OBJECTIVES: To study the molecular mechanisms of LDH-loaded si-NEAT1 for regulating paclitaxel resistance and tumor-associated macrophage (TAM) polarization in breast cancer. METHODS: qRT-PCR and Western blotting were used to detect the expression of lncRNA NEAT1, miR-133b, and PD-L1 in breast cancer SKBR3 cells and paclitaxel-resistant SKBR3 cells (SKBR3-PR). The effects of transfection with si-NEAT1 and miR-133b mimics on MRP, MCRP and PD-L1 expressions and cell proliferation, migration and apoptosis were investigated using qRT-PCR, Western blotting, scratch and Transwell assays, and flow cytometry. Rescue experiments were conducted using si-NEAT1 and miR-133b inhibitor. Human THP-1 macrophages were cultured in the presence of conditioned media (CM) derived from SKBR3 and SKBR3-PR cells with or with si-NEAT1 transfection for comparison of IL-4-induced macrophage polarization by detecting the surface markers. LDH@si-NEAT1 nanocarriers were constructed, and their effects on MRP, MCRP and PD-L1 expressions and cell behaviors of the tumor cells were examined. THP-1 cells were treated with the CM from LDH@si-NEAT1-treated tumor cells, and the changes in their polarization were assessed. RESULTS: SKBR3-PR cells showered significantly upregulated NEAT1 and PD-L1 expressions and lowered miR-133b expression as compared with their parental cells. Transfection with si-NEAT1 and miR-133b mimics inhibited viability, promoted apoptosis and enhanced MRP and BCRP expressions in SKBR3-PR cells. NEAT1 knockdown obvious upregulated miR-133b and downregulated PD-L1, MRP and BCRP expressions. The CM from SKBR3-PR cells obviously promoted M2 polarization of THP-1 macrophages, which was significantly inhibited by CM from si-NEAT1-transfected cells. Treatment with LDH@si-NEAT1 effectively inhibited migration and invasion, promoted apoptosis, and reduced MRP, BCRP and PD-L1 expressions in the tumor cells. The CM from LDH@si-NEAT1-treated SKBR3-PR cells significantly downregulated Arg-1, CD163, IL-10, and PD-L1 and upregulated miR-133b expression in THP-1 macrophages. CONCLUSIONS LDH@si-NEAT1 reduces paclitaxel resistance of breast cancer cells and inhibits TAM polarization by targeting the miR-133b/PD-L1 axis.
Humans ; MicroRNAs/genetics* ; RNA, Long Noncoding/genetics* ; Paclitaxel/pharmacology* ; Breast Neoplasms/metabolism* ; Drug Resistance, Neoplasm ; B7-H1 Antigen/metabolism* ; Cell Line, Tumor ; Female ; Tumor-Associated Macrophages ; Apoptosis ; Cell Proliferation ; Macrophages ; Cell Movement

Objective To analyze the expression of CREM in gastric cancer(GC)and its correlation with prognosis of the patients.Methods TCGA and GEO databases were used to analyze the expression levels of CREM mRNA in GC and adjacent tissues.Immunohistochemistry was used to examine the expression of CREM protein in 43 pairs of GC and adjacent tissues,and the correlation of CREM expression with clinicopathological features of the patients was analyzed.Kaplan-Meier survival analysis was used to explore the relationship between CREM expression and survival of GC patients.LinkedOmics database was used to annotate the GO function and KEGG pathway enrichment of CREM-related genes.Results Database analysis showed that CREM was highly expressed in GC tissues(P<0.05)and positively correlated with poor prognosis in GC patients(P=0.01).Immunohistochemistry results showed significantly higher CREM expression in GC tissues than in paired adjacent tissues(P<0.0001),and its expression level was correlated with T-stage and N-stage of the tumor(P<0.05).The overall survival of GC patients with high expression of CREM was shorter(RR=4.02,P=0.0046).Gene enrichment analysis showed that high CREM expression promotes occurrence and progression of GC very likely through the cell adhesion signaling pathway.Conclusion CREM is highly expressed in GC,and its high expression is associated with a poor prognosis of GC patients,suggesting the potential of CREM to serve as a prognostic indicator for GC.

