiological studies should be conducted to monitor the spread of this newly identified porcine RVB strain.

Effect of Taichi Chuan on health-related physical fitness in adults: A systematic review with meta-analysis.

PURPOSE: Taichi Chuan was previously shown to benefit physical health, but the results were inconsistent. The main reason is that the mechanism is not clear and may be interpreted differently. In this systematic review, we analyzed the data obtained from various randomized controlled trials to identify the effectiveness of Taichi Chuan and the mechanism by which it improves the physical health of adults. METHODS: We systematically searched various databases, including PubMed, Web of Science, Scopus, Embase, EBSCO Host, Science Direct, CNKI, Wan-Fang, and VPCS, and obtained 1448 articles for review. The articles were selected following the PICO eligibility criteria. We performed a systematic review and meta-analysis to interpret the results of the different studies. RESULTS: We included 16 studies in the systematic review. Six of them were of very high quality, ten were of acceptable quality. Overall, the results showed that Taichi Chuan is beneficial to physical fitness, but not all indices supported this statement. Specifically, the effects were significant on Balance (ES = - 0.33; P = 0.02), BMI (ES = - 0.83; P < 0.00001), body fat (ES = - 0.45; P < 0.00001), and vital capacity (ES = 23.39; P = 0.01). However, there were no significant effects on systolic blood pressure (ES = 0.07; P = 0.94) and diastolic blood pressure (ES = 0.03; P = 0.97). CONCLUSION: We found sufficient high-quality evidence to suggest that Taichi Chuan affects balance, BMI, body fat, vital capacity, and flexibility (sit-reach) in adults. The mechanism can be explained by low posture (balance) and moderate intensity of Taichi Chuan. However, no study has explained how to maintain concentration while keeping a dynamic low posture, which made it difficult to validate the finding that Taichi Chuan can reduce sympathetic tension under stress. In this study, we assumed that relaxation methods, which work on the central nervous system that links the body and the mind, might be the key explanation. However, further studies based on scientific, replicable methods need to be performed to confirm our findings.

Prevalence and factors associated with hepatitis C among pregnant women in China: a cross-sectional study.

Pregnant women infected with HCV should be given attention due to their special physiological stage and the effect on offspring health. To examine the prevalence of HCV infection among pregnant women in part of China and explore relevant factors during pregnancy, a cross-sectional study was conducted in four maternal and children health care institutions (MCHC) in Guangdong, Hunan and Chongqing. Pregnant women who were delivered, induced or spontaneous abortion were included and relevant information was collected through the Hospital Information System. Results showed that the prevalence of HCV among pregnant women in four MCHCs was 0.11% (95% CI 0.09-0.13%). Age, occupations, regions, syphilis-infection, intrahepatic cholestasis of pregnancy (ICP), and placenta previa were significant factors (all P < 0.05). Age and syphilis-infection were positively correlated with HCV infection (Z = 3.41, P = 0.0006; OR = 18.16, 95% CI 9.34-35.29). HCV and HBV infection were risk factors of ICP (OR = 4.18, 95% CI 2.18-8.04; OR = 2.59, 95% CI 2.31-2.89). Our study indicates that the prevalence of HCV among pregnant women in the three provinces(city) was low compared with the general population in China. Older age and syphilis-infection increased the risk of HCV infection during pregnancy. HCV infection was a risk factor of ICP. Generally, we need keep a watchful eye on HCV infection and relevant factors mentioned above during pregnancy in clinic, especially those also infected with syphilis. HCV testing based on risk factors is recommended in antenatal care and obstetrics.

Investigations on incidence and relevant factors of allergies in 5725 urban pregnant women: a cohort study in China.

