Resting-state functional connectivity of amygdala subregions predicts treatment outcome for cognitive behavioral therapy in obsessive-compulsive disorder at a 4-month follow-up.

BACKGROUND: Cognitive behavioral therapy (CBT) is considered as the first-line treatment for obsessive-compulsive disorder (OCD). However, the underlying neural mechanisms through which CBT exerts its effects in OCD remain unclear. This study aims to investigate whether the improvement of clinical symptoms in OCD patients after CBT treatment is associated with changes in resting-state functional connectivity (FC) of the amygdala subregion, and whether these changes can be served as potential predictors of four-months treatment efficacy. METHODS: We collected resting-state functional magnetic resonance imaging (rs-fMRI) data from 57 OCD patients and 50 healthy subjects at baseline. In the patient group, rs-fMRI was also obtained after completion of an 8-week CBT treatment and 4 months post-treatment. A whole-brain rsFC analysis was conducted using the amygdala subregion as the seed point. We analyzed the FC patterns in relation to 4 months clinical outcomes to elucidate the long-term efficacy of CBT in OCD patients. RESULTS: Treatment responseat at pre-treatment was found to be associated with reduced rsFC between the left basolateral amygdala(BLA)and left superior temporal gyrus(STG) at baseline. Lower pre-treatment FC were negatively correlated with the severity of OCD symptoms as measured by the Yale-Brown Obsessive Compulsive Severity Scale (Y-BOCS). Moreover, the area under the receiver operating characteristic (ROC) curve for the FC between the left BLA and STG at the end of treatment was 73.0% and 70.4% for the effective-ineffective and remitted or unremitted groups, respectively. At the 4-month follow-up, the area under the ROC curve for the effective-ineffective and remitted or unremitted groups was 83.9% and 76.5%, respectively. CONCLUSION: These findings suggest that brain functional activity in patients with OCD can predict treatment response to CBT, and longitudinal changes in relevant brain functional activity following CBT treatment are associated with treatment response in OCD.

Urease catalyzed high-density sodium alginate microspheres enable high oral bioavailability of macromolecular drugs.

Destruction of insulin caused by the gastric microenvironment and rapid deactivation pose inevitable barriers to oral macromolecular absorption, especially for most peptide and protein drugs. In this study, we developed high-density sodium alginate microspheres composed of magnesium oxide and urease to address these challenges. These microspheres aim to anchor the gastric mucus layer and induce microenvironmental liquefaction, thereby enhancing gastric retention and the protection of insulin. The sedimentation test confirmed the capability of the Ins/Ur/MgO@SA microsphere to rapidly traverse the gastric juice under the influence of gravity. Additionally, the urease immobilized on the Ins/Ur/MgO@SA microspheres catalyzes the hydrolysis of urea in the gastric mucus and promotes the liquefaction of mucus, which is beneficial for microsphere retention. The inclusion of MgO particles and urease, acting as pHM modifiers, helps in adjusting the local pH to avoid gastric acid-induced damage. Subsequently, an in vivo pharmacokinetic experiment verified that the relative bioavailability of the p.o. Ins/Ur/MgO@SA treated group was 15-fold higher than that of the p.o.insulin treated group. Meanwhile, satisfactory blood glucose level (BGL) reduction was observed in diabetic animals. In conclusion, Ins/Ur/MgO@SA microspheres demonstrate high biocompatibility as insulin carriers with prolonged drug release time and increased gastric retention properties, showing a far-reaching strategy for oral macromolecular drug delivery.

miRNA-27b-3p/TPX2 Axis Regulates Clear Cell Renal Cell Carcinoma Cell Proliferation, Invasion and Migration.

