Opening-closing six-qi acupuncture combined with western medication for primary hypertension of liver yang hyperactivity:a randomized controlled trial. / "å¼€é˜–å ­æ°”é’ˆæ³•"è”åˆè¥¿è¯æ²»ç–—è‚é˜³ä¸Šäº¢åž‹åŽŸå‘æ€§é«˜è¡€åŽ‹ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe the clinical efficacy of opening-closing six-qi acupuncture combined with western medication for primary hypertension of liver yang hyperactivity, and explore its action mechanism. METHODS: A total of 96 patients with primary hypertension of liver yang hyperactivity were randomly divided into an acupuncture group (48 cases) and a western medication group (48 cases, 2 cases eliminated, 1 case discontinued). The western medication group was given felodipine sustained-release tablets orally, 5 mg each time, once a day. The acupuncture group was treated with opening-closing six-qi acupuncture at tender points of shaoyang and yangming areas of the head on the basis of the western medication group, once every other day. A total of 4 weeks were required in both groups. The blood pressure before treatment and after 2, 4 weeks of treatment, the TCM syndrome score and serum levels of hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), homocysteine (Hcy) before and after treatment were observed, and the clinical efficacy was evaluated in the two groups. RESULTS: After 2, 4 weeks of treatment, the systolic blood pressure(SBP)and diastolic blood pressure(DBP) in both groups were decreased compared with those before treatment(P<0.05)；except for DBP after 2 weeks of treatment, the SBP and DBP in the acupuncture group were lower than those in the western medication group(P<0.05). After treatment, the TCM syndrome scores and serum levels of hs-CRP, IL-6, Hcy were decreased compared with those before treatment in the two groups(P<0.05), those in the acupuncture group were lower than those in the western medication group(P<0.05).The total effective rate of the acupuncture group was 95.8% (46/48), which was higher than 73.3% (33/45) in the western medication group(P<0.05). CONCLUSIONS: Opening-closing six-qi acupuncture combined with western medication could lower blood pressure, improve symptoms in patients with primary hypertension of liver yang hyperactivity.Its mechanism may be related to down-regulation of inflammatory factors.

Effects of chemical oxygen demand and chloramphenicol on attached microalgae growth: Physicochemical properties and microscopic mass transfer in biofilm.

During the wastewater treatment and resource recovery process by attached microalgae, the chemical oxygen demand (COD) can cause biotic contamination in algal culture systems, which can be mitigated by adding an appropriate dosage of antibiotics. The transport of COD and additive antibiotic (chloramphenicol, CAP) in algal biofilms and their influence on algal physiology were studied. The results showed that COD (60 mg/L) affected key metabolic pathways, such as photosystem II and oxidative phosphorylation, improved biofilm autotrophic and heterotrophic metabolic intensities, increased nutrient demand, and promoted biomass accumulation by 55.9 %, which was the most suitable COD concentration for attached microalgae. CAP (5-10 mg/L) effectively stimulated photosynthetic pigment accumulation and nutrient utilization in pelagic microalgal cells. In conclusion, controlling the COD concentration (approximately 60 mg/L) in the medium and adding the appropriate CAP concentration (5-10 mg/L) are conducive to improving attached microalgal biomass production and resource recovery potential from wastewater.

Long-term toxicity assessment of antibiotics against Vibrio fischeri: Test method optimization and mixture toxicity prediction.

The current luminescent bacteria test for acute toxicity with short contact time was invalid for antibiotics, and the non-uniformed contact times reported in the literature for long-term toxicity assessment led to incomparable results. Herein, a representative long-term toxicity assessment method was established which unified the contact time of antibiotics and Vibrio fischeri within the bioluminescence increasing period (i.e. 10-100% maximum luminescence) of control samples. The effects of excitation and detoxification of antibiotics such as ß-lactams were discovered. Half maximal inhibitory concentration (IC50) of toxic antibiotics (0.00069-0.061 mmol/L) obtained by this method was 2-3 orders of magnitude lower than acute test, quantifying the underestimated toxicity. As antibiotics exist in natural water as mixtures, an equivalent concentration addition (ECA) model was built to predict mixture toxicity based on physical mechanism rather than mathematical method, which showed great fitting results (R2 = 0.94). Furthermore, interaction among antibiotics was investigated. Antibiotics acting during bacterial breeding period had strong synergistic inhibition (IC50 relative deviation from 0.1 to 0.6) such as macrolides and quinolones. Some antibiotics produced increasing synergistic inhibition during concentration accumulation, such as macrolides. The discharge of antibiotics with severe long-term toxicity and strong synergistic inhibition effect should be seriously restricted.

