Analysis Using Various Models on the Effect of Metabolic Surgery on Cardiovascular Disease Risk in the Chinese Population with Obesity.

Background: Some research have indicated that Bariatric and metabolic surgery (BMS) can reduce the risk of cardiovascular disease (CVD) among individuals with obesity. However, there are few reports available that focuses on assessing effect of BMS on the risk of CVD in Chinese population using multiple models. Objective: This research aims to assess the function of BMS on the risk of CVD in Chinese patients with obesity using multiple CVD risk models. Methods: We performed a retrospective analysis of the basic data and glycolipid metabolism data preoperatively and postoperatively from patients with obesity at our hospital. Subgroup analysis was carried out according to different surgical procedures. Then, the function of BMS on the risk of CVD in the Chinese population was assessed using four models, including: China-PAR risk model, Framingham risk score (FRS), World Health Organization (WHO) risk model, and Globorisk model. Results: We enrolled 64 patients, 24 (37.5%) of whom underwent laparoscopic sleeve gastrectomy (LSG) while 40 (62.5%) underwent Roux-en-Y gastric bypass (RYGB). The 10-year CVD risk for patients calculated using the China-PAR risk model decreased from 6.3% preoperatively to 2.0% at 1 year postoperatively and was statistically significantly different. Similarly, the 10-year CVD risk of patients calculated using the FRS, WHO, Global risk model decreased significantly at 1 year postoperatively compared to preoperatively. When the FRS risk model was used to calculate the patients' 30-year postoperative CVD risk, there was a significant decrease at 1 year after surgery compared to the preoperative period. When employing various models to evaluate the 10-year CVD risk for LSG and RYGB, no statistically significant difference was found in the 1-year postoperative RRR between the procedures. Conclusion: The CVD risk after BMS was significantly reduced compared to preoperatively. In terms of improving cardiovascular risk, SG and RYGB appear to be equally effective.

Enhanced Prediction of Malignant Cerebral Edema in Large Vessel Occlusion with Successful Recanalization Through Automated Weighted Net Water Uptake.

BACKGROUND: Malignant cerebral edema (MCE) is associated with both net water uptake (NWU) and infarct volume. We hypothesized that NWU weighted by the affected Alberta Stroke Program Early Computed Tomography Score (ASPECTS) regions could serve as a quantitative imaging biomarker of aggravated edema development in acute ischemic stroke with large vessel occlusion (LVO). The aim of this study was to evaluate the performance of weighted NWU (wNWU) to predict MCE in patients with mechanical thrombectomy (MT). METHODS: We retrospectively analyzed consecutive patients who underwent MT due to LVO. NWU was computed from nonenhanced computed tomography scans upon admission using automated ASPECTS software. wNWU was derived by multiplying NWU with the number of affected ASPECTS regions in the ischemic hemisphere. Predictors of MCE were assessed through multivariate logistic regression analysis and receiver operating characteristic curves. RESULTS: NWU and wNWU were significantly higher in MCE patients than in non-MCE patients. Vessel recanalization status influenced the performance of wNWU in predicting MCE. In patients with successful recanalization, wNWU was an independent predictor of MCE (adjusted odds ratio 1.61; 95% confidence interval [CI] 1.24-2.09; P < 0.001). The model integrating wNWU, National Institutes of Health Stroke Scale, and collateral score exhibited an excellent performance in predicting MCE (area under the curve 0.80; 95% CI 0.75-0.84). Among patients with unsuccessful recanalization, wNWU did not influence the development of MCE (adjusted odds ratio 0.99; 95% CI 0.60-1.62; P = 0.953). CONCLUSIONS: This study revealed that wNWU at admission can serve as a quantitative predictor of MCE in LVO with successful recanalization after MT and may contribute to the decision for early intervention.

Glutathione Depletion-Induced ROS/NO Generation for Cascade Breast Cancer Therapy and Enhanced Anti-Tumor Immune Response.