There is a wide variety of cancer cells that can be linked to the presence of TPX2. However, there is not a lot of evidence regarding its role in the development and maintenance of clear cell renal cell carcinoma (ccRCC). In our study, bioinformatics analysis was performed to obtain differentially expressed mRNAs and miR-NAs in ccRCC. Survival curves predicted correlation of TPX2 expression with patient survival. The upstream regulatory miRNA of TPX2 was predicted to be miRNA-27b-3p through database, and dual luciferase assay verified the targeted relationship. qRT-PCR and Western blot were employed for examination of TPX2 mRNA and protein expression in ccRCC cells. Proliferation, invasion, migration and cell cycle were detected by CCK-8, colony formation, wound healing, Transwell, and flow cytometry assays. The results showed that TPX2 showed very high expression in ccRCC, and patients with higher TPX2 expression had shorter relative survival. Low miRNA-27b-3p expression was found in ccRCC. Knockdown of TPX2 or forced expression of miRNA-27b-3p in ccRCC cells inhibited cell proliferation, migration, invasion, and arrested cell division in G0/G1 phase. Dual luciferase reporter presented that miRNA-27b-3p targeted TPX2 to inhibit its expression. Rescue experiments demonstrated that the miRNA-27b-3p/ TPX2 axis affected the biological functions of ccRCC cells. Concurrent overexpression of miRNA-27b-3p and TPX2 inhibited the facilitating effect of TPX2 on ccRCC cell growth. The results revealed novel regulatory mechanisms involved in ccRCC progression, hoping that it may spark an insight for later discovery about the new therapeutic targets for ccRCC.

CircMAPK9 promotes adipogenesis through modulating hsa-miR-1322/FTO axis in obesity.

Circular RNA (circRNA) is a special category of non-coding RNA that has garnered increasing attention in the exploration of lipid metabolism. However, the functional regulation mechanisms of circRNAs in obesity diseases remain unclear. By whole transcriptome sequencing, a total of 164 circular RNAs were found to exhibit differential expression between lean and obese individuals. RT-qPCR was used to detect significant expression of circMAPK9 in obese individuals, and it was closely related to BMI. Western blot, triglyceride detection, and Oil Red O staining were employed to investigate the role of circMAPK9/hsa-miR-1322/FTO in adipogenesis. In adipocytes, the connection between hsa-miR-1322 and circMAPK9 was verified using fluorescence in situ hybridization, luciferase reporter assay, and RNA immunoprecipitation. It was found that circMAPK9 competed for binding hsa-miR-1322 in the cytoplasm, weakening the inhibitory effect on FTO and promoting adipogenesis. Our study revealed the regulatory mechanism and important role of circMAPK9 in the process of adipogenesis.

A prediction model for predicting the risk of acute respiratory distress syndrome in sepsis patients: a retrospective cohort study.

BACKGROUND: The risk of death in sepsis patients with acute respiratory distress syndrome (ARDS) was as high as 20-50%. Few studies focused on the risk identification of ARDS among sepsis patients. This study aimed to develop and validate a nomogram to predict the ARDS risk in sepsis patients based on the Medical Information Mart for Intensive Care IV database. METHODS: A total of 16,523 sepsis patients were included and randomly divided into the training and testing sets with a ratio of 7:3 in this retrospective cohort study. The outcomes were defined as the occurrence of ARDS for ICU patients with sepsis. Univariate and multivariate logistic regression analyses were used in the training set to identify the factors that were associated with ARDS risk, which were adopted to establish the nomogram. The receiver operating characteristic and calibration curves were used to assess the predictive performance of nomogram. RESULTS: Totally 2422 (20.66%) sepsis patients occurred ARDS, with the median follow-up time of 8.47 (5.20, 16.20) days. The results found that body mass index, respiratory rate, urine output, partial pressure of carbon dioxide, blood urea nitrogen, vasopressin, continuous renal replacement therapy, ventilation status, chronic pulmonary disease, malignant cancer, liver disease, septic shock and pancreatitis might be predictors. The area under the curve of developed model were 0.811 (95% CI 0.802-0.820) in the training set and 0.812 (95% CI 0.798-0.826) in the testing set. The calibration curve showed a good concordance between the predicted and observed ARDS among sepsis patients. CONCLUSION: We developed a model incorporating thirteen clinical features to predict the ARDS risk in patients with sepsis. The model showed a good predictive ability by internal validation.

"Shell-Core" Bilayer Nanoparticle as Chemotherapeutic Drug Co-Delivery Platforms Render Synchronized Microenvironment Respond and Enhanced Antitumor Effects.

