Developing indicators for promoting provincial-level ecological economics in China.

The development of the eco-economy has become an important way to promote sustainable development and address climate change worldwide. Implementing eco-economic developmental policy globally or locally requires establishing precise indicators. Currently, there are many studies on eco-economy indicators at the academic level, but the eco-economy indicators researched at the academic level are difficult to be implemented and applied by local governments in China, and there is a knowledge gap between the political sector and the academic sector in the process of cooperation. This mainly stems from the lack of whole-process research and analysis that combines government practice and academic research. We attempt to analyze the differences in the understanding of eco-economic indicators between academics and government decision-makers through the study of the establishment process of China's local eco-economic indicator system. We try to find out the reasons for the knowledge gap between academics and government decision-makers, and to build a knowledge bridge between government practice and academic research. At the same time, China, as the largest developing country and an emerging country in the construction of ecological civilization, is worth studying and learning from its experience in the construction of eco-economic indicators. Therefore, we systematically study the connotation of China's eco-economy and the development process of the indicators. And we combine with the practical experience, describe the method and specific process of constructing eco-economy indicators at the provincial scale of the Chinese government. Meanwhile, we put forward the limitations of the construction of the eco-economy indicator system in Liaoning Province. In addition, we analyze in detail the characteristics and attributes of the ecological economy indicators in Liaoning Province, as well as the relationship of these indicators to the implementation of national strategies and to the SDGs. The discipline contributions and scientific and technological concerns of the indicator system's creation are reviewed, and additional improvement ideas are presented. It is expected that the practice of eco-economic indicators in China will further promote eco-economy development and provide methodological reference for countries to measure the level of eco-economic development.

Endoscopic Suture With Chemocauterization: An Effective Treatment of Congenital Pyriform Sinus Fistula.

OBJECTIVE: Endoscopic cauterization is an effective method for treating pyriform sinus fistula (PSF). However, these approaches sometimes result in a higher failure rate. We present an effective technique utilizing suture combined with chemocauterization as first-line treatment in patients with PSF and evaluate the safety and efficacy of its use in 126 patients. STUDY DESIGN: Retrospective study. SETTING: Tertiary referral center. METHODS: Retrospective case review of patients treated between March 2012 and June 2021 at our institution with descriptive statistical analysis. RESULTS: A total of 126 patients with PSF were included in this study with a mean age of 14.7 years. There was no sex predilection. The majority of patients presented with a left-sided neck lesion (89.7%). Ten patients presented following prior attempts at the surgery of the PSF at another institution; 8 via open surgery and 2 following endoscopic CO2 laser cauterization; other patients only had a history of repeat incision and drainage or antibiotic treatment. The success rate of obliteration of the internal opening was 96.83% after a single treatment without complications. Following reoperation, a successful outcome was achieved in the remaining 4 patients. Length of stay ranged from 10 to 14 days. No recurrences occurred within 12 to 120 months followed-up. CONCLUSION: Endoscopic suture combined with chemocauterization is a safe and effective treatment of PSF. Surgery can be performed during the acute cervical inflammatory period without increased risk of complication or recurrence, however, patients found to have acute changes affecting the pyriform sinus should be treated with a staged surgery strategy.

Application of the CRISPR/Cas9-based gene editing technique in basic research, diagnosis, and therapy of cancer.

The 2020 Nobel Prize in Chemistry was awarded to Emmanuelle Charpentier and Jennifer Doudna for the development of the Clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease9 (CRISPR/Cas9) gene editing technology that provided new tools for precise gene editing. It is possible to target any genomic locus virtually using only a complex nuclease protein with short RNA as a site-specific endonuclease. Since cancer is caused by genomic changes in tumor cells, CRISPR/Cas9 can be used in the field of cancer research to edit genomes for exploration of the mechanisms of tumorigenesis and development. In recent years, the CRISPR/Cas9 system has been increasingly used in cancer research and treatment and remarkable results have been achieved. In this review, we introduced the mechanism and development of the CRISPR/Cas9-based gene editing system. Furthermore, we summarized current applications of this technique for basic research, diagnosis and therapy of cancer. Moreover, the potential applications of CRISPR/Cas9 in new emerging hotspots of oncology research were discussed, and the challenges and future directions were highlighted.