BACKGROUND: Allergic diseases are highly prevalent in the women of childbearing age. As we know, the immune system could change when pregnancy, which may affect the course of allergic diseases. Meanwhile, they also can affect the course and outcome of pregnancy. The data on incidence of allergies during pregnancy is lacking and conducting clinical trials in pregnant women was limited, therefore, we observed a prebirth cohort to supplement the relevant data and strengthen concerned research conductions. OBJECTIVE: We aim to obtain the incidence of allergies in urban pregnancy and explore the relevant factors of allergic diseases in urban pregnancy. METHODS: We design a multicenter and prospective cohort in 20 institutions above municipal level which were eligible according to the study design from 14 provinces covering all-side of China. This cohort was conducted from 13+6 weeks of gestation to 12 months postpartum and in our study, we chose the prenatal part to analyze. The outcome was developing allergies during pregnancy, which were diagnosed by clinicians according to the uniform criterion from National Health Commission. All the data was collected by electronic questionnaires through tablet computers. RESULTS: The incidence of allergic diseases in urban pregnant women was 21.0% (95%CI 20.0% ~ 22.0%). From social demography data, the history of allergies of pregnant women and their parents had statistical significance(p < 0.01); For exposure to living or working environment, house decoration for less than half a year, exposure to plush toys, disinfectants, insecticides, antihistamines, glucocorticoids, antipyretic analgesics, tocolytic agent and probiotics had statistical significance (all p < 0.05); For psychological status, self-rated depression and anxiety had statistical significance (p = 0.026;p = 0.006). CONCLUSION: The incidence of allergic diseases in urban pregnant women was similar to the former study and kept a medium-high level. The history of allergies of pregnant women and their parents, house decoration time, exposure to plush toys, disinfectants, insecticides, antihistamines, glucocorticoids, antipyretic analgesics, tocolytic agents, probiotics, self-rated depression, and anxiety were relevant factors of allergic diseases during pregnancy.

Relationship between postoperative delirium and preoperative frailty in elderly patients undergoing non-cardiac surgery / 中华麻醉学杂志

Objective:To evaluate the relationship between postoperative delirium and preoperative frailty in elderly patients undergoing non-cardiac surgery.Methods:Elderly patients undergoing non-cardiac surgery at our hospital from March 2019 to July 2022 were collected and their age, comorbidities, gender, smoking history, type of surgery, preoperative albumin, duration of surgery, duration of anesthesia, postoperative hypotension, educational level, nutritional status, American Society of Anesthesiologists (ASA) Physical Status classification, postoperative admission to ICU or not, intraoperative bleeding and preoperative frailty status were collected. The patients were divided into delirium group and non-delirium group according to whether postoperative delirium occurred. The risk factors for postoperative delirium were analyzed by multivariate logistic regression analysis, and the receiver operating characteristic curve was drawn to analyze the value of risk factors in predicting postoperative delirium.Results:There were 74 cases in delirium group and 321 cases in non-delirium group, and the incidence of postoperative delirium was 18.7%. There were statistically significant differences in terms of age ≥70 yr, education level of junior high school and below, poor nutritional status, ASA Physical Status classification Ⅲ, postoperative admission to ICU, proportion of frailty and intraoperative bleeding volume between delirium group and non-delirium group ( P<0.05). The results of logistic regression analysis showed that age, educational level, nutritional status, ASA Physical Status classification, intraoperative bleeding and frailty were all independent risk factors for delirium ( P<0.05). The area under the receiver operating characteristic curve of preoperative frailty predicting postoperative delirium was 0.672 (95% confidence interval 0.605-0.740). Conclusions:Preoperative frailty is an independent risk factor for postoperative delirium in elderly patients undergoing noncardiac surgery, which can predict the occurrence of postoperative delirium to some extent.

Meta-analysis on the treatment of diabetic retinopathy by Yiqi Yangyin Huoxue method / 国际中医中药杂志