Background: Synergistic chemotherapy has been proved as an effective antitumor means in clinical practice. However, most co-administration treatment often lacks simultaneous control over the release of different chemotherapeutic agents. Materials and Methods: ß-cyclodextrin modified hyaluronic acid was the "shell", and the oxidized ferrocene-stearyl alcohol micelles served as the "core", where doxorubicin (DOX) and curcumin (CUR) were loaded in shell and core of the bilayer nanoparticles (BNs), respectively. The pH- and glutathione (GSH)-responsive synchronized release behavior was evaluated in different mediums, and the in vitro and in vivo synergistic antitumor effect and CD44-mediated tumor targeting efficiency were further investigated. Results: These BNs had a spherical structure with the particle size of 299 ± 15.17 nm, while the synchronized release behaviour of those two drugs was proved in the medium with the pH value of 5.5 and 20 mM GSH. The co-delivery of DOX and CUR reduced the IC50 value by 21% compared to DOX alone, with a further 54% reduction after these BNs delivery measurements. In tumor-bearing mouse models, these drug-loaded BNs showed significant tumor targeting, enhanced antitumor activity and reduced systemic toxicity. Conclusion: The designed bilayer nanoparticle could be considered as potential chemotherapeutic co-delivery platform for efficient synchronized microenvironment respond and drug release. Furthermore, the simultaneous and synergistic drug release guaranteed the enhanced antitumor effects during the co-administration treatment.

Screening of Biomarkers in Liver Tissue after Bariatric Surgery Based on WGCNA and SVM-RFE Algorithms.

As the most common chronic liver disease around the world, nonalcoholic fatty liver disease (NAFLD) has a close connection with obesity, diabetes, and metabolic syndrome. Bariatric surgery (BS) is considered to be the most effective treatment for NAFLD. However, the regulatory mechanism of hepatic lipid metabolism after BS remains poorly elucidated. By analyzing two transcriptome datasets regarding liver tissues after BS, namely, GSE83452 and GSE106737, we acquired 110 differentially expressed genes (DEGs). By further analysis of DEGs in terms of the weighted gene coexpression network analysis (WGCNA) and support vector machine-recursive feature elimination (SVM-RFE) algorithms, we identified four crucial genes participating in the regulation of hepatic lipid metabolism: SRGN, THEMIS2, SGK1, and FPR3. In addition, the results of gene set enrichment analysis (GSEA) showed that BS can activate immune-related regulatory pathways and change immune cell infiltration levels. Finally, through cellular level studies, we found that the silencing of SRGN affects the expression of SREBP-1, SIRT1, and FAS during adipogenesis in the liver and the formation of lipid droplets in the liver. In summary, the immune system in the liver is activated after BS, and SRGN participates in the regulation of hepatic lipid metabolism.

A nomogram model based on the combination of the systemic immune-inflammation index and prognostic nutritional index predicts weight regain after laparoscopic sleeve gastrectomy.

BACKGROUND: The high rate of weight regain after laparoscopic sleeve gastrectomy is a great challenge. The systemic immune-inflammation index (SII; calculated by neutrophils, lymphocytes, and platelets) and prognostic nutritional index (PNI; calculated by albumin and lymphocytes) are widely used as prognostic factors in various diseases. OBJECTIVES: The objective of this study was to investigate independent the independent risk factors associated with weight regain in patients after laparoscopic sleeve gastrectomy. SETTING: A single-center retrospective study. METHODS: Weight regain was defined as the percentage of increase in body weight ≥10% in comparison with the nadir weight postoperatively. Eligible patients admitted to the bariatric center of our hospital were consecutively enrolled and grouped according to the occurrence of weight regain within 5 postoperative years. Univariate and multivariate logistic regression analyses were performed to assess potential risk factors. A nomogram model containing the risk factors was then constructed and evaluated by R. RESULTS: A total of 217 patients were enrolled, and 87 (40.1%) patients experienced weight regain. Univariate and logistic regression analyses indicated that depression (odds ratio [OR]: 2.51, 95% confidence interval [CI]: 1.20-5.22, P = .015), psychological counseling (OR: 2.27, 95% CI: 1.20-4.33, P = .017), preoperative C-reactive protein (OR: 2.20, 95% CI: 1.18-4.13, P = .012), and combination of SII-PNI scores (OR: .45, 95% CI: .31-.67, P < .001) were 4 independent risk factors for postoperative weight regain in laparoscopic sleeve gastrectomy patients. The area under the curve of the constructed nomogram model for predicting weight regain was .706. CONCLUSIONS: This study concluded that the combination of the SII-PNI was an independent risk factor for weight regain and that the nomogram model based on the combination of the SII-PNI had a good predictive value.

