Effects of radiofrequency field from 5G communication on fecal microbiome and metabolome profiles in mice.

With the rapid development of 5G networks, the influence of the radiofrequency field (RF) generated from 5G communication equipment on human health is drawing increasing attention in public. The study aimed at assessing the effects of long-term exposure to 4.9 GHz (one of the working frequencies of 5G communication) RF field on fecal microbiome and metabolome profiles in adult male C57BL/6 mice. The animals were divided into Sham group and radiofrequency group (RF group). For RF group, the mice were whole body exposed to 4.9 GHz RF field for three weeks, 1 h/d, at average power density (PD) of 50 W/m2. After RF exposure, the mice fecal samples were collected to detect gut microorganisms and metabolites by 16S rRNA gene sequencing and LC-MS method, respectively. The results showed that intestinal microbial compositions were altered in RF group, as evidenced by reduced microbial diversity and changed microbial community distribution. Metabolomics profiling identified 258 significantly differentially abundant metabolites in RF group, 57 of which can be classified to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Besides, functional correlation analysis showed that changes in gut microbiota genera were significantly correlated with changes in fecal metabolites. In summary, the results suggested that altered gut microbiota and metabolic profile are associated with 4.9 GHz radiofrequency exposure.

A multicenter single-arm trial of neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2-positive breast cancer.

The objective of this multicenter, single-arm trial (ChiCTR1900022293) was to explore the efficacy and safety of neoadjuvant therapy with epirubicin, cyclophosphamide, and pyrotinib followed by docetaxel, trastuzumab, and pyrotinib (ECPy-THPy) in the treatment of patients with stage II-III HER2-positive breast cancer. The present study enrolled patients with stage II-III HER2-positive breast cancer. Epirubicin and cyclophosphamide were administrated for four 21-day cycles, followed by four cycles of docetaxel and trastuzumab. Pyrotinib was taken orally once per day throughout the treatment period. The primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0) rate in the modified intention-to-treat (mITT) population. In total, 175 patients were included. The tpCR rate was 68.6% (95% CI, 60.7-75.8%), while the objective response rate was 89.1%. In the post-hoc subgroup analysis, no association between clinical characteristics and the tpCR rate was observed. The most common grade ≥3 adverse events were diarrhea (54.3%), followed by white blood cell count decreased (5.1%), and neutrophil count decreased (4.6%). In conclusion, the neoadjuvant regimen with ECPy-THPy showed promising pathological response and clinical benefits with an acceptable safety profile in patients with stage II-III HER2-positive breast cancer.

Combined effects of EMP and RF field on emotional behavior in mice.

Background: Recently, concerns about the combined effects of electromagnetic field (EMF) in daily living and occupational environment are rapidly growing. Methods: In this study, we investigated the combined effects of 1-week exposure to electromagnetic pulse (EMP) at 650 kV/m for 1,000 pulses and 4.9 GHz radiofrequency (RF) at 50 W/m2 for 1 h/d in male mice. Open field test, tail suspension test and Y-maze were applied to evaluate anxiety, depression-like behaviors and spatial memory ability, respectively. Results: It was found that compared with Sham group, combined exposure to EMP and RF induced anxiety-like behavior, increased the level of serum S100B and decreased the level of serum 5-HT. The results of quantitative proteomic and KEGG analysis showed that the differentially expressed proteins in hippocampus were enriched in Glutamatergic and GABAergic synapse after combined exposure group, which were verified by western blot. In addition, an obvious histological alteration and autophagy-associated cell death were observed in amygdala instead of hippocampus after combined exposure to EMP and 4.9 GHz RF. Conclusion: Combined exposure to EMP and 4.9 GHz RF could induce emotional behavior alteration, which might be associated with Glutamatergic and GABAergic synapse system of hippocampus and autophagy in amygdala.

Moderate white light exposure enhanced spatial memory retrieval by activating a central amygdala-involved circuit in mice.

