Evaluating the Effectiveness of Radiofrequency Therapy and Manual Pelvic Fascial Release in Treating Myofascial Pelvic Pain.

INTRODUCTION AND HYPOTHESIS: Myofascial pelvic pain (MFPP), characterized by sensitive trigger points in the pelvic floor muscles, leads to chronic pain and affects various aspects of life. Despite the availability of different treatment modalities, there is limited comparative research on their effectiveness. This study compares radiofrequency (RF) therapy and myofascial manual therapy (MMT) in treating MFPP. We aimed to evaluate pelvic floor muscle strength changes, clinical symptoms, and patient comfort during treatment. METHODS: The study involved 176 participants, divided equally into RF and MMT groups. We assessed pelvic floor pain using the Visual Analogue Scale (VAS), muscle strength using the Modified Oxford Scale (MOS) and surface electromyography (sEMG), clinical symptom improvement through questionnaires, and patient discomfort during treatment. RESULTS: Both RF and MMT groups significantly reduced pelvic floor and paraurethral muscle pain (VAS scores, p < 0.001). RF treatment significantly decreased vaginal laxity in its group (p < 0.001), with no notable change in the MMT group (p = 0.818). RF therapy also resulted in greater patient comfort than MMT (p < 0.001). Although both treatments improved clinical symptoms, there was no significant difference between the two (p = 0.692). MOS scores and pelvic floor sEMG values showed no significant differences between the groups before and after treatment (p > 0.05). CONCLUSIONS: Both RF and MMT effectively alleviate pelvic floor pain and improve clinical symptoms in MFPP patients. RF therapy, however, offers additional benefits in reducing vaginal laxity and enhancing treatment comfort.

Development and Improvement of a Piezoelectrically Driven Miniature Robot.

In this paper, we proposed a miniature quadrupedal piezoelectric robot with a mass of 1.8 g and a body length of 4.6 cm. The robot adopts a novel spatial parallel mechanism as its transmission. Each leg of the robot has two degrees of freedom (DOFs): swing and lift. The trajectory necessary for walking is achieved by the appropriate phasing of these two DOFs. A new manufacturing method for piezoelectric actuators was developed. During the stacking process, discrete patterned PZT pieces are used to avoid dielectric failure caused by laser cutting. Copper-clad FR-4 is used as the solder pad instead of copper foil, making the connection between the pad and the actuator more reliable. The lift powertrain of the robot was modeled and the link length of the powertrain was optimized based on the model. The maximum output force of each leg can reach 26 mN under optimized design parameters, which is 1.38 times the required force for successful walking. The frequency response of the powertrain was measured and fitted to the second-order system, which enabled increased leg amplitudes near the powertrain resonance of approximately 70 Hz with adjusted drive signals. The maximum speed of the robot without load reached 48.66 cm/s (10.58 body lengths per second) and the payload capacity can reach 5.5 g (3.05 times its mass) near the powertrain resonance.

Design of polymetallic sulfide NiS2@Co4S3@FeS as bifunctional catalyst for high efficiency seawater splitting.

The shortage of freshwater resources in the world today has limited the development of water splitting, and our eyes have turned to the abundant seawater. The development of relatively low-toxicity and high-efficiency catalysts is the most important area in seawater electrolysis. In this paper, the preparation of NiS2@Co4S3@FeS via a hydrothermal method on nickel foam has been studied for the first time. In the process of vulcanization, Fe will first generate FeS by virtue of its high affinity for vulcanization. Once Fe is vulcanized, the residual sulfur will be used to generate NiS2, while the vulcanization of Co requires a higher sulfur concentration and reaction temperature; thus, Co4S3 will be generated last. NiS2@Co4S3@FeS is confirmed to have excellent hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) catalytic properties in alkaline seawater. Its unique structure allows it to expose more reaction centres, and the synergies between the multiple metals optimize the charge distribution of the material and accelerate the OER and HER kinetics. NiS2@Co4S3@FeS requires overpotentials of only 122 mV and 68 mV for the OER and HER when reaching 10 mA cm-2, which is superior to most catalysts reported to date for seawater electrolysis, and the material displays acceptable stability. In an electrolytic cell composed of both positive and negative electrodes, when the current density is 10 mA cm-2, the NiS2@Co4S3@FeS material displays a low overpotential of only 357 mV for seawater splitting. Density functional theory shows that the FeS electrode has the optimum Gibbs free energy of H to accelerate reaction kinetics, and the synergistic catalysis of the NiS2, Co4S3 and FeS materials promotes the hydrogen production activity of the NiS2@Co4S3@FeS electrode. This work proposes a novel idea for designing environmentally friendly seawater splitting catalysts.

