Porcine epidemic diarrhea virus (PEDV) is an intestinal coronavirus that can cause porcine epidemic diarrhea, leading to diarrhea, vomiting, weight loss, and even death in piglets. Due to the diversity of PEDV strains, traditional vaccines are difficult to sustainably and effectively prevent and control PEDV. This article reviews the strategies and mechanisms of active substances in regulating intracellular signaling pathways, viral proteins, and microbial metabolites to enhance the host immune function against PEDV. It emphasizes the prevention of PEDV resistance and the potential harm of PEDV breaking through interspecies barriers to the human society, aiming to provide reliable theoretical support for the development of new antiviral drugs or vaccines.
Porcine epidemic diarrhea virus/immunology* ; Animals ; Swine ; Swine Diseases/prevention & control* ; Antiviral Agents/pharmacology* ; Coronavirus Infections/virology* ; Viral Vaccines/immunology* ; Humans ; Signal Transduction

By applying "homeostasis" to the study of the meridian and collateral system， the concept of meridian and collateral homeostasis has been proposed which refers to a balanced and stable state of meridian and collateral system， and plays an important role in maintaining body health and can provide a reference for the diagnosis and treatment of diseases. Phenomics realizes the cross-scale correlation from micro-phenotypic data， such as genome， proteome， and metabolome， to macro-phenotypic data， such as physiological state， behavioral activities， and external manifestations. From the perspective of phenomics， this paper proposes a meridian and collateral homeostasis dynamic mapping model of "macroscopic signs and microscopic expression". This model combines macro signs such as the four examinations of traditional Chinese medicine （TCM）， biophysical indicators of acupoints， and micro expression information such as genes， proteins， and metabolism， and systematically investigates the relationship between meridian and collateral homeostasis and health and disease， thereby providing ideas and references for the identification of pre-disease states as well as precise diagnosis and treatment in TCM.

Objective To investigate the effect and mechanism of Di'ao Xinxuekang(hereinafter referred to as Xinxuekang)combined with Simvastatin on atherosclerosis(AS)mice.Methods Eight C57BL/6J mice were used as control group,and 32 ApoE-/-mice were randomly divided into model group,Xinxuekang group(160 mg·kg-1),Simvastatin group(1.3 mg·kg-1)and combined treatment group(Xinxuekang 160 mg·kg-1+Simvastatin 1.3 mg·kg-1),with eight mice in each group.The control group was fed with conventional diet,and the other four groups were fed with high-fat diet.At the same time,each administration group was given intragastric administration according to the above dose,and the volume of intragastric administration was 10 mL·kg-1,once a day for 18 weeks.After administration,the levels of serum total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C)were detected.Oil red O staining was used to observe the formation of aortic plaque and liver lipid accumulation in mice.Serum PCSK9 level was detected by ELISA.The mRNA and protein expression levels of LDLR,HNF1α and SREBP2 in liver tissues were detected by qRT-PCR and Western Blot.Results(1)Compared with the control group,the levels of serum TC,TG and LDL-C in the model group were significantly increased(P＜0.01),and the level of HDL-C was significantly decreased(P＜0.01).The percentage of aortic root plaque area,the percentage of total aortic plaque area and the percentage of liver lipid droplet area were significantly increased(P＜0.01).The mRNA and protein expression levels of LDLR in liver tissue were significantly decreased(P＜0.01),and the serum PCSK9 level was significantly increased(P＜0.01).The mRNA and protein expression levels of HNF1α and SREBP2 in liver tissues were significantly increased(P＜0.05,P＜0.01).(2)Compared with the model group,the levels of serum TC,TG and LDL-C in the Xinxuekang group and the combined treatment group were significantly decreased(P＜0.05,P＜0.01),and the level of HDL-C was significantly increased(P＜0.05).The level of serum LDL-C in Simvastatin group was significantly decreased(P＜0.01).The percentage of aortic root plaque area and the percentage of total aortic plaque area in the Xinxuekang group and the combined treatment group were significantly decreased(P＜0.05,P＜0.01),and the percentage of liver lipid droplet area in each administration group was significantly decreased(P＜0.01).The protein expression level of LDLR in liver tissue of mice in Xinxuekang group and combined treatment group was significantly increased(P＜0.05),the serum PCSK9 level was significantly decreased(P＜0.05,P＜0.01),and the mRNA and protein expression levels of HNF1 α and SREBP2 in liver tissue were significantly decreased(P＜0.05,P＜0.01).(3)Compared with the Simvastatin group,the serum HDL-C level in the combined treatment group was significantly increased(P＜0.05).The percentage of aortic root plaque area and the percentage of liver lipid droplet area were significantly decreased(P＜0.05,P＜0.01).The protein expression level of LDLR in liver tissue was significantly increased(P＜0.01),and the serum PCSK9 level was significantly decreased(P＜0.01).The expression levels of HNF1α protein and SREBP2 mRNA in liver tissues were significantly decreased(P＜0.05,P＜0.01).Conclusion Xinxuekang may play a synergistic effect on lipid-lowering and anti-AS effects of Simvastatin by inhibiting the expressions of SREBP2 and HNF1α and regulating the PCSK9/LDLR signaling pathway.

