BACKGROUND: To date, results on relationship between CYP3A4 gene polymorphism were limited and inconclusive, and no study focused on the influence of CYP3A4 gene-obesity interaction on breast cancer risk, especially in Chinese women. The purpose of this study was to evaluate the impact of four single nucleotide polymorphisms (SNPs) of CYP3A4 gene, the SNP-SNP and gene-environment interactions on the susceptibility to breast cancer in Chinese women. METHODS: Logistic regression was used to explore the relationship between four SNPs of CYP3A4 gene and the risk of breast cancer. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best SNP-SNP and gene-abdominal obesity interaction combinations among four SNPs and abdominal obesity. Haplotype examination among 4 SNPs was conducted using the SHEsis web-based platform. RESULTS: Logistic regression analysis showed that carriers of rs2242480- T allele have significantly higher breast cancer risk, than those with rs2242480- CC genotype, adjusted OR (95%CI) was 1.68 (1.23-2.16) and 2.03 (1.53-2.58) for participants with CT genotype and TT genotype under additive model. We did not find any notable interactions between the four SNPs within the CYP3A4 gene. GMDR model found a significant association in a two-locus model involving rs2242480 and obesity, with a p-value of 0.018. Stratified analysis found that breast cancer risk was the highest in obese participants with rs2242480- CT or TT genotype, compared to those non-obese participants with rs2242480- CC genotype, OR (95%CI) was 3.02 (1.83-4.25). We found that all haplotype combinations were not correlated with breast cancer risk. CONCLUSIONS We found that the T allele of rs2242480 within the CYP3A4 gene and interaction between rs2242480 and obesity were associated with an increased risk of breast cancer. However, the results of this study were only applicable to the Han ethnic group and cannot be generalized to other ethnic groups in China, and more SNPs of CYP3A4 gene should been enrolled in the analysis in the future, to verify the results obtained in this study.
Adult ; Aged ; Female ; Humans ; Middle Aged ; Breast Neoplasms/etiology* ; China/epidemiology* ; Cytochrome P-450 CYP3A/metabolism* ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Haplotypes ; Obesity/epidemiology* ; Polymorphism, Single Nucleotide ; Risk Factors ; East Asian People

Objective:To investigate the inhibitory effect of tripartite motif-containing 25 (TRIM25) on the replication of Japanese encephalitis virus (JEV) in cells and its molecular mechanism.Methods:Human glioma cells (U251 cells) and Kunming mice were infected with JEV, and then the cells and brain tissue samples were collected. The transcription levels of six TRIM genes were detected by real-time PCR, and the expression of TRIM25 in cells was detected by Western blot. U251 and A549 cells overexpressed with TRIM25 and U251 cells knocked out with TRIM25 gene were constructed. Cells were infected with JEV, and the replication of JEV was detected by viral plaque assay, real-time PCR and Western blot. The interaction of TRIM25 with viral proteins was investigated by co-immunoprecipitation (Co-IP) and indirect immunofluorescence assay. The expression of IFN-β in overexpressed TRIM25 cells was detected by real-time PCR and ELISA.Results:JEV infection promoted the expression of TRIM25 in cells and mouse brain tissues. TRIM25 overexpression restricted JEV replication in U251 and A549 cells, while TRIM25 knockout enhanced JEV replication. TRIM25 overexpression upregulated the level of IFN-β in cells. TRIM25 interacted with JEV capsid protein and promoted the degradation of capsid protein.Conclusion:TRIM25 can inhibit the replication of JEV in cells by upregulating IFN-β and promoting the degradation of JEV C protein.

Background::Hepatitis B poses a heavy burden for children in China, however, the national studies on the distributional characteristics and health care costs of children with severe hepatitis B is still lacking. This study aimed to analyze the disease characteristics, health economic effects, and medical cost for children with severe hepatitis B in China.Methods::Based on patient information in the Hospital Quality Monitoring System, cases with severe hepatitis B were divided into four groups according to age, and the etiology and symptoms of each group were quantified. The cost of hospitalization was calculated for cases with different disease processes, and severity of disease. The spatial aggregation of cases and the relationship with health economic factors were analyzed by Moran’s I analysis. Results::The total number of children discharged with hepatitis B from January 2016 to April 2022 was 1603, with an average age of 10.5 years. Liver failure cases accounted for 43.48% (697/1603) of total cases and cirrhosis cases accounted for 11.23% (180/1603). According to the grouping of disease progression, there were 1292 cases without associated complications, and the median hospitalization cost was $818.12. According to the spatial analysis, the aggregation of cases was statistically significant at the prefectural and provincial levels in 2019, 2020, and 2021 (all P <0.05). The number of severe cases was negatively correlated with gross domestic product (Moran’s I <0) and percentage of urban population (Moran’s I <0), and positively correlated with the number of pediatric beds per million population (Moran’s I >0). Conclusion::The number of severe hepatitis B cases is low in areas with high gross domestic product levels and high urban population ratios, and health care costs have been declining over the years.