Objective:To systematically evaluate the clinical efficacy of Yiqi Yangyin Huoxue method for the treatment of diabetic retinopathy (DR).Methods:Clinical research literature about Yiqi Yangyin Huoxue method for the treatment of DR was retrieved from China Biomedical Literature Database (CBM), VIP information Chinese Periodical Service Platform (VIP), China National Knowledge Infrastructure (CNKI), Wanfang data, Cochrane Library and PubMed database from the establishment of the databases to December 31, 2021. RevMan5.3 software was used for meta-analysis.Results:A total of 18 articles were included, with a total of 1 487 patients. The results of meta-analysis showed that Yiqi Yangyin Huoxue method for the treatment of DR had curative effect advantages in improving the total clinical effective rate [ RR=1.31, 95% CI (1.21,1.41), P<0.001], the vision [ MD=0.12, 95% CI (0.07, 0.17), P<0.001], the level of whole blood reduced viscosity low shear [ MD=-2.80, 95% CI (-3.76, -1.84), P<0.001], the level of whole blood reduced viscosity high shear [ MD=-0.69, 95% CI (-1.15, -0.24), P=0.003], and plasma viscosity [ MD=-0.31, 95% CI (-0.51, -0.12), P=0.002], decreasing serum vascular endothelial growth factor [ SMD=-1.04, 95% CI (-1.26, -0.81), P<0.001], increasing TCM symptom score [ MD=-3.79, 95% CI (-6.16,-1.42), P=0.002], reducing the level of tumor necrosis factor-α [ SMD=-2.53, 95% CI (-3.55, -1.50), P<0.001] which were better than that of pure Western medicine ( P<0.05). Conclusion:The application of Yiqi Yangyin Huoxue method for the treatment of DR can improve vision, hemorheology and TCM symptoms, improve the total clinical response rate, and reduce the levels of VEGF and TNF-α, with high clinical safety.

Discussion on the mechanism of Coptidis Rhizoma- Puerariae Lobamle Radix on diabetic retinopathy and diabetic nephropathy "different diseases with the same treatment" based on network pharmacology and molecular docking / 国际中医中药杂志

Objective:To explore the mechanism of Coptidis Rhizoma- Puerariae Lobamle Radix on the treatment of diabetic retinopathy (DR) and diabetic nephropathy (DN) by means of network pharmacology. Methods:The TCMSP and UniProt databases were used to retrieve the active components and targets of Coptidis Rhizoma and Puerariae Lobamle Radix. GeneCards and OMIM databases were used to search for DR and DN genes, and the online tool Venny was used to obtain intersection targets. Cytoscape 3.8.2 software was used to construct a network diagram of "components-targets", and the STRING platform was used to construct a protein interaction (PPI) network. GO function and KEGG pathway enrichment analysis were carried out through the DAVID annotation database. Molecular docking verification was performed. Results:A total of 18 active components and 74 disease-drug intersection targets were screened out from Coptidis Rhizoma- Puerariae Lobamle Radix. GO functional enrichment analysis showed that intersection targets were mainly concentrated in biological processes such as inflammation and apoptosis, involving cellular components such as extracellular space, plasma membrane, and cytoplasm, and was related to molecular functions such as protein binding, ATP binding, and enzyme binding. Enrichment analysis of KEGG revealed that the intersection target may be related to TNF signaling pathway, Toll-like receptor signaling pathway, PI3K-Akt signaling pathway, etc. The results of molecular docking showed that the core component had a good binding energy with the core targets. Conclusion:Coptidis Rhizoma-Puerariae Lobamle Radix may regulate TNF signal pathway, Toll-like receptor signal pathway and PI3K/Akt signal pathway through TNF, IL6, TP53 and other targets, and play a role in inhibiting cell apoptosis, oxidative stress and reducing inflammation.

Effects of DNMT3A on mouse cardiac fibroblast proliferation and migration under high glucose environment / 中国药理学通报

Aim To investigate the effect of DNA methyltransferase 3A (DNMT3A) on the proliferation and migration of cardiac fibroblasts (CFs) in C57 mice under high glucose environment. Methods The hearts of C57 mice were taken from 1 to 3 days. After cutting and digesting, CFs were extracted by differential adherance centrifugattion and observed under microscope. After cell attachment, the cells were cultured under low glucose (5.5 mmol • L

Diesel exhaust inhalation exposure induced toxicity on olfactory bulb in mice through inflammatory response mediated by activating glial cells / 环境与职业医学

