[Expression and significance of fibroblast growth factor receptor 2 in clear cell renal cell carcinoma].

OBJECTIVE: To investigate the expression of fibroblast growth factor receptor 2 (FGFR2) in clear cell renal cell carcinoma (ccRCC; or kidney renal clear cell carcinoma, KIRC), to analyze the relationship between the expression of FGFR2 and the clinical pathological features and prognosis of ccRCC, to study the relationship between the expression of FGFR2 and other molecules, and to explore its role in the development of ccRCC. METHODS: Gene expressional and clinical information of ccRCC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus(GEO) database. Next, the data were transformed and collated. In the study, 104 clinical ccRCC samples and corresponding paracancerous normal tissue samples were collected from Department of Urology, Peking University First Hospital. Immunohistochemistry (IHC) was performed and the staining results were scored, so as to compare the expression of FGFR2 in ccRCC and paracancerous normal tissues. Besides, quantify real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression level of FGFR2 in normal renal epithelial cell lines (293) and ccRCC cell lines (786-O, 769-P, OSRC-2, Caki-1, ACHN, and A498). In addition, the relationship between FGFR2 expression and clinical pathological characteristics (including TNM staging and pathological grading) and survival prognosis in ccRCC patients was further analyzed. Furthermore, the relationship between FGFR2 expression and B cells, T cells, natural killer (NK) cells and neutrophil infiltration in the ccRCC patients was analyzed, and the Biological General Repository for Interactionh Datasets (BioGRID) was used to builds protein-protein interaction (PPI) networks to study molecules that interacted with the FGFR2 protein. RESULTS: In the TCGA database, the expression of FGFR2 was down-regulated in ccRCC tissue samples compared with normal tissue samples, and the expression in the GEO database also showed this differences. Furthermore, FGFR2 expression was downregulated in ccRCC clinical samples and ccRCC cell lines, compared with corresponding paracancerous normal tissue or normal renal epithelial cell lines. In addition, FGFR2 high expression was associated with earlier, lower-level ccRCC and was associated with a better prognosis in the patients with ccRCC. Moreover, FGFR2 expression was not significantly related to B cells, T cells, NK cells and neutrophil infiltration, and the PPI network showed that FGFR2 protein interacted with certain molecules. CONCLUSION: Our work sheds light on the potential role of FGFR2 in the development of ccRCC, suggesting that FGFR2 may serve as a prognostic marker and potential therapeutic target for patients with ccRCC.

Liver Macrophages Stimulate the Expression of Hepatocyte Nuclear Factor-6 and Promote Hepatocyte Proliferation at the Early Stage of Liver Regeneration.

Hepatocyte nuclear factor (HNF-6) is a liver-specific protein and a key component in the differentiation process during the development of mature liver. The immunohistochemical staining and RT-PCR techniques were employed to examine the expression of HNF-6 and proliferation of Ki-67+ cells during the early regeneration of the liver on postsurgery in 3, 6, 12, and 24 h in original model of partial hepatectomy in rats. The earliest proliferating (Ki-67+) cells were observed in 3 h after surgery in liver sinusoids (liver macrophages) and then in liver parenchyma. Expression of HNF-6 in hepatocytes and epithelial cells of the bile ducts attained maximum in 6 h after surgery. At later terms, this parameter somewhat decreased, but still surpassed the control level.

A new diagnostic index for sarcopenia and its association with short-term postoperative complications in patients undergoing surgery for colorectal cancer.

