Cyclodextrin-based metal-organic frameworks transforming drug delivery.

Cyclodextrin-based metal-organic frameworks (CD-MOFs) are gaining traction in the realm of drug delivery due to their inherent versatility and potential to amplify drug efficacy, specificity, and safety. This article explores the predominant preparation techniques for CD-MOFs, encompassing methods like vapor diffusion, microwave-assisted, and ultrasound hydrothermal approaches. Native CD-MOFs present compelling advantages in drug delivery applications. They can enhance drug loading capacity, stability, solubility, and bioavailability by engaging in diverse interactions with drugs, including host-guest, hydrogen bonding, and electrostatic interactions. Beyond their inherent properties, CD-MOFs can be customized as drug carriers through two primary strategies: co-crystallization with functional components and surface post-modifications. These tailored modifications pave the way for controlled release manners. They allow for slow and sustained drug release, as well as responsive releases triggered by various factors such as pH levels, glutathione concentrations, or specific cations. Furthermore, CD-MOFs facilitate targeted delivery strategies, like pulmonary or laryngeal delivery, enhancing drug delivery precision. Overall, the adaptability and modifiability of CD-MOFs underscore their potential as a versatile platform for drug delivery, presenting tailored solutions that cater to diverse biomedical and industrial needs.

Effect of different inhalant allergens on T-cell subsets in adults with bronchial asthma.

Objective: We analyzed the impact of different inhalant allergens on T-lymphocyte subsets in patients diagnosed with bronchial asthma. Methods: The study included 57 bronchial asthma patients and 22 healthy controls. Asthma patients were categorized into dust mite, animal hair, pollen, and mold groups. Flow cytometry was used to measure the cells in the case group and control group. These T-lymphocyte subset markers were evaluated among patients with bronchial asthma caused by different allergens as well as between the case group and control group. Results: Peripheral blood CD4+ T-cells, CD8+ T-cells, CD4/CD8 ratio, and Th17/Treg ratios were all higher in the case group than in the control group (P < 0.05). Peripheral blood T-lymphocyte subsets were compared among the four groups, and it was found that there were statistical differences in the Th17/Treg ratio among the four groups (P < 0.05). There were no significant differences observed among the four groups in terms of CD3+ cells, CD4+ cells, CD8+ cells, Th1 cells, Th2 cells, Th17 cells, Treg cells, Th9 cells, and Th22 cells. Further pairwise comparison was made, and the results suggested that the peripheral blood Th17/Treg ratio in the pollen mixed group was lower than that in the dust mite mixed group, animal hair mixed group, and mold mixed group (P < 0.05). Conclusion: Patients with bronchial asthma show varied T-lymphocyte subset responses to different inhalant allergens. Elevated CD4+ T cells and Th17 cells in peripheral blood could indicate asthma risk. However, small sample size may introduce bias to these findings.

Pyramid Pixel Context Adaption Network for Medical Image Classification With Supervised Contrastive Learning.

Spatial attention (SA) mechanism has been widely incorporated into deep neural networks (DNNs), significantly lifting the performance in computer vision tasks via long-range dependency modeling. However, it may perform poorly in medical image analysis. Unfortunately, the existing efforts are often unaware that long-range dependency modeling has limitations in highlighting subtle lesion regions. To overcome this limitation, we propose a practical yet lightweight architectural unit, pyramid pixel context adaption (PPCA) module, which exploits multiscale pixel context information to recalibrate pixel position in a pixel-independent manner dynamically. PPCA first applies a well-designed cross-channel pyramid pooling (CCPP) to aggregate multiscale pixel context information, then eliminates the inconsistency among them by the well-designed pixel normalization (PN), and finally estimates per pixel attention weight via a pixel context integration. By embedding PPCA into a DNN with negligible overhead, the PPCA network (PPCANet) is developed for medical image classification. In addition, we introduce supervised contrastive learning to enhance feature representation by exploiting the potential of label information via supervised contrastive loss (CL). The extensive experiments on six medical image datasets show that the PPCANet outperforms state-of-the-art (SOTA) attention-based networks and recent DNNs. We also provide visual analysis and ablation study to explain the behavior of PPCANet in the decision-making process.

