The expression level of NOD-like receptors(NLRP3)inflammasome is significantly elevated in breast cancer tissues,and a high level of NLRP3 inflammasomes is closely associated with breast cancer metastasis.Activation of NLRP3 inflammasome can induce the release of inflammatory factors into the tumor microenvironment(TME).These inflammatory factors,by signaling to cancer cells,reshape the TME to promote tumor growth and invasion,ultimately facilitating the process of epithelial-mesenchymal transition.This equips cancer cells with the ability to establish distant metastases and increase the formation of metastatic lesions.This review addresses the current research status and prospects of NLRP3 inflammasomes in the breast cancer TME and their role in breast cancer metastasis.The goal is to provide new insights for the study of breast cancer metastasis mechanisms and treatment strategies.

OBJECTIVE To explore the efficacy of Sour Jujube Seed Decoction combined with Huanglian Wendan Decoction on adult chronic insomnia and its effect on hypnotic withdrawal.METHODS 187 patients with chronic insomnia were included for anal-ysis,including 102 in the traditional Chinese medicine(TCM)group and 85 in the western medicine group.The TCM group was trea-ted with Sour Jujube Seed Decoction combined with Huanglian Wendan Decoction,while the western medicine group was treated with benzodiazepine under the consideration of doctor.The intervention period was 1 month,with assessments using the Pittsburgh Sleep Quality Index(PSQI)conducted before and after the intervention.Follow-up evaluations were performed at 3 months and 6 months re-spectively after the intervention.RESULTS There was no significant difference between the two groups at baseline.After the inter-vention,the PSQI scores of patients in both groups were significantly improved(P<0.01).Among them,the TCM group was better than the western medicine group in the improvement of sleep quality and sleeping pills,total PSQI score reduction(P<0.01).The re-sults of linear regression analysis showed that after controlling for confounding factors,the regression coefficients of the TCM group in two different models were1.821 and 1.922 respectively,and the former was statistically significant(P<0.05).By screening patients who took hypnotics at baseline in the TCM group and comparing them with those in the western medicine group,the influencing factors of hypnotic withdrawal were analyzed.During the 3-month follow-up,25 out of 39 patients in the TCM group and 17 out of 80 patients in the western medicine group had hypnotic withdrawal(χ2= 19.25,P<0.001);during the 6-month follow-up,23 of the 39 patients in the TCM group and 18 of the 79 patients in the western medicine group had hypnotic withdrawal(χ2= 13.53,P<0.001),the with-drawal rate of patients in the TCM group was significantly higher than that in the western medicine group.Further regression analysis showed that after adjusting for confounding factors,the results showed that the western medicine group had a significantly higher rate of not withdrawal than the TCM group at 3 months(OR=5.50,95%CI:2.30～13.72)and 6 months(OR=6.43,95%CI:2.54～17.77),and the results were statistically different(P<0.05).CONCLUSION Sour Jujube Seed Decoction combined with Huangli-an Wendan Decoction is effective in treating adult chronic insomnia and assisting in hypnotic withdrawal.

OBJECTIVE: To investigate the effect of lysosomal-associated protein transmembrane-4 Beta(Laptm4b) deletion on hematopoietic stem/progenitor cells (HSPCs) homeostasis in mice. METHODS: The hematopoietic system specific Laptm4b-deficient mice were constructed. The number and proportion of HSPCs (LSK, LT, ST, MPP, etc) in Laptm4b-deficient mice were analyzed by flow cytometry. Single SLAM-HSC cell was sorted by flow sorter and cultured in vitro to measure the effect of Laptm4b deletion on the colony forming ability of hematopoietic stem cells (HSCs). The effect of Laptm4b-deficient on the reconstitution ability of HSCs in mice was detected by competitive transplantation experiment of SLAM-HSC cells. RESULTS: Laptm4b deficiency could moderately upregulate the proportion of T cells in the peripheral blood of the mice, but showed no significant effect on the proportion and number of HSPCs. Laptm4b deletion showed no effect on the reconstruction ability of HSCs after competitive transplantation, but it could inhibit the colony formation of HSCs in vitro. CONCLUSION LAPTM4B may play a role in HSCs under the proliferation stress. Laptm4b-deficient in mice hematopoietic system showed no significant effect on the HSPCs homeostasis maintenance and reconstruction ability.
Animals ; Cell Proliferation ; Flow Cytometry ; Hematopoietic Stem Cells ; Homeostasis ; Mice ; Transcription Factors