Introduction: As an effective alternative choice to traditional mono-therapy, multifunctional nanoplatforms hold great promise for cancer therapy. Based on the strategies of Fenton-like reactions and reactive oxygen species (ROS)-mediated therapy, black phosphorus (BP) nanoplatform BP@Cu2O@L-Arg (BCL) co-assembly of cuprous oxide (Cu2O) and L-Arginine (L-Arg) nanoparticles was developed and evaluated for synergistic cascade breast cancer therapy. Methods: Cu2O particles were generated in situ on the surface of the BP nanosheets, followed by L-Arg incorporation through electrostatic interactions. In vitro ROS/nitric oxide (NO) generation and glutathione (GSH) depletion were evaluated. In vitro and in vivo anti-cancer activity were also assessed. Finally, immune response of BCL under ultrasound was investigated. Results: Cu2O was incorporated into BP to exhaust the overexpressed intracellular GSH in cancer cells via the Fenton reaction, thereby decreasing ROS consumption. Apart from being used as biocompatible carriers, BP nanoparticles served as sonosensitizers to produce excessive ROS under ultrasound irradiation. The enhanced ROS accumulation accelerated the oxidation of L-Arg, which further promoted NO generation for gas therapy. In vitro experiments revealed the outstanding therapeutic killing effects of BCL under ultrasound via mechanisms involving GSH deletion and excessive ROS and NO generation. In vivo studies have illustrated that the nanocomplex modified the immune response by promoting macrophage and CD8+ cell infiltration and inhibiting MDSC infiltration. Discussion: BCL nanoparticles exhibited multifunctional characteristics for GSH depletion-induced ROS/NO generation, making a new multitherapy strategy for cascade breast cancer therapy.

Effect of Operating Room Care Based on Wutong Mode on Anxiety and Depression of Patients Undergoing Abdominal Surgery: A Single-Center Retrospective Study.

BACKGROUND: The existence of anxiety and depression is not conducive to the rehabilitation of patients, so it is particularly important to apply reasonable and effective nursing methods in operating room to calm the negative emotions of patients. This study aimed to investigate the impact of operating room care utilizing the Wutong mode on the anxiety and depression levels of patients undergoing abdominal surgery.  Methods: The study included 167 patients who underwent abdominal surgery at our hospital from April 2021 to April 2023. These individuals were selected as the research subjects. Based on distinct perioperative management programs, the patients were categorized into the control group (comprising 85 patients receiving conventional perioperative management) and the study group (consisting of 82 patients undergoing operating room care based on the Wutong mode). Comprehensive baseline data, as well as scores from the Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory (BDI), Self-Rating Anxiety Scale (SAS), General Self-Efficacy Scale-6 (GSE-6), and Short-Form-36 Health Survey (SF-36), were collected from all participants. A comparative analysis was performed on sleep status, depression levels, anxiety levels, self-efficacy, and quality of life between the two groups.  Results: Following the intervention, the PSQI scores, as well as BDI and SAS scores of patients in both groups, were significantly reduced compared to pre-intervention levels (p < 0.001). Notably, the study group exhibited markedly lower PSQI scores, BDI scores, and SAS scores compared to the control group post-intervention (p < 0.001). Additionally, the GSE-6 scores of patients in both groups showed a substantial increase after the intervention compared to pre-intervention levels (p < 0.001). The study group demonstrated significantly higher GSE-6 scores and SF-36 scores than the control group after the intervention (p < 0.001).  Conclusion: The Wutong mode-based operating room care has a pronounced impact on patients undergoing abdominal surgery, demonstrating clear clinical application value. This finding offers valuable insights for the development and selection of perioperative nursing plans for patients, providing a significant reference point for healthcare practitioners.

Prevalence, Risk Factors, and Metabolic Characteristics of Metabolically Healthy Obesity in Patients Seeking Bariatric Surgery: A Cohort Study.

BACKGROUND: Bariatric surgery is an effective treatment for morbid obesity. However, a subset of individuals seeking bariatric surgery may exhibit a metabolically healthy obesity (MHO) phenotype, suggesting that they may not experience metabolic complications despite being overweight. OBJECTIVE: This study aimed to determine the prevalence and metabolic features of MHO in a population undergoing bariatric surgery. METHODS: A representative sample of 665 participants aged 14 or older who underwent bariatric surgery at our center from January 1, 2010 to January 1, 2020 was included in this cohort study. MHO was defined based on specific criteria, including blood pressure, waist-to-hip ratio, and absence of diabetes. RESULTS: Among the 665 participants, 80 individuals (12.0%) met the criteria for MHO. Female gender (P = .021) and younger age (P < .001) were associated with a higher likelihood of MHO. Smaller weight and BMI were observed in individuals with MHO. However, a considerable proportion of those with MHO exhibited other metabolic abnormalities, such as fatty liver (68.6%), hyperuricemia (55.3%), elevated lipid levels (58.7%), and abnormal lipoprotein levels (88%). CONCLUSION: Approximately 1 in 8 individuals referred for bariatric surgery displayed the phenotype of MHO. Despite being metabolically healthy based on certain criteria, a significant proportion of individuals with MHO still exhibited metabolic abnormalities, such as fatty liver, hyperuricemia, elevated lipid levels, and abnormal lipoprotein levels, highlighting the importance of thorough metabolic evaluation in this population.