Development of photocontrolled BRD4 PROTACs for tongue squamous cell carcinoma (TSCC).

The catalytic properties of small-molecule proteolysis targeting chimeras (PROTACs) may lead to uncontrolled degradation. Therefore, the main disadvantages of PROTACs are non-cancer specificity and relatively high toxicity, which limit the clinical application of PROTACs. The photocontrolled PROTACs (photoPROTACs) were proposed to overcome this issue, in which they can be triggered by ultraviolet A (UVA) or visible light to induce the degradation of the target protein. Herein, we designed several photoPROTACs to cause the degradation of bromodomain-containing protein 4 (BRD4) on-demand using 365 nm light. The representative compound N2 is proved to induce the degradation of BRD4 upon irradiation. Moreover, compound N2 was successfully applied in vivo to inhibit tumor growth in a zebrafish xenograft model of skin cancer tongue squamous cell carcinoma (TSCC) in a photocontrol manner.

MTDH in macrophages promotes the vasculogenic mimicry via VEGFA-165/Flt-1 signaling pathway in head and neck squamous cell carcinoma.

Vasculogenic mimicry (VM) refers to vessel-like structures formed by aggressive tumor cells and is closely associated with cancer invasion and metastasis. Here, we investigated the effect of macrophage-derived MTDH on VM formation in head and neck squamous cell carcinoma (HNSCC) and its underlying mechanism. Macrophages with MTDH overexpression (Mac-MTDH) promoted cancer cell VM formation, migration, and invasion in vitro. Moreover, MTDH overexpression triggered macrophage polarization into M2 type tumor-associated macrophages. Analysis of HNSCC clinical samples revealed that MTDH+ macrophages were predominantly located in the tumor-stromal region in proximity to VM and correlated with lymph node metastasis. Mechanistically, Mac-MTDH enhanced the expression and secretion of VEGFA-165 rather than other VEGFA isoforms via ß-catenin. The VEGFA-165/Flt-1 axis was responsible for Mac-MTDH's effects in cancer cells through p-STAT3/Twist1/VE-cadherin pathway. Using mouse model, we further confirmed that Mac-MTDH increased VM formation and cancer metastasis in vivo. Furthermore, in subcutaneous xenograft mouse model, HN6 + Mac-MTDH tumor exhibited elevated expression of p-STAT3 and Twist1 than HN6 + Mac-NC tumors. This study revealed that Mac-MTDH promoted VM formation, cancer cell migration and invasion, and cancer metastasis through VEGFA-165/Flt-1 axis, and that macrophage-derived MTDH could be a potential therapeutic target in HNSCC.

PHF20 inhibition promotes apoptosis and cisplatin chemosensitivity via the OCT4­p­STAT3­MCL1 signaling pathway in hypopharyngeal squamous cell carcinoma.

Cisplatin is a widely used platinum­based chemotherapeutic agent for hypopharyngeal squamous cell carcinoma (HSCC). However, resistance to cisplatin limits its use for the treatment of HSCC, and the underlying molecular mechanism requires further investigation. The present study performed functional assays to determine whether the expression of plant homeodomain finger protein 20 (PHF20) may be involved in the apoptosis and cisplatin resistance of HSCC. The expression levels of PHF20 were higher in cisplatin­resistant HSCC cells compared with those in cisplatin­sensitive cells. The inhibition of PHF20 suppressed cell viability but did not affect the migratory and invasive abilities of HSCC cells compared with those of negative control­transfected cells. Furthermore, PHF20 inhibition reduced cell viability by enhancing apoptosis compared with those in the control cells in vitro. Notably, the inhibition of PHF20 sensitized HSCC cells to cisplatin, thus increasing apoptosis via the signal transducer and activator of transcription 3 (STAT3)­myeloid cell leukemia­1 (MCL1) pathway. Octamer­binding transcription factor 4 (OCT4) overexpression restored phosphorylated STAT3­MCL1­mediated apoptosis induced by PHF20 inhibition. In vivo experiments confirmed that PHF20 silencing induced tumor growth and increased apoptosis in HSCC cells compared with those in the control cells. Thus, PHF20 inhibition may promote apoptosis and improve cisplatin chemosensitivity via the OCT4­p­STAT3­MCL1 signaling pathway in HSCC.

Loss of CDH1 promotes the metastasis of hypopharyngeal squamous cell carcinoma through the STAT3-MMP-9 signaling pathway.

