lymorphism of CD14 gene is a risk factor for diabetic nephropathy.

Objective To explore exenatide in the treatment of metformin(MET)alone,sulfonylurea (SU)alone or MET + SU combination therapy with poor glycemic control in type 2 diabetic pa-tients and to find effective nursing measures.Methods 24 patients were randomly divided into the con-trol group and the exenatide group with 12 patients in each group.In the exenatide group,exenatide 5μg twice a day for 4weeks,then 10μg twice a day for 12 weeks.Changes of HbAlc,body weight,BMI,FBG,P2hBG,and rate of adverse reaction were compared between two groups.Results Glycosylated hemoglobin (HbAlc),body weight,BMI,FBG,P2hBG in the control group before and after treatment showed no significant difference,while the exenatide group showed better results compared with those before treatment and the control group.Nursing intervention played evident effect on reducing adverse effect such as nausea,vomiting,diarrhea,low blood sugar,headache.Conclusions For patients with type 2 diabetes,using MET,SU alone or MET + SU combination therapy showed poor results of blood sugar control,addition of exenatide therapy can effectively control blood sugar,nursing intervention can significantly alleviate the adverse effects of patients.

OBJECTIVE: To explore the correlation between histone H3-K9 methylation, DNA methylation and expression of carcinoma suppressor gene MGMT in laryngeal carcinoma Hep-2 cell line. METHOD: 5-Aza-dC was used to deal with Hep-2 cell cultured in vitro. ChIP, MSP and Realtime-PCR were used to detect H3-K9 methylation, DNA methylation, of MGMT gene promoter region and MGMT gene expression before and after treatment with drugs. RESULT: (1) In Hep-2 cell line, gene MGMT was characterized by DNA methylation and histone H3-K9 hypermethylation. (2) 5-Aza-dC was able to reduce H3-K9 methylation of MGMT gene histone in Hep-2 cell line, 5-Aza-dC was able to reverse DNA methylation of MGMT gene histone in Hep-2 cell line, 5-Aza-dC was able to upregulate the down-regulated gene expression of tumor suppressor genes MGMT. CONCLUSION Promoter methylation of cancer suppressor gene MGMT may induce the gene inactivity. DNA methylation may increase H3-K9 methylation. 5-Aza-dC can reduce H3-K9 methylation of tumor suppressor gene MGMT histone by reversing DNA methylation of tumor suppressor gene MGMT, and then the expression of tumor suppressor genes is increased and tumor development is inhibited.
Cell Line, Tumor ; DNA Methylation ; DNA Modification Methylases ; genetics ; metabolism ; DNA Repair Enzymes ; genetics ; metabolism ; Genes, Tumor Suppressor ; Histones ; metabolism ; Humans ; Laryngeal Neoplasms ; genetics ; metabolism ; pathology ; Tumor Suppressor Proteins ; genetics ; metabolism

Objective To investigate the effects of different dialysates on expression of protein kinase C-δ (PKCδ) and apoptosis of U937 cell line. Methods Different dialysates were added into culture fluid with U937 cell line at exponential phase of growth, and groups were divided: fluid A+fluid B group (dialysate A+dialysate B), fluid A+fluid B+rottlerin (PKCδ specific inhibitor)group, fluid A+powder B group (dialysate A+powder B) and fluid A+powder B + rottlerin group. Besides, blank control group and normal control group were established. Cells were harvested 24 h and 48 h after treatment, morphological changes were observed by Hoechst33258 fluorescence staining, cell apoptosis was measured by Annexin-V-FITC/PI double staining, and expression of PKCδ mRNA and protein was detected by RT-PCR and Western blotting, respectively. Results Cell apoptosis significantly increased in fluid A+powder B group, with typical morphology of apoptosis. After treatment for 24 h and 48 h, cell apoptosis rates in fluid A+powder B group were significantly higher than those at corresponding time points in blank control group , normal control group and fluid A+powder B+rottlerin group (P<0.05). Compared with normal control group, blank control group and fluid A+powder B+rottlerin group, the expression of PKCδ mRNA and protein of U937 cells in fluid A+powder B group were significantly increased (P<0.05). There was no significant difference in cell apoptosis rates and expression of PKCδ mRNA and protein between fluid A+fluid B group and blank control group, normal control group and fluid A+fluid B+rottlerin group (P＞0.05). Conclusion Fluid A+powder B can significantly increase apoptosis of U937 cell line, the mechanism of which may be associated with the up-regulation of expression of PKCδ. Compared with fluid A+powder B, fluid A+fluid B is superior in reducing apoptosis of peripheral blood monouclear cells.