AIM: Sarcopenia is a robust prognostic indicator of outcomes after surgery for colorectal cancer (CRC). However, there are no serum markers routinely available for estimating skeletal muscle mass (SMM). The present study aimed to describe a new sarcopenia index (SI), serum creatinine (Scr) × cystatin C-based glomerular filtration rate, and investigate its association with short-term complications after curative resection of CRC. METHOD: Consecutive patients who underwent curative resection of CRC from December 2011 to January 2017 were retrospectively identified. Skeletal muscle cross-sectional area was analysed on L3 computed tomographic images. Receiver operating characteristic curve analysis showed that the cutoff points of SI for sarcopenia were below 56.1 in men and below 43.7 in women. Patients were classified into low and high SI groups in accordance with these cutoff values. The association between SI and body composition and the impact of preoperative SI on postoperative outcomes were analysed. RESULTS: Among 417 patients, SI showed a stronger correlation with skeletal muscle area (SMA) (r = 0.537, P < 0.001) than with the Scr/cystatin C ratio (r = 0.469, P < 0.001) and Scr (r = 0.447, P < 0.001). The low SI group had a lower SMA, lower preoperative haemoglobin, a higher prevalence of sarcopenia and experienced more postoperative complications compared with the high SI group (all P < 0.001). Multivariate logistic regression analysis showed that the independent risk factors for overall complications were low preoperative haemoglobin, low SI, sarcopenia and American Society of Anesthesiologists grade ≥ 3. CONCLUSION: This new SI is a simple and useful surrogate marker for estimating SMM, and is associated with outcomes after CRC surgery.

Preliminary study on the changes of ovarian reserve, menstruation, and lymphocyte subpopulation in systemic lupus erythematosus (SLE) patients of childbearing age.

Objective The main aim of this study was to investigate the ovarian reserve, menstruation, and lymphocyte subpopulation in systemic lupus erythematosus (SLE) patients of childbearing age. Methods We enrolled 40 SLE patients of childbearing age and 40 age-matched healthy controls. Anti-Müllerian hormone (AMH) was tested by electrochemiluminescence, and lymphocyte subsets were tested by flow cytometry. Menstruation situation was obtained by interview. Results The AMH level of the SLE group was significantly lower than that of the control group ( p < 0.001), which was negatively correlated with erythrocyte sedimentation rate (ESR ( r = -0.316, p = 0.047)) and disease activity (SLEDAI ( r = -0.338, p = 0.033)). The AMH concentration of SLE patients with normal menstruation was higher than those with abnormal menstruation ( p < 0.001). The percentages of CD4+ T lymphocytes and NK (natural killer) cells in the SLE group were significantly lower than those in the control group ( p < 0.001). However, the percentages of B cells and CD8+ T lymphocytes in the SLE group were higher than those in the control group ( p < 0.05). Conclusion Decreased AMH and high incidence of abnormal menstruation indicated that autoimmunity activities of SLE can impair the ovarian reserve of female patients. Lymphocytes in SLE patients were in a state of disorder.

[Inflammatory priming adipose derived stem cells significantly inhibit the proliferation of peripheral blood mononuclear cells].

OBJECTIVE: To explored whether adipose derived stem cells (ASCs) could inhibit the pro-liferation of peripheral blood mononuclear cells (PBMCs) and whether inflammatory priming could enhance this property of ASCs. METHODS: We isolated ASCs using collagenase from adipose tissue and expanded them in vitro. Cells were induced to differentiate into adipogenic and osteogenic lineages. The cells at passage 3 to passage 5 were used for the experiments. After carboxy fluoresce in succinimidyl ester (CFSE) staining, PBMCs were co-cultured with inflammatory priming ASCs. The PBMCs cultured without ASCs or with non-treated ASCs defined as control groups. Then we used flow cytometry to detect the proliferation of PBMCs. RESULTS: ASCs had fibroblast-like phenotype and were spindle shaped. They were able to differentiate into cells of adipogenic and osteogenic lineages in specific induction media. ASCs had the CD expression profile consistant with the International Federation for Adipose Therapeutics statement. The percentage of parent cells in PBMC after co-cultured with ASCs increased, though there was no statistical significance. However, when co-cultured with inflammatory priming ASCs, the percentage of parent cells significantly increased (with inflammatory priming ASCs group vs. without ASCs group, 38.7%±10.0% vs. 28.4%±8.9%, P<0.05). This indicated that inflammatory priming ASCs could significantly inhibit the proliferation of PBMCs. CONCLUSION: Inflammatory cytokines can enhance the immunosuppressive ability of ASCs. Our findings may help the application of ASCs in tissue repairment with better results.

Suppressing stathmin-l can inhibit chkl protein expression and reduce the invasion and tumorigenicity of cervical cancer cells.