Quantified trend of photosynthetic rate along the depth of microalgae biofilm.

Compared with suspended microalgae cultivation, attached microalgae cultivation for wastewater treatment has advantages of low biomass recovery costs and high robustness. As a heterogeneous system, the variation of photosynthetic capacity along biofilm depth lacks quantitative conclusions. The distribution curve of oxygen concentration along the depth of attached microalgae biofilm (f(x)) was detected by dissolved oxygen (DO) microelectrode, and a quantified model was built based on mass conservation and Fick's law. It revealed that the net photosynthetic rate at a certain depth (x) in the biofilm showed a linear relationship with the second derivatives of the distribution curve of oxygen concentration (f″(x)). In addition, the declining trend of photosynthetic rate along attached microalgae biofilm was relatively slow compared with the suspended system. The photosynthetic rate at 150-200 µm depth of algae biofilm was only 3.60 %-17.86 % of that at the surface layer. Moreover, the light saturation points of the attached microalgae got lower along the depth of biofilm. Compared to 400 lx light intensity, the net photosynthetic rate of microalgae biofilm at the depths of 100-150 µm and 150-200 µm increased by 389 % and 956 % under 5000 lx, respectively, showing the high photosynthesis potential with increasing light.

Clinical Relevance of Estrogen Reactivity in the Breast Cancer Microenvironment.

Purpose: Estrogen signals play an important role in the phenotype of estrogen receptor-positive breast cancer. However, comprehensive analyses of the effect of responsiveness to estrogen signals on the tumor microenvironment and survival in large cohorts of primary breast cancer patients have been lacking. We aimed to test the hypothesis that estrogen reactivity affects gene expression and immune cell infiltration profiles in the tumor microenvironment and survival. Methods: A total of 3,098 breast cancer cases were analyzed: 1,904 from the Molecular Taxonomy of Breast Cancer (METABRIC) cohort, 1,082 from The Cancer Genome Atlas (TCGA) cohort, and 112 from the Hokkaido University Hospital cohort. We divided the group into estrogen reactivity-high and estrogen reactivity-low groups utilizing the scores of ESTROGEN_RESPONSE_EARLY and ESTROGEN_RESPONSE_LATE in Gene Set Variation Analysis. Results: Breast cancer with high estrogen reactivity was related to Myc targets, metabolism-related signaling, cell stress response, TGF-beta signaling, androgen response, and MTORC1 signaling gene sets in the tumor microenvironment. Low estrogen reactivity was related to immune-related proteins, IL2-STAT5 signaling, IL6-JAK-STAT3 signaling, KRAS signaling, cell cycle-related gene sets, and EMT. In addition, breast cancer with high levels of estrogen reactivity had low immune cytolytic activity and low levels of immunostimulatory cells. It also had low levels of stimulatory and inhibitory factors of the cancer immunity cycle. Patients with high estrogen reactivity were also associated with a better prognosis. Conclusion: We demonstrated the relationship between estrogen reactivity and the profiles of immune cells and gene expression, as well as survival.

Touching tumour-infiltrating lymphocytes in low-risk ductal carcinoma in situ (DCIS) correlate with upgrading to high-grade DCIS.