Traditional Chinese medicines have demonstrated clinical efficacy in preventing and treating chemotherapy-induced peripheral neuropathic pain(CIPNP).However,their specific clinical application and mechanism of action require further in-depth study and exploration.There is thus a need to develop more accurate and clinically relevant animal models that reflect the occurrence and development of human diseases as a tool for research.This review provides an in-depth analysis and discussion of the recent establishment and detection criteria of existing rat and mouse animal models of paclitaxel-induced peripheral neuropathic pain.We also evaluate and explain the application of these models for the prevention and treatment of CIPNP in traditional Chinese medicine,thus providing a theoretical basis and reference for future experimental and mechanistic research on the subject.This research will benefit clinical practice and promotion,offering valuable insights into preventing and treating CIPNP using traditional Chinese medicines.

Objective:To investigate the relationship between serum free triiodothyronine (FT 3) and the severity and prognosis of elderly patients with coronavirus disease 2019 (COVID-19). Methods:Clinical data of the elderly patients aged≥65 years old with COVID-19 who were admitted to the Ninth People′s Hospital of Wuxi from December 27, 2022 to January 18, 2023 were collected. The laboratory examinations of the non-severe and the severe/critical groups were compared. Patients were divided into group T1 (FT 3<2.51 pmol/L), group T2 (FT 3=2.51 to 2.95 pmol/L, ), and group T3 (FT 3>2.95 pmol/L) according to the FT 3 level. Independent sample t test was used for comparison between groups. Logistic regression analysis was performed to evaluate the risk factors for severe/critical disease, and to analyze the risk of severe/critical COVID-19 in elderly patients with different FT 3 levels. The receiver operator characteristic (ROC) curve was drawn to analyze the predictive value of FT 3 on the occurrence of severe/critical disease in patients. Kaplan-Meier survival curve and log-rank test were used to analyze the 30-day survival rate of elderly COVID-19 patients. Results:Among the 190 patients, the FT 3 level in the severe/critical group was (2.54±0.30) pmol/L, which was significantly lower than that in the non-severe group ((2.91±0.69) pmol/L), and the difference was statistically significant ( t=-3.42, P=0.001). Elevated serum FT 3 level was a protective factor for severe/critical disease in elderly COVID-19 patients (odds ratio ( OR)=0.139, 95% confidence interval ( CI) 0.034 to 0.577, P=0.007). There were 66 patients in the T1 group, 61 in the T2 group and 63 in the T3 group, respectively. After adjusted for sex, age, history of lung diseases, history of cardiac diseases, history of hypertension, history of diabetes mellitus, history of cerebral infarction, white blood cell count, lactate dehydrogenase, D-dimer, free thyroxine and thyrotropin, the risk of developing severe/critical disease in group T1 and group T2 were 10.982 folds and 3.695 folds of that in group T3, respectively (both P<0.05). The area under ROC curve of FT 3 of predicting severe/critical COVID-19 in the elderly patients was 0.731. The sensitivity and specificity were 0.733 and 0.659, respectively. The cut-off value was 2.53 pmol/L. The 30-day survival rate in patients with FT 3<2.53 pmol/L was significantly lower than that in patients with FT 3≥2.53 pmol/L ( χ2=13.49, P<0.001). Conclusions:The elevated level of FT 3 is a protective factor for progression to severe/critical disease in elderly patients with COVID-19. The evaluation of serum FT 3 could predict the severity and prognosis of elderly COVID-19 patients.

