Objective To study the gene therapy of metastatic prostate cancer. Methods we investigated the ability of adenoviral vectors expressing cytokines IL-12 and IL-2 to induce regression of tumor in C57BL/6 mice models(n=66) of prostate cancer. Results Adenoviral vectors can express cytokines IL-12 and IL-2 proteins effectively. Only 20%(2/10) of mice inoculated with RM-1 cells engineered AdmIL-12 and AdhIL-2 developed smaller and delayed tumors ( P

Objective:To investigate the predictive value of P-selectin and D-dimer in the early diagnosis of portal vein thrombosis(PVT) in patients submitted to portal hypertension operation. Method:Eighty-two patients were assigned into two groups(PVT group and non-PVT group)after the operative treatment of portal hypertension.The levels of P-selectin and D-dimer were detected dynamically in the patients of two groups.Results:The preoperative levels of P-selectin and D-dimer in the PVT group were higher than those in the non-PVT group respectively(P

Th22,a new subset of helper T cells,which is char-acterized by the secretion of interleukin-22(IL-22),could infil-trate to the epidermis in individuals with inflammatory skin disor-ders.This article introduces the action of Th22 and IL-22 in in-flammatory skin diseases,including psoriasis,atopic dermatitis, systemic lupus erythematosus,systemic sclerosis,aiming at re-vealing the role of Th22 and IL-22 in these diseases,which would not only provide some novel targets of drugs for inflamma-tory skin diseases,but also promote the researches on the pre-vention and treatment of these diseases.

Objective To investigate the relationship between IL‐10 SNPs and breast cancer susceptibility .Methods Collect‐ed 156 blood samples of breast cancer patients as case group and 156 blood samples of health as control .Genotype SNPs of IL‐10‐592 ,‐1082 were analyzed by genomic DNA extraction ,PCR amplification and TOF mass spectrometry .The data was used by statis‐tical analysis .Results IL‐10‐592 C/C ,C/A and A/A site the genotype frequencies were not diversity between two groups(χ2 =3 .26 ,P>0 .05) .IL‐10‐1082 G/G、G/A、A/A site the genotype frequencies were statistically significant between two groups(χ2 =14 .07 ,P<0 .01) .In Logistic multivariate regression analysis found that :be compared with IL‐10‐592 A/A ,carrying IL‐10‐592 C/A ,C/C group respectively the risk of breast cancer were OR=1 .039(95% CI:0 .484 -2 .233) ,P=0 .922 ,OR= 1 .635(95% CI:0 .683-3 .915) ,P =0 .270 ,which had no statistical significance .In Logistic multivariate regression analysis found that :be com‐pared with IL‐10‐1082 A/A ,carrying IL‐10‐1082 G/A、G/G group respectively the risk of breast cancer were OR=0 .424(95% CI:0 .210-0 .855) ,P=0 .016 ,OR=0 .455(95% CI:0 .178 -1 .163) ,P= 0 .100 .Conclusion IL‐10‐592 may be not associated with breast cancer susceptibility .IL‐10‐1082 G/A may be a protection factor with breast cancer susceptibility .

Group II chaperonins, which assemble as double-ring complexes, assist in the refolding of nascent peptides or denatured proteins in an ATP-dependent manner. The molecular mechanism of group II chaperonin assembly and thermal stability is yet to be elucidated. Here, we selected the group II chaperonins (cpn-α and cpn-β), also called thermosomes, from Acidianus tengchongensis and investigated their assembly and thermal stability. We found that the binding of ATP or its analogs contributed to the successful assembly of thermosomes and enhanced their thermal stabilities. Cpn-β is more thermally stable than cpn-α, while the thermal stability of the hetero thermosome cpn-αβ is intermediate. Cryo-electron microscopy reconstructions of cpn-α and cpn-β revealed the interwoven densities of their non-conserved flexible N/C-termini around the equatorial planes. The deletion or swapping of their termini and pH-dependent thermal stability assays revealed the key role of the termini electrostatic interactions in the assembly and thermal stability of the thermosomes.
Acidianus ; metabolism ; Adenosine Triphosphate ; metabolism ; Amino Acid Sequence ; Cryoelectron Microscopy ; Hydrogen-Ion Concentration ; Molecular Sequence Data ; Mutation ; Nucleotides ; metabolism ; Protein Binding ; Protein Folding ; Protein Stability ; Protein Structure, Quaternary ; Sequence Alignment ; Static Electricity ; Temperature ; Thermosomes ; chemistry ; genetics ; metabolism