The purpose of this study was to evaluate the effects of stathmin-l on chkl protein expression in cervical cancer cells and the influ- ences on the cells' invasion and tumorigenicity. Suppressed stathmin-l expression in Hela cells and C33A cells by lentiviral vector were utilized. Real time PCR and Western blot were used to examine the expression of chkl. Cell proliferation and invasion were stud- ied using MTT assays and transwell migration assays.The differences of tumorigenicity in vivo were explored using xenograft experi- ments. In addition, stathmin-l expressions in 24 cervical cancer patients were studied without regional lymph nodes metastasis and 16 metastatic patients by immunohistochemistry assays and real time PCR. This study found downregulating stathmin-l reduced chkl ex- pressions and the proliferation and invasion in cervical cancer cells and reduced the tumorigenicity of tumor cells.

Knockdown of 14-kDa phosphohistidine phosphatase expression suppresses lung cancer cell growth in vivo possibly through inhibition of NF-κB signaling pathway.

In previous study, we reported that 14-kDa phosphohistidine phosphatase (PHP14) was associated with lung cancer cell migration and invasion. We also found that the expression of PHP14 was markedly increased in a part of human lung cancer tissues. In this study, we investigated the impact of PHP14 knockdown on lung cancer cell tumorigenesis in vitro and in vivo, as well as the regulatory pathway. Depletion of endogenous PHP14 expression in lung cancer cells reduced colony formation activity of lung cancer cells in vitro and inhibited the xenograft tumor growth in vivo. Further experiments revealed that the NF-κB signal pathway inhibitor PDTC inhibited the upregulated expression of MMP9 induced by PHP14 overexpression in lung cancer cells. Furthermore, knockdown of PHP14 in lung cancer cells correlated with decreased expression of a subset of NF-κB-regulated genes, such as BCL-2, COX-2, MCP-1, MMP9 and VEGF-C, which play an important role in tumor progression. Together these data suggest that knockdown of PHP14 in lung cancer cells inhibits lung cancer tumor growth in vivo, possibly via regulating the NF-κB pathway.

A new hope: the immunotherapy in small cell lung cancer.

Small cell lung cancer (SCLC) is of a high-grade malignancy with a high metastatic potential and poor clinical prognosis. Unfortunately, SCLC initially exhibits a good response to chemotherapy and radiation therapy, but inevitably, relapses decrease patients' chance of survival. Despite tremendous advances on the development of new chemotherapeutic agents, the prognosis of this disease remains poor. Immunotherapy plays a role in eliciting an anticancer response by modulating the patient's immune response of the tumor. Several studies have demonstrated that abnormal autoimmune regulation has a close relationship with SCLC. Thus, several immunotherapy trials are focused on SCLC treatment, including such approaches as immune checkpoints blockers, tumor vaccine, antigenic targets and adoptive cellular immunotherapy to benefit patients with SCLC. To date, the results from immunotherapy in SCLC have not been promising. For example, tumor vaccines have not been demonstrated to have a significant survival benefit. However, there have been many promising advances with immune checkpoints blockers. This review will provide a general overview of immunotherapy in SCLC. The landmark clinical trials in previous successful immunotherapy studies are summarized here. Finally, the challenges of immunotherapy in SCLC are discussed to facilitate the prediction of possible and valuable strategies for future therapy.

High CXC chemokine receptor 4 expression is an adverse prognostic factor in patients with clear-cell renal cell carcinoma.

BACKGROUND: Aberrant CXC chemokine receptor 4 (CXCR4) expressions in malignant tissues have been reported; however, its role in kidney cancer prognosis remains unknown. The aim of this study was to determine the prognostic value of CXCR4 expression in patients with clear-cell renal cell carcinoma (ccRCC). METHODS: The study included 225 patients with ccRCC. The cohort was split into a training set (n=125) and a validation set (n=100). CXC chemokine receptor 4 expression was analysed by immunohistochemical staining and its correlations with clinicopathologic features and prognosis were evaluated. RESULTS: CXCR4-staining intensity increased gradually accompanied with disease progression from TNM stages I to IV in 225 patients with ccRCC. Moreover, high CXCR4 expression indicated reduced overall survival (OS) in the training (P<0.001) and validation (P<0.001) sets, especially for patients with early-stage (TNM stage I+II) diseases. Furthermore, CXCR4 expression was identified as an independent prognostic factor for OS, and combining TNM stage with CXCR4 expression showed a better prognostic value for OS in both sets. CONCLUSIONS: High CXCR4 expression, an independent adverse prognostic factor, could be combined with TNM stage to generate a predictive nomogram for clinical outcome in patients with ccRCC.

