The inhibition of the breast cancer by PPARγ agonist pioglitazone through JAK2/STAT3 pathway.

Breast cancer, especially triple-negative breast cancer, is one of the deadliest cancers in women. To date, there is a lack of a good therapeutic regimen for it. PPARγ has been reported to be a tumor suppressor and could be activated by many agonists involved in cancer inhibition. Therefore, the expression of PPARγ in breast cancer was analyzed by online software UALCAN whose data were from the TCGA database. The results revealed that the PPARγ expression was reduced in breast cancer tissues. Furthermore, the methylation in the PPARγ promoter was also assayed and the results indicated that the methylation level in the PPARγ promoter in breast cancer tissue was higher than that in normal tissue. In order to verify the methylation in promoter involved in the regulation of gene PPARγ expression, the 5'-Aza and fluorescence assays were performed and the results proved that methylation in promoter participated in gene PPARγ expression regulation. Pioglitazone, a PPARγ agonist, still was not investigated in breast cancer. Therefore, the effects of pioglitazone on breast cancer cells were tested by cell viability, scratch and transwell assays, and results indicated that the pioglitazone has the inhibition effect on the proliferation and migration of breast cancer cells by PPARγ which was correlated with the JAK2/STAT3 pathway. In order to further confirm the inhibition effect of pioglitazone on breast cancer in vivo, the nude mice model was administrated by gavage with pioglitazone. And the results indicated that pioglitazone could inhibit the growth of breast cancer in the PPARγ overexpression group in vivo. In summary, the expression of gene PPARγ was decreased in breast cancer tissues, which was correlated with its methylation in the promoter region. Moreover, pioglitazone could exert its inhibition on breast cancer proliferation and migration by the JAK2/STAT3 pathway.

Promising High-Confinement Regime for Steady-State Fusion.

A reproducible stationary high-confinement regime with small "edge-localized modes" (ELMs) has been achieved recently in the Experimental Advanced Superconducting Tokamak, which has a metal wall and low plasma rotation as projected for a fusion reactor. We have uncovered that this small ELM regime is enabled by a wide edge transport barrier (pedestal) with a low density gradient and a high density ratio between the pedestal foot and top. Nonlinear simulations reveal, for the first time, that the underlying mechanism for the observed small ELM crashes is the upper movement of the peeling boundary induced by an initial radially localized collapse in the pedestal, which stops the growth of instabilities and further collapse of the pedestal, thus providing a physics basis for mitigating ELMs in future steady-state fusion reactors.

New edge coherent mode providing continuous transport in long-pulse H-mode plasmas.

An electrostatic coherent mode near the electron diamagnetic frequency (20-90 kHz) is observed in the steep-gradient pedestal region of long pulse H-mode plasmas in the Experimental Advanced Superconducting Tokamak, using a newly developed dual gas-puff-imaging system and diamond-coated reciprocating probes. The mode propagates in the electron diamagnetic direction in the plasma frame with poloidal wavelength of ∼8 cm. The mode drives a significant outflow of particles and heat as measured directly with the probes, thus greatly facilitating long pulse H-mode sustainment. This mode shows the nature of dissipative trapped electron mode, as evidenced by gyrokinetic turbulence simulations.

Reduced STMN1 expression induced by RNA interference inhibits the bioactivity of pancreatic cancer cell line Panc-1.

Increased expression of STMN1 has been observed in many tumor forms, but its expression and potential biological role in pancreatic cancer is still unknown. In this study, we demonstrated that STMN1 was expressed to a large extent in pancreatic cancer tissues and cell lines as compared to normal pancreatic tissues. Suppression of STMN1 expression via transfection with STMN1-specific siRNA could not only significantly inhibit the proliferation, migration and invasion ability of Panc-1 cells, but also enhance the apoptosis of Panc-1 cells. In addition, downregulation of STMN1 obviously enhanced the acetylation level of α-tubulin. All these results indicated that STMN1 plays an important role in pancreatic cancer development, and might serve as a potential therapeutic target for pancreatic cancer.