BACKGROUND: Hematopoietic stem cells (HSCs) have the ability to differentiate into all subsets of blood cells and self-renew. Large tumor suppressor 1 (LATS1) and large tumor suppressor 2 (LATS2) kinases are essential for cell cycle regulation, organism fitness, genome integrity, and cancer prevention. Here, we investigated whether Lats1 and Lats2 are critical for the maintenance of the self-renewal and quiescence capacities of HSCs in mice. METHODS: Quantitative reverse transcription-polymerase chain reaction was used to determine the expression levels of Lats1 and Lats2 in subsets of progenitor cells and mature bone marrow cells. A clustered regularly interspaced short palindromic repeats system was used to generate Lats1 or Lats2 knockout mice. Complete blood cell counts were used to compare the absolute number of white blood cells, lymphocytes, monocytes, neutrophils, and platelets between Lats1 or Lats2 heterozygotes and littermates. Flow cytometry was used to assess the size of hematopoietic progenitor cells (HPCs) and HSC pools in Lats1 or Lats2 heterozygotes and littermates. The comparison between the two groups was analyzed using Student's t test. RESULTS: Lats1 and Lats2 were widely expressed in hematopoietic cells with higher expression levels in primitive hematopoietic cells than in mature cells. Lats1 or Lats2 knockout mice were generated, with the homozygotes showing embryonic lethality. The size of the HPC and HSC pools in Lats1 (HPC: wild-type [WT] vs. heterozygote, 220,426.77 ± 54,384.796 vs. 221,149.4 ± 42,688.29, P = 0.988; HSC: WT vs. heterozygote, 2498.932 ± 347.856 vs. 3249.763 ± 370.412, P = 0.105) or Lats2 (HPC: WT vs. heterozygote, 425,540.52 ± 99,721.86 vs. 467,127.8 ± 89,574.48, P = 0.527; HSC: WT vs. heterozygote, 4760.545 ± 1518.01 vs. 5327.437 ± 873.297, P = 0.502) heterozygotes were not impaired. Moreover, the depletion of Lats1 or Lats2 did not affect the overall survival of the heterozygotes (Lats1: P = 0.654; Lats2: P = 0.152). CONCLUSION These results indicate that a single allele of Lats1 or Lats2 may be sufficient for normal hematopoiesis.