Mucinous adenocarcinoma of the renal pelvis is rare in clinical practice. This article reported a case of primary renal pelvis mucinous adenocarcinoma mixed with signet ring cell carcinoma. The patient was admitted to hospital due to right low back pain, and was diagnosed with right kidney stones accompanied by hydrops and infection, right kidney abscess, and nonfunctional right kidney after complete examination. Right renal puncture drainage was performed twice, followed by laparoscopic robot assisted right neprectomy. The postoperative pathological diagnosis was right renal pelvis primary mucinous adenocarcinoma (mixed with signet-ring cell carcinoma). Eleven months after the operation, regular "sodium folinate + oxaliplatin + 5-fluorouracil" chemotherapy was performed for 12 courses, and imaging showed no signs of recurrence or metastasis.

Objective To analyze the expression of CREM in gastric cancer(GC)and its correlation with prognosis of the patients.Methods TCGA and GEO databases were used to analyze the expression levels of CREM mRNA in GC and adjacent tissues.Immunohistochemistry was used to examine the expression of CREM protein in 43 pairs of GC and adjacent tissues,and the correlation of CREM expression with clinicopathological features of the patients was analyzed.Kaplan-Meier survival analysis was used to explore the relationship between CREM expression and survival of GC patients.LinkedOmics database was used to annotate the GO function and KEGG pathway enrichment of CREM-related genes.Results Database analysis showed that CREM was highly expressed in GC tissues(P<0.05)and positively correlated with poor prognosis in GC patients(P=0.01).Immunohistochemistry results showed significantly higher CREM expression in GC tissues than in paired adjacent tissues(P<0.0001),and its expression level was correlated with T-stage and N-stage of the tumor(P<0.05).The overall survival of GC patients with high expression of CREM was shorter(RR=4.02,P=0.0046).Gene enrichment analysis showed that high CREM expression promotes occurrence and progression of GC very likely through the cell adhesion signaling pathway.Conclusion CREM is highly expressed in GC,and its high expression is associated with a poor prognosis of GC patients,suggesting the potential of CREM to serve as a prognostic indicator for GC.

Humans ; Asthma/drug therapy* ; Biological Therapy

Objective:To investigate the differences of white matter diffusion properties between vulnerable and resistant individuals to continuous attention after sleep deprivation.Methods:According to the psychomotor vigilance test performance before and after sleep deprivation, the participants were divided into the vulnerable group( n=24) and resistant group( n=25). All participants underwent diffusion tensor imaging (DTI) scans.Tract based spatial statistics(TBSS) was used to compare fractional anisotropy(FA), mean diffusivity(MD), axial diffusivity(AD), radial diffusivity(RD) maps between the two groups.Spearman correlation analysis was conducted by SPSS 24.0 to investigate the relationships between the altered DTI metrics and PVT task performance. Results:(1) Compared with resistant group, FA value of vulnerable group decreased in the body of corpus callosum(x, y, z=-8, 9, 25, t=-7.855), right superior longitudinal fasciculus(x, y, z=-39, -7, 26, t=-6.252), bilateral anterior limb of internal capsule(x, y, z=-13, 8, 13, t=-5.235; x, y, z=12, 8, 3, t=-5.024) and right posterior thalamic radiation(x, y, z=-26, -56, 17, t=-5.469)(TFCE corrected, P<0.05, cluster size≥50 voxel). (2) Compared with resistant group, MD value of vulnerable group increased in the body of corpus callosum(x, y, z=-3, -6, 26, t=7.613), right superior longitudinal fasciculus(x, y, z=-31, -19, 38, t=5.314), bilateral anterior limb of internal capsule(x, y, z=-16, 7, 8, t=6.898; x, y, z=15, 5, 7, t=6.652), splenium of corpus callosum(x, y, z=27, -53, 17, t=6.541), and AD value increased in the right superior longitudinal fasciculus(x, y, z=-33, -19, 39, t=4.892), splenium of corpus callosum(x, y, z=-22, -49, 21, t=5.450), genu of corpus callosum(x, y, z=4, 26, 0, t=4.332), as well as RD value increased in the right superior corona radiata(x, y, z=-17, 1, 33, t=7.558), body of corpus callosum(x, y, z=4, -8, 26, t=6.699), right anterior limb of internal capsule(x, y, z=-12, 7, 3, t=5.212) (TFCE corrected, P<0.05, cluster size≥50 voxel). (3) Correlational analysis revealed that the negative correlations were found between PVT task performance and the FA value in the right superior longitudinal fasciculus( r=-0.492, P<0.001), right anterior limb of internal capsule( r=-0.510, P<0.001), right posterior thalamic radiation( r=-0.502, P<0.001) and body of corpus callosum( r=-0.464, P<0.001). The positive correlations were found between PVT task performance and the MD value in the body of corpus callosum( r=0.500, P<0.001), right superior longitudinal fasciculus( r=0.499, P<0.001), splenium of corpus callosum( r=0.462, P<0.001), right anterior limb of internal capsule( r=0.471, P<0.001), and AD value in right superior longitudinal fasciculus( r=0.643, P<0.001), as well as RD value in right superior corona radiate( r=0.498, P<0.001) (Bonferroni corrected, P<0.003). Conclusion:Differences in the microstructural characteristics of white matter fiber tracts in specific brain regions may constitute the potential neuropathological basis for the phenotypes of vulnerable and resistant individuals to continuous attention after sleep deprivation.

