Overexpressing S100A9 ameliorates NK cell dysfunction in estrogen receptor-positive breast cancer.

BACKGROUND: Estrogen receptor (ER) positive human epidermal growth factor receptor 2 (HER2) negative breast cancer (ER+/HER2-BC) and triple-negative breast cancer (TNBC) are two distinct breast cancer molecular subtypes, especially in tumor immune microenvironment (TIME). The TIME of TNBC is considered to be more inflammatory than that of ER+/HER2-BC. Natural killer (NK) cells are innate lymphocytes that play an important role of tumor eradication in TME. However, studies focusing on the different cell states of NK cells in breast cancer subtypes are still inadequate. METHODS: In this study, single-cell mRNA sequencing (scRNA-seq) and bulk mRNA sequencing data from ER+/HER2-BC and TNBC were analyzed. Key regulator of NK cell suppression in ER+/HER2-BC, S100A9, was quantified by qPCR and ELISA in MCF-7, T47D, MDA-MB-468 and MDA-MB-231 cell lines. The prognosis predictability of S100A9 and NK activation markers was evaluated by Kaplan-Meier analyses using TCGA-BRAC data. The phenotype changes of NK cells in ER+/HER2-BC after overexpressing S100A9 in cancer cells were evaluated by the production levels of IFN-gamma, perforin and granzyme B and cytotoxicity assay. RESULTS: By analyzing scRNA-seq data, we found that multiple genes involved in cellular stress response were upregulated in ER+/HER2-BC compared with TNBC. Moreover, TLR regulation pathway was significantly enriched using differentially expressed genes (DEGs) from comparing the transcriptome data of ER+/HER2-BC and TNBC cancer cells, and NK cell infiltration high/low groups. Among the DEGs, S100A9 was identified as a key regulator. Patients with higher expression levels of S100A9 and NK cell activation markers had better overall survival. Furthermore, we proved that overexpression of S100A9 in ER+/HER2-cells could improve cocultured NK cell function. CONCLUSION: In conclusion, the study we presented demonstrated that NK cells in ER+/HER2-BC were hypofunctional, and S100A9 was an important regulator of NK cell function in ER+BC. Our work contributes to elucidate the regulatory networks between cancer cells and NK cells and may provide theoretical basis for novel drug development.

Comparing survival outcomes between neoadjuvant and adjuvant chemotherapy within T2N1M0 stage hormone receptor-positive, HER2-negative breast cancer: a retrospective cohort study based on SEER database.

BACKGROUND: Guideline recommendations for the application of neoadjuvant chemotherapy (NACT) in T2N1M0 stage hormone receptor-positive, HER2-negative (HR + /HER2-) breast cancer are ambiguous. The debate continues regarding whether NACT or adjuvant chemotherapy (ACT) offers superior survival outcomes for these patients. MATERIALS AND METHODS: Female patients diagnosed with HR + /HER2- breast cancer at T2N1M0 stage between 2010 and 2020, were identified from the Surveillance, Epidemiology, and End Results database and divided into two groups, the NACT group and the ACT group. Propensity score matching (PSM) was utilized to establish balanced cohorts between groups, considering baseline features. Kaplan-Meier (K-M) analysis and the Cox proportional hazards model were executed to assess the efficacy of both NACT and ACT in terms of overall survival (OS) and breast cancer-specific survival (BCSS). A logistic regression model was employed to examine the association between predictive variables and response to NACT. RESULTS: After PSM, 4,682 patients were finally included. K-M curves showed that patients receiving NACT exhibited significantly worse OS and BCSS when compared with patients undergoing ACT. Multivariable Cox analysis indicated that not achieving pathologic complete response (non-pCR) after NACT (versus ACT), was identified as an adverse prognostic factor for OS (HR 1.58, 95% CI 1.36-1.83) and BCSS (HR 1.70, 95% CI 1.44-2. 02). The logistic regression model revealed that low tumor grade independently predicted non-pCR. CONCLUSION: Among T2N1M0 stage HR + /HER2- patients, OS and BCSS of NACT were inferior to ACT. Patients who attained non-pCR after NACT demonstrated significantly worse survival outcomes compared with those who received ACT.

