The value of low-intensity pulsed ultrasound in reducing ovarian injury caused by chemotherapy in mice.

BACKGROUND: Ovarian damage and follicle loss are major side effects of chemotherapy in young female patients with cancer. However, effective strategies to prevent these injuries are still lacking. The purpose of this study was to verify low-intensity pulsed ultrasound (LIPUS) can reduce ovarian injury caused by chemotherapy and to explore its underlying mechanisms in mice model. METHODS: The mice were randomly divided into the Control group, Cisplatin group, and Cisplatin + LIPUS group. The Cisplatin group and Cisplatin + LIPUS group were intraperitoneally injected with cisplatin every other day for a total of 10 injections, and the Control group was injected with saline. On the second day of each injection, the Cisplatin + LIPUS group received irradiation, whereas the other two groups received sham irradiation. We used a variety of biotechnologies to detect the differences in follicle count, granulosa cell apoptosis, fibrosis, transcriptome level, oxidative damage, and inflammation in differently treated mice. RESULT: LIPUS was able to reduce primordial follicle pool depletion induced by cisplatin and inhibit the apoptosis of granulosa cells. Transcriptomic results confirmed that LIPUS can reduce ovarian tissue injury. We demonstrated that LIPUS can relieve ovarian fibrosis by inhibiting TGF-ß1/Smads pathway. Meanwhile, it can reduce the oxidative damage and reduced the mRNA levels of proinflammatory cytokines caused by chemotherapy. CONCLUSION: LIPUS can reduce the toxic effects of chemotherapy drugs on ovaries, inhibit ovarian fibrosis, reduce the inflammatory response, and redcue the oxidative damage, reduce follicle depletion and to maintain the number of follicle pools.

Quantitative systems pharmacology modeling of HER2-positive metastatic breast cancer for translational efficacy evaluation and combination assessment across therapeutic modalities.

HER2-positive (HER2+) metastatic breast cancer (mBC) is highly aggressive and a major threat to human health. Despite the significant improvement in patients' prognosis given the drug development efforts during the past several decades, many clinical questions still remain to be addressed such as efficacy when combining different therapeutic modalities, best treatment sequences, interindividual variability as well as resistance and potential coping strategies. To better answer these questions, we developed a mechanistic quantitative systems pharmacology model of the pathophysiology of HER2+ mBC that was extensively calibrated and validated against multiscale data to quantitatively predict and characterize the signal transduction and preclinical tumor growth kinetics under different therapeutic interventions. Focusing on the second-line treatment for HER2+ mBC, e.g., antibody-drug conjugates (ADC), small molecule inhibitors/TKI and chemotherapy, the model accurately predicted the efficacy of various drug combinations and dosing regimens at the in vitro and in vivo levels. Sensitivity analyses and subsequent heterogeneous phenotype simulations revealed important insights into the design of new drug combinations to effectively overcome various resistance scenarios in HER2+ mBC treatments. In addition, the model predicted a better efficacy of the new TKI plus ADC combination which can potentially reduce drug dosage and toxicity, while it also shed light on the optimal treatment ordering of ADC versus TKI plus capecitabine regimens, and these findings were validated by new in vivo experiments. Our model is the first that mechanistically integrates multiple key drug modalities in HER2+ mBC research and it can serve as a high-throughput computational platform to guide future model-informed drug development and clinical translation.

Application of Auricular Cartilage-Skin Graft in the Reconstruction of Unilateral Cleft Lip Nasal Deformity.

BACKGROUND: Autologous cartilage grafts are increasingly used in the treatment of cleft lip nasal deformity, but nasal alar retraction caused by lining defects often occurs after surgery. We designed a new graft to treat unilateral cleft lip nasal deformity while avoiding nasal alar retraction. METHODS: Nineteen patients in our hospital underwent unilateral cleft lip nasal deformity repair surgery with an auricular cartilage-skin graft. The effect of surgery was evaluated in four aspects: satisfaction with postoperative appearance, nasal aesthetic subunit indices, position of the nasal alar rim and three-dimensional spatial difference. RESULTS: Overall satisfaction with each index was above 90%. The nasal tip angle and nasolabial angle of patients were significantly smaller after surgery than before surgery (P < 0.01). The height of the nostril on the affected side and the length of the nasal columella were greater after surgery than before surgery (P < 0.01). The spatial differences in soft tissue between the unaffected side and the affected side after surgery were significantly smaller than before surgery (P < 0.01). According to the follow-up results of 1-2 years, there were no significant retraction of the nasal alar rim (P > 0.05) and no obvious auricular deformity. All patients had a noticeable improvement in their nasal appearance. CONCLUSION: The auricular cartilage-skin graft, which can not only improve the appearance of the nose but also avoid nasal alar retraction, is an ideal graft to cure unilateral cleft lip nasal deformity. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Development and validation of a collagen signature to predict the prognosis of patients with stage II/III colorectal cancer.

