Bluetongue virus is an arbovirus that seriously harms ruminants such as sheep,this study aims to investigate the molecular mechanism of bluetongue virus infection and host cell interferon antiviral immune response.The study was conducted to characterize the mRNA expression of inter-feron pathway genes by real-time fluorescence quantitative PCR,as well as Western blot analysis of MDA5,TRAF3,RIG-Ⅰ,and TBK1 protein expression in BHK-21 cells induced by BTV with a multiplicity of infections(MOI)of 1 for 18,24,and 36 h.The results showed that the most pro-nounced changes in the expression of interferon signaling pathway genes were observed at 24 h of induction,the gene mRNA expression levels of the IFN-α,IFN-β,RIG-Ⅰ,TBK1,MDA5,VISA,and TRAF3 genes were upregulated.However,the mRNA expression levels of IKKε and TRAF6 genes were downregulated.At the protein level,MDA5 and TBK1 proteins were upregulated while RIG-1 and TRAF3 proteins were downregulated,which showed that BTV infection induces a typeⅠ interferon immune response in BHK-21 cells.This study lays the foundation for further exploring the antiviral immunity mechanism of IFN-Ⅰ signaling pathway regulatory genes in host cells infected with BTV infection.

Objective:To analyze the cause and epidemiological characteristics of an outbreak of cutaneous anthrax in Caoxian County, Heze City, Shandong Province, and to provide scientific basis for anthrax prevention and control.Methods:Using on-site epidemiological investigation methods and the "Anthrax Epidemiological Case Investigation Form", case investigations were conducted based on the epidemiological contact history and close contacts of suspected anthrax cases reported by the national health care system ( n = 83). Scorched skin smears, diseased cattle tissues, soil samples from the slaughter site and smears from slaughter utensils were collected from cases for Real-time PCR testing and pathogenic bacteria isolation and culture, respectively. Anthrax determination criteria were carried out with reference to "Anthrax Diagnosis" (WS 283-2020). Results:A total of 13 cases of cutaneous anthrax were found in this outbreak, including 12 clinically diagnosed cases and one confirmed case (positive Real-time PCR test and isolation of a strain of Bacillus anthracis). The epidemiological investigation determined that the source of infection in this outbreak was diseased cattle, the transmission route was through slaughter of diseased cattle, contact with contaminated utensils and related cattle products, and the patients were mainly engaged in occupations related to cattle slaughter or cattle product collection and sale. A total of 84 samples were collected, including 13 skin scabs, 64 environmental samples and 7 beef samples. Thirty-six positive PCR tests were performed, with a positive rate of 42.86% (36/84). Among them, 100.00% (13/13) were positive for skin scab smear specimens, 29.69% (19/64) for environmental samples and 4/7 for beef samples. A total of 8 strains of Bacillus anthracis were isolated, including 6 environmental specimens, 1 suspected case and 1 beef strain, with an overall detection rate of 9.52% (8/84). Eighty-three close contacts were investigated. Thirteen households involved in the epidemic were disinfected by spraying (200 ml/m 2) with chlorine-containing disinfectant (5 000 mg/L), and a total of 40 households involved in the epidemic were disinfected, covering an area of about 10 765 m 2. Forty-five pieces of suspected contaminated clothing were burned and disposed of, and 152 pieces of kitchenware were soaked. Conclusions:Slaughter of infected cattle, contact with contaminated utensils and related cattle products are the main causes of this skin anthrax outbreak. Strengthening market supervision, deepening inter-animal epidemic prevention, carrying out publicity and education on anthrax prevention and control, and enhancing practitioners' awareness of disease prevention is the key to prevent anthrax from occurring.

Based on ZHU Zhenheng's “six constraints” theory， it is proposed that the formation of pulmonary nodules is closely related to the six constraints， which are constraint of qi， blood， phlegm， fire， dampness and food. All six constraints might lead to pulmonary nodules， among which qi constraint is the dominant one. When qi constraint lasts for a long time， it will turn into fire constraint， resulting in the failure of spleen to transport， which may lead to phlegm constraint， dampness constraint and food constraint； when qi fails to move blood， blood constraint is formulated. Mutual generation of six constraints lead to the disease， and the pathogenesis is interrelated， jointly promoting the occurrence and development of pulmonary nodules. The treatment is mainly to unblock qi， usually using Yueju Pills （越鞠丸）， a classic formula commonly used for six constraints， as the basic formula. And according to the six constraints partiality， it is suggested to flexibly add the medicinals of soothing the liver and rectifying qi， clearing heat and dissipating masses， dissolving phlegm and dissipating masses， fortifying spleen and dissipating dampness， promoting digestion and removing accumulation， invigorating blood and dissolving stasis.