BACKGROUND: Zinc finger and BTB domain-containing protein 46 (Zbtb46) is a transcription factor identified in classical dendritic cells, and maintains dendritic cell quiescence in a steady state. Zbtb46 has been reported to be a negative indicator of acute myeloid leukemia (AML). We found that Zbtb46 was expressed at a relatively higher level in hematopoietic stem and progenitor cells (HSPCs) compared to mature cells, and higher in AML cells compared to normal bone marrow (BM) cells. However, the role of Zbtb46 in HSPCs and AML cells remains unclear. Therefore, we sought to elucidate the effect of Zbtb46 in normal hematopoiesis and AML cells. METHODS: We generated Zbtb46 and Zbtb46Mx1-Cre mice. The deletion of Zbtb46 in Zbtb46Mx1-Cre mice was induced by intraperitoneal injection of double-stranded poly (I). poly (C) (poly(I:C)), and referred as Zbtb46 cKO. After confirming the deletion of Zbtb46, the frequency and numbers of HSPCs and mature blood cells were analyzed by flow cytometry. Serial intraperitoneal injection of 5-fluorouracil was administrated to determine the repopulation ability of HSCs from Zbtb46 and Zbtb46 cKO mice. The correlation between Zbtb46 expression and prognosis was analyzed using the data from the Cancer Genome Atlas. To investigate the role of Zbtb46 in AML cells, we knocked down the expression of Zbtb46 in THP-1 cells using lentiviral vectors expressing small hairpin RNAs targeting Zbtb46. Cell proliferation rate was determined by cell count assay. Cell apoptosis and bromodeoxyuridine incorporation were determined by flow cytometry. RESULTS: The percentages and absolute numbers of HSPCs and mature blood cells were comparable in Zbtb46 cKO mice and its Zbtb46 littermates (Zbtb46vs. Zbtb46 cKO, HPC: 801,310 ± 84,282 vs. 907,202 ± 97,403, t = 0.82, P = 0.46; LSK: 86,895 ± 7802 vs. 102,210 ± 5025, t = 1.65, P = 0.17; HSC: 19,753 ± 3116 vs. 17,608 ± 3508, t = 0.46, P = 0.67). The repopulation ability of HSCs from Zbtb46Mx1-Cre mice was similar to those from Zbtb46 control (P = 0.26). Zbtb46 had elevated expression in AML cells compared to total BM cells from normal control. Knockdown of Zbtb46 in THP-1 cells led to a significant increase in cell apoptosis and reduced cell growth and proliferation. CONCLUSION Collectively, our data indicate that Zbtb46 is essential for survival and proliferation of AML cells, but dispensable for normal hematopoiesis.

[Objective] To investigate the safety and associated factor of external cephalic version (ECV) in third trimester,and to enrich clinical experience to improve the successful rate and lower cesarean section (CS) rate.[Methods] 80 pregnant women conducting ECV in third trimester in the third affiliated hospital of Sun Yat-sen University from September 2015 to July 2017 were enrolled in our study.Divided to successful group and failing group,we compared the clinical characters and pregnancy outcomes.[Results] Of the 80 pregnancy,48 women (60.0％) succeed with cephalic presentation.Compared to the failing group,the successful group is statistically different in parity,BMI and amniotic fluid depth.In the failing group,all women underwent CS with 3/48 in successful group.No women conducted ECV complicated fetal distress and emergency CS,premature rupture of membranes complicated in 11 (13.8％) cases in all women.[Conclusions] ECV is safe for mother and fetus.Encouraging the suitable pregnancy women to conduct ECV and enhancing clinical skills can improve ECV success rate.

Objective:To explore the surgical strategies for the treatment of T1 b gallbladder cancer patients diagnosed intraoperatively or postoperatively.Methods:A retrospective analysis of 42 patients with T1 b gallbladder cancers was performed.There were 14 patients diagnosed intraoperatively and 28 patients diagnosed postoperatively.The reevaluations of T stages were conducted in the 28 T1 b gallbladder cancer patients diagnosed postoperatively by the professional pathologist.After T stage reevaluation,25 confirmed T1 b patients with complete follow-up data were divided into simple cholecystectomy group and radical resection group,and the clinicopathologic characteristics between the two groups were analyzed.Results:Only 2 of the 14 T1 b gallbladder cancer patients diagnosed by the intraoperative frozen specimen proved to be T1b on postoperative paraffin pathology,and for the remaining 13 patients,T2 was in 11 patients,and T3 in one patient.The rate of misdiagnosis was 85.7％ by the intraoperative frozen specimens,postoperative T stages were equal or higher than intraoperative T stages.Two of the 28 postoperatively diagnosed T1b patients were proved to be T2 after reevaluation,the rate of misdiagnosis was 7.1％,the reevaluated T stages were equal to or higher than the previous stages.Twenty-five confirmed T1 b gallbladder cancer patients had complete follow-up data,11 of whom underwent simple cholecystectomy and the remaining 14 radical resections.No patient had vessel or perineural invasion on pathology in the 25 confirmed T1b patients.Metastasis was absent in all the 30 lymph nodes examined,which achieved from 14 patients with radical resection.The survival rate after simple cholecystectomy was comparable to that after radical resection (P =0.361).Only one patient with radical resection had abdominal cavity implantation relapse,who received gallbladder compression during operation and 2 years later died from metastasis.Conclusion:Intraoperatively diagnosed T1 b gallbladder cancer should receive radical resection.Reevaluation of the T stage is necessary and the initial step for postoperative diagnosed T1b gallbladder cancer patients.The pros and cons of radical surgery for definitive T1b patients should be carefully evaluated,and systemic chemotherapy is recommended for those with bile spillover.