Background Air pollution is related to the occurrence and development of mental diseases. Olfactory bulb damage might be the potential prodromal symptom and sign of these diseases. The toxicity of diesel exhaust (DE), one of the main sources of air pollution, on olfactory bulb and the underlying mechanisms remain to be elucidated. Objective To explore the toxicity of DE on mouse olfactory bulb and underlying mechanisms. Methods A total of 40 C57BL/6 mice were randomly divided into four groups for exposure to DE by systemic inhalation: control group (filtered air), low exposure group (750 μg·m−3 DE), medium exposure group (1500 μg·m−3 DE), and high exposure group (3000 μg·m−3 DE). The mouse inhalation exposure to DE was performed 1 h per day for 28 d. HE staining was performed to observe pathological changes in mouse olfactory bulb tissue. TUNEL assay was used to observe apop-tosis in olfactory bulb. Kyoto Encyclopedia of Genes and Genomes (KEGG) was exhibited to explore potential mechanisms of olfactory bulb damage associated with DE. Quantitative real-time PCR (qPCR) was used to determine mRNA expression levels of inflammatory factors including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Immunofluorescence staining was conducted to observed the microglia and astrocyte activation in olfactory bulb. Results The HE staining results showed that the number of periglomerular cells in the glomerular layer of olfactory bulb decreased in a dose-dependent manner, and the cells in the granule cell layer of olfactory bulb became disordered after DE exposure. The TUNEL staining showed that TUNEL positive cells in olfactory bulb tissue and neuronal apoptosis increased in the exposed groups compared with the control group (P＜0.05). The KEGG pathway analysis showed that DE associated with significant enrichment of TNF signaling pathway in olfactory bulb tissue. The qPCR results showed that the TNF-α relative expression level significantly increased by 67% and the IL-6 relative expression level by 340% in the DE high exposure dose group compared with the control group (P＜0.05). According to the immunofluorescence staining results, the numbers of activated microglia and astrocytes in olfactory bulb tissue significantly increased in the DE high exposure group, the relative fluorescence intensity of ionized calcium binding adaptor molecule 1 (IBA-1) increased by 120%, the granule cell layer relative fluorescence intensity of glial fibrillary acidic protein (GFAP) increased by 400%, and the glomerular layer relative fluorescence intensity of GFAP increased by 240% than those in the control group (P＜0.05). Conclusion Inhalation exposure to DE can lead to glial cell activation including microglia and astrocytes in olfactory bulb tissue by activating inflammatory pathways and releasing inflammatory factors TNF-α and IL-6, leading to neuronal apoptosis in olfactory bulb tissue.

Compound Danshen Dripping Pill inhibits hypercholesterolemia/atherosclerosis-induced heart failure in ApoE and LDLR dual deficient mice via multiple mechanisms

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE-/-LDLR-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

Mechanism and inhibition of abnormal chromatographic behavior of serotype type a inactivated foot and mouth disease virus in high-performance size-exclusion chromatography.

High-performance size-exclusion chromatography (HPSEC) has been developed for the rapid and quantitative analysis of inactivated foot and mouth disease virus (FMDV) and adopted by regulatory agencies and vaccine manufacturers. However, strong non-specific adsorption of type A/AKT III FMDV was found on some batches of TSK G4000 SWXL column, which significantly affected the analysis accuracy. The adsorption mechanism was studied by investigating the charge and hydrophobicity of A/AKT III FMDV and another serotype O/Mya 98, as well as several model proteins, by zeta potential and hydrophobic interaction chromatography analysis. Adsorption was related to both the FMDV strain and column lots. Some specific amino acids residues on the A/AKT III FMDV surface may strongly interact with the column if the silica-based stationary phase was not completely diol-modified. Several amino acids and chaotropic salts were screened as additives in the mobile phase to suppress the non-specific adsorption of AKT III FMDV in HPSEC analysis. Results showed that adding 0.4 M of arginine (Arg), lysine (Lys), NaClO4, or NaSCN achieved 100% FMDV recovery and normal retention time. Suppression of interaction between FMDV and the backbone of the silica matrix through competitive binding with residues of FMDV or the matrix is considered as the main mechanism by which these four additives act as suppressors. The addition of Arg, NaClO4, or NaSCN led to an apparent decrease in the thermal dissociation temperature Tm of FMDV, whereas Lys slightly increased viral stability. Finally, the mobile phase comprising 0.4 M Lys was screened as optimum that allowed accurate quantification of both two serotypes of FMDV according to method validation; particularly, a relative standard deviation (RSD) < 5% was achieved for AKT III FMDV using three different lots of columns.