Objective:To explore the sequential chemotherapy efficacy of different chemotherapeutic regimens in ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma.Methods:A retrospective analysis was conducted on clinical and pathological data of 100 patients with platinum-sensitive ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma treated at Peking University Peopel′s Hospital from January 1992 to January 2019. All patients underwent staging surgery or cytoreductive surgery followed by adjuvant chemotherapy. Based on different postoperative adjuvant chemotherapy regimens, patients were divided into the sequential chemotherapy group (70 cases) and the conventional chemotherapy group (30 cases). Clinical and pathological characteristics, chemotherapy efficacy, adverse reactions, and prognosis were compared between the two groups.Results:(1) Clinical and pathological characteristics: the age, tumor types (including ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma), pathological types, International Federation of Gynecology and Obstetrics (FIGO) stage, postoperative residual disease size, presence of neoadjuvant chemotherapy, and total number of chemotherapy cycles were compared between the sequential chemotherapy group and the conventional chemotherapy group. There were no statistically significant differences observed in these characteristics between the two groups (all P>0.05). (2) Chemotherapy efficacy: the median sum of complete response (CR)+partial response (PR) duration in the sequential chemotherapy group was 80.0 months (range: 39 to 369 months), whereas in the conventional chemotherapy group, it was 28.0 months (range: 13 to 52 months). A statistically significant difference was observed between the two groups ( Z=-7.82, P<0.001). (3) Chemotherapy adverse reactions: in the sequential chemotherapy group, 55 cases (79%, 55/70) experienced bone marrow suppression and 20 cases (29%, 20/70) had neurological symptoms. In the conventional chemotherapy group, these adverse reactions occurred in 11 cases (37%, 11/30) and 2 cases (7%, 2/30), respectively. Statistically significant differences were observed between the two groups for both bone marrow suppression and neurological symptoms (all P<0.05). For the other chemotherapy adverse reactions compared between the two groups, no statistically significant differences were observed (all P>0.05). (4) Prognosis: during the follow-up period, the recurrence rate in the sequential chemotherapy group was 73% (51/70) and in the conventional chemotherapy group was 100% (30/30). The median sum of recurrence-free interval was 70.5 months (range: 19 to 330 months) in the sequential chemotherapy group and 15.0 months (range: 6 to 40 months) in the conventional chemotherapy group. Statistically significant differences were observed between the two groups for both recurrence rate and median recurrence-free interval (all P<0.01).In the sequential chemotherapy group, the median progression-free survival (PFS) time was 84.0 months (range: 34 to 373 months), and the median overall survival (OS) time was 87.0 months (range: 45 to 377 months). In contrast, in the conventional chemotherapy group, the median PFS time was 30.5 months (range: 14 to 60 months), and the median OS time was 37.5 months (range: 18 to 67 months). Statistically significant differences were observed between the two groups for both PFS and OS (all P<0.001). In the sequential chemotherapy group, the 3-year, 5-year, and 10-year OS rates were 100% (70/70), 93% (65/70), and 21% (15/70), respectively. In contrast, in the conventional chemotherapy group, the OS rates were 50% (15/30) at 3 years, 3% (1/30) at 5 years, and 0 at 10 years, respectively. The two groups were compared respectively, and the differences were statistically significant (all P<0.05). Conclusions:Sequential chemotherapy significantly prolongs PFS and OS in patients with ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma. The efficacy is superior to that of the conventional chemotherapy, with manageable adverse reactions. The use of sequential chemotherapy as first-line treatment for patients with ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma is recommended.