The Accurate Interpretation and Clinical Significance of Morphological Features of Fine Needle Aspiration Cells in Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) is the most common malignant neoplasm of the thyroid gland; fine needle aspiration cytology is the most basic and reliable diagnostic method before PTC operation. However, it is not clear which cell morphological changes can be used as a reliable standard for the diagnosis of PTC. A retrospective analysis was performed on 337 patients with PTC confirmed by postoperative histology. An additional 197 randomly selected patients with benign thyroid lesions were included in the study and used as a control group. True papillary arrangements, swirl arrangements, and escape arrangements had high specificity, all of which were 100%, but only swirl arrangements had ideal sensitivity (77.61%). The nuclear volume characteristics had a high sensitivity of more than 90%, but the specificities of both nuclear crowding and nuclear overlap were too low, only 16.34% and 23.35%. The sensitivities of five nuclear structural characteristics were more than 90%, but only the specificity of intranuclear cytoplasmic pseudoinclusions (INCIs) reached 100%, nuclear contour irregularity and pale nuclei with powdery chromatin also had ideal interpretation value except for grooves and marginally placed micronucleoli. Although the sensitivity of psammoma bodies (PBs) was low, the specificity was 100%. In terms of preparation methods, the method of liquid-based preparation (LBP) is obviously better than that of conventional smears. The diagnostic efficiency by the combined detection method of parallel tests showed that without reducing the specificity, the sensitivity increased with the increase of the number of morphological characteristics and finally reached 98.81%. The INCIs and swirl arrangements are the most common and important indicators for the diagnosis of PTC, whereas papillary-like arrangements, the crowding and overlap of nuclear, grooves, marginally placed micronucleoli, and multinucleated giant cells are of little significance for the diagnosis of PTC.

Bioinformatic assay reveal the potential mechanism of Guizhi-Shaoyao-Zhimu decoction against rheumatoid arthritis and mild-to-moderate COVID-19.

BACKGROUND AND OBJECTIVE: Patients with rheumatoid arthritis (RA) are more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than healthy population, but there is still no therapeutic strategy available for RA patients with corona virus disease 2019 (COVID-19). Guizhi-Shaoyao-Zhimu decoction (GSZD), Chinese ancient experience decoction, has a significant effect on the treatment of Rheumatism and gout. To prevent RA patients with mild-to-moderate COVID-19 from developing into severe COVID-19, this study explored the potential possibility and mechanism of GSZD in the treatment of this population. METHODS: In this study, we used bioinformatic approaches to explore common pharmacological targets and signaling pathways between RA and mild-to-moderate COVID-19, and to assess the potential mechanisms of in the treatment of patients with both diseases. Beside, molecular docking was used to explore the molecular interactions between GSZD and SARS-CoV-2 related proteins. RESULTS: Results showed that 1183 common targets were found in mild-to-moderate COVID-19 and RA, of which TNF was the most critical target. The crosstalk signaling pathways of the two diseases focused on innate immunity and T cells pathways. In addition, GSZD intervened in RA and mild-to-moderate COVID-19 mainly by regulating inflammation-related signaling pathways and oxidative stress. Twenty hub compounds in GSZD exhibited good binding potential to SARS-CoV-2 spike (S) protein, 3C-like protease (3CLpro), RNA-dependent RNA polymerase (RdRp), papain-like protease (PLpro) and human angiotensin-converting enzyme 2 (ACE2), thereby intervening in viral infection, replication and transcription. CONCLUSIONS: This finding provides a therapeutic option for RA patients against mild-to-moderate COVID-19, but further clinical validation is still needed.