Identification of SOCS3 and PTGS2 as new biomarkers for the diagnosis of gout by cross-species comprehensive analysis.

Background: Gout is the most common inflammatory arthritis in adults. Gout is an arthritic disease caused by the deposition of monosodium urate crystal (MSU) in the joints, which can lead to acute inflammation and damage adjacent tissue. Hyperuricemia is the main risk factor for MSU crystal deposition and gout. With the increasing burden of gout disease, the identification of potential biomarkers and novel targets for diagnosis is urgently needed. Methods: For the analysis of this subject paper, we downloaded the human gout data set GSE160170 and the gout mouse model data set GSE190138 from the GEO database. To obtain the differentially expressed genes (DEGs), we intersected the two data sets. Using the cytohubba algorithm, we identified the key genes and enriched them through GO and KEGG. The gene expression trends of three subgroups (normal control group, intermittent gout group and acute gout attack group) were analyzed by Series Test of Cluster (STC) analysis, and the key genes were screened out, and the diagnostic effect was verified by ROC curve. The expression of key genes in dorsal root nerve and spinal cord of gout mice was analyzed. Finally, the clinical samples of normal control group, hyperuricemia group, intermittent gout group and acute gout attack group were collected, and the expression of key genes at protein level was verified by ELISA. Result: We obtained 59 co-upregulated and 28 co-downregulated genes by comparing the DEGs between gout mouse model data set and human gout data set. 7 hub DEGs(IL1B, IL10, NLRP3, SOCS3, PTGS2) were screened out via Cytohubba algorithm. The results of both GO and KEGG enrichment analyses indicate that 7 hub genes play a significant role in regulating the inflammatory response, cytokine production in immune response, and the TNF signaling pathway. The most representative hub genes SOCS3 and PTGS2 were screened out by Series Test of Cluster, and ROC analysis results showed the AUC values were both up to 1.000. In addition, we found that PTGS2 expression was significantly elevated in the dorsal root ganglia and spinal cord in monosodium urate(MSU)-induced gout mouse model. The ELISA results revealed that the expression of SOCS3 and PTGS2 was notably higher in the acute gout attack and intermittent gout groups compared to the normal control group. This difference was statistically significant, indicating a clear distinction between the groups. Conclusion: Through cross-species comprehensive analysis and experimental verification, SOCS3 and PTGS2 were proved to be new biomarkers for diagnosing gout and predicting disease progression.

The influence of mindfulness meditation combined with progressive muscle relaxation training on the clinical efficacy and quality of life of patients with sarcopenia receiving haemodialysis: a randomised controlled trial.

OBJECTIVE: To study the effect of mindfulness meditation combined with progressive muscle relaxation training on the clinical efficacy and quality of life in patients with sarcopenia receiving maintenance haemodialysis (MHD). METHODS: Eligible patients with sarcopenia in our hospital were randomly assigned to a control group (n = 24) and an intervention group (n = 25). The control group received conventional dialysis treatment, while the intervention group underwent mindfulness meditation combined with progressive muscle relaxation training during the interdialysis period in addition to conventional dialysis treatment. The effect of the intervention was evaluated after 12 weeks. RESULTS: There were no significant differences in the baseline values of various parameters between the two groups. Exercise capacity (sit-to-stand test,handgrip,time to 10 sit-ups) significantly improved in the intervention group after 12 weeks (32.68 ± 8.32 vs 26.50 ± 6.83; 37.42 ± 10.12 vs 28.12 ± 8.51; 19.8 ± 5.40 vs 25.29 ± 7.18) (p < 0.05). In terms of the kidney disease quality of life (KDQOLTM) score, all other dimensions except sexual function, social functioning, burden of kidney disease and work status dimensions showed significant improvement compared to the baseline (p < 0.05). In the control group, only the dialysis staff encouragement (DSE) and patient satisfaction (PS) dimensions showed slight improvements compared to the baseline (p > 0.05). When compared with the control group, the intervention group showed significant improvements in 10 dimensions of exercise capacity and KDQOLTM scores for physical function, role-physical, general health, energy, symptom/problem list, sleep, DSE, pain, cognitive function, emotional well-being and patient PS after 12 weeks (61.30 ± 5.38 vs 42.98 ± 5.73; 57.50 ± 3.55 vs 50.70 ± 3.62) (p < 0.05). Some inflammatory markers, such as the levels of interleukin-6 and high-sensitivity C-reactive protein (30.29 ± 2.96 vs 17.65 ± 3.22; 8.93 ± 0.99 vs 3.02 ± 0.34), showed a decrease during the intervention, while albumin and prealbumin levels were significantly increased compared with the baseline (30.62 ± 1.65 vs 35.60 ± 1.68; 0.32 ± 0.05 vs 0.44 ± 0.07) (p < 0.05). CONCLUSION: Combined intervention training can improve the motor ability and quality of life of patients with sarcopenia within a short period of time.