The tumor, nodes and metastasis (TNM) classification system provides useful but incomplete prognostic information and lacks the assessment of the tumor microenvironment (TME). Collagen, the main component of the TME extracellular matrix, plays a nonnegligible role in tumor invasion and metastasis. In this cohort study, we aimed to develop and validate a TME collagen signature (CSTME) for prognostic prediction of stage II/III colorectal cancer (CRC) and to compare the prognostic values of "TNM stage + CSTME" with that of TNM stage alone. Results indicated that the CSTME was an independent prognostic risk factor for stage II/III CRC (hazard ratio: 2.939, 95% CI: 2.180-3.962, p < 0.0001), and the integration of the TNM stage and CSTME had a better prognostic value than that of the TNM stage alone (AUC(TNM+CSTME) = 0.772, AUC TNM = 0.687, p < 0.0001). This study provided an application of "seed and soil" strategy for prognosis prediction and individualized therapy.

Application of a Modified Perforator Flap of the Transverse Facial Artery for Zygomaticofacial Skin Defect Repair After Tumor Resection.

BACKGROUND: The transverse facial artery is an important source of zygomaticofacial blood, but its perforator flap is rarely reported. The aim of this study was to investigate the utility of a modified perforator flap based on facial aesthetic units and previous anatomic studies of transverse facial arteries. METHODS: All 18 elderly patients with zygomatic facial tumors underwent Mohs surgery. The V-Y and propeller flaps were designed according to the aesthetic unit of the defect site. Only a small portion of the fascia and fat surrounding the blood vessel are left, the rest of the flap is pruned to a thickness closer to the surrounding tissues. The surgical effect was comprehensively evaluated by an expert group. To assess the patient's postoperative quality of life, we administered the FACT-H & N (v 4.0) scale before and after surgery. RESULTS: Among the 18 flaps, 10 were V-Y flaps and 8 were propeller flaps. The flaps of 18 patients survived, with adequate cheek, facial symmetry, and proper mouth opening. The flaps worked well and looked good at both the recipient and donor sites. According to the scale survey, the postoperative patients had a higher quality of life in terms of physiology, psychology, function, and other areas than the preoperative patients ( P <0.05). CONCLUSION: A modified flap of the transverse facial artery can rotate flexibly and repair a larger area, as the blood flow is relatively constant near the zygomatic arch. It has a high clinical value in the treatment of zygomaticofacial tumors.

The mediating effect of self-efficacy on the relationship between diabetes self-management ability and patient activation in older adults with type 2 diabetes.

OBJECTIVE: The aim of this study was to investigate the level of diabetes self-management ability in older patients with type 2 diabetes and analyse its relationship with patient activation. Besides, the mediating effect of self-efficacy on the relationship between the two was assessed in the study. METHODS: Using a cross-sectional design, 200 elderly patients with type 2 diabetes were recruited from the community of Yangzhou, China. The Patient Activation Measure (PAM), The Self-efficacy for Diabetes (SED), and The Summary of Diabetes Self-Care Activities Measure (SDSCA) were used in the questionnaires. Data analysis was performed using SPSS 27.0 and PROCESS macro. RESULTS: Pearson correlation analysis revealed a significant positive correlation (p< 0.01) between diabetes self-management ability and patient activation (r=0.312) and self-efficacy (r=0.367). Self-efficacy partially mediated the effect between patient activation and self-management ability in older patients with type 2 diabetes, and the mediating effect accounted for 49.33% of the total effect (p< 0.001). CONCLUSIONS: Older patients with type 2 diabetes in the community have a moderate level of self-management ability. Patient activation can improve patients' self-management ability through self-efficacy.

Quality evaluation of metabolic and bariatric surgical guidelines.

Objective: To evaluate the quality of surgical guidelines on bariatric/metabolic surgery. Methods: Four independent reviewers used the AGREE II (The Appraisal of Guidelines for Research and Evaluation II) tool to assess the methodological quality of the included guidelines and conducted a comparative analysis of the main recommendations for surgical methods of these guidelines. Results: Nine surgical guidelines were included in this study. Five articles with AGREE II scores over 60% are worthy of clinical recommendation. The field of rigor of development was relatively low, with an average score of 50.82%. Among 15 key recommendations and the corresponding best evidence in the guidelines, only 4 key recommendations were grade A recommendations. Conclusions: The quality of metabolic and bariatric guidelines is uneven, and there is much room for improvement.

Patient-Derived Tumor Organoids Can Predict the Progression-Free Survival of Patients With Stage IV Colorectal Cancer After Surgery.

