The study was performed to detect the binding proteins for advanced glycation end products (AGEs) on human joint synovial cells (HSCs). Normal human synovial cells (type A and type B cells) were isolated and cultured in vitro. Binding assay was performed with radiolabeled human serum albumin modified by AGE (AGE HSA). Specific binding was defined as total binding minus binding in the presence of excess unlabeled AGE HSA. The result showed that: specific dose dependent binding of 125 I AGE HSA to immobilized HSCs was observed with R=4.90 0.75 10 4 /cell , Kd = 1.27 0.19 10 -6 M in type A HSCs , and R= 3.48 0.32 10 5 /cell, Kd= 1.38?0.16 10 -7 M in type B HSCs. TNF ?,IL 1? and AGE HSA upregulated the expression of AGE binding proteins on HSCs. Normal HSCs express specific AGE binding proteins. TNF ?, IL 1? and AGE HSA upregulate the expression of these proteins, suggesting that joint resident cells may be involved in the pathogenesis of dialysis related amyloidosis.

Objective To study the changes in interleukin-32 (IL-32) in rats with Klebsiella bacillus pneumonia and approach its significance. Methods Seventy-two Sprague-Dawley(SD)rats were divide into control group,model group and experimental group by the method of random digits table,then the experimental group was subdivided into 4 hours and 1,3 and 5 days experimental subgroups(each n=6). The rat model of Klebsiella bacillus pneumonia was established by injection of 0.3 mL Klebsiella bacterial suspension into the trachea. Before the establishment of the model in the experimental group,IL-32 inhibitory agent,protease activated receptor-2(PAR2) was injected into the abdominal cavity. After model establishment,at different time points,blood was collected via tail vein to observe the changes in serum levels of IL-32,tumor necrosis factor-α(TNF-α),IL-6 and IL-8 in all the groups. The lungs were removed and stained with hematoxylin-eosin(HE)method to investigate the histopathological changes of the lung tissues under the light microscope. Results Compared to the control group, with the prolongation of time the levels of IL-32,TNF-α,IL-8 and IL-6 were increased gradually in the model group,and reached their peaks at 3 days〔IL-32(ng/L):84.40±28.24 vs. 18.57±3.86,t=5.544,P=0.002;TNF-α(ng/L):79.27±14.64 vs. 17.82±3.86, t=9.994, P=0.000;IL-8(ng/L):55.85±10.90 vs. 16.66±3.76,t=8.544, P=0.000;IL-6(ng/L):56.65±2.57 vs. 28.48±2.11,t=19.693,P=0.000〕;PAR2 could inhibit above indexes significantly,there was statistical difference at 3 days compared with the model group〔IL-32(ng/L):54.13±6.68 vs. 84.40±28.24,t=2.560,P=0.046;TNF-α(ng/L):49.12±3.56 vs. 79.27±14.64,t=4.901,P=0.003;IL-8 (ng/L):22.95±2.52 vs. 55.85±10.90,t=7.204,P=0.000;IL-6(ng/L):36.49±2.63 vs. 56.65±2.57,t=13.443, P=0.000〕. Under the light microscope,the inflammatory changes in the lung tissue in experimental group were milder than those in the model group. Conclusion As a pro-inflammatory cytokine,IL-32 can induce the production of TNF-α,IL-6 and IL-8,and the inhibition of IL-32 production may play a role in suppression of the development of Klebsiella bacillus pneumonia.

Objective To test the hypothesis that advanced glycosylation end products(AGEs) increase cellular inflammation in atherosclerotic plaques. Methods Fifty rabbits were randomly divided into five groups. Hypercholesterolemic (0.5% cholesterol in diet) rabbits received repeated intravenous injection of either AGEs modified rabbit serum albumin (AGEs-RSA ) (group A) or unmodified RSA (group B) for 10 weeks. Rabbits treated with either hypercholesterolemic diet (group C)or with a normal diet(group D) or with a normal diet, and intravenous injection of AGEs-RSA (group E) were served as controls. Aortas were harvested at the 10th week, and lipid deposition was quantitated by oil red 0 staining. Macrophage (RAM-11 positive cells) and T lymphocyte (CD43 positive cells) infiltration, smooth muscle cell(?-actin positive cells) migration and proliferation were determined by using immunohistochemical staining and image-analysis techniques. Results Atherosclerotic plaques could be found in animals fed with hypercholesterolemic diet.Lipid deposition in plaque was significantly higher in group A (71.86%?8.3%) than those in group B (53.76%?3.72%)and group C (56.67%?9.2%). Infiltrations of macrophage[ (23.1?8.5)/0.01 mm2]and T lymphocyte[ (15.1 ? 3.8)/0.01 mm2]as well as migration and proliferation of smooth muscle cell [ (19.2?5.7)/0,01 mm2] in atherosclerotic lesions were significantly increased in animals treated with hypercholesterolemic diet and received injection of AGEs-RSA (group A) when compared with group B [macrophage (14.4? 5.9)70.01 mm2; T lymphocyte (9.1?2.6)/0.01 mm2; smooth muscle cell (12.9?3.8)/0.01 mm2]and group C[macrophage (15.4?4.4)/0.01 mm2; T lymphocyte (10.5?2.2)/0.01 mm2, smooth muscle cell (13.8?3.9)/0.01 mm2]. Neither plaque nor a cellular inflammation was found in animals fed with normal diet (group D)and in those received repeated injections of AGEs-RSA (group E). Conclusion AGEs increase cellular inflammation in atherosclerotic plaques and may accelerate formation of atherosclerosis in AGEs associated diseases.

