Background: Hypoxic pulmonary hypertension (HPH) is one of the important pathophysiological changes in chronic pulmonary heart disease. Hypoxia promotes the phenotypic transformation of pulmonary artery smooth muscle cells (PASMCs). Extracellular exosomes regulate vascular smooth muscle cell (VSMC) phenotypic switch. Aim: Given the importance of exosomes and alveolar epithelial cells (AECs) in HPH, the present study aimed to address the issue of whether AEC-derived exosomes promote HPH by triggering PASMC phenotypic switch. Methods: Cell Counting Kit-8 (CCK-8), TRITC-phalloidin staining, and Western blotting were used to examine the effects of AEC-derived exosomes on cell proliferation, intracellular actin backbone distribution, and expression of phenotypic marker proteins in PASMCs. Transcriptomics sequencing was used to analyze differentially expressed genes (DEGs) between groups. Results: Hypoxia-induced exosomes (H-exos) could promote the proliferation of PASMCs, cause the reduction of cellular actin microfilaments, promote the expression of synthetic marker proteins (ELN and OPN), reduce the expression of contractile phenotypic marker proteins (SM22-alpha and alpha-SMA), and induce the phenotypic transformation of PASMCs. Transcriptomics sequencing analysis showed that the Rap1 signaling pathway was involved in the phenotypic transformation of PASMCs induced by H-exos. Conclusion: The present study identified that hypoxia-induced AEC-derived exosomes promote the phenotypic transformation of PASMCs and its mechanism is related to the Rap1 signaling pathway.

To predict the effects of Dual-source CT imaging technology for preoperative patients with transcatheter aortic valve implantation. This is a parallel, randomly allocated to following two groups: patients with the Dual-source CT imaging technology and with conventional imaging technology, and the clinical material from two groups patients with Aortic valve disease are collected, and the images quality between two group are assessed and then complications in one month after surgery are recorded by follow-up. Our outcomes show that patients by the Dual-source CT imaging technology show less complications compared to patients by conventional imaging technology and imaging quality is better than that in conventional imaging group. In addition, image noise, and contrast-to-noise ratio are also examined by Dual-source CT imaging. We can conclude that the Dual-source CT can effectively reduce the complications, and the Dual-source CT can predict effects of preoperative patients with Aortic valve disease and prevent the development of Aortic valve disease (AVD).

目的 通过回顾下腔静脉的胚胎发育特征、分析其临床CT表现,提高对下腔静脉先天变异CT表现的认识.方法 回顾性收集2015年1月至2020年10月因各种原因于本院行腹部CT平扫及增强扫描或者胸腹部联合CT检查,于门静脉期或延迟期观察下腔静脉的走形及连接,回顾性学习下腔静脉的胚胎发育特征,分析本组病例下腔静脉先天变异的类型、特征以及是否合并其他脏器畸形.结果 本组27例患者,下腔静脉肝段缺如10例,双下腔静脉8例,左位下腔静脉10例,下腔静脉异常延续12例,其中部分病例为几种变异联合存在;本组未收集到下腔静脉后输尿管病例.下腔静脉发育异常合并其他系统异常,共12例(12/27),其中6例合并先天性心脏病,另6例分别合并迷走右锁骨下动脉及夹层、永存左上腔静脉、多脾综合征、脾静脉与肠系膜上静脉汇合异常;其他15例下腔静脉异常是因其他原因行CT检查偶然发现.结论 识别下腔静脉变异对临床操作及治疗具有重要意义;因此,对影像诊断医生而言下腔静脉的观察与评价应该成为日常诊断工作中的基本组成部分.

High-mobility group box 1 (HMGB1) is a non-histone nuclear protein in most eukaryocytes. Inside the nucleus, HMGB1 plays an important role in several DNA events such as DNA repair, transcription, telomere maintenance, and genome stability. While outside the nucleus, it fulfils more complicated functions, including promoting cell proliferation, inflammation, angiogenesis, immune tolerance and immune escape, which may play a pro-tumoral role.Meanwhile, HMGB1 acts as an anti-tumoral protein by regulating immune cell recruitment and inducing immunogenic cell death (ICD) during the carcinogenesis process. Therefore, abnormal expression of HMGB1 is associated with oncogenesis, development, and metastasis of cancer, which may play a dual role of pro-tumor and anti-tumor.