Light exposure can profoundly affect neurological functions and behaviors. Here, we show that short-term exposure to moderate (400 lux) white light during Y-maze test promoted spatial memory retrieval and induced only mild anxiety in mice. This beneficial effect involves the activation of a circuit including neurons in the central amygdala (CeA), locus coeruleus (LC), and dentate gyrus (DG). Specifically, moderate light activated corticotropin-releasing hormone (CRH) positive (+) CeA neurons and induced the release of corticotropin-releasing factor (CRF) from their axon terminals ending in the LC. CRF then activated tyrosine hydroxylase-expressing LC neurons, which send projections to DG and release norepinephrine (NE). NE activated ß-adrenergic receptors on CaMKIIα-expressing DG neurons, ultimately promoting spatial memory retrieval. Our study thus demonstrated a specific light scheme that can promote spatial memory without excessive stress, and unraveled the underlying CeA-LC-DG circuit and associated neurochemical mechanisms.

Effects of radiofrequency field from 5G communications on the spatial memory and emotionality in mice.

The rapid development of 5G network technology has gained much popularity as well as concerns about its adverse effects. In this study, we investigated the effects of 4.9 GHz (one of working frequencies of 5G communication) radiofrequency (RF) field on emotional behaviours and spatial memory in adult male mice. Open field test (OFT), tail suspension test (TST) and Y maze were used to evaluate anxiety, depression-like behaviour and spatial memory ability, respectively. It was found that the anxiety-like behaviour and spatial memory ability of mice did not change, but the depression-like behaviour was induced in mice after 4.9 GHz RF exposure. In addition, the number of neurons significantly reduced and the level of pyroptosis obviously increased in amygdala rather than hippocampus. These results suggested that 4.9 GHz RF exposure could induce depression-like behaviour, which might be associated with the neuronal pyroptosis in amygdala.

Unilateral axilla-bilateral areola approach for thyroidectomy by da Vinci robot vs. open surgery in thyroid cancer: a retrospective observational study.

BACKGROUND: To compare the efficacy and safety of unilateral axilla-bilateral areola (UABA) approach for robot-assisted thyroidectomy with conventional open surgery in thyroid cancer patients. METHODS: The clinicopathological features and surgical outcomes of 194 thyroid cancer patients treated by robotic surgery using the UABA approach and 217 patients treated by open surgery in our department from January 2017 to August 2018 were analysed and compared. RESULTS: The operation time was longer in the robotic group than in the open surgery group. The patients' satisfaction with neck appearance was higher in the robotic group than in the open surgery group (91.2% vs. 21.6%, P<0.01). After total thyroidectomy and central lymph node dissection, the incidence of postoperative transient hypoparathyroidism and postoperative permanent hypoparathyroidism in the open surgery group was 29.7% (44/148) and 6.8% (10/148), higher than that [17.9% (27/151) and 2.0% (3/151)] in the robotic group (P<0.05 respectively). No significant difference was observed in the number of dissected lymph nodes or postoperative serum thyroglobulin (TG) levels or incidence of transient or permanent hoarseness of voice between the two groups. No recurrence or metastasis was found. CONCLUSIONS: Compared with open surgery, UABA robotic surgery preserved the neck appearance and effectively reduced hypoparathyroidism by super-meticulous capsular dissection (SMCD).

Unilateral Axilla-Bilateral Areola Approach for Thyroidectomy by da Vinci Robot: 500 Cases Treated by the Same Surgeon.