Role of MicroRNA-214 in Dishevelled1-Modulated ß-catenin Signalling in Non-Small Cell Lung Cancer Progression.

Background: The mortality of patients with non-small cell lung cancer (NSCLC) is rather high. This is largely because of the lack of specific targets and understanding of the molecular mechanism for early diagnosis. Dishevelled (Dvl) dysregulation leads to malignant progression. We confirmed that Dvl1 expression is associated with a poor prognosis of patients with NSCLC. However, how Dvl1 transmits signals through the Wnt/ß-catenin pathway remains unknown. Methods: In this study, the expression levels of Dvl1 and ß-catenin in resected NSCLC samples were immunohistochemically analysed. Dvl1 cDNA and small interfering RNA against ß-catenin were transfected into NSCLC cells, and their effects on canonical Wnt signalling and biological behaviour of NSCLC cells were analysed. Using bioinformatics analyses, an interaction between microRNA (miR)-214 and ß-catenin was identified; miR-214 expression was determined in NSCLC tissues using quantitative real-time polymerase chain reaction. An exogenous miR-214 (mimic) was used to analyse the biological behaviour of NSCLC cells and the effect of Dvl1 on canonical Wnt activation. Results: Dvl1 overexpression in NSCLC tissues as well as Dvl1 and ß-catenin nuclear coexpression were significantly associated with poor prognosis of NSCLC (P < 0.05). Additionally, Dvl1 promoted Wnt/ß-catenin signalling to enhance the malignant phenotype of NSCLC cells. Moreover, miR-214 directly targeted the 3' untranslated region of ß-catenin to inhibit the activation of canonical Wnt signalling induced by Dvl1. Conclusions: Our results suggest that Dvl1 is a potential therapeutic target for NSCLC and that miR-214 plays an inhibitory role in Dvl1-mediated activation of Wnt/ß-catenin signalling in NSCLC cells, which could affect NSCLC progression.

Nitric oxide electrochemical reduction reaction on transition metal-doped MoSi2N4 monolayers.

Nitric oxide electrochemical reduction (NOER) reactions are usually catalyzed by noble metals. However, the commercial applications are limited by the low atomic utilization and high price, which prompt researchers to turn their attentions to single-atom catalysts (SACs). Recently, a novel two-dimensional semiconducting material MoSi2N4 (MSN) has been synthesized and is suitable for the substrate of SACs due to its high stability, carrier mobility and mechanical strength. Herein, we employed first principles calculations to investigate the catalytic properties of transition metal doped MoSi2N4 monolayers (labelled as TM-MSN, where TM is a transition metal atom from 3d to 5d except Y, Tc, Cd, La-Lu and Hg) in NO reduction. The calculated results demonstrate that the introduction of Zr, Pd, Pt, Mn, Au, or Mo atoms can greatly improve the catalytic NOER performance of a pristine MSN monolayer. Zr-MSN and Pt-MSN monolayers at low coverage exhibit the most superior catalytic activity and selectivity for NH3 production with a limiting potential of 0 and -0.10 V. This work may help guide the application of MSN monolayer in the area of energy conversion.

Human papillomavirus16 E6 but not E7 upregulates GLUT1 expression in lung cancer cells by upregulating thioredoxin expression.

