Objective To analyze the association of polymorphisms of estrogen receptor (ER) α and β genes with systemic lupus erythematosus (SLE) in Chinese Han cohort of Yunnan Province.Methods XbaⅠ and Pvu Ⅱ of ERα gene,Rsa Ⅰ and Alu Ⅰ of ERβ gene were typed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 697 SLE patients and 638 healthy controls.The frequency distribution of the alleles and genotypes were analyzed by Hardy-Weinberg equilibrium test and x2 test.Results ① For ERα gene,the frequency of minor allele of Pvu Ⅱ C in SLE patients was significantly higher than healthy controls (x2=15.427,P=0.001);the allele frequencies of XbaⅠ in SLE patients showed no significant difference compared with healthy controls (P＞0.05).The frequency of minor genotype of Pvu Ⅱ CC in SLE patients was significantly higher than healthy controls (x2=17.371,P=0.011).The frequency of two locus haplotype AATT in SLE patients was significantly lower than healthy controls (x2=6.333,P=0.012);the frequency of the two locus haplotype AACC in SLE patients was significantly higher than healthy controls (x2=7.771,P=0.038).② For ERβ gene,the frequency of minor allele RsaⅠ A in SLE patients was significantly lower than healthy controls (x2=12.595,P=0.013);the allele frequencies of Alu Ⅰ in SLE patients showed no significant differences compared with the healthy controls (P＞0.05).The frequency of minor genotype AA of Rsa Ⅰ in SLE patients was significantly higher than healthy controls (x2=41.456,P=0.000).The frequency of two locus haplotype AAGG in SLE patients was significantly higher than healthy controls (x2=37.063,P=0.000).The frequency of the two locus haplotype AAGA in SLE patients was significantly lower than healthy controls(x2=21.086,P=0.001).③ Pvu Ⅱ C was related with splenomegaly (x2=4.212,P＜0.05).The two locus haplotype AGTC of Xba Ⅰ and Pvu Ⅱ was related with edema (x2=7.898,P＜0.05).Conclusion There are associations between the polymorphisms of ERα and ERβ genes and SLE.The ERα and ERβ genes may be the susceptible genes for SLE in Yunnan Han Chinese Cohort.

Biomedical Research ; Clustered Regularly Interspaced Short Palindromic Repeats ; Humans

Hematoporphyrin monomethyl ether (HMME) combined with He-Ne laser irradiation is a novel and promising photodynamic therapy (PDT)-induced apoptosis that can be applied in vitro on canine breast cancer cells. However, the exact pathway responsible for HMME-PDT in canine breast cancer cells remains unknown. CHMm cells morphology and apoptosis were analyzed using optical microscope, terminal deoxynucleotidyl transferase dUTP nick end labeling fluorescein staining and DNA ladder assays. Apoptotic pathway was further confirmed by Real-time-polymerase chain reaction and Western blotting assays. Our results showed that HMME-PDT induced significant changes in cell morphology, such as formation of cytoplasmic vacuoles and the gradual rounding of cells coupled with decreased size and detachment. DNA fragmentation and cell death was shown to occur in a time-dependent manner. Furthermore, HMME-PDT increased the activities of caspase-9 and caspase-3, and released cytochrome c from mitochondria into the cytoplasm. HMME-PDT also significantly increased both mRNA and protein levels of Bax and decreased P53 gene expression in a time-dependent manner, while the mRNA and protein expression of Bcl-2 were repressed. These alterations suggest that HMME-PDT induced CHMm cell apoptosis via the mitochondrial apoptosis pathway and had anti-canine breast cancer effects in vitro.
Apoptosis* ; Blotting, Western ; Breast Neoplasms* ; Breast* ; Caspase 3 ; Caspase 9 ; Cell Death ; Cytochromes c ; Cytoplasm ; DNA ; DNA Fragmentation ; DNA Nucleotidylexotransferase ; Ether* ; Fluorescein ; Genes, p53 ; Hematoporphyrins* ; In Vitro Techniques ; Mitochondria ; Photochemotherapy ; RNA, Messenger ; Vacuoles