BACKGROUND: Recent studies have shown patient-derived tumor organoids can predict the drug response of patients with cancer. However, the prognostic value of patient-derived tumor organoid-based drug tests in predicting the progression-free survival of patients with stage IV colorectal cancer after surgery remains unknown. OBJECTIVE: This study aimed to explore the prognostic value of patient-derived tumor organoid-based drug tests in patients with stage IV colorectal cancer after surgery. DESIGN: Retrospective cohort study. SETTINGS: Surgical samples were obtained from patients with stage IV colorectal cancer at the Nanfang Hospital. PATIENTS: A total of 108 patients who underwent surgery with successful patient-derived tumor organoid culture and drug testing were recruited between June 2018 and June 2019. INTERVENTIONS: Patient-derived tumor organoid culture and chemotherapeutic drug testing. MAIN OUTCOMES MEASURES: Progression-free survival. RESULTS: According to the patient-derived tumor organoid-based drug test, 38 patients were drug sensitive and 76 patients were drug resistant. The median progression-free survival was 16.0 months in the drug-sensitive group and 9.0 months in the drug resistant group ( p < 0.001). Multivariate analyses showed that drug resistance (HR, 3.38; 95% CI, 1.84-6.21; p < 0.001), right-sided colon (HR, 3.50; 95% CI, 1.71-7.15; p < 0.001), mucinous adenocarcinoma (HR, 2.47; 95% CI, 1.34-4.55; p = 0.004), and non-R0 resection (HR, 2.70; 95% CI, 1.61-4.54; p < 0.001) were independent predictors of progression-free survival. The new patient-derived tumor organoid-based drug test model, which includes the patient-derived tumor organoid-based drug test, primary tumor location, histological type, and R0 resection, was more accurate than the traditional clinicopathological model in predicting progression-free survival ( p = 0.001). LIMITATIONS: A single-center cohort study. CONCLUSIONS: Patient-derived tumor organoids can predict progression-free survival in patients with stage IV colorectal cancer after surgery. Patient-derived tumor organoid drug resistance is associated with shorter progression-free survival, and the addition of patient-derived tumor organoid drug tests to existing clinicopathological models improves the ability to predict progression-free survival.

Exploring the role of sphingolipid-related genes in clinical outcomes of breast cancer.

Background: Despite tremendous advances in cancer research, breast cancer (BC) remains a major health concern and is the most common cancer affecting women worldwide. Breast cancer is a highly heterogeneous cancer with potentially aggressive and complex biology, and precision treatment for specific subtypes may improve survival in breast cancer patients. Sphingolipids are important components of lipids that play a key role in the growth and death of tumor cells and are increasingly the subject of new anti-cancer therapies. Key enzymes and intermediates of sphingolipid metabolism (SM) play an important role in regulating tumor cells and further influencing clinical prognosis. Methods: We downloaded BC data from the TCGA database and GEO database, on which we performed in depth single-cell sequencing analysis (scRNA-seq), weighted co-expression network analysis, and transcriptome differential expression analysis. Then seven sphingolipid-related genes (SRGs) were identified using Cox regression, least absolute shrinkage, and selection operator (Lasso) regression analysis to construct a prognostic model for BC patients. Finally, the expression and function of the key gene PGK1 in the model were verified by in vitro experiments. Results: This prognostic model allows for the classification of BC patients into high-risk and low-risk groups, with a statistically significant difference in survival time between the two groups. The model is also able to show high prediction accuracy in both internal and external validation sets. After further analysis of the immune microenvironment and immunotherapy, it was found that this risk grouping could be used as a guide for the immunotherapy of BC. The proliferation, migration, and invasive ability of MDA-MB-231 and MCF-7 cell lines were dramatically reduced after knocking down the key gene PGK1 in the model through cellular experiments. Conclusion: This study suggests that prognostic features based on genes related to SM are associated with clinical outcomes, tumor progression, and immune alterations in BC patients. Our findings may provide insights for the development of new strategies for early intervention and prognostic prediction in BC.

Integrating single-cell RNA-seq and bulk RNA-seq to construct prognostic signatures to explore the role of glutamine metabolism in breast cancer.