ARID3A enhances chemoresistance of pancreatic cancer via inhibiting PTEN-induced ferroptosis.

Currently, chemotherapy remains occupying a pivotal place in the treatment of pancreatic ductal adenocarcinoma (PDAC). Nonetheless, the emergence of drug resistance in recent years has limited the clinical efficacy of chemotherapeutic agents, especially gemcitabine (GEM). Through bioinformatics analysis, AT-rich Interactive Domain-containing Protein 3A (ARID3A), one of transcription factors, is discovered to possibly participate in this progress. This study thoroughly investigates the potential role of ARID3A in the malignant progression and GEM chemoresistance of PDAC and explores the underlying mechanisms. The results indicate that ARID3A knockdown suppresses tumor development and enhances the sensitivity of PDAC cells to GEM in vitro and vivo. Mechanically, CUT&Tag profiling sequencing, RNA-sequencing and functional studies demonstrates that decreased ARID3A expression alleviates the transcriptional inhibition of phosphatase and tensin homolog (PTEN), consequently leading to glutathione peroxidase 4 (GPX4) depletion and increased lipid peroxidation levels. Activated ferroptosis induced by the inhibition of GPX4 subsequently restricts tumor progression and reduces GEM resistance in PDAC. This research identifies the ferroptosis regulatory pathway of ARID3A-PTEN-GPX4 axis and reveals its critical role in driving the progression and chemoresistance of pancreatic cancer. Notably, both inhibition of ARID3A and enhancement of ferroptosis can increase chemosensitivity to GEM, which offers a promising opportunity for developing therapeutic strategies to combat acquired chemotherapy resistance in pancreatic cancer.

Structural Design and Control Research of Multi-Segmented Biomimetic Millipede Robot.

Due to their advantages of good stability, adaptability, and flexibility, multi-legged robots are increasingly important in fields such as rescue, military, and healthcare. This study focuses on the millipede, a multi-segmented organism, and designs a novel multi-segment biomimetic robot based on an in-depth investigation of the millipede's biological characteristics and locomotion mechanisms. Key leg joints of millipede locomotion are targeted, and a mathematical model of the biomimetic robot's leg joint structure is established for kinematic analysis. Furthermore, a central pattern generator (CPG) control strategy is studied for multi-jointed biomimetic millipede robots. Inspired by the millipede's neural system, a simplified single-loop CPG network model is constructed, reducing the number of oscillators from 48 to 16. Experimental trials are conducted using a prototype to test walking in a wave-like gait, walking with a leg removed, and walking on complex terrain. The results demonstrate that under CPG waveform input conditions, the robot can walk stably, and the impact of a leg failure on overall locomotion is acceptable, with minimal speed loss observed when walking on complex terrain. The research on the structure and motion control algorithms of multi-jointed biomimetic robots lays a technical foundation, expanding their potential applications in exploring unknown environments, rescue missions, agriculture, and other fields.

Construction of a Near-Infrared Fluorescent Probe for Dynamic Monitoring and Early Diagnosis of Heart Failure.