Single-cell landscape of the cellular microenvironment in three different colonic polyp subtypes in children.

BACKGROUND: The understanding of the heterogeneous cellular microenvironment of colonic polyps in paediatric patients with solitary juvenile polyps (SJPs), polyposis syndrome (PJS) and Peutz-Jeghers syndrome (PJS) remains limited. METHODS: We conducted single-cell RNA sequencing and multiplexed immunohistochemistry (mIHC) analyses on both normal colonic tissue and different types of colonic polyps obtained from paediatric patients. RESULTS: We identified both shared and disease-specific cell subsets and expression patterns that played important roles in shaping the unique cellular microenvironments observed in each polyp subtype. As such, increased myeloid, endothelial and epithelial cells were the most prominent features of SJP, JPS and PJS polyps, respectively. Noticeably, memory B cells were increased, and a cluster of epithelial-mesenchymal transition (EMT)-like colonocytes existed across all polyp subtypes. Abundant neutrophil infiltration was observed in SJP polyps, while CX3CR1hi CD8+ T cells and regulatory T cells (Tregs) were predominant in SJP and JPS polyps, while GZMAhi natural killer T cells were predominant in PJS polyps. Compared with normal colonic tissues, myeloid cells exhibited specific induction of genes involved in chemotaxis and interferon-related pathways in SJP polyps, whereas fibroblasts in JPS polyps had upregulation of myofiber-associated genes and epithelial cells in PJS polyps exhibited induction of a series of nutrient absorption-related genes. In addition, the TNF-α response was uniformly upregulated in most cell subsets across all polyp subtypes, while endothelial cells and fibroblasts separately showed upregulated cell adhesion and EMT signalling in SJP and JPS polyps. Cell-cell interaction network analysis showed markedly enhanced intercellular communication, such as TNF, VEGF, CXCL and collagen signalling networks, among most cell subsets in polyps, especially SJP and JPS polyps. CONCLUSION: These findings strengthen our understanding of the heterogeneous cellular microenvironment of polyp subtypes and identify potential therapeutic approaches to reduce the recurrence of polyps in children.

Giant lipoma in the Retzius space resected under laparoscopy: A case report.

Lipoma is a common type of benign soft tissue tumor that can occur in the shoulders, neck and back, in addition to other body parts. The Retzius space is a small anatomical space between the pubic symphysis and the bladder located extraperitoneally and filled with loose fatty connective tissue. Giant lipomas are rare in the Retzius space. A 61-year-old Chinese male arrived at Beijing Yanhua Hospital (Beijing, China) due to frequent urination, and CT scan images of the lower abdomen observed a large pelvic mass and left inguinal hernia. Preoperative clinical manifestations and auxiliary examination suggested that the tumor originated from the urinary bladder wall. The maximum tumor diameter was ~25 cm and abdominal pressure was increased. Therefore, laparoscopic pelvic tumor resection combined with inguinal hernia repair was attempted. Intraoperatively, the tumor was found to originate from the Retzius space and the postoperative pathological diagnosis was lipoma. The present case report may serve as a reference for minimally invasive treatment of this type of rare disease in future.

An overview of 6-shogaol: new insights into its pharmacological properties and potential therapeutic activities.

Ginger (Zingiber officinale Roscoe) has traditionally been used as a cooking spice and herbal medicine for treating nausea and vomiting. More recently, ginger was found to effectively reduce the risk of diseases such as gastroenteritis, migraine, gonarthritis, etc., due to its various bioactive compounds. 6-Shogaol, the pungent phenolic substance in ginger, is the most pharmacologically active among such compounds. The aim of the present study was to review the pharmacological characteristic of 6-shogaol, including the properties of anti-inflammatory, antioxidant and antitumour, and its corresponding molecular mechanism. With its multiple mechanisms, 6-shogaol is considered a beneficial natural compound, and therefore, this review will shed some light on the therapeutic role of 6-shogaol and provide a theoretical basis for the development and clinical application of 6-shogaol.