AIM: To investigate the effect of advanced glycosylation end products(AGEs) modified protein on morphological changes of actin cytoskeleton in primary endothelial cells and the role of MAPK signaling pathways in this pathological procedure.METHODS: Human umbilical vein endothelial cells(HUVECs) were incubated with AGEs modified human serum albumin(AGE-HSA) at concentrations of 12.5,25,50,and 100 mg/L,respectively,for 2,4,8,12 and 24 hours.The cells were treated with different chemical compounds of inhibitors,or adenoviral deliver approach(either dominant positive or negative adenoviral constructs) of MAP kinases to specifically block or activate certain signal transduction pathways under above situations.As control,HSA of the same concentration was administered to cells at the same time.The treated cells were incubated with FITC-phalloidin to stain F-actin.RESULTS: F-actin in HUVECs was rearranged greatly by AGEs in a concentration and time-dependent manners.The unmodified HSA did not influence Factin distributions.The AGEs-induced changes were blocked by pretreatment with SB203580,PD98059 for 30 min,or pre-infection with recombinant virus of dominant negative form of MKK 6b [MKK6b(A)],MEK1 [MEK1(A)] for 24 h,while SP600125 and dominant negative form of MKK7 [MKK7(A)] failed to inhibit the effects of AGEs.Furthermore,the infection of recombinant virus of constitutive active form of MKK6b [MKK6b(E)] or MEK1 [MEK1(E)] could also induced re-arrangement of F-actin,respectively,while the effect elicited by [MKK6b(E)] was abolished by co-infection with recombinant adeno-virus of dominant negative p38?. CONCLUSION: AGEs-induced morphological changes of F-actin in endothelial cells are mediated by p38-and ERK MAPK signal pathways.

From the Confucian perspective,different roles have different ethical considerations for physician-assisted suicide(PAS).From the perspective of patients,Confucianism does not support suicide as a right.For family members,Confucianism does not believe that PAS is more conducive to maintaining the dignity of patients.From a doctor's perspective,supporting PAS not only goes against the original intention of medicine,but may also lead to serious social consequences.In conclusion,Confucianism generally tends to adopt a negative attitude towards PAS.

Objective:To analyze the rash characteristics and diagnosis and treatment process of measles infection in patients with diabetes mellitus and psoriasis, to reduce the clinical diagnosis and treatment delay of such patients.Methods:The clinical data of a patient with diabetes combined with psoriasis and measles infection who was diagnosed and treated in The First Hospital of Yulin in April 2015 were analyzed.Results:The patient was admitted to hospital due to polydipsia and polyuria for 3 years and fever for 3 days. Hypoglycemic and anti-inflammatory treatment after admission was not good. On the third day after hospitalization, rash on the trunk and the extremities was seen. The patient had a history of measles infection. Based on clinical practice, Measles morbillivirus infection was not excluded, and Measles morbillivirus infection was confirmed by pathogen inspection. Measles reinfection was considered to be caused by variation of Measles morbillivirus. The atypical rash formed because of the patient's need for long-term treatment with Acitretin capsule and capotriol for psoriasis. After adjusting the antibiotic treatment, hypoglycemia and antiviral therapy were given, the body temperature was normal and the rash gradually subsided.Conclusion:For patients with type 2 diabetes mellitus and psoriasis, if they have a fever, they should be considered comprehensively to guard against re-infection caused by measles virus mutation. Timely etiological diagnosis is performed to avoid missed diagnosis and delayed treatment.

OBJECTIVETo investigate the phenotype and genotype defect characteristics of a Chinese patient with hereditary factor XI deficiency.

METHODSThe activated partial thromboplastin time (APTT), prothrombin time (PT), FXI activity (FXI:C) of the proband and his relatives were measured by a clotting method using automatic coagulation analyzer. FXI antigen (FXI:Ag) was assayed by enzyme-linked immunosorbent assay (ELISA). Fifteen exons of the F11 gene were amplified by PCR and sequenced. Pymol software was used to analyze the novel mutations.