Cardiac hypertrophy characterized by abnormal cardiomyocyte viscosity is a typical sign of heart failure (HF) with vital importance for early diagnosis. However, current biochemical and imaging diagnostic methods are unable to detect this subclinical manifestation. In this work, we developed a series of NIR-I fluorescence probes for detecting myocardial viscosity based on the pyridazinone scaffold. The probes showed weak fluorescence due to free intramolecular rotation under low-viscosity conditions, while they displayed strong fluorescence with limited intramolecular rotation in response to a high-viscosity environment. Among them, CarVis2 exhibited higher stability and photobleaching resistance than commercial dyes. Its specific response to viscosity was not influenced by the pH and biological species. Furthermore, CarVis2 showed rapid and accurate responses to the viscosity of isoproterenol (ISO)-treated H9C2 cardiomyocytes with good biocompatibility. More importantly, CarVis2 demonstrated excellent sensitivity in monitoring myocardial viscosity variation in HF mice in vivo, potentially enabling earlier noninvasive identification of myocardial abnormalities compared to traditional clinical imaging and biomarkers. These findings revealed that CarVis2 can serve as a powerful tool to monitor myocardial viscosity, providing the potential to advance insights into a pathophysiological mechanism and offering a new reference strategy for early visual diagnosis of HF.

Polyoxometalate-based plasmonic electron sponge membrane for nanofluidic osmotic energy conversion.

Nanofluidic membranes have demonstrated great potential in harvesting osmotic energy. However, the output power densities are usually hampered by insufficient membrane permselectivity. Herein, we design a polyoxometalates (POMs)-based nanofluidic plasmonic electron sponge membrane (PESM) for highly efficient osmotic energy conversion. Under light irradiation, hot electrons are generated on Au NPs surface and then transferred and stored in POMs electron sponges, while hot holes are consumed by water. The stored hot electrons in POMs increase the charge density and hydrophilicity of PESM, resulting in significantly improved permselectivity for high-performance osmotic energy conversion. In addition, the unique ionic current rectification (ICR) property of the prepared nanofluidic PESM inhibits ion concentration polarization effectively, which could further improve its permselectivity. Under light with 500-fold NaCl gradient, the maximum output power density of the prepared PESM reaches 70.4 W m-2, which is further enhanced even to 102.1 W m-2 by changing the ligand to P5W30. This work highlights the crucial roles of plasmonic electron sponge for tailoring the surface charge, modulating ion transport dynamics, and improving the performance of nanofluidic osmotic energy conversion.

Sodium/Potassium ATPase Alpha 1 Subunit Fine-tunes Platelet GPCR Signaling Function and is Essential for Thrombosis.

Background: Thrombosis is a major cause of myocardial infarction and ischemic stroke. The sodium/potassium ATPase (NKA), comprising α and ß subunits, is crucial in maintaining intracellular sodium and potassium gradients. However, the role of NKA in platelet function and thrombosis remains unclear. Methods: We utilized wild-type (WT, α1+/+) and NKA α1 heterozygous (α1+/-) mice, aged 8 to 16 weeks, of both sexes. An intravital microscopy-based, FeCl3-induced carotid artery injury thrombosis model was employed for in vivo thrombosis assessment. Platelet transfusion assays were used to evaluate platelet NKA α1 function on thrombosis. Human platelets isolated from healthy donors and heart failure patients treated with/without digoxin were used for platelet function and signaling assay. Complementary molecular approaches were used for mechanistic studies. Results: NKA α1 haplodeficiency significantly reduced its expression on platelets without affecting sodium homeostasis. It significantly inhibited 7.5% FeCl3-induced thrombosis in male but not female mice without disturbing hemostasis. Transfusion of α1+/-, but not α1+/+, platelets to thrombocytopenic WT mice substantially prolonged thrombosis. Treating WT mice with low-dose ouabain or marinobufagenin, both binding NKA α1 and inhibiting its ion-transporting function, markedly inhibited thrombosis in vivo. NKA α1 formed complexes with leucine-glycine-leucine (LGL)-containing platelet receptors, including P2Y12, PAR4, and thromboxane A2 receptor. This binding was significantly attenuated by LGL>SFT mutation or LGL peptide. Haplodeficiency of NKA α1 in mice or ouabain treatment of human platelets notably inhibited ADP-induced platelet aggregation. While not affecting 10% FeCl3-induced thrombosis, NKA α1 haplodeficiency significantly prolonged thrombosis time in mice treated with an ineffective dose of clopidogrel. Conclusion: NKA α1 plays an essential role in enhancing platelet activation through binding to LGL-containing platelet GPCRs. NKA α1 haplodeficiency or inhibition with low-dose ouabain and marinobufagenin significantly inhibited thrombosis and sensitized clopidogrel's anti-thrombotic effect. Targeting NKA α1 emerges as a promising antiplatelet and antithrombotic therapeutic strategy.