Quantative trait loci of seed traits for soybean in multiple environments.

Seed length and seed width are an important factor to the soybean yield. So the quantitative trait loci (QTL) location for seed length and seed width could assistant the breeding of soybean. In this study, the QTL underlying seed length and seed width were studied. A recombinant inbred line population of soybeans derived from a cross between the American semi-draft cultivars Charleston and Dongnong 594 were used in 7 environments. The quantitative trait loci underlying seed length, seed width, and seed length/seed width were analyzed by the method of composite interval mapping. Then, the epistatic effects and the QTL-environment (QE) interaction effects were also analyzed. Some valuable QTL sites found had great effect to the seed trait. Results showed that 7 QTLs underlying seed length were identified mainly on linkage groups D1a, C2, B1, A1, G, and A2. For the seed width, 7 QTLs were identified on linkage groups D1a and O. Two QTLs of seed length/seed width were identified on linkage groups D1b and C2. No QE interaction was found for QTLs of seed length and seed width in 7 environments. QTLs of seed length/seed width on linkage groups A1 and I had a QE interaction in 7 environments. Seven pairs of QTLs were identified that affected additive x additive epistatic effect of seed length, seed width, and seed length/seed width, which occurred among 8 linkage groups. These results supply a good foundation for molecular assistant breeding for soybean seed trait.

[Gasless submental approach endoscopic removal of thyroglossal cyst].

Objective: To explore the safety and feasibility of gasless submental approach endoscopic removal of thyroglossal cyst. Methods: This work prospectively included the clinical data of 13 patients who underwent the gasless submental approach endoscopic removal of thyroglossal cyst at the Department of Otolaryngology, the First Affiliated Hospital of Chongqing Medical University from August 2021 to February 2022. The operative time, bleeding volumes, postoperative complications, subjective pain levels, satisfaction with incisional scars, neck and facial deformities, and recurrences were prospectively evaluated by visual analogue scale(VAS) score. Results: All of 13 patients were successfully treated using this new technique. The patients had a median age of 38 years, ranging from 24 to 59 years, comprising of 3 males and 10 females. The length of the submental incision was about 3 cm and the median of operation time was 135 minutes. Postoperative complications were minimal. The median volume of blood loss was 10 ml. Surgical site swelling existed in 1 case and dysphagia for more than 1 week occurred in 2 cases. Patients were discharged from the hospital with a median of 3 days after surgery. On a VAS of 0-10 scores, the pain had a median of 2 on the first day after surgery, and the satisfaction with incision scars and neck and facial deformities showed a median of 8 at 6 months after surgery. There were no recurrences during the follow-up period of 9-15 months. Conclusion: Gasless submental approach endoscopic removal of thyroglossal cyst may be a reliable new surgical method that is safe and has cosmetic advantages.

Transforming growth factor-beta1 in inflammatory airway disease: a key for understanding inflammation and remodeling.

Airway diseases such as chronic rhinosinusitis, asthma, and chronic obstructive pulmonary disorder are characterized by inflammation and remodeling. Among inflammatory and extracellular matrix regulatory cytokines, transforming growth factor-beta (TGF-ß) stands central, as it possesses both important immunomodulatory and fibrogenic activities, and should be considered a key for understanding inflammation and remodeling processes. This review will briefly summarize the recent findings on the role of TGF-ß1, from the view points of inflammation and remodeling, and discuss the role of TGF-ß in the upper and lower airway diseases. This may reveal new perspectives in the understanding of airway inflammation and remodeling processes and may open innovative treatment strategies for the regulation of TGF-ß1.

[Characteristics of cervical lymph node metastasis of cN0 laryngeal carcinoma].

