Hyaluronic acid injection is becoming a popular way for penile augmentation. However, only few studies and follow-ups have investigated the various complications of hyaluronic acid injection and ...their corresponding management. In this study, a total of 230 patients who had penile augmentation with hyaluronic acid injection from January 2018 to December 2019 were examined on follow-up for penile girth, complications, and their corresponding management. At 1-month, 3-month, and 6-month postoperative follow-ups, the penile circumference had increased by 2.66 ± 1.24 cm, 2.28 ± 1.02 cm, and 1.80 ± 0.83 cm, respectively. During the entire 6-month follow-up, 4.3% had complications such as subcutaneous bleeding, subcutaneous nodules, and infection. There were no systemic or local allergic reactions among all the patients. All complications were treated accordingly, and no further deterioration or severe sequelae were observed. Although complications of hyaluronic acid injections are mild and rare, these may affect the patient's satisfaction postoperatively. Preoperative redundant prepuce may increase the incidence of penile edema or postoperative gel migration. Standardization of the surgery protocol and elucidation of the effects of other injection parameters are still lacking. Nevertheless, it still highlights the importance of preoperative preparation and surgical technique.
Salviae miltiorrhizae radix et rhizoma is a traditional herbal medicine with anti‐cancer activities. In this work, a trace peak enrichment approach combined with a cell proliferation assay was ...applied for screening cancer cell proliferation inhibitors from the extract of S. miltiorrhiza. A set of 123 peak fractions were prepared, and by comprehensive screening, 21 tanshinones were screened out as cancer cell proliferation inhibitors and their structures were tentatively identified by liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry analysis. The inhibitory activities of nine available screened tanshinones were validated, with their IC50 values ranging from 0.63 to 28.40 μM, indicating their activities strongly inhibit the proliferation of cancer cells. This study presents tanshinones that are potential cancer cell proliferation inhibitors and may explain the anti‐cancer activity of S. miltiorrhiza.
Background Systemic inflammation is currently regarded as a hallmark of cancer. This study aimed to accurately clarify the prognostic value of various inflammatory markers in patients with stage IV ...cancer. Methods This study assessed 2,424 patients with cancer diagnosed with cancer in tumor, node, metastasis (TNM) stage IV. After evaluating the predictive value of 13 inflammatory indicators for patient prognosis using the C index, the lymphocyte C-reactive protein ratio (LCR) was selected to elucidate the prognostic and predictive values in patients with stage IV cancer. Kaplan-Meier and Cox proportional hazards regression models were used to analyze long-term survival. Results A total of 1,457 men (60.1%) and 967 women (39.9%) diagnosed with TNM stage IV cancer were enrolled. A ratio of 2,814 was defined as the optimal cut-off value for the LCR. The LCR was the most accurate prognosis predictor for patients with stage IV cancer among the 13 inflammatory nutritional markers evaluated. The multivariate-adjusted restricted cubic spline plot suggested that LCR had an L-shaped dose-response association with all-cause mortality risk. Patients with lower LCR levels tended to present with worse prognoses. Kaplan-Meier curves and log-rank test results showed that the high LCR groups (LCR greater than or equal to 2,814) exhibited a better prognosis, whereas patients with stage IV cancer of different sex and tumor types (for example, gastrointestinal tumor, non-gastrointestinal tumor, and lung cancer) had a worse survival time. Conclusion The LCR score can be regarded as a stable and useful biomarker to predict prognosis in patients with TNM stage IV compared to other evaluated inflammation indicators. Keywords: Systemic inflammation, Lymphocyte-C-reactive protein ratio, Cancer, Prognosis, Patients with stage IV cancer
Non-small cell lung cancer (NSCLC) is the most common cancer in the world. Gefitinib, an inhibitor of EGFR tyrosine kinase, is highly effective in treating NSCLC patients with activating EGFR ...mutations (L858R or Ex19del). However, despite excellent disease control with gefitinib therapy, innate resistance and inevitable acquired resistance represent immense challenges in NSCLC therapy. Gefitinib potently induces cytoprotective autophagy, which has been implied to contribute to both innate and acquired resistance to gefitinib in NSCLC cells. Currently, abrogation of autophagy is considered a promising strategy for NSCLC therapy. In the present study, YC-1, an inhibitor of HIF-1α, was first found to significantly inhibit the autophagy induced by gefitinib by disrupting the fusion of autophagosomes and lysosomes and thereby enhancing the proapoptotic effect of gefitinib in gefitinib-resistant NSCLC cells. Furthermore, the combinational anti-autophagic and pro-apoptotic effect of gefitinib and YC-1 was demonstrated to be associated with an enhanced of forkhead box protein O1 (FOXO1) transcriptional activity which resulted from an increase in the p-FOXO1 protein level in gefitinib-resistant NSCLC cells. Our data suggest that inhibition of autophagy by targeting FOXO1 may be a feasible therapeutic strategy to overcome both innate and acquired resistance to EGFR-TKIs.
