Adrenomedullin/FOXO3 enhances sunitinib resistance in clear cell renal cell carcinoma by inhibiting FDX1 expression and cuproptosis.

Cuproptosis, a new type of copper-induced cell death, is involved in the antitumor activity and resistance of multiple chemotherapeutic drugs. Our previous study revealed that adrenomedullin (ADM) was engaged in sunitinib resistance in clear cell renal cell carcinoma (ccRCC). However, it has yet to be investigated whether and how ADM regulates sunitinib resistance by cuproptosis. This study found that the ADM expression was elevated in sunitinib-resistant ccRCC tissues and cells. Furthermore, the upregulation of ADM significantly enhanced the chemoresistance of sunitinib compared with their respective control. Moreover, cuproptosis was involved in ADM-regulated sunitinib resistance by inhibiting mammalian ferredoxin 1 (FDX1) expression. Mechanically, the upregulated ADM activates the p38/MAPK signaling pathway to promote Forkhead box O3 (FOXO3) phosphorylation and its entry into the nucleus. Consequently, the increased FOXO3 in the nucleus inhibited FDX1 transcription and cell cuproptosis, promoting chemoresistance. Collectively, cuproptosis has a critical effector role in ccRCC progress and chemoresistance and thus is a relevant target to eradicate the cell population of sunitinib resistance.

Carbonic anhydrase 1 is a promising biomarker for early detection of non-small cell lung cancer.

This study aimed to identify candidate biomarkers associated with stage I non-small cell lung cancer (NSCLC). Sera from three groups, a lung cancer group (n = 11), benign control group (n = 12), and normal control group (n = 10), were collected and pooled. Protein expression profiles were analyzed by a combination of two-dimensional electrophoresis (2DE) and matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). These methods were used to separate, screen, and identify proteins that were differentially expressed between stage I NSCLC and controls. Differentially expressed proteins were validated by both Western blot and ELISA in an expanded sample size (22, 18, and 18 in three groups, respectively). MALDI-MS identified 12 differentially expressed proteins in the lung cancer group compared to the two control groups. Expression of carbonic anhydrase 1 (CA1) was validated by Western blot. CA1 was significantly elevated in the lung cancer group compared to controls. ELISA results confirmed that CA1 in the lung cancer group (3.18 ± 1.27 ng/mL, n = 22) was highly expressed in stage I NSCLC patients compared to those in the benign control group (2.21 ± 0.71 ng/mL, n = 18) and the normal control group (2.04 ± 0.63 ng/mL, n = 18) (P = 0.001). In conclusion, we provide evidence that CA1 is highly expressed in the sera of stage I NSCLC patients. Additionally, CA1 might serve as a novel biomarker for early detection of NSCLC.

Neoadjuvant chemoradiotherapy could improve survival outcomes for esophageal carcinoma: a meta-analysis.

BACKGROUND: The effectiveness of neoadjuvant chemoradiotherapy in patients with resectable esophageal carcinoma remains controversial. AIMS: The purpose of this study was to assess the effect of neoadjuvant chemoradiotherapy on operable esophageal carcinoma. METHODS: We searched PubMed, EMBASE and Web of Science and identified all randomized controlled trials published up until July 2011 that directly compared chemoradiotherapy followed by surgery with surgery alone. The risk ratio (RR) with its corresponding 95 % confidence interval (CI) was the principal measure of effects. RESULTS: Twelve randomized controlled trials that met our inclusion criteria were identified. Chemoradiotherapy followed by surgery was associated with significantly improved 1-year (RR = 0.86, 95 % CI = 0.74-0.98, P = 0.03), 3-year (RR = 0.82, 95 % CI = 0.73-0.92, P = 0.0007) and 5-year (RR = 0.83, 95 % CI = 0.72-0.96, P = 0.01) survival times compared with surgery alone. Subgroup analysis suggested that this benefit was associated with concurrent chemoradiotherapy but not sequential chemoradiotherapy. Neoadjuvant chemoradiotherapy could improve 3- and 5-year survival outcomes for squamous cell carcinoma but not those for adenocarcinoma. Postoperative morbidity (RR = 0.97, 95 % CI = 0.86-1.09, P = 0.56) and mortality (RR = 1.56, 95 % CI = 0.97-2.50, P = 0.07) did not increase in patients treated by chemoradiotherapy. CONCLUSIONS: Our findings revealed that compared with surgery alone, neoadjuvant chemoradiotherapy was associated with improved 1-, 3- and 5-year survival times, but not associated with increased postoperative morbidity and mortality in patients with esophageal carcinoma.