[Retracted] microRNA­206 overexpression inhibits cellular proliferation and invasion of estrogen receptor α­positive ovarian cancer cells.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the western blotting data shown in Fig. 1A and Transwell cell migration data shown in Fig. 4A were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 9: 1703­1708, 2014; DOI: 10.3892/mmr.2014.2021].

Human health risk visualization of potentially toxic elements in farmland soil: A combined method of source and probability.

Human health is adversely affected by potentially toxic elements (PTEs) in the topsoil, entering the bodies via inhalation, ingestion, and dermal contact. To visualize human health risks, we investigated five PTEs (Cd, As, Pb, Hg, and Cr) in 72 farmland topsoil samples from a town in Chongqing City, southwest China. Based on the human health risk assessment model, sequential indicator simulation (SIS) and the positive matrix factorization model (PMF) were used to construct the spatial health risks and to analyze the sources of PTEs; finally, health risks were combined with the source by ArcGIS. Based on our results, the use of SIS is feasible for the prediction of the spatial distribution of PTEs. Among the risks, the non-cancer risk of As for children most likely exceeded the accepted level in some areas, making As a priority pollutant. Although the health risks of soil Cd were acceptable in the region, the spatial probability distribution of Cd> 0.3 mg/kg represents a threat as Cd enters the human food chain. Even if the industrial discharge was the lowest individual contributor (29.33%), due to the impact of industrial discharge, the total non-cancer risk with a high probability (>0.85) for children still exceeded the accepted level in the northwestern area, which should be regarded as the priority pollution source. The combined method was useful to reduce efforts in environmental management, thus providing a basis for soil remediation and pollution source control.

MicroRNA-9 affects isolated ovarian granulosa cells proliferation and apoptosis via targeting vitamin D receptor.

MicroRNAs (miRNAs or miRs)-9 expression was reported to be upregulated in the follicular fluid of patients with polycystic ovary syndrome (PCOS). However, whether miR-9 affects ovarian dysfunction of PCOS and the related mechanisms are still unclear. Here we detected miR-9 and vitamin D receptor (VDR) expression in women with PCOS and controls, and investigated whether miR-9 affects ovarian granulosa cells (GCs) proliferation and apoptosis by targeting VDR. We found increased miR-9 and decreased VDR in the blood and isolated ovarian GCs of women with PCOS compared with the controls. MiR-9 promoted GCs proliferation and inhibited GCs apoptosis in vitro, and these effects were attenuated by its target VDR. High concentrations of insulin upregulated miR-9 expression in GCs. In conclusion this study firstly proved miR-9 affects ovarian GCs proliferation and apoptosis through targeting VDR. MiR-9 might be a potential molecular target for improving the dysfunction of GCs in PCOS.

Ultrasound guided high-intensity focused ultrasound combined with gonadotropin releasing hormone analogue (GnRHa) ablating uterine leiomyoma with homogeneous hyperintensity on T2 weighted MR imaging.