Proteomic and Antibody Profiles Reveal Antigenic Composition and Signatures of Bacterial Ghost Vaccine of Brucella abortus A19.

Brucellosis is an important zoonotic disease that causes great economic losses. Vaccine immunisation is the main strategy for the prevention and control of brucellosis. Although live attenuated vaccines play important roles in the prevention of this disease, they also have several limitations, such as residual virulence and difficulty in the differentiation of immunisation and infection. We developed and evaluated a new bacterial ghost vaccine of Brucella abortus A19 by a new double inactivation method. The results showed that the bacterial ghost vaccine of Brucella represents a more safe and efficient vaccine for brucellosis. We further characterised the antigenic components and signatures of the vaccine candidate A19BG. Here, we utilised a mass spectrometry-based label-free relative quantitative proteomics approach to investigate the global proteomics changes in A19BGs compared to its parental A19. The proteomic analysis identified 2014 proteins, 1116 of which were differentially expressed compared with those in A19. The common immunological proteins of OMPs (Bcsp31, Omp25, Omp10, Omp19, Omp28, and Omp2a), HSPs (DnaK, GroS, and GroL), and SodC were enriched in the proteome of A19BG. By protein micro array-based antibody profiling, significant differences were observed between A19BG and A19 immune response, and a number of signature immunogenic proteins were identified. Two of these proteins, the BMEII0032 and BMEI0892 proteins were significantly different (P < 0.01) in distinguishing between A19 and A19BG immune sera and were identified as differential diagnostic antigens for the A19BG vaccine candidate. In conclusion, using comparative proteomics and antibody profiling, protein components and signature antigens were identified for the ghost vaccine candidate A19BG, which are valuable for further developing the vaccine and its monitoring assays.

Combined immunization with inactivated vaccine reduces the dose of live B. abortus A19 vaccine.

BACKGROUND: Brucella spp. is an important zoonotic pathogen responsible for brucellosis in humans and animals. Brucella abortus A19 strain is a widespread vaccine in China. However, it has a drawback of residual virulence in animals and humans. METHODS: In this study, the BALB/c mice were inoculated with either 100 µL PBS(control group, C group), 109 CFU/mL inactivated B. abortus A19 strain (I group), 105 CFU/mL (low-dose group, L group) 106 CFU/mL live B. abortus A19 strain (high-dose group, H group), or 105 CFU/mL live B. abortus A19 strain combined with 109 CFU/mL inactivated B. abortus A19 strain (LI group). Mice were challenged with B. abortus strain 2308 at 7 week post vaccination. Subsequently, the immune and protective efficacy of the vaccines were evaluated by measuring splenic bacterial burden, spleen weight, serum IgG, interferon-gamma (IFN-γ), interleukin-4 (IL-4) percentage of CD4 + and CD8 + T cells of mice via bacterial isolation, weighing, ELISA and flow cytometry, respectively. RESULTS: The splenic bacterial burden and spleen weight of the mice in group LI were mostly equivalent to the mice of group H. Moreover, Brucella-specific serum IgG, IFN-γ, IL-4, and the percentage of CD4+ and CD8+ T cells of the LI group mice were similar to those of the H group. In the subsequent challenge test, both vaccines conferred protective immunity to wild-type (WT) 2308 strain. In addition, the levels of IL-4 and IFN-γ, CD4+ and CD8+ T cells in these mice were similar to those of the mice in the H group. CONCLUSIONS: Combined immunization with low dose live vaccine and inactivated vaccine allowed to reduce the live B. abortus A19 vaccine, dose with an equivalent protection of the high-dose live vaccine.

