ObjectiveTo explore the effect of Buzhong Yiqitang on the immune imbalance of helper T cell 17 （Th17）/regulatory T cell （Treg） and Notch1 signaling pathway in mice with autoimmune thyroiditis （AIT）. MethodA total of 60 8-week-old NOD.H-2^h4 mice were randomly divided into the normal group， model group， western medicine group （selenium yeast tablet， 32.5 mg·kg^-1）， and low-dose （4.78 g·kg^-1·d^-1）， middle-dose （9.56 g·kg^-1·d^-1）， and high-dose （19 g·kg^-1·d^-1） Buzhong Yiqitang groups， with 10 mice in each group. The normal group was fed with distilled water， and the other groups were fed with water containing 0.05% sodium iodide for eight weeks. After the animal model of AIT was formed spontaneously， the mice were killed under anesthesia after intragastric administration for eight weeks. Serum anti-thyroglobulin antibodies （TGAb）， thyroid-stimulating hormone （TSH）， free triiodothyronine （FT3）， and free thyroid hormone （FT4） were detected by enzyme-linked immunosorbent assay （ELISA）， and thyroid tissue changes were observed by hematoxylin-eosin （HE） staining. The mRNA and protein expressions of retinoid-related orphan receptor-γt （RORγt）， interleukin （IL）-17， forkhead box P3 （FoxP3）， IL-10， Notch1， and hair division-related enhancer 1 （Hes1） in thyroid tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the normal group， the thyroid structure of the model group was severely damaged， and lymphocytes were infiltrated obviously. The levels of serum TGAb， FT3， and FT4 contents were significantly increased， and TSH content was significantly decreased （P<0.01）. The mRNA and protein expression levels of RORγt， IL-17， Notch1， and Hes1 were significantly increased， while those of FoxP3 and IL10 were significantly decreased in the model group （P<0.01）. Compared with the model group， thyroid structural damage and lymphocyte infiltration were improved in the treatment groups， and serum TGAb， FT3， and FT4 contents were significantly decreased. TSH content was increased， and mRNA and protein expression levels of RORγt， IL-17， Notch1， and Hes1 were decreased. mRNA and protein expression levels of FoxP3 and IL-10 were increased to different degrees （P<0.05， P<0.01）， and the middle-dose Buzhong Yiqitang group had the most significant intervention effect. ConclusionBuzhong Yiqitang can alleviate the thyroid structural damage in AIT mice， and its mechanism may be related to improving the abnormal differentiation of Th17/Treg immune cells and inhibiting the activation of the Notch1 signaling pathway.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

OBJECTIVE: To investigate the changes in function of CD8 METHODS: Flow cytometry was used to detect the expressions of PD-1, TIM-3, and LAG-3, which were the markers of exhausted CD8 RESULTS: The expressions of inhibitory receptors (PD-1, TIM3 and LAG-3) on CD8 CONCLUSION The exhausted CD8
CD8-Positive T-Lymphocytes ; Hepatitis A Virus Cellular Receptor 2 ; Humans ; Interferon-gamma ; Lymphocyte Count ; Lymphohistiocytosis, Hemophagocytic

Objective: To investigate the prevalence of allergic rhinitis (AR) in 3 central cities (Chifeng, Hohhot, Ordos) and the surrounding rural areas of Inner Mongolia region, and to look for possible risk factors related to the disease. Methods: From March to October of 2019, a multi-stage stratified random sampling epidemiological survey was conducted in Chifeng, Hohhot, Ordos and rural areas. The AR-related factors of the population were obtained in the form of face-to-face questionnaire survey, and the skin prick test (SPT) was taken for the participants. AR disease was diagnosed according to the "Guidelines for the Diagnosis and Treatment of Allergic Rhinitis (2015, Tianjin)". The daily airborne pollen situation in the three regions was monitored during the same period. SPSS 23.0 was used to analyze all survey results. Results: A total of 6 818 questionnaires were recovered, with 6 393 valid questionnaires. The self-reported prevalence of AR was 27.72% (1 772/6 393) and the confirmed prevalence of AR was 17.10% (1 093/6 393). The prevalence of perennial AR was 1.83% (117/6 393) while the prevalence of seasonal AR was 15.27% (976/6 393). The prevalence of AR diagnosed in females was higher than that in males (19.19% vs 15.34%, χ²=16.594, P<0.001) and the prevalence of females in the two age groups of 36-45 years and 46-55 years was significantly higher than that of males (18.17% vs 9.73%, 14.13% vs 7.25%, χ² value was 23.848, 18.772, respectively, all P<0.001). The prevalence of confirmed diagnoses in ethnic minorities was higher than that of Han nationality, and the prevalence of confirmed diagnoses in urban areas was higher than that in rural areas (23.13% vs 16.20%, 27.27% vs 9.71%, χ² value was 24.516, 336.024, respectively, all P<0.001). The main nasal symptoms of AR patients were sneezing (91.31%), nasal congestion (85.91%) and nasal itching (85.00%). The most common concomitant disease of AR was allergic conjunctivitis (73.99%). Asthma (OR=6.629), food allergy (OR=3.236), drug allergy (OR=1.786), application of antibiotics (OR=1.553), recent home decoration (OR=2.307), and smoking (OR=1.322) were the AR related risk factors. The highest proportion of SPT positive reactions was Artemisia annua (80.15%). The peak period of clinical symptoms of AR patients in Inner Mongolia region was July to September, which was consistent with the second peak period of airborne pollen monitoring. Conclusions: The prevalence of AR in central cities and the surrounding rural areas of Inner Mongolia region is 17.10%, and Artemisia species is the most important pollen allergen in this area. History of asthma, food allergy, drug allergy, antibiotic use, home decoration and smoking history are the related risk factors for AR.
Adult ; Allergens ; China/epidemiology* ; Female ; Humans ; Male ; Middle Aged ; Pollen ; Prevalence ; Rhinitis, Allergic/epidemiology* ; Rhinitis, Allergic, Seasonal ; Urbanization