Objective: To investigate the efficacy and safety of da Vinci robot-assisted thyroidectomy via an unilateral axilla-bilateral areola (UABA) approach. Methods: The clinical data of 500 patients undergoing robotic thyroidectomy via an UABA approach from July 2014 to April 2018 were retrospectively analyzed. All 500 patients were operated on by the same surgeon and divided into two groups by the time sequence. The efficacy and complications were compared between the two groups. Results: Robotic thyroidectomy via an UABA approach was performed successfully in 500 cases, including 196 cases of benign thyroid diseases with a lesion diameter of 3.1 ± 1.3 cm (0.4 - 8.2 cm) and 304 cases of thyroid cancer with a tumor diameter of 1.2 ± 0.7 cm (0.4 - 4.4 cm). Surgical procedures included unilateral lobectomy and total thyroidectomy with or without central lymph node dissection. Among the 500 patients, 9 (1.8%) had transient recurrent laryngeal nerve injury, 1 (0.2%) had permanent unilateral recurrent laryngeal nerve injury, 12 (2.4%) had subcutaneous hemorrhage of the trajectory area, and 6 (1.2%) had subcutaneous infection of the trajectory area after surgery. Among 239 thyroid cancer patients undergoing total thyroidectomy, 45 (18.8%) had transient hypoparathyroidism and 5 (2.1%) had permanent hypoparathyroidism. The incidence of permanent hypoparathyroidism was 1.9% (4/212) among the patients undergoing total thyroidectomy plus unilateral central lymph node dissection, and 3.7% (1/27) among the patients undergoing total thyroidectomy plus bilateral central lymph node dissection. During the follow-up of median 17 months, all patients were satisfied with postoperative appearance of the neck and no structural recurrence or metastases occurred. There was no significant difference in efficacy between the two groups (P > 0.05), while the complication rate in phase 2 was significantly lower than that in phase 1 (P < 0.05) as the surgeon became more proficient in the UABA approach. Conclusion: Robotic thyroidectomy via an UABA approach is simple, safe, and minimally invasive, suitable for radical resection of large benign tumors and early thyroid cancer and central lymph node dissection.

First report of in-situ preservation of a subcapsular parathyroid gland through super-meticulous capsular dissection during robotic radical thyroidectomy.

PURPOSE: Meticulous capsular dissection can preserve the function of the parathyroid gland in most patients, but it is difficult to identify and preserve the subcapsular parathyroid gland. We performed in-situ preservation of the subcapsular parathyroid gland during robotic radical thyroidectomy using super-meticulous capsular dissection, and evaluated its effect on postoperative parathyroid function. METHODS: A 45-year-old woman was admitted with bilateral thyroid nodules. Color Doppler ultrasound demonstrated a 7 × 7 × 6 mm hypoechoic area in the middle and inferior part of the right lobe and 3 × 3 × 3 mm hypoechoic nodule in the middle part of the left lobe. She was diagnosed with right thyroid papillary cancer by fine-needle aspiration. Robotic bilateral thyroidectomy plus right central lymph node dissection was performed. During the left thyroidectomy, we found that the left inferior parathyroid gland was just under the true capsule. Subsequently, the super-meticulous capsular dissection was performed for in-situ preservation of the parathyroid gland. RESULTS: The patient's serum parathyroid hormone concentration was 43.77 pg/ml before and 37.98 pg/ml after surgery (normal: 15-65 pg/ml). Her blood calcium level was 2.21 mmol/l before and 2.18 mol/l after surgery (normal: 2.10-2.65 mmol/l). CONCLUSIONS: The super-meticulous capsular dissection, which could cut through the true capsule to identify subcapsular parathyroid and protect its anatomic structure as well as blood supply, is recommend for in-situ preservation of subcapsular parathyroid gland during robotic radical thyroidectomy.

Clinical significance of internal mammary lymph node metastasis for breast cancer: Analysis of 337 breast cancer patients.