Background and objective: E6 and E7 proteins in human papillomavirus (HPV) 16 are major oncogenes in several types of tumors, including lung cancer. Previous studies have demonstrated that both E6 and E7 oncoproteins can upregulate GLUT1 protein and mRNA expression levels in lung cancer cells. Thus, the present study aimed to investigate the main differences in the molecular mechanisms of GLUT1 expression regulated by E6 and E7. Methods: The double directional genetic manipulation and immunofluorescence were performed to explore the molecular mechanism of E6 or E7 upregulating the expression of GLUT1 in H1299 and A549 cell lines. Results: The overexpression of E6 in well-established lung cancer cell lines upregulated thioredoxin (Trx) protein expression. Notably, plasmid transfection or small interfering RNA transfection with E7 had no regulatory effect on Trx expression. As an important disulfide reductase of the intracellular antioxidant system, Trx plays important role in maintaining oxidative stress balance and protecting cells from oxidative damage. The overexpression of Trx increased the activation of NF-κB by upregulating p65 expression and promoting p65 nuclear translocation, and further upregulated GLUT1 protein and mRNA expression levels. The results of the present study demonstrated that E6, but not E7, upregulated GLUT1 expression in lung cancer cells by activating NF-κB due to the participation of Trx. Conclusion: These results suggest that Trx plays an important role in the pathogenesis of HPV-associated lung cancer, and propose a novel therapeutic target for HPV-associated lung cancer.

Expression and Significance of HPV16 E6/E7 mRNAs in the Bronchial Brush and TBNA Cells of Patients With Small Cell Lung Cancer.

BACKGROUND AND OBJECTIVE: Small cell lung cancer (SCLC) is characterized by rapid growth, strong invasion, and early metastasis. However, the cause of its occurrence remains unclear. High-risk HPV infection is closely related to the occurrence of non-small cell lung cancer and cervical small cell neuroendocrine carcinoma. METHODS: The expression levels of E6 mRNA and E7 mRNA in HPV16 were detected by qRT-PCR in the bronchial brushing and transbronchial needle aspiration (TBNA) of 310 patients with lung cancer and with benign lung diseases. To make the design of this experiment scientific and reasonable, the expression levels in lung squamous cell carcinoma were taken as positive controls, while those in benign cells were taken as negative controls. RESULTS: The expression levels of E6 mRNA and E7 mRNA in SCLC group were significantly higher than those in benign cell group and slight higher than those in squamous cell carcinoma group. The expression levels of E6 mRNA and E7 mRNA in the central type of SCLC were significantly higher than those in the peripheral type of SCLC. CONCLUSIONS: We speculate that the occurrence of some small cell carcinoma is the same as that of some squamous cell carcinoma, which is closely related to HPV16 infection. The overexpression of E6 mRNA and E7 mRNA is in some benign lesion cells, which may be related to HPV transient infection.

Clinicopathologic features and treatment of thymic lymphoepithelioma-like carcinoma: two case reports and literature review.

Lymphoepithelioma-like carcinoma (LELC) is rare in the thymus, and easily misdiagnosed. To improve its clinicopathologic knowledge, we describe two cases of thymic LELC, and investigate their microscopic and immunohistochemical features, treatment, and follow-up with a review of previously published cases. Two patients in the First Affiliated Hospital of China Medical University underwent complete surgical resection for thymic LELC. They were treated with chemotherapy or radiotherapy after operation. Histologically, tumor cells exhibited nest patterns or showed stripe-shaped infiltration in fibrous tissue containing lymphocytes. Tumor was diffusely positive for pan-cytokeratin (CK), CK19, cluster of differentiation 5 (CD5), CD117, epithelial membrane antigen (EMA), and p63, and negative for TdT. Recent follow-up showed that the two patients were alive with no signs of recurrence. We report two cases of thymic LELC with a review of previously published cases to summarize knowledge of their clinicopathological characteristics, which is necessary for accurate diagnosis and clinical treatment.

Noninvasive papillary urothelial carcinoma with pathological features in between low and high grades: A case report.