Objective To observe the potential mechanism of electroacupuncture regulating the erythropoietin-producing hepatocellular receptor B2/erythropoietin-producing hepatocellular receptor-interacting B2/big mitogen-activated protein kinase 1(EphB2/EphrinB2/BMK1) signaling pathway to improve neural damage in vascular dementia rats. Methods Eighty SD male adult rats were randomly divided into a sham surgery group, a model group, a non acupoint electroacupuncture group, a nimodipine group, and an electroacupuncture three needle group. The vascular dementia rat model was made by the modified Pulsinelli four vessel occlusion method. After grouping, the rats in each group were subjected to water maze test, HE staining, Nissl staining, and transmission electron microscopy(TEM) to observe the pathological changes in the hippocampal CA1 area, and the expression of EphB2 and BMK1 in the hippocampal CA1 area was detected by immunohistochemistry; Detection of EphB2 and BMK1 protein expression in rat hippocampal CA1 region was detected by Western blotting. Results Compared with the model group, the escape latency of vascular dementia rats treated with electroacupuncture and nimodipine decreased (P<0.05), while the number of crossing platforms significantly increased (P<0.05); The result of HE staining, Nissl staining and TEM showed that compared with the model group, the neurons in hippocampal CA1 area of rats in the EA Zhisanzhen group and nimodipine group were arranged orderly, and the morphology and structure of cells and organelle were complete; Immunohistochemical method and Western blotting showed that the expression of EphB2 and BMK1 in the CA1 region of hippocampus in the model group was significantly lower than that in the sham surgery group (P<0.05); Compared with the model group, the expression of EphB2 and BMK1 in the hippocampal CA1 region of rats in the electroacupuncture Zhisanzhen group significantly increased (P<0.05), while the expression of EphB2 and BMK1 in the hippocampal CA1 region of rats in the non acupoint electroacupuncture group was not statistically significant (P>0.05). Compared with the nimodipine group, the expression of EphB2 and BMK1 in the hippocampal CA1 region of rats in the electroacupuncture Zhisanzhen group significantly increased (P<0.05). Conclusion Electroacupuncture may improve the damage of hippocampal neurons in vascular dementia rats by increasing the expression of EphB2 and BMK1 in the CA1 region of the hippocampus, thereby improving the learning and memory of vascular dementia rats.

Objective: To identify the clinically relevant factors of steroid-resistant nephrotic syndrome (SSNS) in children and establish a predictive model followed by verifying its feasibility. Methods: A retrospective analysis was performed in a total of 111 children with nephrotic syndrome admitted to Children's Hospital of ShanXi from January 2016 to December 2021. The clinical data of general conditions, manifestations, laboratory tests, treatment, and prognosis were collected. According to the steroid response, patients were divided into SSNS and steroid resistant nephrotic syndrome (SRNS) group. Single factor Logistic regression analysis was used for comparison between the 2 groups, and variables with statistically significant differences were included in multivariate Logistic regression analysis. The multivariate Logistic regression analysis was used to identify the related variables of children with SRNS. The area under the receiver operating characteristic curve (ROC), the calibration curve and the clinical decision curve were used to evaluate its effectiveness of the variables. Results: Totally 111 children with nephrotic syndrome was composed of 66 boys and 45 girls, aged 3.2 (2.0, 6.6) years. There were 65 patients in the SSNS group and 46 in the SRNS group.Univariate Logistic regression analysis showed that the 6 variables, including erythrocyte sedimentation rate, 25-hydroxyvitamin D, suppressor T cells, D-dimer, fibrin degradation products, β2-microglobulin, had statistically significant differences between SSNS and SRNS groups (85 (52, 104) vs. 105 (85, 120) mm/1 h, 18 (12, 39) vs. 16 (12, 25) nmol/L, 0.23 (0.19, 0.27) vs. 0.25 (0.20, 0.31), 0.7 (0.6, 1.1) vs. 1.1 (0.9, 1.7) g/L, 3.1 (2.3, 4.1) vs. 3.3 (2.7, 5.8) g/L, 2.3 (1.9,2.8) vs. 3.0 (2.5, 3.7) g/L, χ²=3.73, -2.42, 2.24, 3.38, 2.24,3.93,all P<0.05), were included in the multivariate Logistic regression analysis. Finally, we found that 4 variables including erythrocyte sedimentation rate, suppressor T cells, D-dimer and β2-microglobulin (OR=1.02, 1.12, 25.61, 3.38, 95%CI 1.00-1.04, 1.03-1.22, 1.92-341.04, 1.65-6.94, all P<0.05) had significant correlation with SRNS. The optimal prediction model was selected. The ROC curve cut-off=0.38, with the sensitivity of 0.83, the specificity of 0.77 and area under curve of 0.87. The calibration curve showed that the predicted probability of SRNS group occurrence was in good agreement with the actual occurrence probability, χ²=9.12, P=0.426. The clinical decision curve showed good clinical applicability. The net benefit is up to 0.2. Make the nomogram. Conclusions: The prediction model based on the 4 identified risk factors including erythrocyte sedimentation rate, suppressor T cells, D-dimer and β2-microglobulin was suitable for the early diagnosis and prediction of SRNS in children. The prediction effect was promising in clinical application.
Male ; Female ; Humans ; Child ; Nephrotic Syndrome/diagnosis* ; Retrospective Studies ; Models, Statistical ; Prognosis ; Steroids/therapeutic use*