BACKGROUND: Distant metastasis is the major cause of death in patients with hypopharyngeal squamous cell carcinoma (HSCC). CDH1 is correlated with tumor invasion and metastasis; however, its function in HSCC remains unclear. METHODS: We used immunohistochemistry (IHC) staining to evaluate the expression of CDH1 in 31 and 78 specimens from primary HSCC patients with and without postoperative lung metastases respectively. Sulforhodamine B (SRB) and CCK-8 assays were used to test the proliferation of HSCC cells. Motility of HSCC cells was investigated by migration and invasion assays. Western blot analysis was used to measure the levels of CDH1 and other proteins. RESULTS: We found that the low expression of CDH1 was significantly associated with postoperative lung metastasis in HSCC (P<0.001). Moreover, CDH1 was reduced concomitantly with the upregulation of MMP-9 in the same HSCC sample. Further mechanistic investigation showed that silencing CDH1 elevated the level of MMP-9, which was coupled with the phosphorylation of STAT3. Subsequently, inhibiting STAT3 either by siRNA transfection or by pharmacological suppression with AG490 attenuated MMP-9 upregulation and prevented the enhanced proliferation and invasion caused by CDH1 loss in FaDu cells. CONCLUSIONS: CDH1 plays vital roles in HSCC metastasis and might serve as a potential therapeutic target for the clinical treatment of HSCC.

MG­132 reverses multidrug resistance by activating the JNK signaling pathway in FaDu/T cells.

Multidrug resistance (MDR) is a major impediment to cancer therapy. MG­132 has been identified to be effective against MDR in several types of cancer. However, the mechanism of MG­132 in head and neck squamous cell carcinomas remains unknown. Based on our previous study, the present detected P­gp and P­gp expression in hypopharyngeal carcinoma FaDu cells, revealing that their expression was lower than that observed in the MDR cell line FaDu/T. To reverse the MDR of FaDu/T cells, the present study introduced MG­132 and demonstrated that the high expression of P­gp/P­gp in FaDu/T cells was attenuated in a time­dependent manner. MG­132 also strengthened the sensitivity of FaDu/T cells to multidrugs. c­Jun N­terminal kinase (JNK) activation was further observed in FaDu/T cells. However, P­gp/P­gp did not decrease when FaDu/T cells were pretreated with SP600125. These results indicated that MG­132 reversed the MDR of hypopharyngeal carcinoma by downregulating P­gp/P­gp, and the underlying mechanism may be associated with the activation the of the JNK signaling pathway.

Elevated AEG-1 expression in macrophages promotes hypopharyngeal cancer invasion through the STAT3-MMP-9 signaling pathway.

Macrophages play a critical role in tumor invasion and metastasis, which remain major causes of mortality in patients with hypopharyngeal cancer. Here we investigate the effect of an oncogene, AEG-1 expressed in macrophages on the invasion of hypopharyngeal cancer cells. AEG-1 is more highly expressed in macrophages of human hypopharyngeal cancer samples compared with adjacent non-tumor controls. Using matrigel invasion assay system, THP-1-derived macrophages with forced AEG-1 overexpression enhance FaDu cell invasion whereas macrophages with AEG-1 silence inhibit. Matrix metalloproteinase 9 (MMP-9), which is important in tumor invasion and metastasis through degrading extracellular matrix, is up-reulated by AEG-1 partly through NF-κB p65 in macrophages. Intriguingly, macrophage AEG-1 also induces MMP-9 up-regulated expression in FaDu cells. Furthermore, macrophage AEG-1 activates signal transducer and activator of transcription 3 (STAT3) in FaDu cells, which is responsible for macrophage AEG-1-induced an increase in MMP-9 expression and invasion of FaDu cells. This is the first to demonstrate that macrophage AEG-1 promotes tumor invasion through up-regulation of MMP-9 in both macrophages and cancer cells. Thus, the results provide evidences that macrophage AEG-1 contributes to promotion of tumor invasion, and represents as a potential target in hypopharyngeal cancer therapy.

Afatinib down-regulates MCL-1 expression through the PERK-eIF2α-ATF4 axis and leads to apoptosis in head and neck squamous cell carcinoma.