PURPOSE: Internal mammary nodes (IMNs) is a major pathway of lymphatic drainage for breast cancer, apart from axillary lymph node (ALN). However, owing to lack of a feasible and safe biopsy method, management of IMNs is still controversial in breast surgery. METHODS: From 2005 to 2009, a total of 337 consecutive breast cancer women patients were recruited. All patients underwent IMNs biopsy through intercostal space or endoscopic lymphatic chain resection. The ER, PR and HER-2 status were retested according to the current ASCO/CAP guidelines. We analyzed the relationship between clinical pathological parameters and IMNs metastasis and investigated the high risk factors and prognostic values of IMNs metastasis in breast cancer. RESULTS: Among 337 patients, 314 patients underwent intercostal space IMNs biopsy and 23 patients underwent endoscopic lymphatic chain resection. A total of 63 (18.69%) patients were pathologically diagnosed with IMNs metastasis. Among them, 28 (44.44%) patients changed the pathological lymph node staging, and 15 cases (23.81%) changed the postoperative comprehensive treatment program and accepted extended postoperative radiotherapy. Multivariate analysis showed that compared with no ALN involvement, the risk of IMNs metastasis was significantly increased in patients with 1-3 ALN involvement (OR = 42.097, 95% CI = 5.225-339.178; P = 0.0004) and ≥4 ALN involvement (OR = 82.429, 95%CI = 10.134-670.496; P < 0.0001). The risk of IMNs metastasis in HER-2 positive patients was significantly higher than that in negative patients (OR = 5.452, 95% CI = 2.353-12.634; P < 0.0001). However, we did not find IMNs involvement was an independent indicator for both overall survival and disease-free survival. CONCLUSIONS: Our clinical practice and data indicated that IMNs biopsy through intercostal space and endoscopic lymphatic chain resection are effective and minimally invasive methods to detect the IMNs status, which may be helpful for accurate tumor staging, risk assessment and option of chemotherapy or radiotherapy to improve the patients' survival.

Robot-assisted internal mammary lymph chain excision for breast cancer: A case report.

RATIONALE: Understanding the status of internal mammary lymph nodes of breast cancer is critical in the accurate staging of breast cancer and the development of accurate therapeutic regimen for selected patients. Current techniques for dissection of internal mammary lymph node biopsy involve endoscopic or Traditional thoracic surgery, An important drawback of the current techniques is the great trauma caused by them. PATIENT CONCERNS: Da Vinci robotic surgery system (Intuitive Surgical Inc. Sunnyvale, CA) was used to perform the internal mammary lymph chain excision for a breast cancer patient with left internal mammary lymph node metastasis. DIAGNOSES: Positron emission tomography-computed tomography examination and Ultrasonography examination. INTERVENTIONS: In this paper, we introduce a Robot-assisted technique for dissection of internal mammary lymph node biopsy with only 3 small trocar ports. This technique reduces the incision size and considerably reduce the trauma. OUTCOMES: The operation lasted a duration of 1.5 hours. The operation was carried out smoothly with removal of 9 internal mammary lymph nodes in total. The amount of intra operative bleeding was less than 10 ml. The patient's postoperative recovery was fast. 11-month postoperative follow-up showed that the patient recovered well after surgery, no local recurrence or distant metastasis was found, and no obvious discomfort was reported. LESSONS: Robot-assisted excision of internal mammary lymph chain in breast cancer is a safe, effective and simple operation with minimal invasion.

Endoscopic nipple sparing mastectomy with immediate implant-based reconstruction versus breast conserving surgery: a long-term study.

To evaluate the differences between endoscopic nipple sparing mastectomy (ENSM) with immediate implant-based reconstruction and breast conserving surgery(BCS) applied to early-stage breast cancer in postoperative outcomes, function, and cosmesis. we made a prospective, non-randomized study reviewed a total of 346 cases of breast cancer from January 2007 to December 2011, including 189 cases of BCS and 157 cases of ENSM. All the patients were followed up to April 2016, with a median follow-up time of 74 months. The operative time, blood loss and drainage, postoperative complications, postoperative cosmesis, local recurrence rate, disease-free survival rate and overall survival rate of the two groups were compared. we found out that the operative time of ENSM was longer than that of BCS. There was no difference in blood loss and drainage, the postoperative complications, the disease-free survival rate and overall survival rate between the two groups. In regarding to cosmesis, patients in the ENSM group were more likely to get a satisfactory postoperative breast appearance. we reached a conclusion that ENSM is a safe and effective operative method retainingadvantages of TSSM to further improve the postoperative cosmetic effect, without increasing other risks. The surgery provides a new choice for patients with early-stage breast cancer.