Conjugated Molecules Based Multi-Component Artificial Photosynthesis System for Producing Multi-Objective Products.

The development of artificial photosynthesis systems that mimics natural photosynthesis can help address the issue of energy scarcity by efficiently utilizing solar energy. Here, it presents liposomes-based artificial photosynthetic nanocapsules (PSNC) integrating photocatalytic, chemical catalytic, and biocatalytic systems through one-pot method. The PSNC contains 5,10,15,20-tetra(4-pyridyl) cobalt-porphyrin, tridipyridyl-ruthenium nitrate, oligo-pphenyl-ethylene-rhodium complex, and creatine kinase, efficiently generating oxygen, nicotinamide adenine dinucleotide (NADH), and adenosine triphosphate with remarkable enhancements of 231%, 30%, and 86%, compared with that of molecules mixing in aqueous solution. Additionally, the versatile PSNC enables simulation of light-independent reactions, achieving a controllable output of various target products. The regenerated NADH within PSNC further facilitates alcohol dehydrogenase, yielding methanol with a notable efficiency improvement of 37%. This work introduces a promising platform for sustainable solar energy conversion and the simultaneous synthesis of multiple valuable products in an ingenious and straightforward way.

Comparison of various prediction models in the effect of Roux-en-Y gastric bypass on type 2 diabetes in the Chinese population 5 years after surgery.

BACKGROUND: Various prediction models of type 2 diabetes (T2D) remission have been externally verified internationally. However, long-term validated results after Roux-en-Y gastric bypass (RYGB) surgery are lacking. The best model for the Chinese population is also unknown. OBJECTIVES: To evaluate the prediction effect of various prediction models on the long-term diabetes remission after RYGB in the Chinese population and to provide reference for clinical use. SETTING: A retrospective clinical study at a university hospital. METHODS: We retrospectively analyzed Chinese population data 5 years after RYGB and externally validated 11 predictive models to evaluate the predictive effect of each model on long-term T2D remission after RYGB. RESULTS: We enrolled 84 patients. The mean body mass index was 41 kg/m2, and the percentage of excess weight loss (%EWL) was 72.3%. The mean glycated hemoglobin level was 8.4% preoperatively and decreased to 5.9% after 5 years. The 5-year postoperative complete and partial remission rates of T2D were 31% and 70.2%, respectively. The ABCD scoring model (sensitivity, 84%; specificity, 76%; area under the curve [AUC], .866) and the Panuzi et al. [34] study (sensitivity, 84%; specificity, 81%; AUC, .842) showed excellent results. In the Hosmer-Lemeshow goodness-of-fit test, calibration values for ABCD and Panuzi et al. [34] were .14 and .21, respectively. The predicted-to-observed ratios of ABCD and Panuzi et al. [34] were .83 and .88, respectively. CONCLUSIONS: T2D was relieved to varying degrees 5 years after RYGB in patients with obesity. The prediction models in ABCD and the Panuzi et al. [34] studies showed the best prediction effects. ABCD was recommended for clinical use because of excellent predictive performance, good statistical test results, and simple and practical design features.

Myricitrin promotes osteogenesis and prevents ovariectomy bone mass loss via the PI3K/AKT signalling pathway.

This study aimed to explore the effect of myricitrin on osteoblast differentiation in mice immortalised bone marrow mesenchymal stem cells (imBMSCs). Additionally, ovariectomy (OVX) mice were employed to examine the effect of myricitrin on bone trabecular loss in vivo. The effect of myricitrin on the proliferation of imBMSCs was evaluated using a cell counting kit-8 assay. Alizarin red staining, alkaline phosphatase staining were performed to elucidate osteogenesis. Furthermore, qRT-PCR and western blot determined the expression of osteo-specific genes and proteins. To screen for candidate targets, mRNA transcriptome genes were sequenced using bioinformatics analyses. Western blot and molecular docking analysis were used to examine target signalling markers. Moreover, rescue experiments were used to confirm the effect of myricitrin on the osteogenic differentiation of imBMSCs. OVX mice were also used to estimate the delay capability of myricitrin on bone trabecular loss in vivo using western blot, micro-CT, tartaric acid phosphatase (Trap) staining, haematoxylin and eosin staining, Masson staining and immunochemistry. In vitro, myricitrin significantly enhanced osteo-specific genes and protein expression and calcium deposition. Moreover, mRNA transcriptome gene sequencing and molecular docking analysis revealed that this enhancement was accompanied by an upregulation of the PI3K/AKT signalling pathway. Furthermore, copanlisib, a PI3K inhibitor, partially reversed the osteogenesis promotion induced by myricitrin. In vivo, western blot, micro-CT, hematoxylin and eosin staining, Masson staining, Trap staining and immunochemistry revealed that bone trabecular loss rate was significantly alleviated in the myricitrin low- and high-dose groups, with an increased expression of osteopontin, osteoprotegerin, p-PI3K and p-AKT compared to the OVX group. Myricitrin enhances imBMSC osteoblast differentiation and attenuate bone mass loss partly through the upregulation of the PI3K/AKT signalling pathway. Thus, myricitrin has therapeutic potential as an antiosteoporosis drug.