Afatinib is the second generation of irreversible inhibitor of EGFR, HER2 and HER4, which has shown encouraging phase II and III clinical outcomes in the treatment of head and neck squamous cell carcinoma (HNSCC). However, the molecular mechanism of afatinib-induced apoptosis in HNSCC is poorly understood. In the present investigation, we discovered that down-regulation of MCL-1, an anti-apoptotic member of BCL-2 family, was responsible for afatinib-triggered apoptosis. And the inactivation of AKT-mTOR signaling caused by afatinib lead to translational inhibition of MCL-1 expression. As a crucial branch of ER stress, PERK-eIF2α-ATF4 axis was also stimulated in HNSCC cells after afatinib incubation. Silencing either eIF2α or ATF4 by siRNA transfection relieved afatinib-caused suppression of AKT-mTOR activity, attenuating MCL-1 down-regulation as well as subsequent apoptosis. Collectively, the results show that afatinib hampers AKT-mTOR activation by stimulating PERK-eIF2α-ATF4 signaling pathway, giving rise to MCL-1 down-regulation mediated apoptosis in HNSCC cells. Therefore, our findings reveal the elaborate molecular network of afatinib-induced apoptosis in HNSCC, which would provide substantial theoretical underpinnings for afatinib clinical application and highlight its promising prospect in HNSCC treatment.

Association between rs12045440 Polymorphism in the CAPZB Intron and Serum TSH Concentrations in Chinese Thyroid Tumor Patients.

The aim of this study was to investigate the possible influence of different genotypes of the lead single nucleotide polymorphisms (SNPs) rs10917468 and rs12045440 in the CAPZB gene on the thyroid function in papillary thyroid carcinoma (PTC) and benign thyroid neoplasm (BN) patients. In the study, a significant association was detected between rs12045440 and serum TSH concentrations in thyroid tumor patients (p = 0.001). After the adjustment of relevant covariates, the difference between the mean serum TSH levels in different genotypes of rs12045440 was still significant in the BN group (p = 0.003) but was not significant in the PTC cases (p = 0.115). No significant association of rs10917468 with TSH levels was found. The SNP rs12045440 was associated with the serum TSH concentrations in Chinese thyroid tumor patients, especially in benign thyroid tumor cases.

Cyclic tensile strain on vocal fold fibroblasts inhibits cigarette smoke-induced inflammation: implications for Reinke edema.

OBJECTIVES: To investigate whether patients with Reinke edema are more extrovertive than patients with carcinoma and, whether cyclic tensile strain (CTS) attenuates cigarette smoke condensate (CSC)-induced inflammation in human vocal fold fibroblasts (HVFF). STUDY DESIGN: In vitro and ex vivo study. METHODS: Clinical investigation and Eysenck personality questionnaire were performed to evaluate the personality and smoking status in individuals among groups. 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay was applied to test the viabilities of cultured HVFF exposed to CSC and/or CTS. The messenger RNA (mRNA) and protein expressions of cluster of differentiation 44 (CD44), cyclooxygenase-2 (COX-2), and matrix metalloproteinase-9 (MMP-9) in tissues from Reinke edema, paracancerous site, normal vocal fold, and in HVFF with different treatments were measured by reverse transcriptase polymerase chain reaction or western blot, respectively. RESULTS: Patients with either Reinke edema or carcinoma were moderate/heavy smokers; the extraversion score, however, was higher in Reinke edema patients than that in carcinoma patients. CD44 mRNA and protein expressions were significantly higher, whereas, COX-2 and MMP-9 expressions were significantly lower in Reinke edema tissues than those in paracancerous tissues. Treatment of HVFF with CSC led to the decrease in cell viability, the reduction in CD44 expression, but, the increase in COX-2 and MMP-9 expressions and, moreover, administration of CTS inhibited such effects of CSC on HVFF. CONCLUSIONS: Our results demonstrate that Reinke edema patients have more extrovert personality characteristics in comparison to carcinoma patients and, importantly, CTS attenuates CSC-induced inflammation in HVFF. Phonatory vibration may be a mechanism for lower expression of proinflammatory mediators in Reinke edema tissues in spite of cigarette smoke exposure.

MG132 reverse the malignant characteristics of hypopharyngeal cancer.