Transthyretin Suppressed Tumor Progression in Nonsmall Cell Lung Cancer by Inactivating MAPK/ERK Pathway.

Background: Lung malignancy is a main source of disease passing all throughout the planet, whereas the transthyretin (TTR) is a specific biomarker for clinical diagnosis. However, its role in lung malignancy stays to be obscure. Materials and Methods: In the current examination, the authors made an endeavor to research impact of abnormal expression of TTR on nonsmall cell lung carcinoma (NSCLC) by overexpression or knockdown of TTR. To further explore the instruments' fundamental mechanism part of TTR in NSCLC, several signal pathways were searched and verified. To confirm the effect of TTR overexpression on tumors, in vivo experiments were conducted. Result: It was found that upregulated TTR clearly stifled cell proliferation, migration, invasion, and expanded apoptosis. Significant suppression of phosphor-extracellular signal-regulated kinase (ERK) was observed in TTR-treated NSCLC cells, implying that TTR was important for cellular progress by regulating mitogen-activated protein kinase/ERK signaling pathway. In in vivo experiment, overexpression of TTR promoted cell apoptosis and inhibited tumor growth. Conclusion: Overall, the results suggest that TTR has a potential antitumor effect in human NSCLC progression, which provides theoretical basis for the diagnosis and treatment of NSCLC. Above all, further understanding of TTR was useful for clinical care. Clinical Trial Registration Number: 2016-08.

[Transmission of Coronavirus via Aerosols and Influence of Environmental Conditions on Its Transmission].

The COVID-19 pandemic has endangered human health and production since 2019. As an emerging disease caused by SARS-CoV-2, its potential transmissibility via aerosols has caused heated debate. This work summarizes the current research findings on virus aerosol generation, aerodynamic properties, and environmental influencing factors on their survivability in order to elucidate coronavirus transmission via aerosols. The occurrence and distinction of SARS-CoV-2, SARS-CoV-1, and MERS-CoV in real atmospheric environments are summarized. The deficiencies of existing research and directions for necessary future research on confirming the airborne transmission mechanism of coronavirus as well as the need for multidisciplinary research are discussed.

Cholinergic α5 nicotinic receptor is involved in the proliferation and invasion of human prostate cancer cells.

Nicotinic acetylcholine receptor (nAChR) subunit α5 (α5­nAChR) is involved in tumor cell proliferation, inhibition of apoptosis, progression of metastasis, and induction of angiogenesis in certain solid tumors. However, the role of α5­nAChR in prostate cancer cell growth and metastasis is unclear. In the present study, the role of α5­nAChR in cell proliferation, migration, invasion and apoptosis was investigated by silencing the expression levels of α5­nAChR in the prostate cancer cell lines DU145 and PC3. A siRNA oligonucleotide targeting α5­nAChR was designed. The cell proliferation of DU145 and PC3 cell lines was analyzed by the Cell Counting Kit­8 (CCK­8) assay. Cell migratory and invasive activities were determined using wound healing and Transwell assays, respectively. Western blot analysis was used to quantify α5­nAChR, p­AKT and p­ERK1/2 levels in DU145 and PC3 cells. Knockdown of α5­nAChR was associated with decreased cell proliferation, migration, invasion and increased apoptosis. In addition, decreased phosphorylation levels of AKT and ERK1/2 were revealed following α5­nAChR knockdown in DU145 and PC3 cells compared with those observed in the scramble control samples. The expression levels of the apoptosis­related proteins were altered following silencing of α5­nAChR. In summary, the data indicated that α5­nAChR was involved in the proliferation and invasion of human prostate cancer cells.

[Clinical trial of treatment of frozen shoulder by intensive moxibustion plus acupuncture].