Evaluation of the tracing effect of carbon nanoparticle and carbon nanoparticle-epirubicin suspension in axillary lymph node dissection for breast cancer treatment.

BACKGROUND: Carbon nanoparticle suspension, using smooth carbon particles at a diameter of 21 nm added with suspending agents, is a stable suspension of carbon pellets of 150 nm in diameter. It is obviously inclined to the lymphatic system. There were some studies reporting that carbon nanoparticles are considered as superior tracers for sentinel lymph nodes because of their stability and operational feasibility. However, there were few study concerns about the potential treatment effect including tracing and local chemotherapeutic effect of carbon nanoparticle-epirubicin suspension on breast cancer with axillary metastasis. METHODS: In the current study, a randomized controlled analysis was performed to investigate the potential treatment effect of carbon nanoparticle-epirubicin suspension on breast cancer with axillary metastasis. A total of 90 breast cancer patients were randomly divided into three equal groups: control, tracer, and drug-load groups. The control group patients did not receive any lymphatic tracers, the tracer group patients were subcutaneously injected with 1 ml carbon nanoparticle suspension, and the drug-load group patients were injected with 3 ml carbon nanoparticle-epirubicin suspension at four separate sites around the areola 24 h before surgery. Modified radical mastectomy, endoscopic subcutaneous mammary resection plus axillary lymph node dissection, and immediate reconstruction with implants or breast-conserving surgery were performed. RESULTS: The mean number of the dissected lymph nodes per patient was significantly higher in the tracer (21.3 ± 6.1) and drug-load (19.5 ± 3.7) groups than in the control group (16.7 ± 3.4) (P < 0.05). Most lymph nodes in the former two groups were stained black (75.7 and 73.3 %, respectively), but with no significant difference between the groups. Most metastatic lymph nodes were also stained black in the tracer group (68.6 %) and drug-load group (78.1 %) and with no significant difference between the groups (P = 0.198). Microscopic examination revealed that the carbon nanoparticles were localized around or among the cancer cell masses and residues of necrotized cancer cells surrounded by fibroblastic proliferation could be found within the stained lymph nodes in the drug-load group. CONCLUSIONS: The majority of axillary lymph nodes were stained black by the suspension of carbon nanoparticles, which helped identify the lymph nodes from the surrounding tissues and avoided aggressive axillary treatment. Thus, a combination therapy of carbon nanoparticles with epirubicin could play an important role in lymphatic chemotherapy without affecting tracing. TRIAL REGISTRATION: ChiCTRTRC13003419.

Mechanism of Regulatory Effect of MicroRNA-206 on Connexin 43 in Distant Metastasis of Breast Cancer.