Flow diversion for unruptured fusiform aneurysms of the proximal middle cerebral artery.

Background: Managing fusiform aneurysms of the proximal (M1) segment of the middle cerebral artery (MCA) is challenging due to difficulties in both surgical and endovascular treatment. In this study, we present our experience using flow diverter stents for managing unruptured M1 segment fusiform aneurysms. Methods: We conducted a retrospective review of the database of our institution to identify all patients who underwent flow diversion treatment for unruptured M1 segment fusiform aneurysms. We collected data on patient demographics, aneurysm characteristics, complications, angiographic follow-up results, and clinical outcomes. Results: A total of 10 patients (five male and five female patients) with 10 unruptured M1 segment fusiform aneurysms were included in the study. The average age of the patients was 48 years (range: 16-64 years); five patients had aneurysms smaller than 10 mm, four had aneurysms measuring between 10 and 25 mm, and one patient had an aneurysm larger than 25 mm. The successful deployment of flow-diverting stents was achieved in all cases. Procedure-related morbidity was observed in 10% of patients, but there were no deaths. All patients showed good outcomes (modified Rankin Scale score of 0-1); eight out of 10 patients had available follow-up angiography results with a mean follow-up period of 11.6 months (range: 6-24 months). Complete occlusion occurred in six out of eight reviewed cases (75%). Conclusion: Our preliminary findings suggest that using flow diversion for treating unruptured fusiform aneurysms in the proximal MCA is feasible and safe, with a satisfactory rate of complete occlusion. However, further studies involving larger case series are needed to validate the durability and efficacy of this treatment approach.

Identification of intrinsic genes across general hypertension, hypertension with left ventricular remodeling, and uncontrolled hypertension.

The purpose of the present article is to identify intrinsic genes across general hypertension (HT), hypertension with left ventricular remodeling (HT-LVR), and uncontrolled hypertension (UN-HT). In total, four microarray datasets (GSE24752, GSE75360, GSE74144, and GSE71994) were downloaded from the GEO database and were used to identify differentially expressed genes (DEGs), respectively. Furthermore, gene set enrichment analysis (GSEA) was utilized to screen for significantly enriched biological pathways across the four datasets above, respectively. Furthermore, weighted gene co-expression network analysis (WGCNA) and functional enrichment analysis were applied to screen out gene modules of interest and potential biological functions, respectively. Finally, a Metascape-based multiple gene list meta-analysis was used to investigate intrinsic genes at different stages of the progression of hypertension. A total of 75 DEGs (63 upregulated genes and 12 downregulated genes, GSE24752) and 23 DEGs (2 upregulated genes and 21 downregulated genes, GSE74144) were identified. However, there were few DEGs identified in GSE75360, GSE71994, and part of the GSE74144 datasets. GSEA and functional enrichment of gene module of interest have indicated that "Heme metabolism," "TNF alpha/NFkB," and "interferon alpha response signaling," and MYC target v1/v2 were enriched significantly in different stages of hypertension progression. Significantly, findings from the multiple gene list meta-analysis suggested that FBXW4 and other 13 genes were unique to the hypertension group, and TRIM11 and other 40 genes were mainly involved in hypertension with the left ventricular remodeling group, while the other 18 genes including F13A1 significantly enriched in uncontrolled hypertension. Collectively, the precise switch of the "immune-metabolic-inflammatory" loop pathway was the most significant hallmark across different stages of hypertension, thereby providing a potential therapeutic target for uncontrolled hypertension treatment.

Modelling and discussion on emission reduction transformation path of China's electric power industry under "double carbon" goal.

China has promised to peak carbon emission before 2030 and to achieve carbon neutrality before 2060 (i.e., "double carbon" goal). Under this background, the emission reduction transformation path of China's electric power industry is studied in this paper. First, several boundary conditions (i.e., assumptions) of electric power structure transformation (i.e., the costs of power generations, the costs of energy storage systems, the developments of carbon sinks, the emission factors, and the quotas of carbon sinks) are given considering the whole society electricity consumption in the future. Second, a transformation path optimization model is established aim to minimize the total cost in the electric power industry. Then, according to the optimization results, the transformation predictions for the power industry under the "30·60 scenario" (i.e., the scenario that can achieve carbon peak and carbon neutrality before 2030 and 2060) are analyzed in detail, and are compared with the ones of "2 °C scenario" and "1.5 °C scenario" defined by IPCC. Furthermore, the influence of different carbon prices on the transformation path is also analyzed. It can be concluded from the simulation results that the "30·60 scenario" is a scenario between "2 °C scenario" and "1.5 °C scenario", and carbon emission can be reduced rapidly under the guidance of high carbon prices.