Advanced Glycation End Products (AGEs) Inhibit Macrophage Efferocytosis of Apoptotic ß Cells through Binding to the Receptor for AGEs.

Pancreatic ß cell apoptosis is important in the pathogenesis of type 2 diabetes mellitus (T2DM). Generally, apoptotic ß cells are phagocytosed by macrophages in a process known as "efferocytosis." Efferocytosis is critical to the resolution of inflammation and is impaired in T2DM. Advanced glycation end products (AGEs), which are increased in T2DM, are known to suppress phagocytosis function in macrophages. In this study, we found that AGEs inhibited efferocytosis of apoptotic ß cells by primary peritoneal macrophages in C57BL/6J mice or mouse macrophage cell line Raw264.7. Mechanistically, AGEs inhibit efferocytosis by blocking Ras-related C3 botulinum toxin substrate 1 activity and cytoskeletal rearrangement through receptor for advanced glycation end products/ras homolog family member A/Rho kinase signaling in macrophages. Furthermore, it was observed that AGEs decreased the secretion of anti-inflammatory factors and promoted the proinflammatory ones to modulate the inflammation function of efferocytosis. Taken together, our results indicate that AGEs inhibit efferocytosis through binding to receptor for advanced glycation end products and activating ras homolog family member A/Rho kinase signaling, thereby inhibiting the anti-inflammatory function of efferocytosis.

Vaccination with a Brucella ghost developed through a double inactivation strategy provides protection in Guinea pigs and cattle.

Vaccination can prevent and control animal brucellosis. Currently, live attenuated vaccines are extensively used to prevent Brucella infection. However, traditional vaccines such as live attenuated vaccines are associated with biological safety risks for both humans and animals. The bacterial ghost (BG) is a new form of vaccine with great prospects. However, bacterial cells cannot be completely inactivated by biological lysis, conferring a safety risk associated with the vaccine. In this study, we developed a Brucella abortus A19 bacterial ghost (A19BG) through a double inactivation strategy with sequential biological lysis and hydrogen peroxide treatment. This strategy resulted in 100% inactivation of Brucella, such that viable bacterial cells were not detected even at an ultrahigh concentration of 1010 colony-forming units/mL. Furthermore, A19BG had a typical BG morphology and good genetic stability. Moreover, it did not induce adverse reactions in guinea pigs. The levels of antibodies, interferon-γ, interleukin-4, and CD4+ T cells in guinea pigs inoculated with the A19BG vaccine were similar to those inoculated with the existing A19 vaccine. Immunization with A19BG conferred a similar level of protection with that of A19 against Brucella melitensis M28 in both guinea pigs and cattle. In conclusion, the combination of biological lysis and H2O2-mediated inactivation is a safe and effective strategy that can serve as a reference for the preparation of BG vaccines.

Progress on the protective effect of heme oxygenase-1 in viral infection / 药学学报

Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that catalyzes the conversion of heme to CO, biliverdin, and iron, which together protect cells from oxidative and inflammatory damage and play an important role in maintaining cell homeostasis. In recent years, HO-1 has also been found to have antiviral biological effects, and the induced expression of HO-1 inhibits the replication of various viruses such as hepatitis C virus, hepatitis B virus, human immunodeficiency virus, dengue virus, ebolavirus, influenza A virus, Zika virus, severe acute respiratory syndrome coronavirus 2, human respiratory syncytial virus, hepatitis A virus and enterovirus 71. The inhibitory effect of HO-1 on these viruses involves three mechanisms, including direct inhibition of virus replication by HO-1 and its downstream products, enhancement of type I interferon responses in host cell, and attenuation of inflammatory damage caused by viral infection. This review focuses on the recent advances in the antiviral effect of HO-1 and its mechanism, which is expected to provide evidence for HO-1 as a potential target for antiviral therapy.

Evaluation and Differential Diagnosis of a Genetic Marked Brucella Vaccine A19ΔvirB12 for Cattle.