BACKGROUNDHelicobacter pylori (H. pylori) frequently colonizes the stomach. Gastroesophageal reflux disease (GERD) is a common and costly disease. But the relationship of H. pylori and GERD is still unclear. This study aimed to explore the effect of H. pylori and its eradication on reflux esophagitis therapy.

METHODSPatients diagnosed with reflux esophagitis by endoscopy were enrolled; based on rapid urease test and Warth-Starry stain, they were divided into H. pylori positive and negative groups. H. pylori positive patients were randomly given H. pylori eradication treatment for 10 days, then esomeprazole 20 mg bid for 46 days. The other patients received esomeprazole 20 mg bid therapy for 8 weeks. After treatment, three patient groups were obtained: H. pylori positive eradicated, H. pylori positive uneradicated, and H. pylori negative. Before and after therapy, reflux symptoms were scored and compared. Healing rates were compared among groups. The χ2 test and t-test were used, respectively, for enumeration and measurement data.

RESULTSThere were 176 H. pylori positive (with 92 eradication cases) and 180 negative cases. Healing rates in the H. pylori positive eradicated and H. pylori positive uneradicated groups reached 80.4% and 79.8% (P = 0.911), with reflux symptom scores of 0.22 and 0.14 (P = 0.588). Healing rates of esophagitis in the H. pylori positive uneradicated and H. pylori negative groups were, respectively, 79.8% and 82.2% (P = 0.848); reflux symptom scores were 0.14 and 0.21 (P = 0.546).

CONCLUSIONSBased on esomeprazole therapy, H. pylori infection and eradication have no significant effect on reflux esophagitis therapy.

Adolescent ; Adult ; Aged ; Amoxicillin ; therapeutic use ; Esomeprazole ; therapeutic use ; Esophagitis, Peptic ; drug therapy ; etiology ; microbiology ; Female ; Gastroesophageal Reflux ; drug therapy ; etiology ; microbiology ; Helicobacter Infections ; complications ; drug therapy ; Helicobacter pylori ; drug effects ; pathogenicity ; Humans ; Male ; Middle Aged ; Tinidazole ; therapeutic use ; Young Adult

Objective To study the optimal waist circumference (WC) cut-off values for identifying metabolic risk factors in middle-aged and elderly subjects in Shandong Province of China.
Methods A total of 2 873 men and 5 559 women were included in this cross-sectional study. Metabolic syndrome (MetS) was diagnosed according to the definition of Chinese Diabetes Society in 2004. The relation between WC and MetS was analyzed by multivariate logistic regression analysis. The optimal WC cut-off values were identified using the area under the ROC curve and the different diagnostic criteria for central obesity were compared.
Results The WC was the risk factor for MetS independent of BMI, blood glucose, blood lipid, and blood pressure. The optimal WC cut-off value was 83.8 cm and 91.1 cm for identifying MetS in women and men, respectively. Compared with 80 cm and 85 cm for women and men, 85 cm and 90 cm had a higher Youden index for identifying all metabolic risk factors and MetS in women and men.
Conclusion The appropriate WC cut-off value is 85 cm and 90 cm for identifying central obesity and MetS in women and men in Shandong Province of China.