RATIONALE: Urinary bladder urothelial carcinoma is the most common malignant tumor in the urinary system, and noninvasive papillary urothelial carcinoma (NIPUC) comprises most bladder malignancies. NIPUC grading is important for therapeutic and clinical protocol selection. Here, we report a case of NIPUC with pathological features in between low (LG-NIPUC) and high (HG-NIPUC) grades NIPUC. PATIENT CONCERNS: A 72-year-old male, presenting with a 20-year history of hypertension and 5 months of hematuria. DIAGNOSES: Computed tomography examination revealed a tumor in the urinary bladder neck. Microscopic investigation revealed that most tumor tissue samples had a branching papillary architecture, with well-developed fibrous-vascular cores. Tumor cells were slightly crowded, with somewhat altered cell polarity and cell adhesion. Immunohistochemistry showed positive Ki67 staining, mostly in the basal layer, while p53 staining was rarely positive. These samples were diagnosed as LG-NIPUC. However, a few tumor tissue samples presented mildly fused papillary architectures without cell polarity or adhesion. Most nuclei stained intensely and were pleomorphic. All epithelial tissue layers were ki67 positive, and the p53 positive rate was higher than that in the LG samples. Therefore, these were classified as HG-NIPUC. INTERVENTIONS: The tumor was completely resected during lithotomy postural surgery. OUTCOMES: The patient is alive with a good recovery during 3 months after the surgery. LESSONS: We diagnosed this patient as having LG-NIPUC with local HG-NIPUC components. HG- and LG-HIPUC have different outcomes. This case is a new challenge for the pathological grading of NIPUC. An intermediate HIPUC grade might need to be added to the original NIPUC grading system.

HPV 16 E6/E7 Promote the Glucose Uptake of GLUT1 in Lung Cancer Through Downregulation of TXNIP Due to Inhibition of PTEN Phosphorylation.

High-risk human papillomavirus (HPV) infection play an important role in the development of lung cancer. Our previously study showed that E6 and E7 in HPV16 upregulated the expression of GLUT1 in lung cancer cells. However, whether they can promote the glucose uptake by GLUT1 and the underlying molecular mechanism has not been identified. It has been reported that thioredoxin interacting protein (TXNIP) regulates both the expression of GLUT1 and its glucose uptake. We speculate that high risk HPV16 infection may be closely related to TXNIP expression. Therefore, we associate HPV16 with TXNIP to explore the potential molecular mechanism of their regulation of GLUT1 expression and glucose uptake. Using double directional genetic manipulation in lung cancer cells, we showed that HPV16 E6/E7 proteins downregulated the expression of p-PTEN in lung cancer cells, the knockdown of PTEN further inhibited the expression of TXNIP, the inhibition of TXNIP further promoted the accumulation of HIF-1α by inhibiting the translocation of nuclear HIF-1α to the cytoplasm, and subsequently upregulated the expression of GLUT1 at the protein and mRNA levels. More interestingly, we found that the knockdown of TXNIP played a decisive role to promote the glucose uptake by GLUT1. Together, these findings suggested that the PTEN-TXNIP-HIF-1α axis might be related to the E6/E7-mediated expression of GLUT1 and its glucose uptake.

HPV16 E6/E7 promote the translocation and glucose uptake of GLUT1 by PI3K/AKT pathway via relieving miR-451 inhibitory effect on CAB39 in lung cancer cells.