Optically controlled background-free terahertz switching in chiral metamaterial.

We demonstrate a multiband background-free terahertz (THz) switch in photoactive chiral metamaterial using polarization conversion. Orthogonal arrangement of two asymmetrical split-ring apertures allows a high polarization conversion efficiency and low copolarization transmission. The chiral metamaterial embedded with photoactive silicon promises a dynamic control on cross-polarization transmission and thus enables an efficient background-free THz switch. The on/off state of THz metamaterial switching can be efficiently controlled by an optical pump. The realization of a cross-polarization THz switch provides a new mechanism of mode switching to control THz wave propagation and will be a promising candidate for polarization devices.

Preoperative platelet count in predicting lymph node metastasis and prognosis in patients with non-small cell lung cancer.

Recent studies have shown an indirect link between platelet count and blood vessel metastasis, but this association with lymphatic vessels metastasis has not been established in NSCLC. So we investigated whether an association exists between preoperative platelet count and lymph node metastasis in NSCLC patients. Between January 2001 and January 2011, platelet counts were obtained from 883 NSCLC patients who were resistant to chemotherapy, radiotherapy, and surgery. The preoperative platelet counts, tumor metastasis, and overall survival of NSCLC patients were analyzed for correlations via statistical analysis. Upon considering patients according to their TNM lymph node metastasis stage (N0-N3), multiple comparison analyses revealed that the mean preoperative platelet count of the N0 group was significantly lower than that of the N1-N3. Analysis of variance showed that the preoperative platelet count of patients in stage I was significantly lower than that of those in stages II, III, and IV, with no significant difference among the latter three stages. According to the Kaplan-Meier survival analysis, the overall survival of patients with platelet counts <214.5 × 109/L was significantly longer than that of those with platelet counts ≥214.5 × 109/L. Cox regression analysis indicated that, besides preoperative platelet count, patient age, gender, and TNM stage were independent prognostic factors. In conclusion, preoperative platelet count was significantly associated with metastasis of lymph nodes in NSCLC patients. Preoperative platelet count may be a reliable biomarker of lymph node metastasis possibility and an independent prognostic factor of overall survival in patients with NSCLC.

A comparison of radiofrequency Coblation and cold steel excision in the treatment of idiopathic vocal process granulomas.

OBJECTIVE: To compare the effectiveness of radiofrequency Coblation assisted excision and cold steel excision in the treatment of idiopathic vocal process granulomas. METHODS: A retrospective study was performed of patients with idiopathic vocal process granulomas who underwent radiofrequency Coblation excision or cold steel excision between January 2013 and January 2020. The recurrence rate was compared among the two groups at six months post-operatively. RESULTS: Of the 47 patients with vocal process granulomas, 28 were in the cold steel excision (control) group and 19 were in the Coblation-assisted group. The recurrence rate in the control group was significantly higher than that in the Coblation-assisted group (60.7 per cent vs 5.3 per cent; p < 0.001). In addition, the voice recovery of the Coblation-assisted group was significantly better than that of the control group; vocal quality recovered one month after surgery in the Coblation-assisted group. CONCLUSION: Radiofrequency Coblation should be considered the optimal method when approaching idiopathic vocal process granulomas surgically.

Skp2/p27 axis regulates chondrocyte proliferation under high glucose induced endoplasmic reticulum stress.