The association among thriving in life, quality of life, and suicidal ideation in Chinese urban older adults: the moderating effects of attitude toward own aging.

BACKGROUND: As the global trend of population aging intensifies, the health and well-being of the older population has gradually become a focus of attention for the global community. This study assessed the status of thriving in life among Chinese urban older adults and identified its relationship with attitude toward own aging and quality of life (QoL). It also tested whether attitude toward own aging moderates the association between thriving in life and Qol or between thriving in life and suicidal ideation. METHODS: Primary data were collected through a cross-sectional survey among urban older adults from three provinces in China. They were invited to complete an anonymous survey using face-to-face interviews from December 2019 to January 2020. Data from 764 older adults were analyzed. RESULTS: Approximately 44.39% of participants reported positive responses toward the four domains of thriving in life. Thriving in life and attitude toward own aging had a significant association with QoL. Thriving in life was a protective factor for suicidal ideation for older adults. Moreover, attitude toward own aging moderated the association between thriving in life and QoL and that between thriving in life and suicidal ideation. CONCLUSIONS: Chinese urban older adults were reportedly thriving in life, which contributed to increased QoL and reduced suicidal ideation. Notably, the study revealed that more positive attitudes towards own aging were associated with higher levels of thriving in life, better QoL, and reduced suicidal ideation. Targeted interventions for older adults should be devised to promote thriving in life and prevent negative attitudes of older people towards their own aging, further raising QoL and reducing suicidal ideation.

Establishment and validation of an artificial intelligence web application for predicting postoperative in-hospital mortality in patients with hip fracture: a National cohort study of 52,707 cases.

BACKGROUND: In-hospital mortality following hip fractures is a significant concern, and accurate prediction of this outcome is crucial for appropriate clinical management. Nonetheless, there is a lack of effective prediction tools in clinical practice. By utilizing artificial intelligence and machine learning techniques, this study aims to develop a predictive model that can assist clinicians in identifying geriatric hip fracture patients at a higher risk of in-hospital mortality. METHODS: A total of 52,707 geriatric hip fracture patients treated with surgery from 90 hospitals were included in this study. The primary outcome was postoperative in-hospital mortality. The patients were randomly divided into two groups, with a ratio of 7:3. The majority of patients, assigned to the training cohort, were used to develop the AI models. The remaining patients, assigned to the validation cohort, were used to validate the models. Various machine learning algorithms, including logistic regression (LR), decision tree (DT), naïve Bayesian (NB), neural network (NN), eXGBoosting machine (eXGBM), and random forest (RF), were employed for model development. A comprehensive scoring system, incorporating 10 evaluation metrics, was developed to assess the prediction performance, with higher scores indicating superior predictive capability. Based on the best machine learning-based model, an AI application was developed on the Internet. In addition, a comparative testing of prediction performance between doctors and the AI application. FINDINGS: The eXGBM model exhibited the best prediction performance, with an AUC of 0.908 (95% CI: 0.881-0.932), as well as the highest accuracy (0.820), precision (0.817), specificity (0.814), and F1 score (0.822), and the lowest Brier score (0.120) and log loss (0.374). Additionally, the model showed favorable calibration, with a slope of 0.999 and an intercept of 0.028. According to the scoring system incorporating 10 evaluation metrics, the eXGBM model achieved the highest score (56), followed by the RF model (48) and NN model (41). The LR, DT, and NB models had total scores of 27, 30, and 13, respectively. The AI application has been deployed online at https://in-hospitaldeathinhipfracture-l9vhqo3l55fy8dkdvuskvu.streamlit.app/ , based on the eXGBM model. The comparative testing revealed that the AI application's predictive capabilities significantly outperformed those of the doctors in terms of AUC values (0.908 vs. 0.682, P <0.001). CONCLUSIONS: The eXGBM model demonstrates promising predictive performance in assessing the risk of postoperative in-hospital mortality among geriatric hip fracture patients. The developed AI model serves as a valuable tool to enhance clinical decision-making.

A web-based dynamic predictive model for postoperative nausea and vomiting in patient receiving gynecological laparoscopic surgery.