BACKGROUND: HPV16 E6/E7 proteins are the main oncogenes and only long-term persistent infection causes lung cancer. Our previous studies have shown that HPV16 E6/E7 protein up-regulates the expression of GLUT1 in lung cancer cells. However, whether E6 and E7 protein can promote the glucose uptake of GLUT1 and its molecular mechanism are unclear. METHODS: The regulatory relationships of E6 or E7, miR-451, CAB39, PI3K/AKT, and GLUT1 were detected by double directional genetic manipulations in lung cancer cell lines. Immunofluorescence and flow cytometry were used to detect the effect of CAB39 on promoting the translocation to the plasma membrane of GLUT1. Flow cytometry and confocal microscopy were performed to detect the glucose uptake levels of GLUT1. RESULTS: The overexpression both E6 and E7 proteins significantly down-regulated the expression level of miR-451, and the loss of miR-451 further up-regulated the expression of its target gene CAB39 at both protein and mRNA levels. Subsequently, CAB39 up-regulated the expression of GLUT1 at both protein and mRNA levels. Our results demonstrated that HPV16 E6/E7 up-regulated the expression and activation of GLUT1 through the HPV-miR-451-CAB39-GLUT1 axis. More interestingly, we found that CAB39 prompted GLUT1 translocation to the plasma membrane and glucose uptake, and this promotion depended on the PI3K/AKT pathway. CONCLUSION: Our findings provide new evidence to support the critical roles of miR-451 and CAB39 in the pathogenesis of HPV-related lung cancer.

Human papillomavirus 16 (HPV 16) E6 but not E7 inhibits the antitumor activity of LKB1 in lung cancer cells by downregulating the expression of KIF7.

BACKGROUND: The E6 and E7 proteins in human papillomavirus 16 (HPV 16) are the main oncogenes in the occurrence of lung cancer. In recent studies, we found that E6 and E7 downregulated the expression of LKB1 in lung cancer cells. However, it is still unclear how E6 and E7 regulate LKB1 in lung cancer cells. METHODS: Double directional genetic manipulation and nuclear plasma separation technology were performed to explore the molecular mechanism of E6 and E7 inhibiting the antitumor activity of LKB1 in well-established lung cancer cell lines. RESULTS: E6 but not E7 significantly downregulated the expression of tumor suppressor KIF7 at protein level, and the inhibition of KIF7 further reduced the expression of LKB1 both in the nuclei and in the cytoplasm, whereas reduced the expression of p-LKB1 in the cytoplasm only. This suggested that HPV 16 E6 but not E7 downregulates the antitumor activity of LKB1 by downregulating the expression of p-LKB1 in the cytoplasm only. CONCLUSIONS: Here, we demonstrated for the first time that E6 but not E7 inhibits the antitumor activity of LKB1 in lung cancer cells by downregulating the expression of KIF7. Our findings provide new evidence to support the important role of KIF7 in the pathogenesis of lung cancer and suggests new therapeutic targets.

HPV16 E6/E7 upregulate hTERC mRNA and gene amplification levels by relieving the effect of LKB1 on Sp1 phosphorylation in lung cancer cells.

BACKGROUND: There is an immediate need for research on the mechanism underlying telomerase activation and overexpression. MATERIALS & METHODS: A total of 174 patients with lung cancer (n = 106) and benign lung disease (n = 68) were recruited for the current study. The mRNA expression levels of E6, E7, LKB1, Sp1, and hTERC in brushing cells were detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and hTERC amplification was also detected by fluorescence in situ hybridization (FISH). To investigate the potential mechanism, bidirectional genetic manipulation was performed in well-established lung cancer cell lines. RESULTS: Our results indicated that the mRNA expression levels of E6, E7, Sp1, and hTERC and the amplification level of hTERC were significantly increased in the malignant group compared with those of the benign group (p < 0.01). Conversely, the mRNA expression level of LKB1 was significantly decreased in the malignant group (p < 0.01). The correlation between E6, E7, Sp1, and hTERC expression was positive but was negative with LKB1 (p < 0.01). Our results also showed that HPV16 E6/E7 downregulated the expression of LKB1 at both the protein and mRNA levels. The loss of LKB1 upregulated Sp1 expression, and also promoted Sp1 activity. Sp1 further upregulated hTERC at the mRNA and gene amplification levels. Thus, we proposed a HPV-LKB1-Sp1-hTERC axis of E6/E7 upregulation of hTERC expression. CONCLUSION: We demonstrated for the first time that E6 and E7 promoted hTERC mRNA expression and the amplification of hTERC by relieving the effect of LKB1 on the phosphorylation of Sp1. Sp1 further activated hTERC by directly binding to the promoter regions of hTERC.