PURPOSE: Breast cancer is the most frequently diagnosed malignancy in women worldwide. MicroRNAs (miRNAs) are thought to serve as potential biomarkers in various cancers, including breast cancer. METHODS: We evaluated the miRNA expression profiles in 1,083 breast cancer samples and 104 normal breast tissues from The Cancer Genome Atlas database. We used the edgeR package of R software to analyze the differentially expressed miRNAs in normal and cancer tissues, and screened survival-related miRNAs by Kaplan-Meier analysis. A receiver operating characteristic curve was generated to evaluate the accuracy of these miRNAs as molecular markers for breast cancer diagnosis. Furthermore, the functional role of these miRNAs was verified using cell experiments. Targets of candidate miRNAs were predicted using 9 online databases, and Gene Ontology (GO) functional annotation and pathway analyses were conducted using Database for Annotation, Visualization and Integrated Discovery online tool. RESULTS: A total of 68 miRNAs showed significantly different expression patterns between the groups (p < 0.001), and 13 of these miRNAs were significantly associated with poor survival (p < 0.05). Three miRNAs with high specificity and sensitivity, namely, miR-148b-3p, miR-190b, and miR-429, were selected. In vitro experiments showed that the overexpression of these 3 miRNAs significantly promoted the proliferation and migration of MDA-MB-468 and T47D cells and reduced the apoptosis of T47D cells. GO and pathway enrichment analyses revealed that the targets of these dysregulated miRNAs were involved in many critical cancer-related biological processes and pathways. CONCLUSION: The miR-148b-3p, miR-190b, and miR-429 may serve as potential diagnostic and prognostic markers for breast cancer. This study demonstrated the roles of these 3 miRNAs in the initiation and progression of breast cancer.
Apoptosis ; Biological Phenomena ; Biological Processes ; Biomarkers ; Breast Neoplasms ; Breast ; Diagnosis ; Female ; Gene Ontology ; Genome ; Humans ; In Vitro Techniques ; Kaplan-Meier Estimate ; MicroRNAs ; ROC Curve ; Sensitivity and Specificity

ObjectiveTo explore the effects of Bushen Jianpi prescription on the autophagy and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway in the patients with aplastic anemia （AA）. MethodA total of 30 AA patients admitted to Xiyuan Hospital and 6 healthy donors who were prepared to undergo peripheral blood hematopoietic stem cell transplantation in 304 Hospital from September 2020 to August 2021 were enrolled and assigned into an AA group and a control group. The AA group was treated with Bushen Jianpi prescription combined with cyclosporin A （CsA） and androgen for 3 months. The mononuclear cells from bone marrow in the AA group before and after treatment and the peripheral blood of the control group were collected. Transmission electron microscopy was then employed to detect autophagosomes. Western blotting was employed to determine the protein levels of microtuble-associated protein 1 light chain 3 （LC3）Ⅰ， LC3Ⅱ， mTOR， phosphorylated （p）-mTOR， Akt， p-Akt， PI3K， and p-PI3K， and real-time polymerase chain reaction （PCR） to determine the mRNA levels of LC3， mTOR， Akt， and PI3K. ResultIn the AA group， the treatment was completed in 29 patients， and the total response rate was 51.72% （15/29）. ① The AA group showed lower levels of white blood cell （WBC）， hemoglobin （HGB）， platelet （PLT）， and absolute neutrophil count （ANC） in the peripheral blood （P<0.01） and lower number of intracellular autophagosomes than the control group before treatment. Moreover， the AA group showed lower mRNA level of LC3 （P<0.01） and protein levels of LC3Ⅰ and LC3Ⅱ （P<0.01） and higher mRNA levels of mTOR， Akt， and PI3Kα （P<0.01） and protein levels of Akt， p-Akt， PI3K， p-PI3K， mTOR， and p-mTOR （P<0.01） than the control group. ② In AA group， the levels of HGB and PLT elevated （P<0.05） and the number of intracellular autophagosomes increased after treatment compared with those before treatment. Moreover， the mRNA level of LC3 and the protein levels of LC3Ⅰ and LC3Ⅱ were up-regulated （P<0.01）， the mRNA levels of mTOR， Akt， and PI3Kα （P<0.01） and the protein levels of Akt， p-PI3K （P<0.01）， p-Akt， PI3K， mTOR， p-mTOR （P<0.05） were down-regulated after treatment. ConclusionAA patients show lower autophagy levels， while Bushen Jianpi prescription can effectively improve the autophagy level and down-regulated the expression of PI3K/Akt/mTOR signaling pathway in AA patients.