OBJECTIVE: The aim of this study was to develop a web-based dynamic prediction model for postoperative nausea and vomiting (PONV) in patients undergoing gynecologic laparoscopic surgery. METHODS: The patients (N = 647) undergoing gynecologic laparoscopic surgery were included in this observational study. The candidate risk-factors related to PONV were included through literature search. Lasso regression was utilized to screen candidate risk-factors, and the variables with statistical significance were selected in multivariable logistic model building. The web-based dynamic Nomogram was used for model exhibition. Accuracy and validity of the experimental model (EM) were evaluated by generating receiver operating characteristic (ROC) curves and calibration curves. Hosmer-Lemeshow test was used to evaluate the goodness of fit of the model. Decision curve analysis (DCA) was used to evaluate the clinical practicability of the risk prediction model. RESULTS: Ultimately, a total of five predictors including patient-controlled analgesia (odds ratio [OR], 4.78; 95% confidence interval [CI], 1.98-12.44), motion sickness (OR, 4.80; 95% CI, 2.71-8.65), variation of blood pressure (OR, 4.30; 95% CI, 2.41-7.91), pregnancy vomiting history (OR, 2.21; 95% CI, 1.44-3.43), and pain response (OR, 1.64; 95% CI, 1.48-1.83) were selected in model building. Assessment of the model indicates the discriminating power of EM was adequate (ROC-areas under the curve, 93.0%; 95% CI, 90.7%-95.3%). EM showed better accuracy and goodness of fit based on the results of the calibration curve. The DCA curve of EM showed favorable clinical benefits. CONCLUSIONS: This dynamic prediction model can determine the PONV risk in patients undergoing gynecologic laparoscopic surgery.

Efficacy and safety of PARP inhibitors combined with antiangiogenic agents in the maintenance treatment of ovarian cancer: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials.

Background: Poly (ADP-ribose) polymerase (PARP) inhibitor and antiangiogenic agent monotherapy have shown to be effective as maintenance treatment in patients with ovarian cancer (OC). However, there is currently a lack of evidence-based study to directly compare the effects of combination therapy with these two drugs. Therefore, this study aimed to compare the efficacy and safety of combination therapy with PARP inhibitors and antiangiogenic agents in women with OC using a meta-analysis. Methods: An exhaustive search of literature was undertaken using multiple databases, including PubMed, Web of Science, Embase, and the Cochrane Library to identify pertinent randomized controlled trials (RCTs) published up until 17 December 2023. The data on progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were pooled. We computed the pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) for PFS and OS, along with the relative risks (RRs) and 95% CIs for AEs. Trial sequential analysis, heterogeneity test, sensitivity analysis, and publication bias assessment were performed. Stata 12.0 and Software R 4.3.1 were utilized for all analyses. Results: This meta-analysis included 7 RCTs with a total of 3,388 participants. The overall analysis revealed that combination therapy of PARP inhibitors and antiangiogenic agents significantly improved PFS (HR = 0.615, 95% CI = 0.517-0.731; 95% PI = 0.379-0.999), but also increased the risk of AEs, including urinary tract infection (RR = 1.500, 95% CI = 1.114-2.021; 95% PI = 0.218-10.346), fatigue (RR = 1.264, 95% CI = 1.141-1.400; 95% PI = 1.012-1.552), headache (RR = 1.868, 95% CI = 1.036-3.369; 95% PI = 0.154-22.642), anorexia (RR = 1.718, 95% CI = 1.320-2.235; 95% PI = 0.050-65.480), and hypertension (RR = 5.009, 95% CI = 1.103-22.744; 95% PI = 0.016-1580.021) compared with PARP inhibitor or antiangiogenic agent monotherapy. Our study has not yet confirmed the benefit of combination therapy on OS in OC patients (HR = 0.885, 95% CI = 0.737-1.063). Additionally, subgroup analyses further showed that combination therapy resulted in an increased risk of AEs, encompassing thrombocytopenia, vomiting, abdominal pain, proteinuria, fatigue, headache, anorexia, and hypertension (all p < 0.05). Conclusion: Our study demonstrated the PFS benefit of combination therapy with PARP inhibitors and antiangiogenic agents in patients with OC. The OS result need to be updated after the original trial data is mature. Clinicians should be vigilant of AEs when administering the combination therapy in clinical practice. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023494482.