Brucella abortus is an important zoonotic pathogen that causes severe economic loss to husbandry and poses a threat to human health. The B. abortus A19 live vaccine has been extensively used to prevent bovine brucellosis in China. However, it is difficult to distinguish the serological response induced by A19 from that induced by natural infection. In this study, a novel genetically marked vaccine, A19ΔvirB12, was generated and evaluated. The results indicated that A19ΔvirB12 was able to provide effective protection against B. abortus 2308 (S2308) challenge in mice. Furthermore, the safety and protective efficacy of A19ΔvirB12 have been confirmed in natural host cattle. Additionally, the VirB12 protein allowed for serological differentiation between the S2308 challenge/natural infection and A19ΔvirB12 vaccination. However, previous studies have found that the accuracy of the serological detection based on VirB12 needs to be improved. Therefore, we attempted to identify potential supplementary antigens with differential diagnostic functions by combining label-free quantitative proteomics and protein chip technology. Twenty-six proteins identified only in S2308 were screened; among them, five proteins were considered as potential supplementary antigens. Thus, the accuracy of the differential diagnosis between A19ΔvirB12 immunization and field infection may be improved through multi-antigen detection. In addition, we explored the possible attenuation factors of Brucella vaccine strain. Nine virulence factors were downregulated in A19ΔvirB12. The downregulation pathways of A19ΔvirB12 were significantly enriched in quorum sensing, ATP-binding cassette transporter, and metabolism. Several proteins related to cell division were significantly downregulated, while some proteins involved in transcription were upregulated in S2308. In conclusion, our results contribute to the control and eradication of brucellosis and provide insights into the mechanisms underlying the attenuation of A19ΔvirB12.

Progress in Application of Population Pharmacokinetic and Pharmacodynamic Models in Research on Traditional Chinese Medicine / 中国实验方剂学杂志

In recent years， the role of quantitative pharmacological models in applicable population of drugs and dose optimization has been widely recognized. In order to improve the efficiency of clinical development and optimize clinical rational drug use， quantitative pharmacological models are being gradually introduced into the research of traditional Chinese medicine （TCM）. There are various types of quantitative pharmacological models， among which the following three models are commonly used：①Population pharmacokinetic （PPK） model， which is mainly used to explore the pharmacokinetic characteristics in different populations.②Pharmacokinetic-pharmacodynamic （PK-PD） model， which is used to reveal the internal relationship among dose， time and efficacy. ③PPK-PD model， which integrates both the characteristics of PPK model and PK-PD model. The paper summarizes the application of the above three models in TCM， and extracts the main ideas and methods of TCM model research， in order to provide reference for clinical research and rational use of TCM.

Belatacept: a new weapon in anti-rejection battlefield / 器官移植

As a co-stimulatory blocker against CD28 receptor, belatacept has been approved and applied to the treatment of rejection in organ transplantation in Europe and America. Belatacept has been proven to outperform calcineurin inhibitor (CNI) in improving the long-term survival rate of recipients and grafts, and enhancing graft function. Nevertheless, it might cause a high incidence of rejection. To resolve this issue, transplant workers have attempted to optimize belatacept immunosuppressive regimen and achieved good clinical efficacy. Although belatacept has been proven to exert poor effect on memory T cells, it has potential value in exploring new co-stimulatory molecular targets to optimize immunosuppressive regimes due to its specificity for immune cells and mild adverse effects. In this article, the advent of co-stimulatory blocker, clinical efficacy and application of belatacept, and the causes of belatacept-resistant rejection were reviewed.

The 1H T1 dispersion curve of fentanyl citrate to identify NQR parameters.

We report the 1H T1 dispersion curve between 0 and 5 â€‹MHz for the synthetic opioid fentanyl citrate (C28H36N2O8). The structures in the curve can be used to estimate the 14N nuclear quadrupole resonance (NQR) frequencies of the material. Density functional theory predictions of the NQR parameters of several fentanyl citrate compounds are also reported. The predictions for the aniline nitrogen are consistent with structures in the observed T1 data. To help interpret the fentanyl citrate results the T1 dispersion curve for the explosive ammonium nitrate is also presented.