A dual-nanozyme-loaded black phosphorus multifunctional therapeutic platform for combined photothermal/photodynamic/starvation cancer therapy.

The typical hypoxia of tumor microenvironments seriously affects the efficacy of starvation therapy (ST) and photodynamic therapy (PDT). Therefore, it is of great significance to prepare a multimodal combined therapy nanocomposite with the ability to relieve tumor hypoxia. It is an effective method to release oxygen into the tumor microenvironment using a nanoenzyme. In this work, two-dimensional black phosphorus nanosheets (BPNSs) were used as photothermal reagents and photosensitized agents due to the unique physical properties and also used as nano-carriers for the in situ reduction deposition of Au nanoparticles and fragmented MnO2 coatings. Finally, polyethylene glycol was introduced to obtain the nanocomposite BP@Au@MnO2-PEG (i.e., AMGP). In the tumor microenvironment, MnO2 can catalyze endogenous H2O2 to produce oxygen, improving the effect of ST and PDT. H2O2 generated via the catalytic oxidation of glucose by Au nanoparticles can continue to be used as the substrate catalyzed by MnO2. Meanwhile, black phosphorus nanosheets have excellent photothermal properties for photothermal treatment. The results of in vitro and in vivo experiments indicated that AMGP nanocomposites have good combined antitumor efficacies and biosafety.

ROS Generative Black Phosphorus-Tamoxifen Nanosheets for Targeted Endocrine-Sonodynamic Synergistic Breast Cancer Therapy.

Introduction: Tamoxifen (TAM) has proven to be a therapeutic breakthrough to reduce mortality and recurrence in estrogen receptor-positive (ER+) breast cancer patients. However, the application of TAM exhibits low bioavailability, off-target toxicity, instinct and acquired TAM resistance. Methods: We utilized black phosphorus (BP) as a drug carrier and sonosensitizer, integrated with TAM and tumor-targeting ligand folic acid (FA) to construct TAM@BP-FA for synergistic endocrine and sonodynamic therapy (SDT) of breast cancer. The exfoliated BP nanosheets were modified through in situ polymerization of dopamine, followed by electrostatic adsorption of TAM and FA. The anticancer effect of TAM@BP-FA was evaluated through in vitro cytotoxicity and in vivo antitumor model. RNA-sequencing (RNA-seq), quantitative real-time PCR, Western blot analysis, flow cytometry analysis and peripheral blood mononuclear cells (PBMCs) analysis were performed for mechanism investigation. Results: TAM@BP-FA had satisfactory drug loading capacity, the TAM release behavior can be controlled through pH microenvironment and ultrasonic stimulation. An amount of hydroxyl radical (∙OH) and singlet oxygen (1O2) were as expected generated under ultrasound stimulation. TAM@BP-FA nanoplatform showed excellent internalization in both TAM-sensitive MCF7 and TAM-resistant (TMR) cells. Using TMR cells, TAM@BP-FA displayed significantly enhanced antitumor ability in comparison with TAM (7.7% vs 69.6% viability at 5µg/mL), the additional SDT further caused 15% more cell death. RNA-seq unraveled the TAM@BP-FA antitumor mechanisms including effects on cell cycle, apoptosis and cell proliferation. Further analysis showed additional SDT successfully triggering reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) reduction. Moreover, PBMCs exposed to TAM@BP-FA induced an antitumor immune response by natural killer (NK) cell upregulation and immunosuppression macrophage reduction. Conclusion: The novel BP-based strategy not only delivers TAM specifically to tumor cells but also exhibits satisfactory antitumor effects through targeted therapy, SDT, and immune cell modulation. The nanoplatform may provide a superior synergistic strategy for breast cancer therapy.