Exploring the Mechanism of KLF15 on the Biological Activity and Autophagy of Gastric Cancer Cells based on PI3K/Akt/Mtor Signaling Pathway.

OBJECTIVE: To explore the mechanism of KLF15 on the biological activity and autophagy of gastric cancer cells based on the PI3K/Akt/mTOR signaling pathway. MATERIAL AND METHODS: The gastric cancer AGS cells were divided into the Con group, pcDNANC group, pcDNA-KLF15 group, LY294002 group and IGF-1 group. RT-PCR was used to detect the expression of KLF15 in human gastric mucosal cells and gastric cancer cells; MTT method to detect cell proliferation; Transwell method to detect cell invasion; flow cytometry to detect cell apoptosis; Western blotting to detect PI3K, Akt, mTOR in cells, LC3, Beclin1, p62 protein expression.P<0.05 was used to indicate statistical significance. RESULTS: Compared with the human gastric mucosal cell line GES-1 cells, the expression of KLF15 in human gastric cancer cell lines MKN-28, MFC, SCG-7901 and AGS cells was significantly decreased, And the expression of KLF15 in AGS cells, was the lowest (P=0.006). Compared with the Con group, The expression of KLF15 in the cells of the PCDNA-KLF15 group was significantly increased (P=0.018); There was no significant difference in the expression of KLF15 between the Con group and the PCDNA-NC group (P=0.225). Compared with the Con group, the proliferation and invasion abilities of the cells in the pcDNA-KLF15 group were significantly reduced, And the apoptosis ability was significantly increased (P=0.019). The ratio of LC3II/LC31 and the expression of Beclin1 Protein in the control group were significantly higher than those in the Con group (P=0.017). CONCLUSION: Overexpression of KLF15 can inhibit the proliferation and invasion of Gastric cancer cells and promote cell apoptosis and autophagy, and its mechanism may be related to the regulation of the PI3K/Akt/mTOR signaling pathway.

Chronic infectious unilateral giant thyroid cyst related to diabetes mellitus: A case report.

BACKGROUND: Patients rarely develop complicated infections in thyroid cysts. Here, we describe a patient with chronic infected unilateral giant thyroid cyst related to diabetes mellitus (DM). CASE SUMMARY: A 66-year-old male was admitted due to an evident neck lump for 5 d after approximately 40 years of gradually progressive neck mass and 7 years of DM. Doppler ultrasound and computed tomography scan showed a giant lump in the left thyroid gland lobe. He was diagnosed with a large thyroid nodule complicated by tracheal dislocation and had surgical indications. Surgical exploration revealed evident inflammatory edema and exudation between the left anterior neck muscles, the nodule and glandular tissue. Fortunately, inflammatory lesions did not affect major neck vessels. Finally, a left partial thyroidectomy was performed. Macroscopic observation showed that the cystic thyroid mass consisted of extensive cystic wall calcification and was rich in massive rough sand-like calculi content and purulent matter. Postoperative pathology confirmed benign thyroid cyst with chronic infection. CONCLUSION: The progression of this chronic infectious unilateral giant thyroid cyst may have been related to DM, and identifying blood vessels involvement can prevent serious complications during operation.

Full endoscopic laminotomy decompression versus anterior cervical discectomy and fusion for the treatment of single-segment cervical spinal stenosis: a retrospective, propensity score-matched study.