Aim To explore the possibility of resveratrol ( RES) combined with irinotecan ( IRI) in the treatment of colorectal cancer ( CRC ) and the underlying molecular mechanism of RES ameliorating IRI chemoresistance of CRC cells. Methods CRC cells used in this study were HT-29 and RKO cells. The effects of RES, IRI and their combination on the proliferation of CRC cells were analyzed by MTT assay and colony formation assay. The effects of RES,IRI and their combination on the migration of CRC cells were assessed by Wound-healing assay. On this basis,the role of RES in regulating IRI chemoresistance of CRC cells and the underlying molecular mechanisms were further explored. Results The proliferation and migration ability of CRC cells in the RES and IRI combined treatment group were significantly lower than those in the IRI treated group, which showed that RES could enhance the inhibiting effect of IRI on the proliferation and migration of CRC cells, indicating that RES was able to a-meliorate the chemoresistance of CRC cells to IRI. And remarkably lower marker proteins expression levels of EGFR/AKT/mTOR signaling pathway in the RES and IRI combined treatment group was observed. Moreover, both EGFR activator (NSC 228155) and AKT activator (SC79) could reverse the ameliorating effect of RES on IRI chemoresistance of CRC cells, whereas AKT inhibitor (MK2206 ) could partially reverse the effect of NSC 228155. Conclusions RES can inhibit the proliferation and migration of CRC cells by down-regulating EGFR/AKT/mTOR signaling pathway, so as to ameliorate the chemoresistance of CRC cells to IRI, suggesting that RES combined with IRI can be a promising novel treatment for CRC.

Heat stroke(HS)is a serious life-threatening disease caused by heat injury and characterized by a core body temperature>40℃with central nervous system dysfunction and multi-organ failure.The main pathophysiological manifestations of HS are the thermal acute phase response and thermoregulatory imbalance.Proteins are particularly sensitive to heat,and the thermal environment can cause massive protein denaturation,resulting in the deposition of unfolded and misfolded proteins in the cytoplasm,causing cellular dysfunction and even death.The unfolded protein response(UPR),mainly divided into the endoplasmic reticulum UPR and the mitochondrial UPR,is an important physiological process that helps proteins to fold correctly or degrade irretrievably denatured proteins.This paper summarizes the regulatory mechanisms of UPR,the relationship between UPR and severe diseases,as well as the relationship between HS and UPR to provide new ideas for the treatment of HS.