BACKGROUND: MicroRNA-206 (miR-206) and connexin 43 (Cx43) are related with the distant metastasis of breast cancer. It remains unclear whether the regulatory effect of miR-206 on Cx43 is involved in metastasis of breast cancer. METHODS: Using quantitative real-time polymerase chain reaction and Western blot, the expressions of miR-206 and Cx43 were determined in breast cancer tissues, hepatic and pulmonary metastasis (PM), and cell lines (MCF-10A, MCF-7, and MDA-MB-231). MCF-7/MDA-M-231 cells were transfected with lentivirus-shRNA vectors to enhance/inhibit miR-206, and then Cx43 expression was observed. Cell counting kit-8 assay and Transwell method were used to detect their changes in proliferation, migration, and invasion activity. The mutant plasmids of Cx43-3' untranslated region (3'UTR) at position 478-484 and position 1609-1615 were constructed. Luciferase reporter assay was performed to observe the effects of miR-206 on luciferase expression of different mutant plasmids and to confirm the potential binding sites of Cx43. RESULTS: Cx43 protein expression in hepatic and PM was significantly higher than that in the primary tumor, while no significant difference was showed in messenger RNA (mRNA) expression. MiR-206 mRNA expression in hepatic and PM was significantly lower than that in the primary tumor. Cx43 mRNA and protein levels, as well as cell proliferation, migration, and invasion capabilities, were all significantly improved in MDA-MB-231 cells after reducing miR-206 expression but decreased in MCF-7 cells after elevating miR-206 expression, which demonstrated a significantly negative correlation between miR-206 and Cx43 expression (P = 0.03). MiR-206 can drastically decrease Cx43 expression of MCF-7 cells but exerts no effects on Cx43 expression in 293 cells transfected with the Cx43 coding region but the lack of Cx43-3'UTR, suggesting that Cx43-3'UTR may be the key in Cx43 regulated by miR-206. Luciferase expression showed that the inhibition efficiency was reduced by 46.80% in position 478-484 mutant, 16.72% in position 1609-1615 mutant; the inhibition was totally disappeared in double mutant (P = 0.02). CONCLUSIONS: MiR-206 can regulate the expression of Cx43, the cytobiological activity, and the metastasis of breast cancer through binding to the two binding sites in Cx43-3'UTR: position 478-484 and position 1609-1615.

miR-381 suppresses C/EBPα-dependent Cx43 expression in breast cancer cells.

Cx43 (connexin43) is an enhancer of the metastasis of breast cancer cells. Our previous study identified miR-381 as an indirect suppressor of Cx43 gene expression, with the precise mechanism being not understood. In the present study, using a reporter gene assay, we found that miR-381 suppressed Cx43 gene expression via the promoter region -500/-250. With site-directed gene mutation, we demonstrated that miR-381 could directly bind with the sequences CACUUGUAU in the 3'-UTR so as to inhibit C/EBPα (CCAAT/enhancer-binding protein α) expression. C/EBPα was further identified as a novel transcription factor by binding to a canonic element (AATTGTC) locating at -459/-453 in the promoter region of the Cx43 gene. Functionally, we demonstrated that miR-381 suppressed C/EBPα- and Cx43-dependent migration and invasion of breast cancer cells. Finally, we revealed that decreased levels of miR-381 as well as increased expression of C/EBPα and Cx43 in the metastatic breast cancer cells and tissues. Therefore we are the first to identify that miR-381 suppresses C/EBPα-dependent Cx43 expression in breast cancer cells. The miR-381-C/EBPα-Cx43 axis might be a useful diagnostic and therapeutic target of metastatic breast cancer.

Identification of miR-200a as a novel suppressor of connexin 43 in breast cancer cells.

Both miRNAs (miRs) and connexin 43 (Cx43) were important regulators of the metastasis of breast cancer, whereas the miRs regulating Cx43 expression in breast cancer cells were still obscure. In the present study, we scanned and found miR-1, miR-206, miR-200a, miR-381, miR-23a/b and miR-186 were functional suppressors of human Cx43 mRNA and protein expression. Specially, we demonstrated that only miR-200a could directly target the 3'-untranslated region (3'-UTR) of human Cx43 gene. Functionally, overexpression of Cx43 in MCF cells potentiated the migration activity, whereas additional miR-200a treatment notably prevented this effect. Finally, we demonstrated that decreased levels of miR-200a and elevated expression of Cx43 in the metastatic breast cancer tissues compared with the primary ones. Thus, we are the first to identify miR-200a as a novel and direct suppressor of human Cx43, indicating that miR200a/Cx43 axis might be a useful diagnostic and therapeutic target of metastatic breast cancer.