OBJECTIVE: Anterior cervical discectomy and fusion (ACDF) is the standard procedure for the treatment of cervical spinal stenosis (CSS), but complications such as adjacent segment degeneration can seriously affect the long-term efficacy. Currently, posterior endoscopic surgery has been increasingly used in the clinical treatment of CSS. The aim of this study was to compare the clinical outcomes of single-segment CSS patients who underwent full endoscopic laminotomy decompression or ACDF. METHODS: 138 CSS patients who met the inclusion criteria from June 2018 to August 2020 were retrospectively analyzed and divided into endoscopic and ACDF groups. The propensity score matching (PSM) method was used to adjust the imbalanced confounding variables between the groups. Then, perioperative data were recorded and clinical outcomes were compared, including functional scores and imaging data. Functional scores included Visual Analog Scale of Arms (A-VAS) and Neck pain (N-VAS), Japanese Orthopedic Association score (JOA), Neck Disability Index (NDI), and imaging data included Disc Height Index (DHI), Cervical range of motion (ROM), and Ratio of grey scale (RVG). RESULTS: After PSM, 84 patients were included in the study and followed for 24-30 months. The endoscopic group was significantly superior to the ACDF group in terms of operative time, intraoperative blood loss, incision length, and hospital stay (P < 0.001). Postoperative N-VAS, A-VAS, JOA, and NDI were significantly improved in both groups compared with the preoperative period (P < 0.001), and the endoscopic group showed better improvement at 7 days postoperatively (P < 0.05). The ROM changes of adjacent segments were significantly larger in the ACDF group at 12 months postoperatively and at the last follow-up (P < 0.05). The RVG of adjacent segments showed a decreasing trend, and the decrease was more marked in the ACDF group at last follow-up (P < 0.05). According to the modified MacNab criteria, the excellent and good rates in the endoscopic group and ACDF group were 90.48% and 88.10%, respectively, with no statistically significant difference (P > 0.05). CONCLUSION: Full endoscopic laminotomy decompression is demonstrated to be an efficacious alternative technique to traditional ACDF for the treatment of single-segment CSS, with the advantages of less trauma, faster recovery, and less impact on cervical spine kinematics and adjacent segmental degeneration.

Percutaneous endoscopic lumbar discectomy combined with platelet-rich plasma injection for lumbar disc herniation: analysis of clinical and imaging outcomes.

OBJECTIVE: To evaluate the clinical efficacy and imaging outcomes of percutaneous endoscopic lumbar discectomy (PELD) combined with platelet-rich plasma (PRP) for the treatment of lumbar disc herniation (LDH). METHODS: A total of 155 patients with LDH between January 2020 and June 2022 were retrospective analyzed, of which 75 underwent PELD with PRP and 80 underwent PELD only. Clinical functional scores and imaging data were compared. Clinical functional scores included visual analog scale of leg pain (VAS-LP) and back pain (VAS-BP), Japanese Orthopedic Association score (JOA), Oswestry Disability Index (ODI) and modified MacNab criteria. Imaging data included disc height index (DHI), spinal cross-sectional area (SCSA), disc protrusion size (DPZ), and ratio value of disc grey scales (RVG). RESULTS: Both groups showed clinical improvement, and VAS-LP, VAS-BP, JOA and ODI were significantly improved in the PRP group compared with the control group at 3, 6 and 12 months postoperatively (P < 0.05). At the last follow-up, the differences in SCSA, DPZ and RVG between the two groups were statistically significant (P < 0.05), with the PRP group being superior to the control group. The excellent and good rates of the modified Macnab criteria in the PRP group and control group were 93.3% and 90%, respectively, with no statistically significant difference (P > 0.05). No serious complications occurred during the follow-up period. CONCLUSION: PELD combined with PRP is a safe and effective method for treating patients with LDH. PRP injection was beneficial for delaying disc degeneration and promoting disc remodeling.

[Identification of Protein-Coding Gene Markers in Breast Invasive Carcinoma Based on Machine Learning].

Objective To screen out the biomarkers linked to prognosis of breast invasive carcinoma based on the analysis of transcriptome data by random forest (RF),extreme gradient boosting (XGBoost),light gradient boosting machine (LightGBM),and categorical boosting (CatBoost). Methods We obtained the expression data of breast invasive carcinoma from The Cancer Genome Atlas and employed DESeq2,t-test,and Cox univariate analysis to identify the differentially expressed protein-coding genes associated with survival prognosis in human breast invasive carcinoma samples.Furthermore,RF,XGBoost,LightGBM,and CatBoost models were established to mine the protein-coding gene markers related to the prognosis of breast invasive cancer and the model performance was compared.The expression data of breast cancer from the Gene Expression Omnibus was used for validation. Results A total of 151 differentially expressed protein-coding genes related to survival prognosis were screened out.The machine learning model established with C3orf80,UGP2,and SPC25 demonstrated the best performance. Conclusions Three protein-coding genes (UGP2,C3orf80,and SPC25) were screened out to identify breast invasive carcinoma.This study provides a new direction for the treatment and diagnosis of breast invasive carcinoma.