Background
Changes in body composition and systemic inflammation are important characteristics of cancer cachexia. This multi‐centre retrospective study aimed to explore the prognostic value of the ...combination of body composition and systemic inflammation in patients with cancer cachexia.
Methods
The modified advanced lung cancer inflammation index (mALI), which combines body composition and systemic inflammation, was defined as appendicular skeletal muscle index (ASMI) × serum albumin/neutrophil‐lymphocyte ratio. The ASMI was estimated according to a previously validated anthropometric equation. Restricted cubic splines were used to evaluate the relationship between mALI and all‐cause mortality in patients with cancer cachexia. Kaplan–Meier analysis and Cox proportional hazard regression analysis were used to evaluate the prognostic value of mALI in cancer cachexia. A receiver operator characteristic curve was used to compare the effectiveness of mALI and nutritional inflammatory indicators in predicting all‐cause mortality in patients with cancer cachexia.
Results
A total of 2438 patients with cancer cachexia were enrolled, including 1431 males and 1007 females. The sex‐specific optimal cut‐off values of mALI for males and females were 7.12 and 6.52, respectively. There was a non‐linear relationship between mALI and all‐cause mortality in patients with cancer cachexia. Low mALI was significantly associated with poor nutritional status, high tumour burden, and high inflammation. Patients with low mALI had significantly lower overall survival (OS) than those with high mALI (39.5% vs. 65.5%, P < 0.001). In the male population, OS was significantly lower in the low mALI group than in the high group (34.3% vs. 59.2%, P < 0.001). Similar results were also observed in the female population (46.3% vs. 75.0%, P < 0.001). mALI was an independent prognostic factor for patients with cancer cachexia (hazard ratio HR = 0.974, 95% confidence interval CI = 0.959–0.990, P = 0.001). For every standard deviation SD increase in mALI, the risk of poor prognosis for patients with cancer cachexia was reduced by 2.9% (HR = 0.971, 95%CI = 0.943–0.964, P < 0.001) in males and 8.9% (HR = 0.911, 95%CI = 0.893–0.930, P < 0.001) in females. mALI is an effective complement to the traditional Tumour, Lymph Nodes, Metastasis (TNM) staging system for prognosis evaluation and a promising nutritional inflammatory indicator with a better prognostic effect than the most commonly used clinical nutritional inflammatory indicators.
Conclusions
Low mALI is associated with poor survival in both male and female patients with cancer cachexia and is a practical and valuable prognostic assessment tool.
Metformin has beneficial effects of preventing and treating cancers on type 2 diabetic patients. However, the role of metformin in non-diabetic cancer patients and the precise molecular mechanisms ...against cancer have not yet been sufficiently elucidated. We recently reported that the pseudokinase protein TRIB3 acts as a stress sensor linking metabolic stressors to cancer promotion by inhibiting autophagy and ubiquitin-proteasomal degradation systems; genetically abrogating of TRIB3 expression reduces tumourigenesis and cancer progression. Thus, TRIB3 is a potential therapeutic target for diverse cancers. In this study, we found that metformin attenuates melanoma growth and metastasis by reducing TRIB3 expression in non-diabetic C57BL/6 mice and diabetic KK-Ay mice; overexpression of TRIB3 protects metformin from the activation of autophagic flux, the clearance of accumulated tumour-promoting factors and the attenuation of tumour progression. We further elucidated that TRIB3 acts as an adaptor to recruit lysine acetyltransferase 5 (KAT5) to SMAD3 and induce a phosphorylation-dependent K333 acetylation of SMAD3, which sustains transcriptional activity of SMAD3 and subsequently enhances TRIB3 transcription. Metformin suppresses SMAD3 phosphorylation and decreases the KAT5/SMAD3 interaction, to attenuate the KAT5-mediated K333 acetylation of SMAD3, reduce the SMAD3 transcriptional activity and subsequent TRIB3 expression, thereby antagonizes melanoma progression. Together, our study not only defines a molecular mechanism by which metformin protects against melanoma progression by disturbing the KAT5/TRIB3/SMAD3 positive feedback loop in diabetes and non-diabetes mice, but also suggests a candidate diverse utility of metformin in tumour prevention and therapy because of suppressing stress protein TRIB3 expression.