OBJECTIVE: The study aimed to evaluate the safety and efficiency of ultrasound-guided high-intensity focused ultrasound (USgHIFU) combined with gonadotropin-releasing hormone analogue (GnRHa)-ablating symptomatic uterine leiomyoma with homogeneous hyperintensity on T2 weighted MRI prospectively. METHODS: A total of 34 patients with 42 symptomatic uterine leiomyomas with homogeneous hyperintensity on T2 weighted MRI were enrolled in our study. In the patient who had multiple uterine leiomyomas, only one dominant leiomyoma was treated. According to the principles of voluntariness, 18 patients underwent a 3-month therapy of GnRHa (once a month) before the high-intensity focused ultrasound (HIFU) treatment, while 16 patients received only HIFU treatment. Enhanced MRI was performed before and after GnRHa and HIFU treatment. Evaluation of the main indicators included treatment time, sonication time, treatment efficiency, non-perfused volume (NPV) (indicative of successful ablation) ratio and energy effect ratio; adverse events were also recorded. RESULTS: The treatment time and sonication time of the combination group were 102.0 min (55.8-152.2 min) and 25.4 min (12.2-34.1 min); however, they were 149.0 min (87.0-210.0 min) and 38.9 min (14.0-46.7 min) in the simple USgHIFU group. The treatment and sonication time for the combination group was significantly shorter than that for the simple USgHIFU group. Treatment efficiency, NPV ratio and energy effect ratio were 46.7 mm3 s-1 (28.5-95.8 mm3 s-1), 69.2 ± 29.8% (35.5-97.4%) and 9.9 KJ mm-3 (4.5-15.7 KJ mm-3) in the combination group, respectively; but, the lowest treatment efficiency, lowest NPV ratio and more energy effect ratio were observed in the simple HIFU group, which were 16.8 mm3 s-1 (8.9-32.9 mm3 s-1), 50.2 ± 27.3% (0-78.6%) and 23.8 KJ mm-3 (12.4-46.2 KJ mm-3), respectively. Pain scores in the combination group were 3.0 ± 0.5 points (2-4 points)-significantly less than the simple USgHIFU group. There were no significant adverse reactions in either group. CONCLUSION: Our data suggest that USgHIFU combined with GnRHa may be performed to ablate symptomatic uterine leiomyoma with homogeneous hyperintensity on T2 weighted MRI. Advances in knowledge: The conclusions indicate that GnRHa can improve the effectiveness of the USgHIFU treatment of a homogeneous hyperintense leiomyoma on T2 weighted MRI, and combination treatment could be a promising alternative treatment for the uterine leiomyoma.

microRNA-206 overexpression inhibits cellular proliferation and invasion of estrogen receptor α-positive ovarian cancer cells.

The expression levels of estrogen receptor (ER α) are closely associated with estrogen-dependent growth, invasion and response to endocrine therapy in ERα-positive ovarian cancer. However, the underlying regulatory mechanisms remain to be fully understood. Previous studies have demonstrated that ERα is a direct target of microRNA (miR)-206. miR-206 has been found to be an important tumor suppressor in several cancer types, including ovarian, gastric and laryngeal cancer. However, the specific role of miR-206 in ovarian cancer remains unclear. The aim of the present study was to investigate the role of miR-206 in ER-a positive ovarian cancer in vitro. The present study demonstrated that miR-206 is significantly downregulated in ERα-positive but not ERα­negative ovarian cancer tissues, compared with normal ovarian epithelium tissue. It was also found that the expression of miR-206 was decreased in ERα-positive ovarian cancer cell lines, CAOV-3 and BG-1, compared with normal ovarian epithelium tissues. This suggests that miR-206 may play a role in ERα-positive ovarian cancer cells via an estrogen-dependent mechanism. Further analysis revealed that 17ß-E2 treatment significantly promoted cellular proliferation and invasion of estrogen-dependent CAOV-3 and BG-1 cells, which could be reversed by the introduction of miR-206 mimics. In conclusion, the present study suggests that miR-206 has an inhibitory role in estrogen-dependent ovarian cancer cells. Thus, miR-206 may be a promising candidate for the endocrine therapy of ERα-positive ovarian cancer.

Single-dose intra-articular bupivacaine versus morphine after arthroscopic knee surgery: a meta-analysis of randomized-controlled studies.