OBJECTIVE: To establish a secondary hemophagocytic lymphohistiocytosis(HLH) mouse model, and to investigate the effect of ruxolitinib on the disease manifestation of model mice. METHODS: Wild type C57BL/6 mice were randomly divided into 4 groups: two groups of mice were intraperitoneally injected with CpG oligodeoxynucleotide 1826 (CpG-ODN1826) every other day to induce HLH, and other two groups were control groups. One group of the CpG-ODN1826 groups and one of the control groups were given ruxolitinib, and other two groups were given the same amount of PBS. Blood samples, serum ferritin and hepatic/spleen weights of experimental mice were detected and serum cytokine levels were measured by ELISA. RESULTS: Compared with the control groups, the levels of white blood cells, hemoglobin and platelets in the CpG-ODN1826 groups were significantly lower (P＜0.05); and liver/body weight, spleen/body weight, serum ferritin, sCD25, IL-10, IL-1β, IFN-Ƴ, IL-12p70, GM-CSF, TNF-α and IL-18 levels significantly increased (P＜0.05). There was no significant difference in the levels of IL-2, IL-4, IL-5, IL-6, IL-22, IL-13, IL-27 and IL-23 between the two groups (P＞0.05). The spleen in CpG group had disordered internal structure, expanding red pulp and hyperplastic nucleated cells. The liver had severe perivascular inflammations. The spleen/weight of the ruxolitinib-treated mice in the CpG-ODN1826 group was significantly smaller than that of the unapplied ruxolitinib (P＜0.05). CONCLUSION The CpG-ODN1826 can induce secondary HLH symptoms in wild type C57BL/6 mice. Ruxolitinib can alleviate the symptoms of splenomegaly in HLH model mice.
Animals ; Disease Models, Animal ; Lymphohistiocytosis, Hemophagocytic ; Mice ; Mice, Inbred C57BL ; Pyrazoles

OBJECTIVE: To determine the effects of hawthorn extract on serum lipid levels, pathological changes in aortic atherosclerosis plaque, inflammatory factors, and apoptosis-related protein and mRNA expression in apolipoprotein E gene knockout (ApoE) mice. METHODS: Thirty-six ApoE mice were fed with a high-fat diet starting at the age of 8 weeks. Mice were randomly divided into 3 groups by a random number table including model group, hawthorn extract group, and simvastatin group, 12 mice in each group. Twelve 8-week-old C57BL/6 mice were fed a basic diet and served as control. The mice in the control and model groups were administered 0.2 mL saline daily, the mice in the hawthorn extract and simvastatin groups were administered with 50 mg/kg hawthorn extract or 5 mg/kg simvastatin daily for 16 weeks. After 16 weeks, plasma lipids including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were determined by an enzymatic assay. Aortic atherosclerotic lesions were observed by light microscopy, scanning and transmission electron microscopy, respectively. Plasma levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-1β (IL-1β), adiponectin (APN), and hypersensitive C-reactive protein (hs-CRP) were measured by enzyme-linked immunosorbent assay (ELISA). Protein and mRNA expressions of Bax and Bcl-2 in the aorta were assessed by Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. RESULTS: Compared to the control group, the plasma levels of TC, TG and LDL-C were significantly increased and HDL-C were significantly decreased in the model group (P<0.01). Compared to the model group, treatment with hawthorn extract significantly decreased the plasma levels of TC, TG, and LDL-C and increased the plasma level of HDL-C in ApoE mice (P<0.01). The levels of MCP-1, IL-1ß, and hs-CRP in the model group were significantly increased and APN was significantly decreased compared with the control group (P<0.01). Compared to the model group, treatment with hawthorn extract decreased the levels of MCP-1, IL-1ß, and hs-CRP and increased the APN level (P<0.01). Compared to the control group, the protein and mRNA expression of Bax in the model group were significantly increased and the expression of Bcl-2 was significantly decreased (P<0.01). Hawthorn extract also reduced the protein and mRNA expression of Bax and increased the Bcl-2 expression in the aorta (P<0.01). CONCLUSION Hawthorn extract has anti-atherosclerosis and stabilizing unstable plaque effects. The mechanism may be related to the inflflammation and apoptosis signaling pathways.
Animals ; Aorta ; pathology ; ultrastructure ; Apoptosis ; drug effects ; Atherosclerosis ; blood ; complications ; drug therapy ; Crataegus ; chemistry ; Inflammation ; blood ; complications ; drug therapy ; Inflammation Mediators ; metabolism ; Lipids ; blood ; Male ; Mice, Inbred C57BL ; Plant Extracts ; pharmacology ; therapeutic use ; RNA, Messenger ; genetics ; metabolism ; bcl-2-Associated X Protein ; metabolism