AIMS: To examine our hypothesis that a higher number of touching tumour-infiltrating lymphocytes (TILs) in low-risk ductal carcinoma in situ (DCIS) detected in a setting such as an active surveillance clinical trial correlates with upgrading to high-grade DCIS (HG-DCIS) in the subsequent excisional biopsy. METHODS AND RESULTS: The clinical inclusion criteria of the Comparison of Operative versus Monitoring and Endocrine Therapy (COMET) trial were applied to women who were mammographically screened between 2007 and 2017. In the core needle biopsy, touching TILs were assessed by counting the number of TILs touching the ductal basement membrane or away from it by one lymphocyte thickness. The highest number of TILs around a single involved duct and the average number among involved ducts were recorded. DCIS was graded as low or intermediate. Twenty-six of 129 (20.2%) cases had upgrading [14 (10.9%) to pure HG-DCIS, and 12 (9.3%) to invasive carcinoma, two of them with concurrent HG-DCIS]. An increased average number of touching TILs and intermediate-grade DCIS correlated with upgrading to HG-DCIS in 11 of 16 (68.8%) cases, and a decreased average number of touching TILs and low-grade DCIS correlated with no upgrading in 89 of 113 (78.8%) cases [accuracy of 0.775; area under the curve (AUC) of 0.746]. An increased highest number of touching TILs and intermediate-grade DCIS correlated with upgrading to HG-DCIS in 12 of 16 (75%) cases, and a decreased highest number of touching TILs and low-grade DCIS correlated with no upgrading in 82 of 113 (72.6%) cases (accuracy of 0.7287; AUC of 0.734). A highest number of touching TILs of ≥10 correlated with upgrading to invasive carcinoma and/or HG-DCIS (P = 0.018). CONCLUSIONS: Intermediate-grade and touching TILs may be good variables to examine in the COMET trial and to correlate with the risk of upgrading.

Low intratumoral genetic neutrophil-to-lymphocyte ratio (NLR) is associated with favorable tumor immune microenvironment and with survival in triple negative breast cancer (TNBC).

Patients with triple negative breast cancer (TNBC) have a poor prognosis. A novel prognostic biomarker may guide management by appropriately selecting patients for particular treatments. Peripheral blood neutrophil-to-lymphocyte ratio (NLR) was reported to associate with cancer progression, thus we hypothesized that intratumor genetic NLR will reflect tumor immune microenvironment (TIME) and breast cancer biology. The intratumoral genetic NLR previously defined as the ratio of CD66b (CEACAM8) and CD8 (CD8A) gene expressions was utilized to analyze total of 2,994 patients from METABRIC, TCGA, GSE21094, GSE22358, GSE25088, GSE32646, and GSE2603 cohorts. Intratumoral genetic NLR did not correlate with cancer stage nor clinical parameters of cancer cell proliferation such as Nottingham histological grade or MKI67 expression levels in neither the METABRIC or TCGA cohorts. Intratumoral genetic NLR-high breast cancer was not associated with pathologic complete response (pCR) after neoadjuvant chemotherapy in 5 independent cohorts with different regimens. Despite these results, intratumoral genetic NLR-high TNBC demonstrated worse disease-free, disease-specific, and overall survival. Intratumoral genetic NLR-low TNBC enriched multiple immune-related gene sets, was associated with higher favorable immune-related scores and with a favorable TIME, whereas no gene sets enriched to NLR-high TNBC. In conclusion, intratumoral genetic NLR-low TNBC was associated with favorable TIME and with better survival.

Immune cytolytic activity is associated with reduced intra-tumoral genetic heterogeneity and with better clinical outcomes in triple negative breast cancer.

Evaluation of the functional aspects if the tumor immune microenvironment (TIME), such as the recently introduced cytolytic activity score (CYT) index have been under the spotlight in cancer research; however, clinical relevance of immune cell killing activity in breast cancer has never been analyzed in large patient cohorts. We hypothesized that CYT reflects the immune activity of TIME and can predict patient survival. A total of 7533 breast cancer patients were analyzed as both discovery and validation cohorts. We found that high CYT was associated with advanced histological grade and triple-negative breast cancer (TNBC). High CYT in tumors was significantly associated with better survival in TNBC, but unexpectedly, not in other breast cancer subtypes. High CYT TNBC included both favorable immune-related, as well as unfavorable (suppressive) inflammation-related gene sets, and characterized by high infiltration with T cells and B cells. High CYT TNBC was associated with high homologous recombination deficiency and low somatic copy number alteration score and less mutant allele tumor heterogeneity, but not with tumor mutation burden (TMB). Although CYT was not associated with pathological complete response after neoadjuvant chemotherapy, it was significantly associated with high expression of multiple immune checkpoint molecules. In conclusion, CYT of TNBC is associated with enhanced anti-cancer immunity, less intra-tumoral heterogeneity, and with better survival.

Altered Expression of Secreted Mediator Genes That Mediate Aggressive Breast Cancer Metastasis to Distant Organs.