Objective To study patient delay and the influencing factors of the elderly patients with pulmonary tuberculosis（PTB），so as to provide evidence for developing effective prevention and control strategies. Methods Derived the information from PTB management information system in 2010-2019 of the tuberculosis patients who were aged 60 years or older in Huai'an City, described and analyzed the influencing factors of patient delay. Results The median time of PTB patients delay in Huaian was 21 day, while the rate was 65.91%. Multivariate logistic regression analysis results showed that compared with permanent residents, city dwellers, the first diagnosis unit specialized hospital, and the patient source referral, the patient delay risks of the floating residents（OR = 2.942 , 95% CI: 2.461-3.518）, the country dwellers（OR = 1.528,95% CI :1.377-1.697）, the first diagnosis unit general hospital（OR = 1.203,95% CI: 1.087-1.333）, and the patient source recommendation （OR = 2.395,95% CI: 1.960-2.928）were higher, Compared with the peasants（OR = 0.315 , 95% CI : 0.213-0.512）, new patients（OR = 0.812 , 95% CI : 0.689-0.974） and sputum smear positive patients（OR = 0.866 , 95% CI : 0.780-0.962）, the patient delay risks of the non-peasants, recurrent patients, and sputum negative patients were lower. Conclusion The patient delay of the elderly patients with pulmonary tuberculosis（PTB）in Huaian was serious, the influencing factors of patient delay were type of household registration, current residence, occupation, type of first-time unit, source of patient , classification of treatment, and the sputum test results.

Objective To investigate the expression of sialic acid-binding immunoglobulin-like-lectin-1 (Siglec-1)in the peripheral blood mononuclear cell (PBMC) of patients with autoimmune thyroiditis ( AIT) and its relationship with AIT. To explore the moduratory role of activated Siglec-1 on the differentiation of T cells and the promotion of in flammation after PBMC culture. Methods The peripheral whole blood and serum samples were collected from 30 AIT patients with normal thyroid function and 30 sex-and age-matched controls. The expression of sSiglec-1 in serum was detected by ELISA. The expression of Siglec-1 in PBMC was detected by RT-PCR and WB. The expression of Siglec-1 in CD14+ monocytes and the proportion of Th1 and Th17 cells in each group were detected by flow cytometry. The PBMC in AIT or control was stimulated with NaI in the presence or absence of LPS for 72 h. The expression of Siglec-1 in CD14+ monocytes and the proportion of Th1 and Th17 cells were detected by flow cytometry. Results sSiglec-1 in serum, Siglec-1 mRNA, and Siglec-1 protein in AIT patients'PBMC were higher than those in control group ( P＜0. 01). The expression of Siglec-1 in CD14+ monocytes by flow cytometry and differentiation of Th1 and Th17 cells were significantly higher than that in control group ( both P＜0. 01). The expression of Siglec-1 in control and AIT patients was up-regulated by 5×10-5 mmol/L to 1×10-2 mmol/L stimulated with NaI in the presence or absence of LPS for 72 h (P＜0.01), but the differentiation of Th1 and Th17 cells was up-regulated only in patients (P＜0.01), and in a dose-dependent manner. Conclusion Elevated Siglec-1 expression in PBMCs and monocytes can potentially serve as a biomarker for AIT. Iodine may affect Th1 and Th17 cell differentiation by activating Siglec-1 to adjust the AIT immune response.