For 2D transition metal dichalcogenides (TMDs), the layer thickness has a greater impact on its thermoelectric properties. Herein, the thermoelectric properties of Janus monolayer and bilayer HfSSe ...are studied based on first‐principles calculations combined with Boltzmann equations, and the thermoelectric properties of bilayer HfSSe are also investigated with different stacking types. Owing to the influence of the interlayer coupling, the degradation of the phonon dispersion curve and the change of the phonon scattering intensity of the bilayer HfSSe lead to the decrease of its lattice thermal conductivity. In addition, the increase in the degeneracy of the electronic band structure of the bilayer HfSSe and the change in the density of states also change the thermoelectric transport properties of electrons. Integrating the coupling of high power factor and low thermal conductivity, the maximum ZT values at room temperature for n‐type doping are predicted as 3.24 and 5.54 for monolayer and SeHfS/SHfSe, respectively. And the ZT values increase to 3.24 and 5.54 as the temperature increases to 600 K. The result manifests that both monolayer and bilayer HfSSe are promising thermoelectric materials, and the layer thickness and stacking types also significantly affect the thermoelectric properties of the 2D TMDs materials.
2D HfSSe, as a typical layered material, exhibits excellent thermoelectric performance due to its high power factor and low lattice thermal conductivity.
Microbial oligosaccharides have been regarded as one of the most appealing natural products attributable to their potent and selective bioactivities, such as antimicrobial activity, inhibition of ...α-glucosidases and lipase, interference of cellular recognition and signal transduction, and disruption of cell wall biosynthesis. Accordingly, a handful of bioactive oligosaccharides have been developed for the treatment of bacterial infections and type II diabetes mellitus. Given that naturally occurring oligosaccharides have increasingly gained recognition in recent years, a comprehensive review is needed. The current review highlights the chemical structures, biological activities and divergent biosynthetic origins of three subgroups of oligomers including the acarviosine-containing oligosaccharides, saccharomicins, and orthosomycins.
Background： At present, a diagnostic tool with high specificity for impaired endometrial receptivity, which may lead to implantation failure, remains to be developed. We aimed to assess the different ...endometrial microRNA （miRNA） signatures for impaired endometrial receptivity by microarray analysis. Methods： A total of 12 repeated implantation failure （RIF） patients and I0 infertile patients, who conceived and delivered after one embryo transfer attempt, were recruited as RIF and control groups, respectively. Endometrial specimens from the window of implantation （WOI） were collected from these two groups. MiRNA microarray was conducted on seven and five samples from the RIF and control groups, respectively. Comparative, functional, and network analyses were performed for the microarray results. Quantitative real-time polymerase chain reaction （PCR） was performed on other samples to validate the expression of specific miRNAs. Results： Compared with those in the control group, the expression levels of 105 miRNAs in the RIF group were found to be significantly up- or down-regulated （at least 2-fold） by microarray analysis. The most relevant miRNA functional sets of these dysregulated miRNAs were miR-30 family, human embryonic stern cell regulation, epithelial-mesenchymal transition, and miRNA tumor suppressors by tool for annotations ofmicroRNA analysis. Network regulatory analysis found 176 miRNA-mRNA interactions, and the top 3 core miRNAs were has-miR-4668-5p, has-miR-429, and has-miR-5088. Expression levels of the 18 selected miRNAs in new samples by real-time PCR were found to be regulated with the same trend, as the result ofmicroarray analysis. Conclusions： There is a significant different expression of certain miRNAs in the WOI endometrium for RIF patients. These miRNAs may contribute to impaired endometrial receptivity.
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