A comparison of the pregnancy outcomes between ultrasound-guided high-intensity focused ultrasound ablation and laparoscopic myomectomy for uterine fibroids: a comparative study.

Objective: To compare the pregnancy outcomes between ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation and laparoscopic myomectomy (LM).Materials and methods: This study included 676 women with symptomatic uterine fibroids who wished to become pregnant underwent USgHIFU or LM at three hospitals in China from 1 May 2009 to 31 May 2018. The related information of pregnancy and delivery were followed up and analyzed using the chi-square test and two-sided Student t-test.Results: The median follow-up duration was 5 (1-8) years; 20 patients (2.9%) were lost to follow-up. 320 patients were treated with UsgHIFU, and 336 were treated with LM. Two hundred nineteen (68.4%) women became pregnant after USgHIFU ablation, and 224 (66.7%) became pregnant after LM. Four hundred forty-three patients had 501 pregnancies (natural pregnancies, 405; in vitro fertilisation-embryo transfer pregnancies, 38). Average times to pregnancy were 13.6 ± 9.5 months after USgHIFU and 18.9 ± 7.3 months after LM (p < 0.05). The rate of cesarean delivery was lower in the USgHIFU group (41.6%) than in the LM group (54.9%) (p < 0.05). Incidences of placenta increta, placenta previa, and postpartum hemorrhage were low after USgHIFU compared with after LM. Incidences of preterm birth, fetal distress, fetal growth restriction, and puerperal infection were higher after USgHIFU than after LM. There was a risk of uterine rupture after both procedures.Conclusions: Compared with LM, USgHIFU ablation can significantly shorten the time to pregnancy, although pregnancy rates of the two procedures are similar. Some risks in pregnancy and delivery after HIFU should be evaluated and monitored.

The Morphological Analysis of Cells in the Bronchoscopic Brushing and TBNA of Patients with Lung Adenocarcinoma.

Biopsy, brushing, and transbronchial needle aspiration (TBNA) are the most common methods for diagnosis of lung adenocarcinoma and are taken during the same diagnostic bronchoscopic procedure. However, it is not clear what the morphological diagnostic criteria of cytology by brushing or TBNA are. A retrospective analysis was performed on 136 patients who underwent video bronchoscopy examination for diagnostic purposes. All the subjects were performed brushing or TBNA and confirmed as lung adenocarcinoma by biopsy or postoperative pathology. An additional 140 randomly selected patients with benign lung diseases were included in the study and used as a control group. The benign cells usually confused with adenocarcinoma cells were ciliated columnar cells, mucous columnar cells, ciliated cuboid cells, and reactive ciliated cells, respectively. The number of cases diagnosed as adenocarcinoma cells, carcinoma cells, suspicious cancer cells, and atypical proliferative cells by cytology was 101, 11, 20, and 4, respectively. The main basis for the interpretation of adenocarcinoma cells is the enlargement of individual nucleus, the arrangements of multistage papillary, and the general enlargement of nuclei, while the main clue for the interpretation of suspicious cancer cells and dysplasia cells comes from escape cells. The results suggested that the degree of nuclear enlargement, multiple papillary arrangement, and escape cells or escape trend cells are important clues for the interpretation of lung adenocarcinoma cells, while the atypical proliferative cells were similar to escape cells or escape trend cells, which were essentially benign cells beside the cancer.

HPV 16 E6/E7 up-regulate the expression of both HIF-1α and GLUT1 by inhibition of RRAD and activation of NF-κB in lung cancer cells.