OBJECTIVE: Diabetes mellitus is closely related to osteoarthritis (OA) and may be an independent risk factor for the development of OA. As one of the main characteristics of diabetes, endoplasmic reticulum (ER) stress resulting from glucose metabolism disorder is one of the main causes of cartilage degeneration. The aim of our study is to illuminate the effect of high glucose to chondrocytes (CHs) and the role of Skp2 in high-glucose induced ER stress in CHs. PATIENTS AND METHODS: We compared the ER stress status between healthy and diabetic OA cartilage using Western blot and quantitative reverse-transcription polymerase chain reaction (RT-PCR) methods. Different concentration of glucose was used to culture CHs for both 24 h and 72 h. Furthermore, Tunicamycin (TM) and 4-Phenylbutyric acid (4-PBA) were used to mediate ER stress of CHs, and human recombinant Skp2 protein was used to promote Skp2 expression. CH viability was determined by CCK8 assay, and cell proliferation was determined by flow cytometry. Western and RT-PCR were performed to measure related gene expression. RESULTS: ER stress makers GADD34, GRP78, and MANF were upregulated in diabetic OA cartilage. The long-term high glucose increased GADD34, GRP78, and MANF expression, but decreased collagen II and proliferation of CHs, and Skp2 expression was negative related to the ER stress level. Additionally, Skp2 overexpression partly reversed ER stress-induced collagen II and proliferation suppression by the suppression of p27 expression. CONCLUSIONS: High glucose raises the ER stress in CHs and overexpression of Skp2 promotes CH proliferation under high glucose treatment.

Frequent genomic alterations and better prognosis among young patients with non-small-cell lung cancer aged 40 years or younger.

BACKGROUND: The subgroup of young patients with non-small-cell lung cancer (NSCLC) is poorly understood. We retrospectively studied the clinical characteristics, gene mutations, and outcomes of patients with NSCLC (aged ≤ 40 years). RESULTS: Of the 7494 patients with lung cancer diagnosed from February 2001 to October 2016, 252 aged ≤ 40 years showed NSCLC. We divided their cases into non-squamous cell carcinoma and squamous cell carcinoma groups according to their histology results. Of the 252 young NSCLC patients, 173 (69%) patients had stage IIIB or IV, and 196 (78%) had never smoked. The four most common metastases were intrapulmonary lesions, pleura, bone, and brain. Among patients with adenocarcinoma, 29 (40%, n = 73) harbored epidermal growth factor receptor (EGFR) mutations, 25 (34%, n = 74) harbored anaplastic lymphoma kinase (ALK) translations, and 1 (14%, n = 7) harbored ROS proto-oncogene 1 receptor tyrosine kinase (ROS1) translations. The median progression-free survival (PFS) and overall survival (OS) were 3.3 and 27.6 months for patients receiving chemotherapy (n = 65), and 12.1 and 33.6 months for patients receiving EGFR tyrosine kinase inhibitors (TKIs) (n = 13), respectively. Patients receiving crizotinib had a median PFS time of 21.9 months (n = 8). CONCLUSIONS: Young patients are associated with an increased likelihood of gene mutations and can receive a better prognosis when patients harboring gene mutations are treated with EGFR-TKIs or ALK inhibitors.

[Characteristics of Dix-Hallpike test induced nystagmus].

Objective:To retrospectively analyze the characteristics of 100 cases with Dix-Hallpike test induced nystagmus, especially the vertical downward component.Method:One hundred cases with positive Dix-Hallpike test between December 2017 and January 2018 were included in this study. Dix-Hallpike test and roll test were performed in all patients, and the max slow phase velocity (SPV), latency and duration of positional nystagmus were analyzed with SPSS 22.0 software.Result:According to the difference in the direction and duration of the nystagmus in the head-hanging position on Dix-Hallpike test, 100 patients were classified into 9 types. When only the vertical components were considered, 56 cases presented with bilateral or unilateral vertical upward component, among which 52 cases had unilateral torsional with vertical upward component, 4 cases had bilateral torsional with vertical upward component; 7 cases presented with vertically upward in one side and the vertically downward in the other side; 47 cases presented with bilateral or unilateral vertical downward component. In addition, 8 cases showed the reverse phase nystagmus. Of the 100 patients with positive Dix-hallpike, 20 cases were positive in roll test and 5 cases showing horizontal nystagmus and 15 cases showing torsional and vertical nystagmus.Conclusion:Vertical component in the positional nystagmus was common, and care should be taken to interpret the nystagmus into the underlying disorder.