Background: The preoperative assessment of cervical lymph node metastasis (LNM) is considered a challenging clinical problem in papillary thyroid microcarcinoma (PTMC) patients. Ultrasonic examination is significant for the cervical LNM in PTMC patients, but there are difficulties and limitations in observing lymph nodes in the cervical central region. Objectives: To investigate the diagnostic value of dual-energy computed tomography (DECT) iodine for characterization of PTMC and better prediction of metastatic cervical lymph nodes of PTMC. Patients and Methods: Ninety-five patients with PTMC who underwent DECT examinations were retrospectively enrolled in the study. The iodine image morphological features of primary tumor were analyzed in the arterial phase and quantitative DECT parameters of the primary tumor were recorded in the arterial and venous phase. Chi-square test and independent-sample t test were performed to compare the differences of morphological features and quantitative parameters of tumors between LNM and non-LNM groups. Receiver operating characteristic curves were generated to assess the diagnostic performance of each DECT parameter and their combinations. Results: Six primary tumor morphological features of the LNM group demonstrated significant differences compared with the non-LNM group (all p < 0.05). Normalized iodine concentration (NIC) and normalized CT value in the LNM group were significantly higher than those of the non-LNM group in both arterial and venous phase, respectively (all p < 0.001). The area under the curve (AUC) was improved from 0.814 to 0.843 after adding maximum diameter compared with incomplete thyroid capsule alone. In addition, the combination of NICs in arterial and venous phases had higher AUC than other quantitative parameters. Conclusion: Morphological features and quantitative parameters of DECT are valuable for predicting cervical LNM in patients with PTMC.

The role of autophagy in tongue squamous cell carcinoma (TSCC) cisplatin resistance is unclear. We aimed to identify a possible synergistic effect of autophagy inhibitors and cisplatin in TSCC cells and explore the underlying mechanism. Our results indicate that autophagic flux was high in TSCC cells; Autophagy inhibitor bafilomycin A1 increased cisplatin cytotoxicity in TSCC cells by inhibiting lysosomal uptake of platinum and enhancing intracellular platinum ion binding to DNA; Autophagy gene (Atg5) knockout in TSCC cells did not duplicate the above-mentioned sensitization of bafilomycin A1. Furthermore, we found that cisplatin resistance of TSCC cells was related to cisplatin inducing lysosome biogenesis in a TFEB-dependent manner, which was regulated by c-Abl. In summary, this is the first study to show that Bafilomycin A1 increases the sensitivity of TSCC cells to cisplatin by inhibiting lysosomal function but not autophagy. Lysosomes may be a potential target to increase cisplatin cytotoxicity toward TSCC cells.

Metastasis is the major cause of treatment failure in anaplastic thyroid carcinoma (ATC) patients. In the preliminary study, we demonstrated that interleukin (IL)-11 expression is positively correlated with distant metastasis in ATC. However, the mechanisms underlying remain largely unknown. Here, we found that cobalt chloride (a hypoxia mimetic) promoted IL-11 expression via HIF-1α activation. Furthermore, the resultant increase in IL-11 expression significantly induced epithelial-mesenchymal transition (EMT) in ATC cells, accompanied by Akt/GSK3β pathway activation and increased invasive and migratory abilities. Conversely, HIF-1α or IL-11 knockdown, or treating cells with a neutralizing antibody against IL-11, a PI3K inhibitor, or Akt inhibitor V, significantly suppressed the induction of EMT and counteracted the enhancements in invasive and migratory abilities. These results indicate that hypoxia increases IL-11 secretion in ATC cells via HIF-1α induction and that IL-11 then induces EMT in these cells via the PI3K/Akt/GSK3β pathway, ultimately improving their invasive and migratory potential. This study elucidates the prometastatic role played by IL-11 in ATC metastasis and indicates it as a potential target for the treatment of cancer metastasis. However, many questions remain to be explored.

The purpose of this study was to evaluate the outcome in sinonasal mucosal melanoma (SMM).

We have investigated the clinical characteristics and prognostic factors of squamous cell carcinoma (SCC) of the tongue after definitive radiotherapy for nasopharyngeal carcinoma, and evaluated the effect of common therapeutic regimens for these patients. We retrospectively reviewed follow-up data for patients whose nasopharyngeal carcinoma had been treated by radiotherapy, and selected the 68 who had then developed SCC of the tongue, in the border of the tongue in half, and in the dorsum in 25 (37%). Eight of the 68 patients had clinical lymph node metastasis (12%), and 45 presented with stage I-II disease at the time of the diagnosis of the SCC (66%). Resection or radiotherapy alone was an effective treatment for patients with stage I-II SCC of the tongue, but patients with stage III-IV disease had a poor prognosis, despite being given multidisciplinary treatment. Multivariate analysis showed that the risk factors that independently influenced the survival of these patients were use of alcohol, recurrence of their nasopharyngeal carcinoma, the latency period, and the clinical TNM stage. Tongue SCC after radiotherapy was generally at an early stage and commonly occurred on the border or the dorsum of the tongue, with few lymph node metastases. Resection or radiotherapy is an effective treatment, and the risk factors that independently influenced the survival of patients indicate that improving the technique of radiotherapy and close follow-up after nasopharyngeal cancer are vitally important.