OBJECTIVES: This meta-analysis compared the earliest clinical effects of intra-articular bupivacaine and morphine for pain management following arthroscopic knee surgery. MATERIALS AND METHODS: A comprehensive literature search was conducted using MEDLINE (1966 to 2013), the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Google Scholar databases for identification of randomized-controlled trials that compared IA bupivacaine and morphine for postoperative pain. The relative risk, weighted mean difference (WMD), and their corresponding 95% confidence intervals (CI) were calculated using RevMan statistical software. RESULTS: Bupivacaine and morphine group had similar acute postoperative pain scores (WMD: 0.07; 95% CI, -0.18 to 0.32; P=0.60); number of patients requiring supplementary analgesia (relative risk: 0.74; 95% CI, 0.42 to 1.31; P=0.30) for the trials in this meta-analysis (n=13); and side effects (relative risk: 0.63; 95% CI, 0.39 to 1.02, P=0.06). Even though, the time to first analgesic request resulted in a significant difference (WMD: 66.59; 95% CI, 11.75 to 122.14, P=0.02), this result was not supported by the sensitivity analysis. CONCLUSIONS: On the basis of the currently available literature, this study failed to demonstrate a significant difference between single-dose intra-articular bupivacaine and morphine at the end of the arthroscopic knee surgery in terms of pain relief, need for supplementary analgesics, times interval before the first request for additional analgesic, and short-term side effects. LEVEL OF EVIDENCE: Level II-meta-analysis of Level I and II studies.

Single-dose intra-articular bupivacaine after knee arthroscopic surgery: a meta-analysis of randomized placebo-controlled studies.

PURPOSE: The purpose of this meta-analysis was to examine the efficacy and safety of single-dose intra-articular bupivacaine in the management of pain after knee arthroscopic surgery. METHOD: The comprehensive literature search, using MEDLINE, the Cochrane Central Register of Controlled Trials, and Embase databases, was conducted to identify randomized controlled trials that used single-dose intra-articular bupivacaine for postoperative pain. The relative risk (RR), weighted mean difference (WMD), and their corresponding 95 % confidence intervals (CIs) were calculated using RevMan(®) statistical software. RESULT: Twenty-three studies (n = 1287) were included (647 subjects in bupivacaine group and 640 subjects in the control group). Statistically significant differences were observed in the VAS values (WMD -1.1; 95 % CI -1.7 to -0.5), number of patients requiring supplementary analgesia (RR 0.83; 95 % CI 0.74-0.94), and time to first analgesic request (WMD 129.3; 95 % CI 15.4-243.1) among the bupivacaine group when compared to the control group. However, short-term side effects had no significant difference between these two groups (RR 0.73; 95 % CI 0.44-1.24). CONCLUSIONS: On the basis of the currently available literature, single-dose intra-articular bupivacaine was shown to be significantly better than placebo at relieving pain after knee arthroscopic surgery. More high-quality randomized controlled trials with long follow-up are highly required for examining the safety of single-dose intra-articular bupivacaine. Besides, routine use of single-dose intra-articular bupivacaine is still an effective way for pain management after knee arthroscopic surgery.

The CUSUM analysis of the learning curve for endoscopic thyroidectomy by the breast approach.

OBJECTIVES: To evaluate the learning curve for endoscopic thyroidectomy by the breast approach (ETBBA) based on the cumulative summation (CUSUM) technique. METHODS: The study included 110 consecutive patients who underwent ETBBA by a single surgeon between January 2009 and May 2012 at the Xiangya Hospital of Central South University, Changsha, China. The learning curve was evaluated using the CUSUM technique. The patients were chronologically arranged into 3 phases by the CUSUM analysis for operative time. Demographic data and operative parameters were also analyzed. RESULTS: The mean operative time (OT) was 125.3 minutes. The conversion rate for technical difficulties and the definitive complication rate were 6.4% and 10%, respectively. The learning curve was analyzed mainly by OT using the CUSUM technique. There was a significant improvement in the average OT (P < .05) after the first 27 patients and again after the first 67 patients (P < .05). A downward trend in OT was found up to the last patient. There were similarities in gender, tumor size, extent of surgery, blood loss, histology, hospital stay, conversion rate, and complications among the 3 phases. Comparison of 2 neighboring phases also showed no significant differences in age. CONCLUSIONS: ETBBA performed by surgeons has a remarkable learning curve. There were 27 cases in the early stage of the learning curve, whereas mastery level could be achieved with 67 cases.

Validation of the European Organization for Research and Treatment of Cancer cervical cancer module for Chinese patients with cervical cancer.