Bioinformatics analysis to obtain critical genes regulated in subcutaneous adipose tissue after bariatric surgery.

Bariatric surgery (BS) is a dependable method for managing obesity and metabolic diseases, however, the regulatory processes of lipid metabolism are still not well elucidated. Differentially expressed genes (DEGs) were analysed through three transcriptomic datasets of GSE29409, GSE59034 and GSE72158 from the GEO database regarding subcutaneous adipose tissue (SAT) after BS, and 37 DEGs were identified. The weighted gene co-expression network analysis (WGCNA), last absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine-recursive feature elimination (SVM-RFE) algorithms further screened four key genes involved in the regulation of STMN2, SFRP4, APOE and MXRA5. The GSE53376 dataset was used to further confirm the differential expression of SFRP4, APOE and MXRA5 in the postoperative period. GSEA analysis reveals activation of immune-related regulatory pathways after surgery. Finally, the silencing of MXRA5 was found by experimental methods to affect the expression of PPARγ and CEBPα during the differentiation of preadipocytes, as well as to affect the formation of lipid droplets. In conclusion, SAT immunoregulation was mobilized after BS, while MXRA5 was involved in the regulation of lipid metabolism.

Real-time automatic prediction of treatment response to transcatheter arterial chemoembolization in patients with hepatocellular carcinoma using deep learning based on digital subtraction angiography videos.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) is the mainstay of therapy for intermediate-stage hepatocellular carcinoma (HCC); yet its efficacy varies between patients with the same tumor stage. Accurate prediction of TACE response remains a major concern to avoid overtreatment. Thus, we aimed to develop and validate an artificial intelligence system for real-time automatic prediction of TACE response in HCC patients based on digital subtraction angiography (DSA) videos via a deep learning approach. METHODS: This retrospective cohort study included a total of 605 patients with intermediate-stage HCC who received TACE as their initial therapy. A fully automated framework (i.e., DSA-Net) contained a U-net model for automatic tumor segmentation (Model 1) and a ResNet model for the prediction of treatment response to the first TACE (Model 2). The two models were trained in 360 patients, internally validated in 124 patients, and externally validated in 121 patients. Dice coefficient and receiver operating characteristic curves were used to evaluate the performance of Models 1 and 2, respectively. RESULTS: Model 1 yielded a Dice coefficient of 0.75 (95% confidence interval [CI]: 0.73-0.78) and 0.73 (95% CI: 0.71-0.75) for the internal validation and external validation cohorts, respectively. Integrating the DSA videos, segmentation results, and clinical variables (mainly demographics and liver function parameters), Model 2 predicted treatment response to first TACE with an accuracy of 78.2% (95%CI: 74.2-82.3), sensitivity of 77.6% (95%CI: 70.7-84.0), and specificity of 78.7% (95%CI: 72.9-84.1) for the internal validation cohort, and accuracy of 75.1% (95% CI: 73.1-81.7), sensitivity of 50.5% (95%CI: 40.0-61.5), and specificity of 83.5% (95%CI: 79.2-87.7) for the external validation cohort. Kaplan-Meier curves showed a significant difference in progression-free survival between the responders and non-responders divided by Model 2 (p = 0.002). CONCLUSIONS: Our multi-task deep learning framework provided a real-time effective approach for decoding DSA videos and can offer clinical-decision support for TACE treatment in intermediate-stage HCC patients in real-world settings.

An Innovative Breast-Conserving Oncoplastic Technique for Treating Small to Medium Volume Breasts With a Tumor in the Lower Quadrant: The Folding Flap Technique.