Objective: To investigate the incidence of occult cervical lymph node metastasis and the common neck level of metastases in cN0 laryngocarcinoma, and the relationship between the clinicopathologic features of laryngocarcinoma and cervical lymph node metastasis. Methods: A total of 506 cases with cN0 laryngocarcinoma treated at the First Affiliated Hospital of Chongqing Medical University between March 2011 and March 2018 were enrolled, and their medical records and follow-up data were retrospectively analyzed. Of them, 211 cases of were glottic carcinoma in stage T1 without neck dissection and they were observed by clinical follow-up; other 295 cases, including glottic carcinoma, supraglottic carcinoma and hypopharyngeal carcinoma in stage T2-T4 were treated with surgical resection of the primary lesions and selective neck dissection. SPSS 22.0 software was used to analyze the data. Results: The total incidence of cervical lymph node metastasis was 10.87%(55/506), with a lower incidence in T1 stage glottic carcinoma(6/211,2.84%) than that in other cases(49/295,16.61%). The incidence of cervical lymph node metastasis in glottic carcinoma (29/426, 6.81%) was lower than those in supraglottic carcinoma (22/71,30.99%) and subglottic carcinoma (4/9) (χ(2)=35.810,P<0.01).The pN+ rates of glottic carcinoma at T1, T2, T3 were 2.84%(6/211), 5.31%(6/113), 16.05%(13/81), and 19.05%(4/21), respectively (χ(2)=18.572, P<0.01). The pN+ rates of supraglottic carcinoma at T2, T3 and T4 were 3/13, 32.50%(13/40) and 6/13, respectively (χ(2)=3.649,P>0.05). The incidence of cervical lymph node metastasis in poorly differentiated carcinoma (17/42, 40.48%) was higher than those in moderately differentiated carcinoma (26/205, 12.68%) and high differentiated carcinoma(12/246, 4.88%)(χ(2)=36.356, P<0.01). Moreover, 85 pN+ lymph nodes were obtained by selective neck dissection, respectively 43(50.59%) in level Ⅱa, 30(35.29%) in level Ⅲ, 1(1.18%) in level Ⅳ and 11(12.94%) in level Ⅵ. Conclusions: The occult cervical lymph node metastasis was frequently found in cN0 laryngocarcinoma. Selective neck dissection should be performed with surgery for the primary lesions in T3-T4 glottic laryngeal cancer, T2-T4 supraglottic laryngeal cancer and subglottic carcinoma, and the neck dissection for level Ⅱa and Ⅲ is appropriate. It is required to detect pre-laryngeal and pre-tracheal lymph nodes in patients with subglottic laryngeal carcinoma.

[Holistic concept of rhinoplasty].

In the past 20 years, nasal cavity plasty was operated by the otolaryngologists, while external rhinoplasty was usually implemented by the plastic surgeon respectively. The holistic concept is about the integrity, unity and connection of things and phenomena.Considering the structure and function of the external nose and the nasal cavity as a whole,we review the holistic concept in rhinoplasty and put forward the operation of holistic rhinoplasty, including the nasal cavity plasty and external rhinoplasty, correcting the structure problems of nasal cavity and the external nose deformity, and restoring its physiological and cosmetic functions at the same time.

Ultrafast two-dimensional lithium beam emission spectroscopy diagnostic on the EAST tokamak.

A diagnostic instrument is described for the Experimental Advanced Superconducting Tokamak (EAST) for the measurement of the edge plasma electron density profile and plasma turbulence properties. An accelerated neutral lithium beam is injected into the tokamak and the Doppler shifted 670.8 nm light emission of the Li2p-2s transition is detected. A novel compact setup is used, where the beam injection and observation take place from the same equatorial diagnostic port and radial-poloidal resolution is achieved with microsecond time resolution. The observation direction is optimized in order to achieve a sufficient Doppler shift of the beam light to be able to separate from the strong edge lithium line emission on this lithium coated device. A 250 kHz beam chopping technique is also demonstrated for the removal of background light. First results show the capability of measuring turbulence and its poloidal flow velocity in the scrape-off layer and edge region and the resolution of details of transient phenomena like edge localized modes with few microsecond time resolution.