OBJECTIVE: To compare the clinical therapeutic effect of intensive moxibustion plus acupuncture and simple acupuncture therapy in the treatment of frozen shoulder so as to provide a reference for clinical practice. METHODS: A total of 60 patients with frozen shoulder were randomly divided into intensive moxibustion plus acupuncture group and simple acupuncture group (n＝30 per group). Acupoints Jianyu (LI15), Jianzhen (SI9), Jianliao (TE14), Tiaokou (ST38), Chengshan (BL57) and Ashi points (Extra) were punctured with filiform needles which were manipulated till the patients experienced feelings of soreness and distension in the local region, followed by retaining the needles for 40 min. For patients of the moxibustion plus acupuncture group, after acupuncture, an ignited moxa-stick segment was applied to the affected shoulder for 40－50 min. After the treatment, all patients were ordered to make a shoulder exercise (anteflexion, rear protraction, abduction and upthrow movements, etc.). The visual analogue scale (VAS) was used to assess the pain severity, and the Constant-Murley shoulder assessment scale (the total score is 100 points, including 15 points in pain severity and 20 points in daily living activities, 40 points in joint motion range, and 25 points in myodynamia) used to assess the functional state of the shoulder, and the "Standards for Diagnosis and Therapeutic Effect Evaluation of Diseases of Traditional Chinese Medicine"(1994) were employed to evaluate the therapeutic effect. RESULTS: Following the treatment, intra-group comparison showed that the VAS score was significantly reduced in both groups in comparison with their own pre-treatment (P<0.05), and the total scores of Constant-Murley scale, the scores of activities of daily living and active motion range, as well as the scores of pain integration and myodynamia, were all considerably increased in the two groups in comparison with their own pre-treatment (all P<0.05). The therapeutic effect of the moxibustion plus acupuncture was significantly superior to that of the simple acupuncture in reducing VAS score and increasing total score of Constant-Murley scale, and scores of activities of daily living and active motion range, as well as the scores of pain integration (P<0.05). Of the two 29 cases in the moxibustion plus acupuncture and simple acupuncture groups, 19 (65.52%) and 10 (34.48%) were cured, 8 (27.58%) and 12 (41.38%) experienced improvement, 2 (6.90%) and 7 (24.14%) were failed, with the effective rate being 93.10% and 75.86%, respectively. The therapeutic effective rate of the moxibustion plus acupuncture was evidently higher than that of the simple acupuncture (P<0.05)．. CONCLUSION: The therapeutic effect of intensive moxibustion plus acupuncture is superior to that of simple acupuncture in improving symptoms of frozen shoulder in patients.

Custom-made Prosthesis for Reconstruction after Radical Resection for Chondrosarcoma of Manubrium.

The clinical incidence of tumors in the manubrium is not high. Regardless of whether the tumor is primary or metastatic, the tumor should be completely removed as long as the patient is able to tolerate the surgery. This procedure can lead to sternal defects. Deciding on the method of defect reconstruction is a critical problem that clinicians face. In this , to reduce the limitations of the patient's upper body movement after surgery due to the inflexibility in the connections of the sternal prosthesis, we created a prosthesis using a computer-assisted design method and a 3-D technique, to completely preserve the agility of the sternum and maximize the patient's post-operational movement. The method used in the present study takes into consideration the individual's chest anatomy, sternum stress, and many other biological characteristics. Care is taken to measure the sternum size accurately, to provide personalized treatment, to accomplish precise results, and to reduce potential future damage. The patient's shoulder function was improved following the procedure.

Clinical significance of mechanical ventilation on ischemic-reperfusion injury caused by lung chest trauma and VEGF expression levels in peripheral blood.