Background: Here, we describe an innovative oncoplastic technique for small to medium volume breasts with a tumor in the lower quadrant and this technique could provide sufficient tissue to avoid visible defects after tumor removal and help reshape the natural shape of the breast. Methods: A detailed procedure for the folding flap technique is described step by step. Then, the results of a retrospective analysis of patients treated using this technique, including complications and disease recurrence rate, between January 2017 and November 2021 are reported. Aesthetic outcomes were evaluated on a 5-point scale proposed by the Paris Breast Center. Results: A total of 52 patients underwent surgery with the folding flap technique, The average operation time was 98.4 min (range, 75-120 min), and the mean bleeding volume was 56.5 mL (range, 20-100 mL). A margin-positive result was confirmed in 1 patient who underwent re-excision. Short-term postoperative complications were observed in 7 patients, including 4 with fat liquefaction, 2 with seroma, and 1 with skin redness and swelling. No flap necrosis was observed. The median follow-up time was 28.6 months (range, 9-58 months), and 2 patients experienced local recurrence. The mean aesthetic score was 4.7 points, with 36 patients scoring 5 points and 26 patients scoring 4 points, respectively. Conclusions: The folding flap technique, as an innovative and favorable oncoplastic technique for treating small- to medium-volume breasts with a tumor in the lower quadrant, could retain sufficient tissue to fill the residual cavity after the operation while improving the aesthetic outcome of the breast.

Notoginsenoside R1 relieves the myocardial infarction via activating the JAK2/STAT3 signaling pathway in vivo and in vitro.

Myocardial infarction (MI), caused by continuous ischemia and hypoxia of the coronary artery, is one of the major causes of human mortality. This study aimed to investigate the role of notoginsenoside R1 (NGR1) in MI therapy. In vitro and in vivo models of MI were established by hypoxia/reoxygenation (H/R)-treatment of H9C2 cells and through the ligation of the left anterior descending coronary artery of rats, respectively. CCK-8 and EdU assays were performed to measure cell viability and proliferation, respectively. Flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were performed to determine the apoptotic rate of cells. Western blot was used to determine protein expression. The MI area was analyzed by 2,3,5-triphenyltetrazolium chloride (TTC) staining. NGR1 promoted viability and proliferation, and inhibited the apoptotic rate of H/R-treated H9C2 cells. In addition, NGR1 downregulated the protein expression of caspase-3 and Bax, and upregulated Bcl-2 expression in H/R-treated H9C2 cells. The JAK2/STAT3 signaling pathway was activated following NGR1 treatment in vivo and in vitro, and inhibition of the JAK2/STAT3 signaling pathway reversed the effects of NGR1 on H/R-treated H9C2 cells. Finally, NGR1 reduced the area of MI. NGR1 relieved MI in vivo and in vitro by activating the JAK2/STAT3 signaling pathway.

Functional New Transcription Factors (TFs) Associated with Cervical Cancer.

The goal of this research was to find noval transcription factors (TFs) that are involved in cervical carcinogenesis. The Gene Expression Omnibus (GEO) database was utilized to analyze ten cervical cancer datasets using the Robust Rank Aggregation (RRA) technique. Survival and differential expression were validated using GEPIA (Gene Expression Profiling Interactive Analysis). The transcriptional regulatory network and putative targets were built using Cytoscape. A real-time PCR (quantitative real-time polymerase chain reaction) experiment was used to confirm the mRNA expression. Using public cervical cancer single-cell RNA-sequencing (scRNA-seq), bulk TCGA-CESC RNA-seq, and microarray datasets, coexpression correlations between putative targets and TFs were confirmed. After combining the results of 10 datasets, 8 TFs, including EMX2 (Empty Spiracles Homeobox 2), were chosen among 385 robust DEGs. In the normal female reproductive tract, EMX2 is extensively expressed, but it is reduced in cervical cancer. Overexpression EMX2 suppresses the proliferation of HeLa cells. 12 potential targets of EMX2 were selected. Our research has revealed evidence that EMX2 acted as a tumor suppressor in cervical cancer and PDZRN3 might be possible target of EMX2 in cervical cancer. It might be a therapeutic target in the future.

Copper-induced tumor cell death mechanisms and antitumor theragnostic applications of copper complexes.

Recent studies found that unbalanced copper homeostasis affect tumor growth, causing irreversible damage. Copper can induce multiple forms of cell death, including apoptosis and autophagy, through various mechanisms, including reactive oxygen species accumulation, proteasome inhibition, and antiangiogenesis. Hence, copper in vivo has attracted tremendous attention and is in the research spotlight in the field of tumor treatment. This review first highlights three typical forms of copper's antitumor mechanisms. Then, the development of diverse biomaterials and nanotechnology allowing copper to be fabricated into diverse structures to realize its theragnostic action is discussed. Novel copper complexes and their clinical applications are subsequently described.