Wnt3 knockdown sensitizes human non-small cell type lung cancer (NSCLC) cells to cisplatin via regulating the cell proliferation and apoptosis.

OBJECTIVE: Aberrant activation of (Wingless and mouse homolog Int-1) Wnt/ß-catenin signaling pathways closely involved in the occurrence and progression of several types of human malignancies. This research was undertaken to elucidate the important role of (Wingless and mouse homolog Int-1) in lung cancer. PATIENTS AND METHODS: Wnt3 expression in lung cancers and their respective normal tissues were examined by immunoblotting and immunohistochemistry. Then, Wnt3 was regulated with RNA interference (RNAi) technology in human lung cancer A549 cells, and the cell proliferation, cell cycle, cell invasion/metastasis, and apoptosis were evaluated. RESULTS: In all cases, Wnt3 expression was significantly elevated in lung cancers compared with normal tissues. Knocking down Wnt3 in A549 lung cancer cells by small interfering RNAs transfection led to a distinct reduction of Wnt3 in both transcript and protein levels. Knockdown of Wnt3 expression in lung cancer cells inhibited the expression of ß-catenin and cyclin D1 genes in Wnt/ß-catenin pathway. It also significantly blocked cellular proliferation, delayed cell cycle and suppressed cell invasion/metastasis, accompanied by a higher apoptosis rate. CONCLUSIONS: We conclude that the upregulation of Wnt3 plays a crucial role in lung tumorigenesis by inducing proliferation, migration, and invasion and inhibiting apoptosis of cancer cells. Wnt3 might be a potential target for the treatment of lung cancer.

[Lipoma of the pharyngeal opening auditory tube:a case report].

A young female complained left ear fullness for over three months. She has a history of tympanocentesis one year before. Nasal endoscopic inspection reported that left nose pharynx ministry is derived from the vegetations of eustachian tube. Pure tone audiometry found that the left ear took conductive deafness. We could see the reteacerd tympanic membrane with eardrum effusion by using of endotoscpe. Finally the nasal endoscopic surgery confirmed the excision of lesion of pharyngeal opening auditory tube.

Hybrid metamaterial switching for manipulating chirality based on VO2 phase transition.

Polarization manipulations of electromagnetic waves can be obtained by chiral and anisotropic metamaterials routinely, but the dynamic and high-efficiency modulations of chiral properties still remain challenging at the terahertz range. Here, we theoretically demonstrate a new scheme for realizing thermal-controlled chirality using a hybrid terahertz metamaterial with embedded vanadium dioxide (VO2) films. The phase transition of VO2 films in 90° twisted E-shaped resonators enables high-efficiency thermal modulation of linear polarization conversion. The asymmetric transmission of linearly polarized wave and circular dichroism simultaneously exhibit a pronounced switching effect dictated by temperature-controlled conductivity of VO2 inclusions. The proposed hybrid metamaterial design opens exciting possibilities to achieve dynamic modulation of terahertz waves and further develop tunable terahertz polarization devices.

Decreased autophagy: a major factor for cardiomyocyte death induced by ß1-adrenoceptor autoantibodies.

Cardiomyocyte death is one major factor in the development of heart dysfunction, thus, understanding its mechanism may help with the prevention and treatment of this disease. Previously, we reported that anti-ß1-adrenergic receptor autoantibodies (ß1-AABs) decreased myocardial autophagy, but the role of these in cardiac function and cardiomyocyte death is unclear. We report that rapamycin, an mTOR inhibitor, restored cardiac function in a passively ß1-AAB-immunized rat model with decreased cardiac function and myocardial autophagic flux. Next, after upregulating or inhibiting autophagy with Beclin-1 overexpression/rapamycin or RNA interference (RNAi)-mediated expression of Beclin-1/3-methyladenine, ß1-AAB-induced autophagy was an initial protective stress response before apoptosis. Then, decreased autophagy contributed to cardiomyocyte death followed by decreases in cardiac function. In conclusion, proper regulation of autophagy may be important for treating patients with ß1-AAB-positive heart dysfunction.