Establishment of a Nomogram Based on Inflammatory Response-Related Methylation Sites in Intraoperative Visceral Adipose Tissue to Predict EWL% at One Year After LSG.

Background: Laparoscopic sleeve gastrectomy (LSG) is considered as an effective bariatric and metabolic surgery for patients with severe obesity. Chronic low-grade inflammation of adipose tissue is associated with obesity and obesity-related complications. Objective: This study intends to establish a nomogram based on inflammatory response-related methylation sites in intraoperative visceral adipose tissue (VAT) to predict excess weight loss (EWL)% at one-year after LSG. Methods: Based on EWL% at one-year after LSG, patients were divided into two groups: the satisfied group (group-A, EWL%≥50%) and the unsatisfied group (group-B, EWL%<50%). Next, we defined genes corresponding to the methylation sites in the 850 K methylation microarray as methylation-related genes (MRGs). We then took the intersection of MRGs and inflammatory response-related genes. After that, inflammatory response-related methylation sites were identified based on overlapping genes. Moreover, difference analysis was carried out to obtain inflammatory response-related differentially methylated sites (IRRDMSs) between group-A and group-B. LASSO analysis was used to identify the hub methylation sites. Finally, we developed a nomogram based on the hub methylation sites. Results: There were 26 patients in the study, with 13 in group-A and 13 in group-B. After data filtering and difference analysis, 200 IRRDMSs were identified (143 hypermethylated sites and 57 hypomethylated sites). Then, we identified three hub methylation sites (cg03610073, cg03208951, and cg18746357) by LASSO analysis and built a predictive nomogram (Area under the curve=0.953). Conclusion: The predictive nomogram based on three inflammatory-related methylation sites (cg03610073, cg03208951, and cg18746357) in intraoperative visceral adipose tissue can predict one-year EWL% after LSG effectively.

Network Pharmacology and Molecular Docking Analysis on Molecular Targets and Mechanisms of Fei Jin Sheng Formula in the Treatment of Lung Cancer.

BACKGROUND: Fei Jin Sheng Formula (FJSF) is widely used in clinical treatment of lung cancer. But the underlying active ingredients and mechanisms are unclear. OBJECTIVE: To investigate the active components and functional mechanisms of FJSF in treating lung cancer using a network pharmacology approach and molecular docking combined with vitro experiments Methods: Based on the TCMSP and related literature, the chemical components of related herbs in FJSF were collected. The active components of FJSF were screened by ADME parameters, and the targets were predicted by the Swiss Target Prediction database. The "drug-active ingredient-target" network was constructed by Cytoscape. Disease-related targets of lung cancer were acquired from GeneCards, OMIM, and TTD databases. Then drug-disease intersection target genes were obtained through the Venn tool. GO analysis and KEGG pathway enrichment analysis were performed via the Metascape database. Cytoscape was used to construct a PPI network and perform topological analysis. Kaplan-Meier Plotter was used to analyze the relationship between DVL2 and the prognosis of lung cancer patients. xCell method was used to estimate the relationship between DVL2 and immune cell infiltration in lung cancer. Molecular docking was performed by AutoDockTools-1.5.6. The results were verified by experiments in vitro. RESULTS: FJSF contained 272 active ingredients and 52 potential targets for lung cancer. GO enrichment analysis is mainly related to cell migration and movement, lipid metabolism, and protein kinase activity. KEGG pathway enrichment analysis mainly involves PI3K-Akt, TNF, HIF-1, and other pathways. Molecular docking shows that the compound Xambioona, quercetin and methyl palmitate in FJSF has a strong binding ability with NTRK1, APC, and DVL2. Analysis of the data in UCSC to analyze the expression of DVL2 in lung cancer shows that DVL2 was overexpressed in lung adenocarcinoma tissues. Kaplan-Meier analysis shows that the higher DVL2 expression in lung cancer patients was associated with poorer overall survival and poorer survival in stage I patients. It was negatively correlated with the infiltration of various immune cells in the lung cancer microenvironment. Vitro Experiment showed that Methyl Palmitate (MP) can inhibit the proliferation, migration, and invasion of lung cancer cells, and its mechanism of action may be to downregulate the expression of DVL2. CONCLUSION: FJSF may play a role in inhibiting the occurrence and development of lung cancer by downregulating the expression of DVL2 in A549 cells through its active ingredient Methyl Palmitate. These results provide scientific evidence for further investigations into the role of FJSF and Methyl Palmitate in the treatment of lung cancer.