Effect of Ginsenoside Rh1 on Proliferation, Apoptosis, and Oxidative Stress in Vascular Endothelial Cells by Regulation of the Nuclear Erythroid 2-related Factor-2/Heme Oxygenase-1 Signaling Pathway.

ABSTRACT: This study aimed to investigate the role of ginsenoside Rh1 in regulating the proliferation, apoptosis, and oxidative stress in oxidized low-density lipoprotein (ox-LDL)-treated human vascular endothelial cells (VECs) and the underlying mechanisms. VECs were treated with ox-LDL to generate an in vitro atherosclerosis model. The effect of ginsenoside Rh1 on cell viability and proliferation was examined by MTT and colony formation assays, respectively, and cell apoptosis was determined by flow cytometry and transferase dUTP nick end-labeling assay. The levels of reactive oxygen species, malondialdehyde, and superoxide dismutase activity were detected using biological assays. Finally, the effect of ginsenoside Rh1 on the levels of BAX and BCL-2 and the nuclear erythroid 2-related factor-2/heme oxygenase (HO)-1 signaling pathway was determined by quantitative real-time polymerase chain reaction and western blot assays. Treatment with ginsenoside Rh1 significantly increased the proliferation and decreased the apoptosis of ox-LDL-treated VECs in a dose-dependent manner. Moreover, ginsenoside Rh1 also relieved oxidative stress in ox-LDL-treated VECs by activating the Nrf2/HO-1 signaling pathway. Thus, ginsenoside Rh1 affects the proliferation, apoptosis, and oxidative stress in ox-LDL-treated VECs by activating the Nrf2/HO-1 signaling pathway.

Periodic offset boosting for attractor self-reproducing.

The special regime of multistability of attractor self-reproducing is deeply decoded based on the conception of offset boosting in this letter. Attractor self-reproducing is essentially originated from periodic initial condition-triggered offset boosting. Typically, a trigonometric function is applied for attractor self-reproducing. The position, size, and clone frequency determine the selected periodic function. Specifically, in-depth investigation on three elements of sinusoidal quantity is taken into account and then a universal law of attractor self-reproducing is built: the original position of an attractor determines the initial phase and the size of attractor sets the amplitude, while the reproducing interval between two attractors determines the frequency of the trigonometric function. It is found that the product of amplitude and frequency is a constant determined by the reproducing periodic function. The positive and negative switching of the slope in sinusoidal function also leads to the waste of phase space since in general there is no attractor reproduced at the region with negative slope except that new polarity balance is reconstructed paying back the attractor with conditional symmetry. Three-element-oriented offset boosting makes attractor self-reproducing more designable, achievable, and adjustable, which brings great convenience to engineering applications.

An innovative oncoplastic technique for immediate small to medium volume breast reconstruction in lower inner quadrant cancer: The Zhuo-technique.

BACKGROUND: Insufficient glandular tissue in the lower quadrant of the breast is the main source of difficulty in repairing defects after oncoplastic surgery. Especially in small to medium sized breasts, this issue is more common. Here, we describe a novel oncoplastic approach that could help to solve this problem. MATERIALS AND METHODS: Retrospective analysis of breast cancer patients with tumors in the lower inner quadrants, who underwent Zhuo's technique between January 2017 and August 2019. Aesthetic outcomes were evaluated in terms of the Paris Breast Center's 5-point scale. The work was reported according to the STROCSS criteria. RESULTS: Nine patients (mean age 54 years) with small to medium volume breast received Zhuo's oncoplastic technique after tumor excision. The mean size tumor was 18.0 mm. The median follow-up time was 27.0 months. Sentinel lymph node biopsy results for all patients were negative. None of the patients had local recurrences or metastases and postoperative complications were not observed. Seven patients (77.8%) achieved aesthetic scores of 5 and two patients (22.2%) achieved 4 points. CONCLUSIONS: Zhuo's oncoplastic technique could provide a favorable and flexible surgical approach for small to medium volume breast with tumors of the lower inner quadrant with a low risk of recurrence and good aesthetic results. PROTOCOL REGISTER: Chinese clinical trial register No. ChiCTR2100043484.