Heterogeneity is the characteristic of breast tumors, making it difficult to understand the molecular mechanism. Alteration of gene expression in the primary tumor versus the metastatic lesion remains challenging for getting any specific targeted therapy. To better understand how gene expression profile changes during metastasis, we compare the primary tumor and distant metastatic tumor gene expression using primary breast tumors compared with its metastatic variant in animal models. Our RNA sequencing data from cells revealed that parental cell and the metastatic variant cell are different in gene expression while gene signature significantly altered during metastasis to distant organs than primary breast tumors. We found that secreted mediators encoding genes (ANGPTL7, MMP3, LCN2, S100A8, and ESM1) are correlated with poor prognosis in the clinical setting as divulged from METABRIC and TCGA-BRCA cohort data analysis.

Significance of Removing Comedonecrosis as an Exclusion Criterion in Mammary Low-Risk Ductal Carcinoma In Situ Managed in an Active Surveillance Clinical Trial.

OBJECTIVES: This study aims to investigate the consequences of comedonecrosis omission as an exclusion criterion of the Comparison of Operative vs Monitoring and Endocrine Therapy (COMET) trial. METHODS: The clinical inclusion criteria of the COMET trial were applied on women who were mammographically screened between 2007 and 2017 and had a diagnosis of low- or intermediate-grade ductal carcinoma in situ (DCIS). The percentage of ductal diameter occupied by necrosis was calculated. RESULTS: Twenty-six of 129 (20.2%) cases were upgraded. Larger calcification span correlated with upgrade (P = .02), with the best cutoff of 1.1 cm, and negative predictive value of 86%. When solely analyzing cases with no comedonecrosis (n = 76), none of the variables correlated with upgrade. Comedonecrosis was significantly correlated with upgrade to invasive carcinoma (P = .041), with the best cutoff of 53% of ductal diameter occupied by necrosis. CONCLUSIONS: Results indicate that comedonecrosis and span of mammographic calcifications could be risk factors in women managed with active surveillance.

Organoids Are Limited in Modeling the Colon Adenoma-Carcinoma Sequence.

The colon adenoma-carcinoma sequence is a multistep genomic-altering process that occurs during colorectal cancer (CRC) carcinogenesis. Organoids are now commonly used to model both non-cancerous and cancerous tissue. This study aims to investigate how well organoids mimic tissues in the adenoma-carcinoma sequence by comparing their transcriptomes. A total of 234 tissue samples (48 adenomas and 186 CRC) and 60 organoid samples (15 adenomas and 45 CRC) were analyzed. We found that cell-proliferation-related gene sets were consistently enriched in both CRC tissues and organoids compared to adenoma tissues and organoids by gene set enrichment analysis (GSEA). None of the known pathways in the colon adenoma-carcinoma sequence were consistently enriched in CRC organoids. There was no enrichment of the tumor microenvironment-related gene sets in CRC organoids. CRC tissues enriched immune-response-related gene sets, whereas CRC organoids did not. The proportions of infiltrating immune cells were different between tissues and organoids, whereas there was no difference between cancer and adenoma organoids. The amounts of cancer stem cells and progenitor cells were not different between CRC and adenoma organoids, whereas a difference was noted between CRC and adenoma tissues. In conclusion, we demonstrated that organoids model only part of the adenoma-carcinoma sequence and should be used with caution after considering their limitations.

miR-885-5p suppresses osteosarcoma proliferation, migration and invasion through regulation of ß-catenin.

MicroRNAs (miRs) have been reported to serve key roles in cancer. To investigate the function of miR-885-5p in osteosarcoma, the expression levels of miR-885-5p were analyzed in 85 osteosarcoma tissue samples and adjacent non-cancerous tissue samples, using reverse transcription-quantitative polymerase chain reaction analysis. It was demonstrated that miR-885-5p was downregulated in osteosarcoma tissues and cell lines. Notably, the expression level of miR-885-5p was closely associated with tumor size, Tumor-Node-Metastasis stage and lymph node metastasis. Additionally, low expression levels of miR-885-5p also predicted a poor prognosis of osteosarcoma. To further decipher the roles of miR-885-5p in osteosarcoma, it was determined that ß-catenin, a key component of the Wnt signaling pathway, was a target of miR-885-5p. Furthermore, several functional experiments, including a colony formation assay, CCK-8 assay, wound healing assay and Transwell invasion assay, revealed that miR-885-5p suppressed cell proliferation, migration and invasion through inhibition of ß-catenin. The results of the present study provide a novel insight into the molecular roles of miR-885-5p in osteosarcoma.