Chronic infection of HPV16 E6/E7 is frequently associated with lung cancers, especially in non-smokers and in Asians. In our previous studies, we found that HPV16 E6/E7 up-regulated HIF-1α at protein level and further up-regulated GLUT1 at both protein and mRNA levels in well-established lung cancer cell lines. In one of our further mechanism study, the results demonstrated that HPV16 E6/E7 up-regulated the expression of GLUT1 through HPV-LKB1-HIF-1α-GLUT1 axis. However, there are multiple pathways involved in HPV16 E6/E7 regulation of HIF-1α expression. In current study, using double directional genetic manipulation in well-established lung cancer cell lines, we showed that both E6 and E7 down-regulated the expression of RRAD at both protein and mRNA levels. Like LKB1, RRAD is one of the cancer suppressor genes. The loss of RRAD further activated NF-κB by promoted cytoplasmic p65 translocated to nucleus, and up-regulated the expression level of the p-p65 in nucleus. Furthermore, p-p65 up regulated HIF-1α and GLUT1 at both protein and mRNA levels. Thus, we proposed HPV16 E6/E7 up-regulated the expression of GLUT1 through HPV-RRAD-p65- HIF-1α- GLUT1 axis. In conclusion, we demonstrated for the first time that E6 and E7 promoted the expression of HIF-1α and GLUT1 by relieving the inhibitory effect of RRAD which resulted in the activation of NF-κB by promoting cytoplasmic p65 translocated to nucleus, and up-regulated the expression of the p-p65 in nucleus in lung cancer cells. Our findings provided new evidence to support the critical role of RRAD in the pathogenesis of HPV-related lung cancer, and suggested novel therapeutic targets.

Glucose Transporter 1 Promotes the Malignant Phenotype of Non-Small Cell Lung Cancer through Integrin ß1/Src/FAK Signaling.

Background: Glucose transporter 1 (GLUT1) is the main factor of Warburg effect, which is associated with poor prognosis in many tumors. However, the underlying molecular mechanism of GLUT1 in the progression of non-small cell lung cancer (NSCLC) is unclear. Methods: We used quantitative real-time PCR to detect GLUT1 mRNA expression in bronchial brushing samples and performed Western Blot and biological behavior testing to check the effect of GLUT1 on NSCLC cell proliferation, migration, invasion and apoptosis. Results: We found that the C(t) normalized value of GLUT1 in malignant bronchial brushing samples was significantly higher than that in benign samples (P<0.05). GLUT1 significantly increased the expressions of cyclin A, cyclin D1, cyclin E, cyclin dependent kinase 2 (CDK2), CDK4, CDK6 and matrix metalloproteinase 2 (MMP2), but decreased the expressions of p53 and p130 in NSCLC cells. The biological behavior testing indicated that GLUT1 enhanced NSCLC cell proliferation, invasion and migration but inhibited cell apoptosis. In addition, GLUT1 upregulated the expression of integrin ß1 and promoted the phosphorylation of focal adhesion kinase (FAK, phosphorylation at Tyr576/577) and Src (Src phosphorylation at Tyr530). siRNA knock down of integrin ß1 expression suppressed GLUT1 induced NSCLC cell biological behavior, as well as the phosphorylation of FAK and Src. Conclusion: Taken together, our data confirms that GLUT1 promotes the malignant phenotype of NSCLC through integrin ß1/Src/FAK signaling, which provides a new therapeutic target for the treatment and research of lung cancer.

The Role of Autophagy in Sepsis: Protection and Injury to Organs.

Sepsis is a systemic inflammatory disease with infection, and autophagy has been shown to play an important role in sepsis. This review summarizes the main regulatory mechanisms of autophagy in sepsis and its latest research. Recent studies have shown that autophagy can regulate innate immune processes and acquired immune processes, and the regulation of autophagy in different immune cells is different. Mitophagy can select damaged mitochondria and remove it to deal with oxidative stress damage. The process of mitophagy is regulated by other factors. Non-coding RNA is also an important factor in the regulation of autophagy. In addition, more and more studies in recent years have shown that autophagy plays different roles in different organs. It tends to be protective in the lungs, heart, kidneys, and brain, and tends to be damaging in skeletal muscle. We also mentioned that some drugs can regulate autophagy. The process of modulating autophagy through drug intervention appears to be a new potential hope for the treatment of sepsis.