BACKGROUND: Intra-articular injection of cells targeting to change the microenvironment in lesions can act on early osteoarthritis of inflammatory chondrocytes. Implanted cells affect the progress of the disease by the cell characteristics. OBJECTIVE: To explore the synergistic effect of mesenchymal stem cells from human knee adipose (ADMSCs) and synovial tissues (SDMSCs) to inhibit the degeneration of inflammatory chondrocytes. METHODS: ADMSCs, SDMSCs and inflammatory chondrocytes were primary cultured. Under in vitro two-dimensional culture conditions, cell proliferation assay (MTS) was performed to detect the proliferation of three kinds of cells. Differences in chondrogenic markers at mRNA and protein levels between three kinds of adherent cells were detected by quantitative PCR and immunofluorescence. Under in vitro three-dimensional mixed culture conditions, three groups were set up: (1) ADMSCs+inflammatory chondrocytes (A+C group), (2) SDMSCs+inflammatory chondrocytes (S+C group), and (3) ADMSCs-SDMSCs+inflammatory chondrocytes (A+S+C group). Alcian blue staining, safranin O staining and type Ⅱ collagen immunohistochemistry staining were performed on the mixed-cultured cell mass paraffin sections followed by quantitative analysis. Chondrogenic differentiation in each group was detected by quantitative PCR. Culture supernatants were collected to detect the secretion of pro-inflammatory and anti-inflammatory factors by enzyme-linked immunosorbent assay. RESULTS AND CONCLUSION: Under the two-dimensional culture, the proliferative rate of ADMSCs was significantly higher than that of inflammatory chondrocytes and SDMSCs (P < 0.05). The expression of type Ⅱ collagen mRNA and protein and proteoglycan protein in inflammatory chondrocytes was significantly higher than that in the other two kinds of cells (P < 0.01). Under the three-dimensional culture, the percentage of chondrogenic area per total area was significantly higher in the A+S+C group than the S+C and A+C groups (P < 0.05). The expression of type Ⅱ collagen and proteoglycan was significantly higher in the A+S+C group than the S+C and A+C groups (P < 0.05). Compared with the other two groups, the S+C group showed higher levels of interleukin 1, interleukin 6, and tumor necrosis factor α, but lower level of interleukin 10 (P < 0.05). To conclude, the combined use of ADMSCs and SDMSCs synergistically inhibits the degeneration of inflammatory chondrocytes.

Aged ; Biliary Tract Diseases ; surgery ; China ; Humans

IG-105, N-(2,6-dimethoxypyridine-3-yl)-9-methylcarbazole-3-sulfonamide, a novel antimicrotubule agent, showed potent anticancer activity in a variety of human tumor cells in vitro and in vivo. In order to characterize the metabolism and the possible drug-drug interaction of IG-105, we carried out a series of experiments. Drug metabolizing enzymes involved in IG-105 metabolism were investigated by using pooled human liver microsomes (HLMs) and recombinant cytochrome P450 isoforms (rP450s) respectively. The possible metabolites were analyzed by liquid chromatography-orbitrap-mass spectrometry (LC-Orbitrap-MS). The inhibitory effect of IG-105 on main P450 enzymes was also evaluated. The results showed that IG-105 can be metabolized by a series of rP450s, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4 and CYP3A5, with the major contribution enzymes being CYP1A2, CYP2B6, CYP2C19, and CYP3A. Three metabolites (M1-M3) were identified and demethylation was the major phase I metabolic reaction for IG-105. IG-105 moderately inhibited CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A enzyme activities with IC₅₀ values of 6.42, 23.64, 0.39, 1.4, and 3.14 μmol·L^-1, respectively. Since the biotransformation of IG-105 involves multiple enzymatic pathways, the compound is less likely to be a victim of a concomitantly used medicine which inhibits activity of one of the CYPs. However, as IG-105 showed medium to strong inhibition on CYP1A2, CYP2D6, CYP3A, and CYP2C19, caution is particularly needed when IG-105 is co-administrated with other anticancer drugs which are mainly metabolized by the above enzymes.