In order to reverse the malignant characteristics of hypopharyngeal cancer, the proteasome inhibitor MG132 was introduced into FaDu/T cells and the mechanisms underlying its effects were investigated. The multi-drug resistance (MDR) sensitivities of FaDu/T and FaDu/T-MG132 cancer cells to several chemotherapeutics were investigated by a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) assay. Apoptosis was measured by staining cells with Annexin V and propidium iodide (PI) double staining. Reverse transcription-polymerase chain reaction and western blot analysis were conducted to detect mRNA and corresponding protein levels of the MDR- and apoptosis-related genes P-glycoprotein (P-gp), caspase-3, Bcl-2 and Bax. The nuclear protein of nuclear factor κ-light-chain-enhancer of activated B cells. (NF-κB) and p53 were also investigated via western blot analysis. Compared with FaDu/T cells, the drug resistance of FaDu/T + MG132 cells to cisplatin (DDP), 5-fluorouracil (5-FU), doxorubicin (Dox) and vincristine (VCR) decreased. With increased expression of caspase-3 and Bax and decreased expression of Bcl-2, the anti-apoptotic ability markedly decreased in FaDu/T + MG132 cells. P-gp and NF-κB significantly decreased; however, p53 increased in FaDu/T + MG132 cells. These results suggested that the proteasome inhibitor MG132 reversed the malignant characteristics of FaDu/T by enhancing apoptosis and inhibiting P-gp. MG132 was also able to inhibit the nuclear translocation of NF-κB and increase the expression of p53.

The probable role of tumor stem cells for lymph node metastasis in supraglottic carcinoma.

Tumor stem cells (TSC), which are considered as likely candidates for the origin of cancer, are deduced to be responsible for tumor metastasis theoretically. We therefore investigated whether TSC were associated with lymph node metastasis in supraglottic carcinoma. Immunohistochemistry was performed for CD44, CD133, and LYVE-1 to detect TSC and lymphatic vessel density (LVD) in 66 primary supraglottic carcinoma tissue samples from 30 patients with lymph node metastasis (N+) and 36 patients without (N0). Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot were used to detect the expression of CD44 and CD133 at mRNA and protein levels in N+ and N0 primary tumors. The LVD was 22.4 ± 10.26 in 30N+ and 6.8 ± 4.09 in 36N0 samples subjected to immunohistochemistry, which was associated with their clinical nodal stages. There were 43.33% CD44-positive and 93.33% CD133-positive samples in 30N +, and 13.89% CD44-positive and 44.44% CD133-positive samples in 36N0 (P < 0.05). However, in each positive slide, there were only 5∼10% CD44-positive cells, but 70∼85% CD133-possitive cells. The expressions of CD44 and CD133 of N+ obtained through RT-PCR and Western blot were significantly higher than those of N0. These results suggest that TSC identified through CD44-positive cells in N+ were significantly higher than those in N0, indicating that TSC may be responsible for lymph node metastasis. CD133, whose expression is not restricted to TSC, may be unspecific for TSC identification in hypostatic supraglottic carcinoma.

Can E-cadherin and CD34 be used as indicators of prognosis for hepatocellular carcinoma patients?

BACKGROUND: The high postoperative recurrence of hepatocellular carcinoma (HCC) is a problem that would benefit from the identification of indicators of recurrence and prognosis. In the past few years, research has shown that E-cadherin and CD34 can be used as indicators of the invasion of malignant tumors. In the present study, we investigated the expression of E-cadherin and CD34 in HCC patients. METHODS: Expression levels of E-cadherin and CD34 in 41 HCC samples were detected using two-step immunohistochemical methods and compared with clinical pathological parameters and survival rate. RESULTS: The positive rates of E-cadherin and CD34 expression in 41 HCC cases were 48.78% and 100%, respectively. Expression of E-cadherin was significantly lower in patients with larger tumors, a high risk invasion and Edmondson classification III or IV (p<0.05). There was a significant relationship between CD34 expression and age and tumor invasiveness (p<0.05). There was no significant relationship between expression of CD34 and E-cadherin by Spearman statistical analysis (p>0.05). The survival rate in patients with negative expression of E-cadherin was significantly lower. CONCLUSIONS: The expression of CD34 cannot be used singly as a prognostic indicator for HCC patients. The co-expression of E-cadherin and CD34 cannot be used as a prognostic indicator for HCC patients. Clin Chem Lab Med 2008;46:1122-6.