OBJECTIVE To compare the acute toxicity characteristics and differences of water extracts from unprocessed and different processed products of Psoraleae Fructus in mice. METHODS Kunming mice were divided into 36 groups, including Psoraleae Fructus raw product group, stir-fried group, salt-baked group, Leigong group, and wine soaked group, as well as control group. Each group of mice was given a single intragastric administration of 0.04 mL·g-1 and observed for 14 d. The body weight, serum biochemical indices, and mortality of the mice were detected, and the LD50 value was calculated to study the toxicity differences of Psoraleae Fructus raw product and different processed products. RESULTS There was no statistically significant difference in the body weight of mice before administration in different groups. On the first day of administration, some mice in the administration group showed a certain decrease in body weight. The LD50 values of the Psoraleae Fructus raw product group, stir-fried group, salt-baked group, Leigong group, and wine soaked group were 63.20, 56.92, 51.95, 88.61, 59.02 g·kg-1, respectively. Compared with the control group, the serum ALT and TBA levels in the male mice in the Psoraleae Fructus raw product group were significantly increased; the serum ALT, AST, and TBA levels in the stir-fried group were significantly increased, but the ALP level was not statistically significant; the serum ALP, ALT, AST, and TBA levels in the salt-baked group, Leigong group, and wine soaked group were significantly increased. Compared with the control group, the serum ALP, ALT, AST, and TBA levels in female mice in the Psoraleae Fructus raw product group, salt-baked group, Leigong group, and wine soaked group were significantly increased; the serum ALT, AST, and TBA levels in the stir-fried group were significantly increased; all groups had significantly decreased TP levels. Pathological results showed that there was no abnormality in the liver of mice in the control group; the liver of mice in the Psoraleae Fructus raw product group, stir-fried group, salt-baked group, Leigong group, and wine soaked group had pathological changes such as vacuolar degeneration of liver cells, glycogen degeneration of liver cells, loose cytoplasm of liver cells, and partial central hepatocellular hypertrophy; the degree of liver damage in mice caused by different processed products compared with the raw product group: raw product group > wine soaked group > stir-fried group > salt-baked group > Leigong group. Among them, the wine soaking method caused the highest degree of liver damage, while the Leigong method caused the least. CONCLUSION Psoraleae Fructus has different toxicities after being processed by different methods. According to LD50, the toxicity of Leigong method processed products is significantly reduced.

Drimane-type sesquiterpenoids are widely distributed in fungi. From the ethyl acetate extract of the earwig-derived Aspergillus sp. NF2396, seven new drimane-type sesquiterpenoids, named drimanenoids A-G (1-7), were isolated. Their structures were elucidated by diverse spectroscopic analysis including high-resolution ESI-MS, one- and two-dimensional NMR spectroscopy. Drimanenoids A-F (1-6) are new members of drimane-type sesquiterpenoid esterified with unsaturated fatty acid side chain at C-6. Drimanenoids C (3), D (4) and F (6) showed antibacterial activity against five types of bacteria with different inhibition diameters. Drimanenoid D (4) exhibited moderate cytotoxicity against human myelogenous leukemia cell line K562 with an IC₅₀ value of 12.88 ± 0.11 μmol·L^-1.
Humans ; Polycyclic Sesquiterpenes ; Sesquiterpenes/chemistry* ; Aspergillus/chemistry* ; Magnetic Resonance Spectroscopy ; Molecular Structure