RESULTSThe APTT of the proband was significantly prolonged (70.3 s, reference 34.5 s) with decreased FXI activity (6%, reference 50%-150%) and FXI antigen (1.9%, reference 50%-150%). The FXI activity and FXI antigen of his son was 31% and 39%, respectively. Two heterozygous F11 mutations were identified in the proband, which included a G to T substitution at nucleotide 1296 in exon 11 resulting in substitution of glycine by valine at codon 400 (p.Gly400Val) and a A to T substitution at nucleotide 1691 in exon 14 resulting in substitution of arginine (AGA) by a termination codon (TGA) at codon 532 (p.Arg532Ter). Analysis using Pymol indicated that the number of hydrogen bonds has changed, which led to a transformation of the structure of the FXI protein. The son of the proband was found to be heterozygous for the c.1296G to T (p.Gly400Val) mutation. NM_13142 c.1691A to T (p.Arg532Ter) is a novel mutation based on HGMD professional 2016.4. Based on 2015 Guidelines of ACMG, it is PVS1 (very strong pathogenicity).

CONCLUSIONThe compound heterozygous mutations of F11 NM_13142 c.1296G to T (p.Gly400Val) and F11 NM_13142 c.1691A to T(p.Arg532Ter) probably underlies the FXI deficiency in the proband.

【Objective】 To investigate the relationship between hepatitis B virus X （HBx） protein and EGFR promoter， and the role of HBx protein in activating EGFR/PI3K/p-Akt signaling pathway and inhibiting apoptosis. 【Methods】 EGFR promoter plasmids were constructed and the relationship between HBx and EGFR promoters was characterized using a luciferase reporter assay. EGFR-overexpressing trophoblast cells were constructed， and EGFR expression in the overexpressing cells was knocked down using EGFR shRNA. The expression and localization of EGFR/PI3K/p-Akt were detected by Western blotting and confocal laser microscopy. Cell apoptosis was analyzed using flow cytometry. HBV plasmids carrying either full-length HBx or HBx with a deletion mutation （ΔHBx） and HBx plasmids were transfected into two types of trophoblast cells； HBx and PI3K/p-Akt protein expressions were detected by Western blotting. Cell apoptosis was analyzed using flow cytometry. 【Results】 Co-transfection of HBx and EGFR promoter plasmids in JEG-3 and HTR-8/Svneo cells significantly elevated the expression of EGFR promoter driven luciferase compared with the control group （P<0.01）. In EGFR-overexpressing cells， the expression of PI3K/p-Akt was significantly increased （P<0.01）， whereas the apoptosis rate was significantly decreased for JEG-3 cells and HTR-8/Svneo cells （both P<0.01）. These results were reversed in the EGFR-knock down group. When the intracellular HBx protein was expressed in JEG-3 and HTR-8 cells， PI3K/p-Akt protein expression was significantly increased （both P<0.05）， and the proportion of apoptosis was significantly decreased （both P<0.05）. 【Conclusion】 In placental trophoblast cells， HBx protein activates the expression of EGFR by acting on the EGFR promoter， and inhibits the apoptosis of trophoblast cells via the downstream EGFR/PI3K/p-Akt signaling pathway.

Objective To explore whether indoor light-assisted therapy can rapidly improve depression and anxiety symptoms in patients with depression,as well as the safety of indoor-light-assisted therapy.Methods From September 2021 to December 2022,patients with depression were recruited from the Mental Health Center of the First Hospital of Hebei Medical University.According to the random number table method,patients were divided into test group and control group.The test group was treated with light therapy 30 minutes from 7:30 am to 8:00 am daily for 2 weeks in addition to antidepressant therapy.Antidepressant therapy was continued after completion of light therapy and patients were followed up for 2 weeks.The control group was treated with regular antidepressants throughout the four-week trial.Hamilton depression scale(HAMD17)and the Hamilton anxiety scale(HAMA)were used to assess the clinical symptoms at the baseline and the end of every week of treatment.Safety was evaluated using patient adverse events,anterior segment photography and visual testing.Results A total of 80 patients were enrolled,including 40 in the test group and 40 in the control group.The data of dropped were processed for missing values and then included in the statistical analysis.At the 1st(20.0％vs.0.0％)and 2nd(45.0％vs.17.5％)weekend of treatment,the response rate in the test group was significantly higher than that in the control group.There was an interaction between the time point and the group in HAMD17 total score(F=9.66,P<0.01).The scores of HAMD17 at the end of every week in the test group were significantly lower than that in the control group(P<0.05).There were significant differences in the reduction rate of total score in HAMD17[33.3％(25.0％,43.3％)vs.13.9％(9.9％,19.8％)]and HAMA[22.4％(16.5％,35.3％)vs.14.2％(4.4％,26.9％)]between the two groups(P<0.05).Incidences of adverse effect were not significantly different between the two groups(12.5％vs.10.0％,P=1.00).There were no severe adverse events or mania was reported in the test group and the eye examination showed no abnormality.Conclusion Compared with antidepressant therapy alone,indoor light therapy combined with antidepressant can quickly improve depression and anxiety symptoms in patients with depression,shorten the duration of depression treatment,and has good safety.