BACKGROUND: Pathological cardiac hypertrophy is one of the main activators of heart failure. Currently, no drug can completely reverse or inhibit the development of pathological cardiac hypertrophy. To this end, we proposed a silicate ion therapy based on extract derived from calcium silicate (CS) bioceramics for the treatment of angiotensin II (Ang II) induced cardiac hypertrophy. METHODS: In this study, the Ang II induced cardiac hypertrophy mouse model was established, and the silicate ion extract was injected to mice intravenously. The cardiac function was evaluated by using a high-resolution Vevo 3100 small animal ultrasound imaging system. Wheat germ Agglutinin, Fluo4-AM staining and immunofluorescent staining was conducted to assess the cardiac hypertrophy, intracellular calcium and angiogenesis of heart tissue, respectively. RESULTS: The in vitro results showed that silicate ions could inhibit the cell size of cardiomyocytes, reduce cardiac hypertrophic gene expression, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and b-myosin heavy chain (b-MHC), decrease the content of intracellular calcium induced by Ang II. In vivo experiments in mice confirmed that intravenous injection of silicate ions could remarkably inhibit the cardiac hypertrophy and promote the formation of capillaries, further alleviating Ang II-induced cardiac function disorder. CONCLUSION This study demonstrated that the released silicate ions from CS possessed potential value as a novel therapeutic strategy of pathological cardiac hypertrophy, which provided a new insight for clinical trials.

Objective To explore the application method and value of mind mapping in the clinical teaching of general practitioners for the purpose of improving the teaching qualities. Methods A total of 60 GPs were divided into the test group and control group, undergoing the mind mapping teaching and tra-ditional teaching, respectively. The clinical knowledge achievements were compared in the two groups, and the results were analyzed. At the same time, a questionnaire was conducted. Results The difference between two groups in theoretical teaching was statistically significant (P<0.05), and there was no significant difference in physical examination (P>0.05). In addition, the results of the questionnaire survey showed that the test group was better than the control group in medical knowledge, self-learning ability, interpersonal communication ability, team cooperation ability and other dimensions. Conclusion Mind mapping is an effective teaching tool for general practitioners.