Objective:To investigate the efficacy and safety of ixazomib combined with lenalidomide and dexamethasone (IRd) regimen in treatment of multiple myeloma (MM) patients in the real world practice.Methods:The clinical data of 24 MM patients treated with IRd regimen from January 2019 to January 2021 in the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively analyzed, and their efficacy and adverse reactions were analyzed. Among the 24 patients, 5 patients were relapsed and refractory (relapsed/refractory group), and 19 newly treated patients (conversion group) who responded to bortezomib induction therapy but converted to IRd regimen due to adverse reactions or other reasons.Results:The 24 patients were treated for a median of 4 cycles (2-7 cycles), with 8 cases of complete remission (CR), 6 cases of very good partial remission (VGPR), 8 cases of partial remission (PR), 1 case of disease progression (PD), 1 case of minimal response (MR), and the overall response rate (ORR) was 91.7% (22/24); the median progression-free survival (PFS) time was 15 months (95% CI 6.6-23.4 months); 6 CR patients were negative for minimal residual disease (MRD). The common adverse reactions were hematological adverse reactions, peripheral neuropathy, fatigue, gastrointestinal reactions, and infections. The incidence rate of grade 3-4 adverse reactions was 25.0% (6/24). In the relapsed/refractory group, the best efficacy was VGPR in 1 case, PR in 3 cases, and MR in 1 case, all patients withdrew from the IRd regimen therapy due to PD after transient remission or poor effect; in the conversion group, the best efficacy was CR in 8 cases, VGPR in 5 cases, PR in 5 cases, and PD in 1 case, 57.9% (11/19) patients maintained their original best response, and 36.8% (7/19) patients improved their best response to CR; the difference in median PFS time between the two groups was statistically significant (7 months vs. not reached, P = 0.018). Conclusions:The IRd regimen is safe and effective for MM patients, especially for the conversion patients after effective bortezomib induction therapy. Although patients with relapsed/refractory MM who have previously used multi-line therapy respond to IRd regimen, the duration of remission is limited.

[This corrects the article DOI: 10.1016/j.apsb.2021.09.017.].

ObjectiveTo observe that effect of Ersi decoction on rats with rheumatoid arthritis （RA） induced by using the complete Freund's adjuvant emulsion containing bovine type Ⅱ collagenand and elucidate underlying menchanisms involving to inhibit inflammation and joint synovial angiogenesis. MethodThe rat model of RA was established by immune induction with complete Freund's adjuvant emulsion containing bovine type Ⅱ collagen. All male SD rats were randomly divided into blank group， RA model group， methotrexate group（1.0 mg·kg^-1）， and low-， medium- and high-dose group（30，15，7.0 g·kg^-1·d^-1）of Ersi decoction， with 8 rats in each group. Except the blank group， rats in the methotrexate group and Ersi decoction groups were given corresponding doses of methotrexate and Ersi decoction after establishment of RA induced by strengthen immunity，respectively，and those in the model group and blank group received normal saline of equivalent volume，once a day for 28 days. After the administration， the degree of joint swelling of rats in each group was analyzed by joint swelling volume and index. The small animal ultrasound imaging system was used to detect the score and area of synovial hyperplasia of knee joint in right lower limb of rats and hematoxylin-eosin（HE）staining to observe the histomorphological changes in joint synovium of rats. The levels of tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） were measured by enzyme-linked immunosorbent assay（ELISA）. Immunohistochemistry was employed to analyze the expression of CD31 and vascular endothelial growth factor receptor 2（VEGFR2） in in joint synovium. ResultCompared with the blank group， the model group demonstrated significant increase in joint swelling volume and index， inflammatory cytokines including TNF-α and IL-1β in serum， the score and area of synovial hyperplasia of knee joint in right lower limb， obvious pathological changes in the synovium and the expression of CD31 and VEGFR2 in joint synovium. Medium and high-dose Ersi decoction significantly alleviated the pathological changes of synovium tissue， attenuated joint swelling volume and index and decreased the expression of CD31 and VEGFR2 in joint synovium as compared with the model group. Moreover， high-dose Ersi decoction showed significantly lower levels of TNF-α and IL-1β in serum， and the score and area of synovial hyperplasia of knee joint in right lower limb. But medium-dose Ersi decoction only showed lower levels of TNF-α and area of synovial hyperplasia of knee joint. ConclusionErsi decoction could reduce synovial inflammation and hyperplasia through inhibiting synovial angiogenesis in rats with RA induced by bovine type Ⅱ collagen for achieving the effect of reducing RA joint damage， which provides an important reference for anti-RA of Ersi decoction in clinical application.