BACKGROUNDOsteoarthritis (OA) is the most common form of human polyarthritis. Many genetic factors have been implicated in OA. It was reported that a polymorphism in the gene of interleukin-6 (IL-6) was associated with OA of knee. The aim of this study was to determine whether functional IL-6 promoter -174G/C (rs1800795) polymorphisms confer susceptibility to knee OA.

METHODSA meta-analysis was conducted on the association between the IL-6 polymorphism and knee OA. Electronic search at PubMed, EMBASE, Weipu database, and Wanfang database was conducted to select studies. Case-control studies containing available genotype frequencies of IL-6 -174G/C were chosen, and odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of this association.

RESULTSA total of seven studies involving 6 464 subjects (knee OA 3 331 and controls 3 133) were considered in this study. The results suggested that the variant genotypes were not associated with knee OA risk in all genetic models (additive model: OR = 1.144, 95% CI 0.934-1.402, P = 0.194; recessive model: OR = 1.113, 95% CI 0.799-1.550, P = 0.526; dominant model: OR = 1.186, 95% CI 0.918-1.531, P = 0.191). A symmetric funnel plot, the Begg's test (P > 0.05), suggested that the data lacked publication bias.

CONCLUSIONSThis meta-analysis does not support the idea that rs1800795 genotype is associated with increased risk of knee OA. However, to draw comprehensive and more reliable conclusions, further prospective studies with larger numbers of participants worldwide are needed to examine the association between rs1800795 polymorphism and knee OA.

Humans ; Interleukin-6 ; genetics ; Osteoarthritis, Knee ; epidemiology ; genetics ; Polymorphism, Genetic ; genetics ; Promoter Regions, Genetic ; genetics

BACKGROUNDT8590C polymorphism of CYP4A11 has been associated with hypertension, though with conflicting results. The aim of this study was to quantitatively summarize the evidence for CYP4A11 T8590C polymorphism and hypertension risk.

METHODSElectronic search of PubMed and the Chinese Biomedicine database was conducted to select studies. Case-control studies containing available genotype frequencies of T8590C were chosen, and odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of this association.

RESULTSSeven case-control studies, including 3 295 cases and 3 192 controls, were identified. The meta-analysis, stratified by ethnicity, showed that individuals with the C allele carriers (CC+CT) had increased risk of hypertension in over all (OR = 1.184, 95% CI: 1.063-1.319, P = 0.002) and in others (OR = 1.217, 95% CI: 1.045-1.419, P = 0.012). The results among Asians did not suggest an association (OR = 1.152, 95% CI: 0.990-1.342, P = 0.068). A symmetric funnel plot, the Egger's test (P = 0.863), and the Begg test (P = 0.393) were all suggestive of the lack of publication bias.

CONCLUSIONSThis meta-analysis suggests the CYP4A11 T8590C polymorphism may be a risk factor for hypertension. Future well-designed large studies might be necessary to validate this association in different populations incorporated with environmental factors in the susceptibility of hypertension.

Case-Control Studies ; Cytochrome P-450 CYP4A ; Cytochrome P-450 Enzyme System ; genetics ; Humans ; Hypertension ; genetics ; Polymorphism, Genetic ; genetics ; Risk Factors

Statins inhibit the activity of enzyme 3-hydroxy-3-methyl-acetyl coenzyme A reductase and further inhibit cholesterol synthesis. Statins are the most widely used cholesterol-lowering drugs in clinical practice. Studies have found that statins also play a positive role in periodontitis treatment. In this paper, we reviewed the functions of statins in bone metabolism and anti-inflammation in periodontitis. In addition, the application of statins as a local drug delivery system in the treatment of periodontitis was described.