We investigated the clinical significance of mechanical ventilation on ischemic-reperfusion injury caused by lung chest trauma as well as vascular endothelial growth factor (VEGF) expression levels in peripheral blood. Sixty-eight patients with severe chest trauma complicated with acute respiratory distress syndrome that were treated at our Tianjin Hospital from September 2013 to July 2016 were recruited. These patients were randomly and evenly divided into two groups, the research group and the control group. Thirty-four age and gender matched healthy people were selected as the normal group. Routine treatment was given to both the research and control groups, but mechanical ventilation was used in the research group. We detected pulmonary vascular resistance (PVR) and alveolar-arterial oxygen difference (AaDO2) for patients in both groups before treatment, and after treatment for 1, 3, 6 and 12 h. We also tested PMN, superoxide dismutase (SOD), malondialdehyde (MDA), NO and Ang II value 30 min before and after treatment. We used the ELISA-test to detect VEGF expression levels in peripheral blood, followed by a statistical analysis. PVR levels of different time points in the research group were significantly lower than control group after treatment. The AaDO2 value of the control group is much smaller than research group (P<0.5) after treatment for 1, 3 or 6 h. PMN count difference and MDA level in the research group is significantly lower than the control group after treatment for 30 min, but SOD and NO levels are much higher. Ang II levels of the research group in left atrial blood is significantly lower than control group (P<0.05). By comparing the hospitalization times, we found that patients in the research group have a shorter duration in hospital than the control group; differences are statistically significant (P<0.05). Additionally, compared to control group, research group VEGF expression levels in peripheral blood are significantly lower (P<0.05). Therefore, mechanical ventilation can reduce the high VEGF expression levels in serum caused by ischemic-reperfusion and can be used for clinical application.

Thoracic Endoscopic-Assisted Mini-Open Surgery for Thoracic and Thoracolumbar Spinal Cord Compression.

Intervertebral disc herniation is a common cause of spinal cord compression, especially for the thoracic and thoracolumbar spinal cord, which has limited buffer space in the spinal canal. Spinal cord compression usually causes decreased sensation and paralysis of limbs below the level of compression, urinary and fecal incontinence, and/or urinary retention, which brings great suffering to the patients and usually requires surgical intervention. Thoracotomy or abdominothoracic surgery is usually performed for the thoracolumbar cord compression caused by hard intervertebral disc herniation. However, there is high risk of trauma and complications with this surgery. To reduce the surgical trauma and obtain good visibility, we designed athoracic endoscopic-assisted mini-open surgery for thoracic and thoracolumbar disc herniation, and performed this procedure on 10 patients who suffered from hard thoracic or thoracolumbar spinal cord compression. During the procedure, the thoracic endoscopy provided clear vision of the surgical field with a good light source. The compression could be fully exposed and completely removed, and no nerve root injury or spinal cord damage occurred. All patients achieved obvious recovery of neurological function after this procedure. This technique possesses the merits of minimal trauma, increased safety, and good clinical results. The aim of this study is to introduce this thoracic endoscopic-assisted mini-open surgery technique, and we believe that this technique will be a good choice for the thoracic and thoracolumbar cord compression caused by hard intervertebral disc herniation.

Neoadjuvant Chemoradiotherapy Improving Survival Outcomes for Esophageal Carcinoma: An Updated Meta-analysis.

BACKGROUND: The effectiveness of neoadjuvant chemoradiotherapy (NCRT) treatment for patients with esophageal carcinoma (EC) remains controversial. The aim of this study was to compare the effect of NCRT followed by surgery (NCRTS) with surgery alone (SA) for EC. METHODS: The PubMed, EMBASE, and the Cochrane Library databases were electronically searched up to August 2015 for all the published studies that investigated EC patients receiving either NCRTS or SA, and the reference lists were also manually examined for the eligible studies. The risk ratio (RR) with 95% confidence intervals (CI s) as effective size was determined to assess the 1-, 3-, 5-year survival rates (SRs), postoperative morbidity, and postoperative mortality. Heterogeneity was determined using the Q-test. The Begg's test and Egger's test were used for assessing any potential publication bias. RESULTS: Of 1120 identified studies, 16 eligible studies were included in this analysis (involving 2549 patients). Overall, the pooled results suggested that NCRTS was associated with significantly improved 1-year (RR: 1.07, 95% CI: 1.02-1.13), 3-year (RR: 1.26, 95% CI: 1.14-1.39), and 5-year (RR: 1.36, 95% CI: 1.18-1.56) SRs. However, the results also indicated that NCRTS had no or little effect on postoperative morbidity (RR: 0.93, 95% CI: 0.82-1.05) and postoperative mortality (RR: 1.17, 95% CI: 0.56-2.44). CONCLUSIONS: Compared with SA, NCRTS can increase 1-, 3-, and 5-year SRs in patients with EC.