Background: Although breast cancer (BC) treatment has entered the era of precision therapy, the prognosis is good in the case of comprehensive multimodal treatment such as neoadjuvant, endocrine, and targeted therapy. However, due to its high heterogeneity, some patients still cannot benefit from conventional treatment and have poor survival prognoses. Amino acids and their metabolites affect tumor development, alter the tumor microenvironment, play an increasingly obvious role in immune response and regulation of immune cell function, and are involved in acquired and innate immune regulation; therefore, amino acid metabolism is receiving increasing attention. Methods: Based on public datasets, we carried out a comprehensive transcriptome and single-cell sequencing investigation. Then we used 2.5 Weighted Co-Expression Network Analysis (WGCNA) and Cox to evaluate glutamine metabolism-related genes (GRGs) in BC and constructed a prognostic model for BC patients. Finally, the expression and function of the signature key gene SNX3 were examined by in vitro experiments. Results: In this study, we constituted a risk signature to predict overall survival (OS) in BC patients by glutamine-related genes. According to our risk signature, BC patients can obtain a Prognostic Risk Signature (PRS), and the response to immunotherapy can be further stratified according to PRS. Compared with traditional clinicopathological features, PRS demonstrated robust prognostic power and accurate survival prediction. In addition, altered pathways and mutational patterns were analyzed in PRS subgroups. Our study sheds some light on the immune status of BC. In in vitro experiments, the knockdown of SNX3, an essential gene in the signature, resulted in a dramatic reduction in proliferation, invasion, and migration of MDA-MB-231 and MCF-7 cell lines. Conclusion: We established a brand-new PRS consisting of genes associated with glutamine metabolism. It expands unique ideas for the diagnosis, treatment, and prognosis of BC.

Mediation Effect of Self-Efficacy Between Health Beliefs and Glycated Haemoglobin Levels in Elderly Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study.

Purpose: To explore the mediating effect of self-efficacy in the relationship between glycated haemoglobin (HbA1c) levels and health beliefs in community elderly patients with type 2 diabetes. Patients and Methods: From January to March 2022, convenience sampling was adopted to investigate 200 elderly patients with type 2 diabetes in a community in Yangzhou, China. Data were collected using the Health Beliefs Questionnaire, Self-efficacy for Diabetes, and Medication Compliance Questionnaire. Laboratory parameters included HbA1c, fasting blood glucose, postprandial blood glucose, total cholesterol, triglyceride, high-density-lipoprotein cholesterol, and low-density-lipoprotein cholesterol levels. Correlation, linear regression, and mediation analyses were performed using SPSS 27.0. Results: HbA1c levels were higher in men (women vs men: 6.80% [6.08%, 7.73%] vs.7.30% [6.30%, 9.18%]) and employed (employed vs not employed vs retired: 7.60% [6.90%, 10.45%] vs 5.85% [5.40%, 6.95%] vs 7.10% [6.20%, 8.20%]) and low self-efficacy (low vs high: 13.1% [6.55%, 13.85%] vs 6.8% [6.10%, 7.70%]). HbA1c levels were negatively associated with health beliefs (r = -0.246) and self-efficacy (r = -0.240; p<0.01). Linear regression showed that perceived susceptibility, severity, benefit, and barriers, cues to action, and self-efficacy explained 50% of the variance in HbA1c levels after adjusting for sex and current work status. The mediation effect of self-efficacy was partial between health beliefs and HbA1c levels and accounted for 24.65% of the total effect (p < 0.001). Conclusion: Health beliefs influenced the improvement of self-efficacy in older patients with type 2 diabetes mellitus, which in turn could improve HbA1c control. Self-efficacy plays a partial mediating role between health beliefs and Hba1c levels in elderly patients with type 2 diabetes.

A Meta-Analysis of the Effectiveness of Telemedicine in Glycemic Management among Patients with Type 2 Diabetes in Primary Care.

Introduction: Telemedicine interventions are gradually being used in primary health care to help patients with type 2 diabetes receive ongoing medical guidance. The purpose of this study was to analyze the effectiveness of using telemedicine in primary health care for the management of patients with type 2 diabetes. Methods: A systematic search was conducted from database inception to August 2021 in nine databases, including PubMed, Web of Science, Cochrane Library, EMBASE, EBSCO, CNKI, Wanfang Data, VIP, and CBM. Data extraction and quality assessment were performed for studies that met the inclusion criteria. The meta-analysis was performed using Review Manager 5.4 (Cochrane) and Stata v.16.0SE (College Station, TX, USA). Results: A total of 32 articles were included in this study. Analysis showed a reduction in glycated hemoglobin, fasting glucose, and postprandial glucose after the telemedicine intervention. Systolic blood pressure and self-efficacy improved significantly, but there was no significant improvement in weight, lipid metabolism, or diabetes awareness. Subgroup analysis based on the duration of intervention showed significant improvement in glycated hemoglobin at 6 months of intervention. Conclusions: Telemedicine interventions may help patients with type 2 diabetes to effectively control blood glucose and improve self-management in primary health care. There is only moderate benefit, and the benefit may not be sustained beyond 6 months. However, the evidence for the improvement in lipid metabolism is insufficient and further studies are needed.