Rosuvastatin suppresses TNF-α-induced matrix catabolism, pyroptosis and senescence via the HMGB1/NF-κB signaling pathway in nucleus pulposus cells.

Intervertebral disc degeneration is mainly caused by irregular matrix metabolism in nucleus pulposus cells and involves inflammatory factors such as TNF-α. Rosuvastatin, which is widely used in the clinic to reduce cholesterol levels, exerts anti-inflammatory effects, but whether rosuvastatin participates in IDD remains unclear. The current study aims to investigate the regulatory effect of rosuvastatin on IDD and the potential mechanism. In vitro experiments demonstrate that rosuvastatin promotes matrix anabolism and suppresses catabolism in response to TNF-α stimulation. In addition, rosuvastatin inhibits cell pyroptosis and senescence induced by TNF-α. These results demonstrate the therapeutic effect of rosuvastatin on IDD. We further find that HMGB1, a gene closely related to cholesterol metabolism and the inflammatory response, is upregulated in response to TNF-α stimulation. HMGB1 inhibition or knockdown successfully alleviates TNF-α-induced ECM degradation, senescence and pyroptosis. Subsequently, we find that HMGB1 is regulated by rosuvastatin and that its overexpression abrogates the protective effect of rosuvastatin. We then verify that the NF-κB pathway is the underlying pathway regulated by rosuvastatin and HMGB1. In vivo experiments also reveal that rosuvastatin inhibits IDD progression by alleviating pyroptosis and senescence and downregulating HMGB1 and p65. This study might provide new insight into therapeutic strategies for IDD.

An Assessment of the Effect of Bariatric Surgery on Cardiovascular Disease Risk in the Chinese Population Using Multiple Cardiovascular Risk Models.

Background: Many studies have reported that bariatric surgery may reduce postoperative cardiovascular risk in patient with obesity, but few have addressed this risk in the Chinese population. Objective: To assess the impact of bariatric surgery on cardiovascular disease (CVD) risk in the Chinese population using the World Health Organization (WHO) risk model, the Global risk model, and the Framingham Risk Score. Methods: We retrospectively analyzed data collected on patient with obesity who underwent bariatric surgery at our institution between March 2009 and January 2021. Their demographic characteristics, anthropometric variables, and glucolipid metabolic parameters were assessed preoperatively and at their 1-year postoperative follow-up. Subgroup analysis compared body mass index (BMI) < 35 kg/m2 and BMI ≥ 35 kg/m2, as well as gender. We used the 3 models to calculate their CVD risk. Results: We evaluated 61 patients, of whom 26 (42.62%) had undergone sleeve gastrectomy (SG) surgery and 35 (57.38%) Roux-en-Y gastric bypass (RYGB) surgery. Of the patients with BMI ≥ 35 kg/m2, 66.67% underwent SG, while 72.97% with BMI < 35 kg/m2 underwent RYGB. HDL levels were significantly higher at 12 months postoperatively relative to baseline. When the models were applied to calculate CVD risk in Chinese patients with obesity, the 1-year CVD risk after surgery were reduced lot compared with the preoperative period. Conclusion: Patient with obesity had significantly lower CVD risks after bariatric surgery. This study also demonstrates that the models are reliable clinical tools for assessing the impact of bariatric surgery on CVD risk in the Chinese population.

Solar-powered multi-organism symbiont mimic system for beyond natural synthesis of polypeptides from CO2 and N2.

Developing artificial symbionts beyond natural synthesis limitations would bring revolutionary contributions to agriculture, medicine, environment, etc. Here, we initiated a solar-driven multi-organism symbiont, which was assembled by the CO2 fixation module of Synechocystis sp., N2 fixation module of Rhodopseudomonas palustris, biofunctional polypeptides synthesis module of Bacillus licheniformis, and the electron transfer module of conductive cationic poly(fluorene-co-phenylene) derivative. The modular design broke the pathway to synthesize γ-polyglutamic acid (γ-PGA) using CO2 and N2, attributing to the artificially constructed direct interspecific substance and electron transfer. So, the intracellular ATP and NADPH were enhanced by 69 and 30%, respectively, and the produced γ-PGA was enhanced by 104%. The strategy was further extended to produce a commercial antibiotic of bacitracin A. These achievements improve the selectivity and yield of functional polypeptides with one click by CO2 and N2, and also provide an innovative strategy for creating photosynthetic systems on demand.