Development of a high current 60 keV neutral lithium beam injector for beam emission spectroscopy measurements on fusion experiments.

A 60 keV neutral lithium beam system was designed and built up for beam emission spectroscopy measurement of edge plasma on the KSTAR and EAST tokamaks. The electron density profile and its fluctuation can be measured using the accelerated lithium beam-based emission spectroscopy system. A thermionic ion source was developed with a SiC heater to emit around 4-5 mA ion current from a 14 mm diameter surface. The ion optic is following the 2 step design used on other devices with small modifications to reach about 2-3 cm beam diameter in the plasma at about 4 m from the ion source. A newly developed recirculating sodium vapour neutralizer neutralizes the accelerated ion beam at around 260-280 °C even during long (<20 s) discharges. A set of new beam diagnostic and manipulation techniques are applied to allow optimization, aiming, cleaning, and beam modulation. The maximum 60 keV beam energy with 4 mA ion current was successfully reached at KSTAR and at EAST. Combined with an efficient observation system, the Li-beam diagnostic enables the measurement of the density profile and fluctuations on the plasma turbulence time scale.

Cell therapy of a knee osteoarthritis rat model using precartilaginous stem cells.

OBJECTIVE: To explore the effect and mechanism of precartilaginous stem cells (PSCs) engraftment-inducing tissue repair in a knee osteoarthritis (OA) rat model. MATERIALS AND METHODS: Knee osteoarthritis (OA) model was constructed in Sprague Dawley (SD) rats by partial removal of the medial meniscus of the right knee. PSCs were engrafted by injecting precartilaginous stem cells (PSCs) into the right knee cavity. At 4 and 8 weeks after model construction, the serum levels of interleukine (IL)-1ß, tumor necrosis factor (TNF)-α, and IL-6 were assessed using enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was performed to assess the histopathology of synovial membrane and cartilage. Western blot analysis was used to assess Notch1, Bcl-2 and Bax levels in the articular cartilage. RESULTS: At 4 and 8 weeks, OA rats demonstrated significantly higher IL-1ß, TNF-α, and IL-6 levels than normal rats (p < 0.05), whereas PSCs treatment prominently attenuated IL-1ß upregulation (p < 0.05). In OA rats, the number of chondrocytes dramatically decreased over time in OA rats, with disruption of chondrocytes organization and cell layers. PSCs alleviated the deterioration of cartilage, as evidenced by the relatively smooth articular surface, distinct tidemark and clear cell layers. The model and treatment groups demonstrated substantially higher Notch1 expression. The Bcl-2/Bax value in the OA rats was lower than the control group, while PSCs treatment led to increase in Bcl-2/Bax value. CONCLUSIONS: PSCs treatment downregulated the expression of inflammatory cytokines, alleviating osteoarthritis in the knee of rats. Notch1 signaling pathway plays an important role in this ameliorating effect of PSCs treatment.

Advanced neutral alkali beam diagnostics for applications in fusion research (invited).

Diagnosing the density profile at the edge of high temperature fusion plasmas by an accelerated lithium beam is a known technique since decades. By knowledge of the relevant atomic physics rate coefficients, the plasma electron density profile can be calculated from the relatively calibrated light profile along the beam. Several additional possibilities have already been demonstrated: Charge Exchange Resonance Spectroscopy (CXRS) for ion temperature/flow and Zeeman polarimetry for edge plasma current; therefore the Li-beam diagnostic offers a wealth of information at the plasma edge. The weaknesses of the method are the relatively faint light signal, background light, and technical difficulties of the beam injector which usually seriously limit the applicability. In this talk, we present systematic developments in alkali-beam diagnostics (Li, Na) for the injector and the observation system and detectors which resulted in strongly increased capabilities. Advanced systems have been built, and microsecond scale density profile, turbulence, and zonal flow measurement have been demonstrated. A novel edge current measurement technique has also been designed, and components have been tested with potential microsecond-scale time resolution. Additional possibilities of these advanced systems for spectral measurements (CXRS and various Zeeman schemes) are also discussed.