Objective The objective of this study was to investigate the expression of interleukin-38(IL-38)in patients with breast cancer and its regulatory function to CD8+T cell activity.Methods 44 patients with breast cancer,25 patients with benign breast tumor,and 20 controls,who were treated in the First Affiliated Hospital of Xinxiang Medical University from July 2020 and Sep-tember 2022.Mononuclear cells from plasma and peripheral blood of all subjects were isolated,tumor-infiltrating lymphocytes from tumor tissues of breast cancer patients were isolated,and CD8+T cells were purified.IL-38 protein level in the plasma was measured by enzyme-linked immunosorbent assay(ELISA).The relative level of IL-38 mRNA in the tissue was semi-quantified by real-time quantitative PCR.Recombinant human IL-38 was used to stimulate CD8+T cells from peripheral blood and tumor tissue from patients with breast cancer.A co-culture system was established between CD8+T cells and breast cancer MCF-7 cell line.The percentage of target cell death was calculated by measuring lactate dehydrogenase level in the supernatants.The levels of perforin,granzyme B,inter-feron-γ and tumor necrosis factor-α(TNF-α)in the supernatants were measured by ELISA.The immune checkpoint molecules ex-pression in CD8+T cells were detected by flow cytometry.Results The levels of plasma IL-38 were significantly higher in patients with breast cancer(74.23±19.88 pg/mL)compared with in patients with benign breast tumor(62.87±16.27 pg/mL,P=0.018)and controls(61.77±12.75 pg/mL,P=0.013).The relative expression of IL-38 mRNA in tumor tissues was significantly higher than in para-tumor tissues(1.57±0.22 vs.1.00±0.18,P<0.001).The proportion of target cell death induced by peripheral and tumor-in-filtrating CD8+T cells,and the levels of perforin and granzyme B secretion in direct contact co-culture group were higher than those in indirect contact co-culture group(P<0.05).There were no significant differences of either interferon-γ or TNF-α levels between di-rect contact and indirect contact co-culture group(P>0.05).In the direct contact co-culture group,the levels of target cell death pro-portion,perforin,granzyme B,interferon-γ and TNF-α l in the IL-38 stimulation group were lower than those in the non-stimulation group(P<0.05).In the indirect contact co-culture group,the target of cell death proportion,interferon-γ and TNF-α the IL-38 stimulation group were also lower than those in the non-stimulation group(P<0.05).However,there were no statistical differences of either perforin or granzyme B levels between the IL-38 stimulation group and non-stimulation group within the indirect contact co-culture group(P>0.05).There were also no differences in the levels of immune checkpoint molecules in CD8+T cells between the non-stimulation group and the IL-38 stimulation group(P>0.05).Conclusion Highly expressed IL-38 in patients with breast cancer may be involved in inducing CD8+T cell functional failure.

Objective Based on U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,the signal mining of tizanidine adverse drug events(ADEs)was conducted to explore the occurrence characteristics of ADE,hoping to provide references for the safe clinical application of tizanidine.Methods The reporting odds ratio(ROR)and medicines and healthcare products regulatory agency methods(MHRA)were used to analyse the ADE of tizanidine using FAERS registration data from the first quarter of 2004 to the second quarter of 2022.After valid signals were obtained,the MedDRA was used for translation and system organ classification.Results A total of 7 135 reports of tizanidine ADE were obtained,including 1 732 patients,1 304 ADE types were involved.According to the results of 2 ADE signal mining methods,at the preferred term(PT)level,177 signals were detected.There were 32 PT signals not included in the drug instructions,including potassium wasting nephropathy,cardio-respiratory arrest,and foetal growth restriction etc.In 1 732 patients,the number of ADE cases of female was 2.37 times that in male(1 057 vs.446),and the age group between 40 and 64 accounted for a large proportion(36.03％).The highest proportion(32.79％)reported by consumers.The system organ class involved mainly included various neurological diseases and psychosis.The median time to onset of tizanidine-related ADEs was 75 d(interquartile range:28-223 d),but it was necessary to be vigilant that ADE may still occur 1 year after starting the drug(13.38％).Conclusion This study aims to suggest that clinical application of tizanidin-related ADE should be paid full attention to the occurrence of ADE such as potassium-wasting nephropathy and suicidally completed,as well as key populations such as women and patients of 40-64 years old.

Objective:To analyze the clinical phenotype and genetic characteristics for a child with Canavan disease.Methods:A child who was admitted to the Children's Hospital Affiliated to Shandong University on April 9, 2021 for inability to uphold his head for 2 months and increased muscle tone for one week was subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing.Results:Genetic testing revealed that the child has harbored compound heterozygous variants of the ASPA gene, including a paternally derived c. 556_559dupGTTC (p. L187Rfs*5) and a maternally derived c.919delA (p. S307Vfs*24). Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+ PM2_Supporting+ PM3). Conclusion:The c. 556_559dupGTTC (p.L187Rfs*5) and c. 919delA (p.S307Vfs*24) compound heterozygous variants of the ASPA gene probably underlay the pathogenesis of Canavan disease in this child.