To evaluate the treatment and prognosis of oral mucosal melanoma (OMM) and provide basic data for clinical treatment. Retrospective analysis of clinicopathological data on OMM from January 1976 to December 2005. Survival analysis was performed and Kaplan-Meier analysis was used to compare the effects of clinicopathological factors on survival using SPSS 18.0 software. A Cox model was applied for multivariate analysis. The 3-year and 5-year overall survival (OS) rates of 51 cases of OMM were 35.0% and 20.7%, respectively. Lymph node metastatic sites were predominantly at levels Ib-III (29/31, 93.5%). Patients of age ≥55 years and size ≥4 cm had a lower survival rate than those of aged <55 years and size <4 cm. The 3-year OS and 5-year OS of patients who underwent surgery combined with biotherapy or biochemotherapy (70.1% and 58.4%, respectively) were significantly higher than that of patients who underwent other therapeutic regimens (including surgery, chemotherapy, surgery combined with radiotherapy or surgery combined with chemotherapy) (25.0% and 12.5%, respectively). Multivariate analysis showed that surgery combined with biotherapy or biochemotherapy and neck dissection were effective treatments for OMM. Patients aged ≥55 years had a worse prognosis than those aged <55 years. OMM has a poor prognosis, but multimodality treatment including surgery combined with biotherapy may improve the prognosis. In patients aged ≥55 years with tumor size ≥4 cm, increasing the scope of resection may be effective. Elective levels I-III neck dissection should be considered in TanyNOMO cases.

Our investigation aims to evaluate the significance of TRB3, an endoplasmic reticulum stress (ERS)-inducible gene, and explore its relationship with AKT in oral tongue squamous cell carcinoma (OTSCC). Expression of TRB3 and phosphorylated AKT (p-AKT) in OTSCC tissues and adjacent normal tissues were assessed by RT-PCR, Western blot and immunohistochemistry assay. Correlation of TRB3 and AKT was validated by TRB3 adenovirus plasmid (Ad-TRB3) transfection and short hairpin RNA (shRNA) inhibition. The mRNA expression of TRB3 was significantly higher than adjacent noncancerous tissues by RT-PCR in 15 of 18 specimens of OTSCC (83.3%, P < 0.01). Both of TRB3 and AKT were highly expressed in 13 of 18 (72.2%) specimens of OTSCC comparing with adjacent noncancerous tissues by Western blot assay (P < 0.05). TRB3 was significantly elevated in 49.2% (63/128) of pathologically confirmed specimens and 13.3% (4/30) of adjacent noncancerous specimens by immunohistochemical analysis (P < 0.01). TRB3 overexpression was closely correlated with tumor pathological T stage, lymph node metastasis and tumor recurrence. In addition, both mRNA and protein expression of TRB3 was increased under thapsigargin (TG) or tunicmycin (TU)-induced ERS in Tca8113 and CAL-27 cells. Moreover, expression of p-AKT protein decreased when Ad-TRB3 was transected with OTSCC Tca8113 cells. However, expression of p-AKT protein increased when TRB3 was inhibited by TRB3 shRNA inhibition. TRB3 expression was closely correlated with OTSCC prognosis. Under ERS, TRB3 was up-regulated, resulting in inhibiting the activation of AKT in OTSCC.

OBJECTIVE:To investigate the treatment and prognosis of the patients with oral mucosal melanoma (OMM).METHODS:The clinicopathological and follow-up data of patients with OMM in Sun Yat-sen University Cancer Center from January 1976 to December 2005 were analyzed retrospectively.RESULTS:Fifty-one cases were analyzed. The pathological lymph node metastasis rate was 61% (31/51) and the affected sites were confined to level I(b)-III (94%). The overall three year and five yearsurvival rates were 35% and 21% respectively. No significant difference of three year and five year survival rates were found between the group of incisional biopsy and the group of excisional biopsy. The prognosis was not affected by pigmentation. The survival rate of the patients receiving surgery combined with biotherapy or biochemotherapy was significantly higher than that of the patients treated by other modalities (P = 0.003).CONCLUSIONS:In patients with OMM, lymph node metastasis was mostly confined to level I(b)-III. Incisional biopsy and pigmentation were not associated with an unfavorable prognosis. The prognosis of the patients with OMM was poor and the patients may get a better prognosis by receiving surgery combined with biotherapy or biochemotherapy.