[Clinical observation of saccharomyces boulardii combined with cetirizine hydrochloride in children allergic rhinitis].

Objective:To study the treatment efficacy of Saccharomyces boulardii combined with Cetirizine Hydrochloride of children with allergic rhinitis (AR) and the influence of IFN-γ and interleukin-4 (IL-4) Level in serum.Method:Ninty cases of children were randomly divided into observation group and control group (both n=45).The control group with levocetirizine hydrochloride drops, 5 mL/time for 2-6 years old, 10 mL/time for >6 years old , qd oral. Group based on the combination of Saccharomyces boulardi, 0.25 g/time for <3 years old, qd, > 3 years old, 0.25 g, bid. Four weeks for a course of treatment, and set 30 cases for the health group.Result:The level of serum IFN-γ was significantly lower in the two groups than in the healthy group (P < 0.01), while the level of IL-4 was significantly higher than that of the healthy group (P < 0.01). After treatment, the levels of IFN-γ of both groups were up-regulated And the level of IL-4 were down-regulated , but the effect of the treatment group was more obvious (P < 0.01). The total effective rate was 91.11% in the observation group, which was significantly higher than that in the control group (68.89%,χ2=6.94, P < 0.01). After treatment, the symptom scores of the two groups were lower than those before treatment, but the observation group was significantly lower than the control group (P < 0.01). Compared with the control group, the observation group was significantly better than the control group (P < 0.01).Conclusion:The combination of Saccharomyces boulardi and levocetirine hydrochloride in the treatment of children with AR has obvious clinical efficacy, and its mechanism may be related to the correction of interferon IFN-γ and IL-4.

[Rosai-Dorfman disease with nasal septum involvement:two cases report].

Clinical data of 2 cases with Rosai-Dorfman disease(RDD) originating from nasal septal mucosa were reported retrospectively,and the pertinent literature was reviewed. Without specific clinical features,RDD in nasal cavity could be misdiagnosed easily. Pathology revealed different morphologies of cell proliferation with engulfed lymphocytes,plasma cells and neutrophils. Immunohistochemical staining showed S-100(+),CD68(+)，CD1(-).RDD disease generally has a benign course and is self-limited. Its diagnosis depends mainly on biopsy．As for the treatment of this disease,the strategies are not systemic and standard. Surgical treatment is used to excise the mass in nasal cavity,glucocorticoids treatment after surgery is inconclusive. The long-term effect need to be further observed．.

[Analysis of the clinical characteristics of fungus ball sphenoid sinusitis].

Objective:To analyze the clinical characteristics of fungus ball sphenoid sinusitis(FBSS) and its differences from fungus ball maxillary sinusitis(FBMS). Method:A retrospective analysis was made for 50 patients with FBSS and 273 patients with FBMS in the corresponding period, which were confirmed by postoperative pathological diagnosis. And the related factors and clinical characteristics of them were analyzed. Result:FBSS were common disease in women around 50 years old. The left side FBSS was more common than the right side. About 40 percent of patients' disease course was less than half a year.FBSS had many presenting symptoms such as headache, nasal obstruction, nasal mucus with blood, smelly nasal secretions, eye ache bilges or nasion acheand tears spill. However, headache, eye ache bilges and tears spill were more common in FBSS compared with FBMS(P<0.05). The CT scan showed that there were calcification shadows in the diseased softtissue of sinus cavity.It could be accompanied by local bone thickening, sclerosis and coloboma. Only one case had a secondary surgery in 50 cases of FBSS. The surgery cure rate was as high as 98 percent. Conclusion:FBSS had various of clinical symptoms.Some presenting symptoms such as headache, eye ache bilges, and tears spill had relative specificity. CT diagnosis was more specific, and the endoscopic sphenoidotomy was the most effective treatment.