ObjectiveTo investigate the predictive indicators of early efficacy of Bushen Shengxue prescription combined with western medicine in the treatment of aplastic anemia， and provide prognosis indicators for the treatment of aplastic anemia （AA） with kidney-tonifying therapy in traditional Chinese medicine （TCM） combined with western medicine. MethodA total of 126 patients treated by Bushen Shengxue prescription combined with western medicine in 19 hospitals including Xiyuan Hospital of the China Academy of Chinese Medical Sciences from September 2018 to March 2021 were selected for a retrospective study. The therapy was proven to be effective after six months of treatment. According to the efficacy after 4 months of treatment， the patients were assigned into a 4-month effective group and a 4-month ineffective group. The age， sex， disease severity （including severe aplastic anemia and non-severe aplastic anemia）， course of disease， degree of bone marrow nucleated cell proliferation， baseline hemogram levels ［including white blood cell count （WBC）， absolute neutrophil count （ANC）， hemoglobin （HGB）， platelets （PLT）， and reticulocytes （RET）］， T lymphocytes subsets， and the expression levels of T-box transcription factor （T-bet） and GATA-binding protein-3 （GATA-3） were compared between the two groups before treatment. ResultThe proportions of patients within the age ranges of ［20， 40） and ［60， 80） were higher in the 4-month effective group （P<0.05）. The sex， disease severity， course of disease， and comorbidities had no significant differences between the two groups. The 4-month effective group had higher baseline levels of HGB， WBC， ANC， and PLT than the 4-month ineffective group （P<0.05）， and there was no significant difference in the RET level between the two groups before treatment. Binary Logistic regression analysis showed that the PLT level before treatment was an independent factor affecting the onset time， while other indicators did not affect the onset time. The receiver operating characteristic （ROC） curve was established to analyze the value of PLT level before treatment for predicting the onset time， and the area under the curve was 0.691. With the critical value of 40.5×10⁹/L， the sensitivity and specificity of the prediction that the therapy will take effect within 4 months were 0.569 and 0.893， respectively. The two groups of patients were graded according to age ｛（14， 20）， ［20， 40）， ［40， 60）， and ［60， 80）｝ and PLT level before treatment （PLT<40×10⁹/L， PLT≥40×10⁹/L）. The proportion of the patients with PLT≥40×10⁹/L before treatment in the 4-month effective group was significantly higher than that in the 4-month ineffective group （P<0.05）. The degree of bone marrow nucleated cell proliferation before treatment had no significant difference between the two groups. The level of total T lymphocytes in the 4-month effective patients was lower than that in the 4-month ineffective patients before treatment （P<0.05）. The levels of Th1 cells， Th2 cells， CD4⁺ T cells， and CD8⁺ T cells showed no significant differences between the two groups before treatment. The T-bet expression level in the 4-month effective group was higher than that in the 4-month ineffective group before treatment （P<0.05）， while the expression level of GATA-3 showed no significant difference between the two groups before treatment. ConclusionBushen Shengxue prescription combined with western medicine will achieve faster effect for the patients within the age ranges of ［20， 40） or ［40， 60）， with higher levels of HGB， WBC， ANC， and PLT （especially those with PLT≥40×10⁹/L）， lower level of total T lymphocytes， or higher T-bet expression level before treatment.

ObjectiveMyelodysplastic syndromes （MDS） is a group of clonal hematopoietic stem cell disorders，and this study aims to investigate the expression of hypoxia-inducible factor-1α（HIF-1α） in the bone marrow cells of patients with MDS and its correlation with the clinical features of MDS，the therapeutic efficacy of arsenic-containing Chineseherbal compound，and the survival prognosis. MethodAccording to the inclusion and exclusion criteria，27 MDS patients treated with arsenic-containing Chinese herbal compound in the Department of Hematology，Xiyuan Hospital，China Academy of Chinese Medical Sciences from January 2022 to September 2022 were included，and their bone marrow samples were collected by myelotomy. HIF-1α expression level in bone marrow cells was detected by real-time polymerase chain reaction （PCR） to analyze its correlation with clinical features，and logistic and Cox regression was used to analyze the risk factors affecting the efficacy and prognostic survival of MDS patients. ResultThe HIF-1α mRNA expression level was lower in bone marrow cells of MDS patients than in healthy subjects. HIF-1α was positively correlated with the degree of myelodysplasia（r=0.384，P<0.05） and bone marrow granulocytic system%（G%）（r=0.560，P<0.01）. Logistic regression showed that HIF-1α was a risk factor for the prognosis in the follow-up of the efficacy of treatment（P<0.05）and Cox regression showed that HIF-1α was an independent factor affecting the survival prognosis of MDS patients ［odds ratio（OR）=398.968，95% confidence interval（CI）（1.281，116 858.743），P<0.05］. ConclusionThe level of HIF-1α expression in bone marrow cells of MDS patients was closely related to the degree of clinical myelodysplasia and G%，and HIF-1α was a risk factor for the efficacy for and survival prognosis of MDS patients.