ObjectiveTo explore the effects of Wumeisan on gut lactase activity and microflora diversity of mice with dysbacteriosis diarrhea. MethodThe mice were randomly divided into 4 groups， namely， the normal group， the model group， and the low-dose and high-dose Wumeisan groups， with 8 mice in each group. The mouse model was made by gavage of mixed antibiotics for 7 d， and the low-dose and high-dose Wumeisan groups （5.98， 11.96 g·kg^-1） were given gavage for 7 d continuously. The normal group and the model group were given the same volume of sterile water. The changes in the body weight， food intake， and diarrhea of mice were recorded. Feces were collected after the last administration， and the lactase activity was detected by the colorimetric method. The gut microbiota changes were detected by the 16S rRNA high-throughput sequencing technology. ResultCompared with those in the normal group， the mice in the model group had dilute and soft stools， reduced body mass， reduced food intake， reduced lactase activity， significantly reduced intestinal flora diversity， and significant changes in the relative abundance phylum and genus levels of flora. Compared with the model group， Wumeisan reduced the diarrhea rate of mice， promoted the rapid recovery of body weight and food intake， increased the lactase activity decreased by antibiotic， improved the community abundance and diversity of mice with dysbacteriosis， and made the species composition closer to that in the normal group. The abundance of three phyla （Bacteroidota， Proteobacteria， Verrucomicrobiota） and nine genera （Odoribacter， Enterococcus， Clostridium innocuum group， etc.） of mice with diarrhea were regulated by Wumeisan. Among them， norank f Muribaculaceae， norank f norank o Clostridia UCG-014， Lachnospiraceae NK4A136 group， and Odoribacter showed significant positive correlation with the body weight and lactase activity， and Escherichia-Shigella， Enterobacter， Enterococcus， and Clostridium innocuum group showed significant positive correlation with the diarrhea rate. Function prediction showed that the high-dose Wumeisan significantly reseted 6 functional levels of metabolism， genetic information processing， and human diseases， and had positive effects on endocrine and metabolic diseases， immune diseases， infectious disease， and parasitic infectious diseases. ConclusionWumeisan can relieve the symptoms of dysbacteriological diarrhea by increasing the lactase activity and regulating the gut microbiota composition.

Objective:To investigate the infection status of Kaeng Khoi virus (KKV) in bat flies in Yunnan province.Methods:Specimens of the ectoparasitic bat flies on bats in Baoshan city in 2014 and Ruili city in 2017 were collected and identified, virus isolation was performed by cell culture. The positive isolates were amplified and sequenced to obtain the complete genome sequences, and homology comparison and phylogenetic analysis were carried out.Results:Three positive isolates (WDBC1704, WDBC1710 and BSBC1406) were identified from bat flies in Ruili city and Baoshan city. The supernatant was inoculated into BHK-21 cells for virus isolation, all of which could cause cytopathic effects (CPE) included shrinking, rounding and falling off of BHK-21 cells. The complete genome sequences of the three positive isolates were produced by RT-PCR and high-throughput sequencing. Phylogenetic analysis showed that the S, M, and L genes of all three positive isolates were in the same evolutionary branch as the original KKV strain PSC-19 isolated in Thailand. In this study, three KKV strains isolated were most closely related to the previous isolate WDBC1403 from Yunnan province, of which the BSBC1406 strain formed a small independent branch. The sequence comparison showed that there were significant differences in the M gene among the three isolates. The similarity between BSBC1406 and the other two strains (WDBC1704 and WDBC1710) was only 78.0%-78.1%, the amino acid similarity of the Gc protein in the open reading frame region was 85.3%.Conclusions:Three KKV strains from bat flies were quite different from the prototype strain, especially the BSBC1406 strain was somewhat different from other isolates and may have undergone variation. Surveillance of KKV carried by vector insects in Yunnan province and its relationship with human diseases should be strengthened.