PURPOSE: The aim of our study was to assess, for the first time, the validity, reliability, and acceptability of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire (QLQ) cervical cancer module (CX24) in Chinese cervical cancer patients. PATIENTS AND METHODS: One hundred fifteen outpatients with cervical cancer in the First Affiliated Hospital of Xinxiang Medical University from May 2013 to July 2013 were included in this study. All participants self-administered the EORTC QLQ-CX24 and the core questionnaire (EORTC QLQ-C30), and the Karnofsky Performance Scale was performed to evaluate scores. Data were analyzed with Cronbach's α coefficient, Pearson correlation test, multitrait scaling analysis, and Mann-Whitney U test. RESULTS: Scale reliability was confirmed by Cronbach's α coefficients for internal consistency, which ranged from 0.71 to 0.82. Convergent and discriminant validity were confirmed by multitrait scaling analysis, which revealed three (3.4%) scaling errors for symptom experience scales and zero (0%) for body image as well as sexual/vaginal functioning scales. Higher missing value rate occurred in sexuality-related items. The clinical validity of the Chinese version of the EORTC QLQ-CX24 was demonstrated by the ability to discriminate among patients in different International Federation of Gynecology and Obstetrics stages. CONCLUSION: The EORTC QLQ-CX24 was proved to be a reliable and valid instrument with which to measure the quality of life in cervical cancer patients in the People's Republic of China.

Oral contraceptive use and uterine leiomyoma risk: a meta-analysis based on cohort and case-control studies.

PURPOSE: To review the epidemiological and clinical evidence for the association between oral contraceptives (OCs) and uterine leiomyoma (UL). METHODS: Several databases (Pubmed, Cochrane Central, OVID, SpringerLink, Clinical Evidence, and Google scholar) and reference lists were searched through March 2012 with no restrictions. INCLUSION CRITERIA: cohort or case-control studies; the exposure of interest was OCs; the outcome of interest was UL; relative risk (RR) or odds ratio (OR) (or data to calculate them) were reported. Two independent reviewers assessed eligibility criteria and extracted data. RESULTS: Eleven literatures involving 8,990 UL patients and 1,31,055 participants were included from 3,017 studies initially found. The influence of OCs on UL risk was assessed by comparing "ever", "current" or "former" users and "never" users. Meta-analysis indicated that OCs use did not increase UL morbidity ("ever" vs "never": risk ratio [RR] 0.88; 95 % confidence interval [95 % CI] 0.75-1.04. "current" vs "never": RR 0.43; 95 % CI 0.25-0.73. "former" vs "never": RR 0.96; 95 % CI 0.84-1.08). Dose-response analysis showed the risk of UL morbidity was reduced by 17 % in "ever" users for 5 years or more (P trend = 0.006). However, the results have to be viewed with caution because there was significant heterogeneity (I (2): from 64 to 92 %). CONCLUSIONS: Although the role of potential bias and evidence of heterogeneity should be carefully evaluated, the present study suggests that UL should not be considered a contra-indication for OCs use.

Complications following dorsal versus volar plate fixation of distal radius fracture: a meta-analysis.

OBJECTIVES: A meta-analysis to compare complication rates following volar or dorsal surgical fixation of distal radius fracture. METHODS: A detailed search of PubMed®/MEDLINE® was undertaken to identify randomized and nonrandomized controlled trials published before 25 August 2012 that compared volar with dorsal fixation, in patients with distal radius fracture. RESULTS: A quantitative meta-analysis of 12 trials (952 patients) was performed. There was no between-group difference in the overall rate of complications. Volar fixation was associated with significant increases in neuropathy (relative risk [RR] 2.19; 95% confidence intervals [CI] 1.27, 3.76) and carpal tunnel syndrome (RR 4.56; 95% CI 1.02, 20.44), and a reduction in tendon irritation, compared with the dorsal approach (RR 0.38; 95% CI 0.17, 0.86). CONCLUSIONS: Dorsal fixation offers a lower risk of neuropathy and carpal tunnel syndrome than the volar approach, but a higher risk of tendon irritation. Patients with a distal radius fracture can expect similar outcomes after volar or dorsal surgery.