Objective: To analyze the infection composition and drug resistance to Gram-negative (G^-) bacilli in children′s respiratory tract in Suzhou, in order to provide evidence for rational use of antibiotics clinically. Methods: G^- bacilli culture samples were collected from 21 561 cases of nasopharyngeal secretions from patients with respiratory tract infection admitted at the Department of Respiratory, Children′s Hospital of Soochow University from January 2007 to December 2016, including 21 246 cases in general wards, and 315 patients who were transferred to the respiratory department after treatment in the Intensive Care Unit(ICU), and the children were divided into the general ward group and the ICU group, and the pathogens were compared and the changes in bacterial susceptibility were dynamically observed between the 2 groups. Results: The primary G^-bacteria for respiratory infection was Haemophilus influenzae, followed by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii.The detection rates of Klebsiella pneumoniae and Pseudomonas aeruginosa in the ICU group were 16.8% (21/125 strains)and 14.4%(18/125 strains), respectively, which were significantly higher than those in the general ward group [10.0%(208/2 071 strains), 9.2%(190/2 071 strains)]. The detection rates of G^-bacteria in the ICU group were 33.7%(106/315 cases), which were significantly higher than those in the general ward group [9.4%(1 997/21 246 cases)], and the difference was statistically significant(χ²=210.325, P<0.001). The rare G^-bacillus such as Stenotrophomonas maltophilia, Acinetobacter junii and Burkholderia onion were higher in the ICU group [17.6%(22/125 strains)] than that in the general ward group [6.4% (132/2 071 strains)]. The rate that of G^-bacteria with two or more mixed infection in ICU group [17.0% (18/106 cases)] was significantly higher than in the general ward group [3.4%(68/1 997 cases)], and the difference was statistically significant(χ²=47.3, P<0.05). For the mixed infection, the ICU group was mainly composed of Klebsiella pneumoniae mixed with Pseudomonas aeruginosa or Escherichia coli, while the general ward group was composed of Haemophilus influenzae mixed with Pseudomonas aeruginosa or Escherichia coli.The sensitivity of Haemophilus influenzae to Ampicillin, Sultamicillin, Cefuroxime, Cefaclor and Azithromycin decreased, and the sensitivity to Chloramphenicol, Tetracycline and Trimethoprim+ Sulfamethoxazole increased year by year, and there were statistically significant differences in different years (all P<0.05). The sensiti-vity to Escherichia coli to Ceftazidime decreased year by year, and the sensitivity to Ampicillin and Levofloxacin increased year by year, and there were statistically significant differences in different years (all P<0.05). The sensitivity to Klebsiella pneumoniae to Cefoperazone/Sulbactam and imipenem decreased, and the sensitivity to Ciprofloxacin and Levofloxacin increased, and there were statistically significant differences in different years (all P<0.05). The sensitivity to Pseudomonas aeruginosa, Cefoperazone/Sulbactam and Ceftriaxone decreased year by year, and the sensitivity to Levofloxacin increased, and there were statistically significant differences in different years (all P<0.05). The detection rate of carbapenem-resistant strains of Klebsiella pneumoniae and Pseudomonas aeruginosa showed an increasing trend, and there were statistically significant differences in different years (all P<0.05). Conclusions The primary G^-bacteria for respiratory infections is Haemophilus influenzae, G^-bacilli especially, the mixed infection of G^-bacilli, is more likely to cause severe and critical respiratory infections.The resistance rate of G^-bacteria infection in children′s respiratory tract to commonly used antibiotics is generally on the rise.