BACKGROUND: G protein-coupled receptor kinase 2 (GRK2) could participate in the regulation of diverse cells via interacting with non-G-protein-coupled receptors. In the present work, we explored how paroxetine, a GRK2 inhibitor, modulates the differentiation and activation of immune cells in rheumatoid arthritis (RA). METHODS: The blood samples of healthy individuals and RA patients were collected between July 2021 and March 2022 from the First Affiliated Hospital of Anhui Medical University. C57BL/6 mice were used to induce the collagen-induced arthritis (CIA) model. Flow cytometry analysis was used to characterize the differentiation and function of dendritic cells (DCs)/T cells. Co-immunoprecipitation was used to explore the specific molecular mechanism. RESULTS: In patients with RA, high expression of GRK2 in peripheral blood lymphocytes, accompanied by the increases of phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR). In animal model, a decrease in regulatory T cells (T regs ), an increase in the cluster of differentiation 8 positive (CD8 + ) T cells, and maturation of DCs were observed. Paroxetine, when used in vitro and in CIA mice, restrained the maturation of DCs and the differentiation of CD8 + T cells, and induced the proportion of T regs . Paroxetine inhibited the secretion of pro-inflammatory cytokines, the expression of C-C motif chemokine receptor 7 in DCs and T cells. Simultaneously, paroxetine upregulated the expression of programmed death ligand 1, and anti-inflammatory cytokines. Additionally, paroxetine inhibited the PI3K-AKT-mTOR metabolic pathway in both DCs and T cells. This was associated with a reduction in mitochondrial membrane potential and changes in the utilization of glucose and lipids, particularly in DCs. Paroxetine reversed PI3K-AKT pathway activation induced by 740 Y-P (a PI3K agonist) through inhibiting the interaction between GRK2 and PI3K in DCs and T cells. CONCLUSION Paroxetine exerts an immunosuppressive effect by targeting GRK2, which subsequently inhibits the metabolism-related PI3K-AKT-mTOR pathway of DCs and T cells in RA.
G-Protein-Coupled Receptor Kinase 2/metabolism* ; Arthritis, Rheumatoid/immunology* ; Animals ; Dendritic Cells/metabolism* ; Paroxetine/therapeutic use* ; Proto-Oncogene Proteins c-akt/metabolism* ; Mice ; Humans ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Male ; Phosphatidylinositol 3-Kinases/metabolism* ; Lymphocyte Activation/drug effects* ; Female ; T-Lymphocytes/metabolism* ; Middle Aged

In this work,near infrared carbon quantum dots(NIR-CDs)were synthesized by hydrothermal method using biomass material Clausena lansium leaves.The synthesized NIR-CDs emitted maximum fluorescence signal at 677 nm,which was independent of excitation wavelength.The characterization results showed that there were abundant groups on the surface of NIR-CDs.Pd2+could form non-fluorescent compounds with the surface groups of NIR-CDs,resulting in fluorescence quenching(Fluorescence signal was denoted as F0).Because chlorpromazine hydrochloride(CPZ)parent nucleus contained unoxidized S atom,CPZ could form stable colored complex with Pd2+under acidic conditions.In the presence of CPZ,Pd2+dissociated from the surface of NIR-CDs and bonded with CPZ,so that the fluorescence signal could be restored(Fluorescence signal was denoted as F).An"on-off-on"fluorescence sensor was thus constructed.The fluorescence signal recovery value of NIR-CDs(△F=F-F0)showed a good linear relationship with the concentration of CPZ in the range of 5.68-28.43 μg/mL,and the detection limit(3σ)was 0.078 μg/mL.The sensor was applied to determination of CPZ in pharmaceutical preparations,and the recoveries were 94％-106％.The developed fluorescence sensor was expected to be used in quality control of actual pharmaceutical preparations.

Chronic kidney disease(CKD)will eventually progress to end-stage kidney disease and has become one of the common obstinate diseases in China,which becomes a serious threat to human life.Traditional Chinese medicine(TCM)shows unique advantages in treating CKD.In the view of Professor Lyu Zhiping,disharmony,in particular the disharmony of yin and yang of kidney,contributes to the core pathogenesis of CKD.Disharmony between kidney and other organs,and disharmony between kidney and exogenous pathogens together with pathological products lead to the complication of yin and yang,superficial and interior,deficiency and excess syndromes in the progression of the disease.Professor Lyu recommended that the clinical medication for CKD should be based on harmonizing therapy by harmonizing shaoyang meridian,harmonizing the spleen and stomach,and harmonizing collaterals and resolving blood stasis,thus to protect kidney function and slow down the progression of CKD.Based on years of clinical experience,professor Lyu formulated the Shen Qi Shenkang Prescription,which aims at primarily tonifying the kidney,and assisting by harmonizing the lung and spleen,clearing heat,removing dampness and eliminating turbid,thus to treat symptoms and root cause simultaneously,and then stronger clinical efficacy for CKD can be achieved.