Objective To study the clinical management way for HPV+/papanicolaou (Pap)-during cervical cancer screening.Methods To analyze retrospectively the data from the patients who had loop electrical excision procedure (LEEP) for biopsy confirmed cervical intraepithelial neoplasia (CIN)Ⅱ in Peking University People's Hospital from Jan.2010 to Dec.2014.Results (1) For biopsy confirmed CINⅡ,HPV positive rate was 98.5％ (135/137),Pap test positive [≥atypical squamous cell of undetermined significance (ASCUS)] rate was 69.3％ (95/137),there was significant difference between them (x5=43.32,P＜0.01).(2) For the 42 patients with HPV+/Pap-,whose cytology slides were reviewed again.Among them,the interpretations of there were 16 cases confirmed as the same before,while 26 cases were changed to abnormal (≥ASCUS).Cytology be misdiagnosed was 19.0％ (26/137) at the first review.Among the 26 cases,13 (50.0％) cases were missed for the little amount of abnormal cells,8 (30.8％) cases for mild atypical morphology changed;the other 5 (19.2％) cases missed for stain problems.(3) For the cervical LEEP samples,37 cases of the pathology diagnosis were upgrade to CIN Ⅲ+,among them,2 cases of microinvasive cervical carcinoma,1 case of invasive cancer,34 cases of CIN Ⅲ;37 cases were CINⅠ or no lesion found;63 cases were still CIN Ⅱ.Four to six months later after LEEP,the cytology abnormal rate was 11.7％ (16/137),and the HR-HPV positive rate was 34.3％ (47/137).Conclusions Compared with cytology alone,cytology combined with HPV testing increase the sensitivity of cervical high grade lesion.For the cases of HPV+/Pap-cases,the cytology slides should be reviewed.The quality control of cervical exfoliate sample collection and interpretation should be strengthened.LEEP procedure is not only a treatment method,but also it could provide samples to confirm the diagnosis.

Objective: To explore the efficacy and safety of chimeric antigen receptor T (CAR-T) cells in the treatment of central nervous system leukemia (CNSL). Methods: Two leukemia patients with CNSL were treated with CD19-CAR-T cells. The process and results of the entire treatment is reported and related literature review is conducted. Results: The patients were diagnosed as acute myeloid leukemia (AML)-M₂ with B lymphoid antigen expression and B cell acute lymphoblastic leukemia(B-ALL) by morphology and immunophenotype assay. The immunophenotype was consistent with the abnormal manifestations of AML-M₂ and B-ALL. Their clinical manifestations and laboratory tests met the diagnostic criteria of CNSL. The diagnosis was clear and the two patients were treated with CD19-CAR-T cell immunotherapy. Central nervous system symptoms were relieved. The imaging abnormalities of patient one has disappeared but cytokines release syndrome (CRS) occurred during the treatment. Cerebrospinal fluid of patient two was negative and no obvious CRS reaction was found. Conclusions CAR-T cell immunotherapy is likely to induce the remission of CNSL and improve the prognosis.

Recent insights collectively suggest the important roles of lysyl oxidase (LysOX) in the pathological processes of several acute and chronic neurological diseases, but the molecular regulatory mechanisms remain elusive. Herein, we explore the regulatory role of LysOX in the seizure-induced ferroptotic cell death of neurons. Mechanistically, LysOX promotes ferroptosis-associated lipid peroxidation in neurons via activating extracellular regulated protein kinase (ERK)-dependent 5-lipoxygenase (Alox5) signaling. In addition, overexpression of LysOX via adeno-associated viral vector (AAV)-based gene transfer enhances ferroptosis sensitivity and aggravates seizure-induced hippocampal damage. Our studies show that pharmacological inhibition of LysOX with β-aminopropionitrile (BAPN) significantly blocks seizure-induced ferroptosis and thereby alleviates neuronal damage, while the BAPN-associated cardiotoxicity and neurotoxicity could further be reduced through encapsulation with bioresponsive amorphous calcium carbonate-based nanocarriers. These findings unveil a previously unrecognized LysOX-ERK-Alox5 pathway for ferroptosis regulation during seizure-induced neuronal damage. Suppressing this pathway may yield therapeutic implications for restoring seizure-induced neuronal injury.

ADAM Proteins ; blood ; deficiency ; ADAMTS13 Protein ; Adult ; Female ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Purpura, Thrombotic Thrombocytopenic ; blood ; etiology