Downregulation of CXCL12 in mesenchymal stromal cells by TGFß promotes breast cancer metastasis.

Mesenchymal stromal cells (MSCs) are one of major components of the tumour microenvironment. Recent studies have shown that MSC tumour residence and their close interactions with inflammatory factors are important factors that affect tumour progression. Among tumour-associated inflammatory factors, transforming growth factor ß (TGFß) is regarded as a key determinant of malignancy. By employing a lung metastasis model of a murine breast cancer, we show here that the prometastatic effect of MSCs was dependent on their response to TGFß. Interestingly, we found that MSC-produced CXCL12, an important chemokine in tumour metastasis, was markedly inhibited by TGFß. Furthermore, silencing of CXCL12 in TGFß-unresponsive MSCs restored their ability to promote tumour metastasis. We found that 4T1 breast cancer cells expressed high levels of CXCR7, but not of CXCR4, both of which are CXCL12 receptors. In presence of CXCL12, CXCR7 expression on tumour cells was decreased. Indeed, when CXCR7 was silenced in breast cancer cells, their metastatic ability was inhibited. Therefore, our data demonstrated that sustained expression of CXCL12 by MSCs in the primary tumour site inhibits metastasis through reduction of CXCR7, while, in the presence of TGFß, this CXCL12 effect of MSCs on tumour cells is relieved. Importantly, elevated CXCR7 and depressed CXCL12 expression levels were prominent features of clinical breast cancer lesions and were related significantly with poor survival. Our findings reveal a novel mechanism of MSC effects on malignant cells through which crosstalk between MSCs and TGFß regulates tumour metastasis.

[The guiding role of preoperative visual analog scale symptom scores in patients with chronic rhinosinusitis during perioperative period].

Objective:To assess the guiding role of preoperative visual analog scale(VAS) symptom scores in patients with chronic rhinosinusitis(CRS) during perioperative period.Method:The patients with CRS undergoing endoscopic sinus surgery were divided into experimental group and control group according to doctor group.Preoperative VAS symptom scores which including the overall symptom score and every single symptom scores were assessed. Patients with symptom(nasal congestion, nasal discharge, dizziness or headache, hypoamia or anosmia, rhinocnesmus, sneeze) scores more than 5 points were taken corresponding appropriate strategies in experimental group, but conventional empirical measures in control group during perioperative period.Nasal endoscopic surgeries were performed under local or general anesthesia after preoperative preparation. Postoperative followup were performed in six months and one year for the overall symptom and each symptom scores in both groups. SPSS17.0 was used for statistical analysis.Result:There was no statistical difference in general condition, overall symptom score and every symptom scores before operation between experimental group(120 cases) and control group(82 cases) (P >0.05). At the three time points (preoperative, six months, one year after operation), significant differences were found in the two groups about VAS overall symptom score (P <0.05). Except hypoamia, VAS for the other symptoms in different postoperative time showed statistical significance (P <0.05).Conclusion:Preoperative VAS symptom score can be used not only in the evaluation of severity and treatment effect,but also in the guiding of perioperative treatment for CRS, which is worthy of using widely in clinic.

Retarding field analyzer for the EAST plasma boundary.

A novel bi-directional Retarding Field Analyzer (RFA) probe has been installed on a fast reciprocating drive system on the Experimental Advanced Superconducting Tokamak (EAST) to measure the ion temperature and fast electron fluxes. A Langmuir probe assembly was added on the top of the RFA head to control the RFA position relative to the last closed flux surface and to have a possibility to measure the electron density and temperature as well. Except the ion temperature, the fast electron fluxes from both ion and electron drift sides have been measured during lower hybrid current drive. The RFA probe has been also used to measure the fast electrons associated with edge localized modes (ELMs), indicating their substantial presence in the scrape-off-layer plasma of EAST.