ObjectiveTo investigate the effect of video-based educational intervention combined with maternal presence on perioperative adverse outcomes in preschool children undergoing general anesthesia， including cooperation in anesthesia induction， perioperative anxiety， pain and agitation during recovery. MethodsA total of 300 preschool children scheduled for general anesthesia in our hospital from June to December 2023 were randomly assigned to control group （n=150） and intervention group （n=150）. The control group received routine recovery care. For the intervention group， in addition to routine recovery care， a preoperative visit was scheduled one day before surgery. During this visit， mothers were guided to watch anesthesia videos with their children. During the waiting period in the operating room and 30 minutes after awakening， the mothers were guided to accompany the children for more than 30 minutes. Recovery conditions were recorded using the surgical anesthesia information system， and the children’s anesthetic induction compliance， perioperative anxiety， pain， and agitation were evaluated and recorded using the modified Yale Preoperative Anxiety Scale （m-YPAS）， the Induction Compliance Scale （ICC）， the Children’s Pain Behavior Scale （FLACC）， and the Pediatric Agitation and Emergence Delirium Scale （PAED）. ResultsOn the preoperative visit day， there were no statistically significant differences in baseline data between the two groups （P > 0.05）. For perioperative anxiety， the m-YPAS scores of the intervention group were significantly lower than those of the control group， both when entering the operating room waiting area （35.27±6.48 vs. 41.79±6.68， P < 0.05） and 30 minutes after postoperative recovery （20.13±7.05 vs. 35.75±9.51， P < 0.05）. In terms of anesthesia induction cooperation， the ICC scores of the intervention group were significantly lower than those of the control group （1.84±0.95 vs. 3.17±0.62， P < 0.05）， and the proportion of good induction cooperation was significantly higher than that of the control group （24.00% vs. 12.67%， P < 0.05）. There was no significant difference in awakening duration between the two groups， but the intervention group had a significantly shorter length of stay in the post-anesthesia care unit than the control group （0.90±0.29 hours vs. 1.29±0.42 hours， P < 0.001）. For perioperative agitation， the PAED scores of the intervention group were significantly lower than those of the control group （entering in the operating room waiting area： 8.5 vs. 9.2， P < 0.05； 30 minutes after postoperative recovery： 4.2 vs. 7.8， P < 0.05）. In terms of pain scores， the FLACC scores of the intervention group were also significantly lower than those of the control group， both when entering the operating room waiting area （ 5.3 vs. 6.7， P < 0.05； 30 minutes after postoperative recovery： 2.1 vs. 4.9， P < 0.05）. ConclusionsVideo-based educational intervention combined with maternal presence reduces the perioperative anxiety， pain and agitation of preschool children undergoing general anesthesia， and improved the compliance of anesthesia induction. It is recommended to promote this intervention measure in clinical practice.

Objective To verify the feasibility and safety of three-dimensional(3D)image acquisition by C-arm combined with orthopedic robot-assisted iliosacral screw fixation through S3 vertebra.Methods From July 2023 to June 2024,a total of 4 patients with closed pelvic fracture were surgically treated.Preoperative pelvic CT 3D reconstruction showed the presence of an ideal iliosacral screw bone channel through S3 vertebra which required screw fixation.There was no such channel through the S1 vertebra,or the stability of fixation through the S3 channel was better than that through the S1 channel.The 3D image acquisition by C-arm combined with orthopedic surgical robot was used to insert screws.Follow-ups were conducted for at least 6 months after surgery to assess fracture healing and limb function.Results All the 4 patients were successfully implanted with a S2 and a S3 iliosacral screw,and all the 8 screws did not penetrate the cortical bone.Three cases had excellent Majeed scores and 1 case had good scores at 3 months after surgery.Follow-ups were conducted for 18,12,7,and 6 months after surgery,respectively,and all fractures healed smoothly without any loosening or breakage of screws.Conclusion 3D image acquisition by C-arm combined with orthopedic robot-assisted iliosacral screw fixation through S3 vertebra is feasible,safe and effective.

Objective To verify the feasibility and safety of three-dimensional(3D)image acquisition by C-arm combined with orthopedic robot-assisted iliosacral screw fixation through S3 vertebra.Methods From July 2023 to June 2024,a total of 4 patients with closed pelvic fracture were surgically treated.Preoperative pelvic CT 3D reconstruction showed the presence of an ideal iliosacral screw bone channel through S3 vertebra which required screw fixation.There was no such channel through the S1 vertebra,or the stability of fixation through the S3 channel was better than that through the S1 channel.The 3D image acquisition by C-arm combined with orthopedic surgical robot was used to insert screws.Follow-ups were conducted for at least 6 months after surgery to assess fracture healing and limb function.Results All the 4 patients were successfully implanted with a S2 and a S3 iliosacral screw,and all the 8 screws did not penetrate the cortical bone.Three cases had excellent Majeed scores and 1 case had good scores at 3 months after surgery.Follow-ups were conducted for 18,12,7,and 6 months after surgery,respectively,and all fractures healed smoothly without any loosening or breakage of screws.Conclusion 3D image acquisition by C-arm combined with orthopedic robot-assisted iliosacral screw fixation through S3 vertebra is feasible,safe and effective.