Effects of CX3CR1 and CXCR2 antagonists on running-dependent intramuscular neutrophil recruitments and myokine upregulation.

Muscle contractile activity stimulates intramuscular recruitment of immune cells including neutrophils emerging to serve as a prerequisite for exerting proper muscular performance, although the underlying mechanisms and their contributions to myokine upregulation remain ill-defined. We previously reported that pharmacological inhibition of CX3CR1, a fractalkine receptor, dampens gnawing-dependent neutrophil recruitment into masseter muscles along with compromising their masticatory activity. By using a running exercise model, we herein demonstrated that hindlimb muscles require collaborative actions of both CX3CR1- and CXCR2-mediated signals for achieving neutrophil recruitment, upregulation of myokines including interleukin (IL)-6, enhanced GLUT4 translocation, and adequate endurance capability. Mechanistically, we revealed that a combination of CX3CR1 and CXCR2 antagonists, i.e., AZD8797 and SB2205002, inhibits exercise-inducible ICAM-1 and fractalkine upregulations in the area of the endothelium and muscle-derived CXCL1 upregulation, both of which apparently contribute to the intramuscular neutrophil accumulation in working muscles. Intriguingly, we also observed that 2 h of running results in intramuscular augmentation of innate lymphoid type 2 cells (ILC2s) markers, i.e., Bcl11b mRNA levels and anti-GATA-3-antibody-positive signals, and that these effects are completely abolished by administration of the combination of CX3CR1 and CXCR2 antagonists. Taken together, our findings strongly suggest that the exercise-evoked regional interplay among working myofibers, the adjacent endothelium, and recruited immune cells including neutrophils and possibly ILC2s, mediated through these local factors, plays a key role in the organization of the intramuscular microenvironment supporting the performance of hindlimb muscles during running.NEW & NOTEWORTHY This study provides compelling evidence that running-dependent intramuscular neutrophil recruitment requires both CX3CR1- and CXCR2-mediated signals that prime not only myofiber-derived myokine upregulations but also endothelium ICAM-1 and fractalkine expressions. The results revealed the importance of the exercise-evoked regional interplay among working myofibers, the adjacent endothelium, and recruited immune cells, including neutrophils and possibly ILC2s, which plays a key role in the organization of the intramuscular microenvironment supporting the performance of hindlimb muscles during running.

Study on the regulatory effect of Panax notoginseng saponins combined with bone mesenchymal stem cell transplantation on IRAK1/TRAF6-NF-κB pathway in patients with diabetic cutaneous ulcers.

Panax notoginseng saponins (PNSs) have been found as the major active ingredient of Panax notoginseng (Burkill) F.H.Chen (PN) leaves, which has the effect of reducing inflammatory response, facilitating fibroblast proliferation, as well as promoting angiogenesis. This study aimed to investigate the molecular basis of PNS combined with bone mesenchymal stem cells (BMSCs) for treating diabetic cutaneous ulcers (DCU) and its mechanism of action. METHODS: A total of 75 SD rats were selected to make diabetic cutaneous ulcers model. According random number table method, the rats were randomly divided into a control group, a DCU group, a BMSCs group, a PNS group and BMSCs + PNS group. Five groups of rats were given without treatment. After being treated for 7 days, the rats were anesthetized with pentobarbital, and granulation tissue was collected from the central point of the wound. They were used for pathological analysis, Western blot (WB) and polymerase chain reaction (PCR) assays. RESULTS: The wound healing area was the largest in the BMSCs + PNS group. HE staining results showed that the PNS + BMSCs group could promote the formation of new epidermis and reduce the infiltration of inflammatory cells. Immunohistochemistry (IHC) results showed that the PNS + BMSCs group could up-regulate the expression of Ki67 protein and cell proliferation. In addition, PNS combined with BMSCs up-regulated the expression of miR-146-5p and down-regulated the expression of IL-1ß, IL-6 and TNF-α, IRAK1, TRAF6 and p65 in the NF-κB signaling pathway (p < 0.05). CONCLUSIONS: PNS combined with bone mesenchymal stem cell transplantation up-regulated miR-146a-5p targeting and binding to IRAK1/TRAF6, inhibiting the activation of NF-κB pathway, which reduced the inflammatory response of DCU and facilitated the skin healing of DCU. Thus, this study provides a theoretical basis and a novel therapeutic option for the treatment of DFU with PNS combined with BMSCs.