Objective:To investigate the effect of SCN1A gene polymorphism (SCN1A-rs3812718) on the alterations of spontaneous brain activity using amplitude of low-frequency fluctuations (ALFF) of MR in patients with temporal lobe epilepsy (TLE).Methods:A total of 37 TLE patients (TLE group) admitted to the Epilepsy Center of the 900th Hospital of Joint Logistic Team from March 2018 to August 2019 were retrospectively analyzed, and another 28 healthy volunteers matched for gender, age, and years of education with the TLE group were selected as the healthy control group (HC group). Sixty-five subjects were divided into four groups by genotype and diagnosis: 34 cases in AA/AG-TLE subgroup, 3 cases in GG-TLE subgroup, 20 cases in AA/AG-HC subgroup and 8 cases in GG-HC subgroup. All subjects underwent sagittal 3D-T 1WI and resting-state functional MRI using a Siemens 3.0 T Trio Tim MR scanner. Then ALFF values of the four groups were calculated using DPABI by the MATLAB 2010 platform. The ALFF values between two groups were compared by independent samples t-test. The ALFF values of different genotypes at rs3812718 locus in TLE and HC group were analyzed by multivariate analysis of variance to find out the corresponding brain regions with interaction, and then post hoc simple effect analysis was performed. Results:The ALFF values in TLE group significantly increased in left marginal lobe, left parahippocampal gyrus, left fusiform gyrus, left hippocampus, right insular lobe and right inferior temporal gyrus (Alphasim corrected P<0.001) and decreased in the left superior frontal gyrus, left middle frontal gyrus, left inferior frontal gyrus, right middle frontal gyrus, right precuneus, left precuneus, bilateral cingulate gyrus and right angular gyrus (Alphasim correction P<0.05) compared with HC group. Subjects carrying the non-risk G allele had higher ALFF values in the right inferior temporal gyrus, right fusiform gyrus, and right cerebellum than subjects carrying the risk A allele ( t=3.30, Alphasim corrected P=0.002). There was a significant interaction effect on posterior cerebellar lobe, left anterior cerebellar lobe, left inferior temporal gyrus, left superior parietal lobule and right precuneus of TLE patients with SCN1A-rs3812718 genotype. Post-hoc simple effect analysis showed that ALFF significantly increased in the left posterior cerebellar lobe, left anterior cerebellar lobe, left inferior temporal gyrus and left fusiform gyrus in GG-TLE subgroup ( t=5.97, P<0.001), but significantly decreased in the right superior parietal lobule, right precuneus, right posterior cerebellar lobe in AA/AG-TLE subgroup compared to the HC group. Compared with GG-TLE subgroup, ALFF in left posterior cerebellar lobe, left fusiform gyrus and left inferior temporal gyrus decreased in AA/AG-TLE subgroup. Conclusion:SCN1A gene polymorphism in the rs3812718 locus affects spontaneous neural activity in resting state, which may be one of the pathophysiological mechanisms of TLE.

Objective:To explore the association of cardiometabolic index(CMI) and other body fat evaluation indicators [body mass index(BMI), waist circumference(WC), waist to height ratio(WHtR), lipid accumulation index(LAP)] with the prevalence of metabolic syndrome(MS) as well as the predictive value of the above indicators for MS.Methods:A total of 10 140 residents over 40 years old in Guiyang city who participated in the " Epidemiological study on tumor risk of type 2 diabetes patients in China" in 2011 were recruited. The 2005 International Diabetes Federation diagnostic criteria were used to identify MS. Logistic regression was used to analyze the association of CMI and other body fat evaluation indicators with MS. Receiver operating characteristic(ROC) curve was used to evaluate the predictive value and the optimal cut-off point of different indicators. Taking the best cut-off point value of each index as the boundary, the prevalence of MS was evaluated again by Chi square test.Results:The prevalence of MS in the study population was 39.81%(27.23% for men and 44.39% for women). Logistic regression analysis showed that the risk of MS increased with increasing CMI and quartile level of other body fat evaluation indicators in both men and women( P<0.05). The risks of MS in CMI Q4 group were 17.15(95% CI 11.64-25.27) for male and 45.14(95% CI 37.07-54.96) for female compared with Q1 group. In male, the area under curve(AUC) of MS by predicted CMI was 0.761(sensitivity 79.8%, specificity 63.2%, optimal cut-off point 0.71). WC displayed the highest value of AUC among the body fat evaluation indicators. In women, the AUC value of MS predicted by CMI was 0.831(sensitivity 76.8%, specificity 75.7%, optimal cut-off point 0.65), higher than those of BMI and WHtR while lower than those of WC and LAP. Further calculating the prevalence of MS with the best cut-off point value of each index as the boundary, WC was still the best predictor for male, while CMI was only secondary to LAP for women. Conclusion:CMI and other body fat evaluation indicators are significantly associated with MS. CMI could be used to predict MS.