Identification and RNAi-based function analysis of trehalase family genes in Frankliniella occidentalis (Pergande).

BACKGROUND: Insects utilize trehalases (TREs) to regulate energy metabolism and chitin biosynthesis, which are essential for their growth, development, and reproduction. TREs can therefore be used as potential targets for future insecticide development. However, the roles of TREs in Frankliniella occidentalis (Pergande), a serious widespread agricultural pest, remain unclear. RESULTS: Three TRE genes were identified in F. occidentalis and cloned, and their functions were then investigated via feeding RNA interference (RNAi) and virus-induced gene silencing (VIGS) assays. The results showed that silencing FoTRE1-1 or FoTRE1-2 significantly decreased expression levels of FoGFAT, FoPGM, FoUAP, and FoCHS, which are members of the chitin biosynthesis pathway. Silencing FoTRE1-1 or FoTRE2 significantly down-regulated FoPFK and FoPK, which are members of the energy metabolism pathway. These changes resulted in 2-fold decreases in glucose and glycogen content, 2-fold increases in trehalose content, and 1.5- to 2.0-fold decreases in chitinase activity. Furthermore, knocking down FoTRE1-1 or FoTRE1-2 resulted in deformed nymphs and pupae as a result of hindered molting. The VIGS assay for the three FoTREs revealed that FoTRE1-1 or FoTRE2 caused shortened ovarioles, and reduced egg-laying and hatching rates. CONCLUSION: The results suggest that FoTRE1-1 and FoTRE1-2 play important roles in the growth and development of F. occidentalis, while FoTRE1-1 and FoTRE2 are essential for its reproduction. These three genes could be candidate targets for RNAi-based management and control of this destructive agricultural pest. © 2024 Society of Chemical Industry.

A DiffeRential Evolution Adaptive Metropolis (DREAM)-based inverse model for continuous release source identification in river pollution incidents: Quantitative evaluation and sensitivity analysis.

The identification of continuous pollution sources for rivers is of great concern for emergency response. Most studies focused on instantaneous river pollution sources and associated incidents. There is a dire need to address continuous pollution sources, as pollutant discharge may impose a major impact on the water ecosystem. Therefore, in this study, a novel inverse model is proposed to identify the continuous point sources in river pollution incidents that would estimate the source strength, location, release time, and spill time. The proposed inverse model combines the advanced DiffeRential Evolution Adaptive Metropolis (DREAM) algorithm and the forward transport advection-dispersion equation to infer the posterior probability distribution of source parameters for quantifying uncertainties. In addition, the performance of the DREAM-based model is compared with those of the Metropolis-Hastings (MH)-based and genetic algorithm (GA)-based models. The results show that the DREAM-based model performs accurately for both the hypothetical and the field tracer cases. The comparative analysis shows that the DREAM-based model performs better in saving computation time, improving the accuracy of results, and reconstructing pollutant concentrations. Observation errors significantly influence the accuracy of the identification results from the DREAM-based model. In addition, a comprehensive sensitivity analysis of the DREAM-based model is conducted. The identification results from the DREAM-based model are sensitive to the dispersion coefficient and river velocity. The accuracy of the inverse model could be improved by increasing the monitoring number and by monitoring locations closer to the spill site. The findings of this study can improve decision-making during emergency responses to sudden river pollution incidents.

Uridine diphosphate glucosyltransferases are involved in spinosad resistance in western flower thrips Frankliniella occidentalis (Pergande).

Uridine diphosphate glucosyltransferases (UGTs) play crucial roles in the insect detoxification system and are associated with pesticide resistance. Our previous transcriptomic analysis of spinosad-susceptible (Ivf03) and resistant (NIL-R) Frankliniella occidentalis revealed numerous upregulated UGT genes in the NIL-R strain, suggesting their potential contribution to spinosad resistance. To investigate this hypothesis, here we conducted UGT activity assays and spinosad induction experiments, employing RNA interference (RNAi) techniques for gene function validation. We found significantly elevated UGT activity in the NIL-R strain compared to Ivf03, with 5-nitrouracil showing a substantial synergistic effect on the resistant strain. Eighteen UGT genes were identified in F. occidentalis, with gene expansion and duplication observed within families UGT466, 467, and 468. Ten out of the eighteen UGTs exhibited higher expression levels in NIL-R, specifically FoUGT466B1, FoUGT468A3, and FoUGT468A4 consistently being upregulated across nymphs, males, and females. RNAi-based functional validation targeting these three UGT genes led to increased susceptibility to spinosad in a life stage-, sex-, and dose-dependent manner. These results indicate that UGTs are indeed involved in spinosad resistance in F. occidentalis, and the effects are dependent on life stage, sex, and dose. Therefore, sustainable control for F. occidentalis resistance should always consider these differential responses.

Comparison of the efficacy of fish oil and probiotic supplementation on glucose and lipid metabolism in patients with type 2 diabetes: a systematic review and network meta-analysis.

BACKGROUND: Abnormalities in glucose and lipid metabolism contribute to the progression and exacerbation of type 2 diabetes mellitus (T2DM). Fish oil and probiotics are dietary supplements that have the potential to improve glucose and lipid metabolism. However, their efficacy remains unclear in T2DM patients. METHODS: PubMed, Embase, and the Cochrane Library were retrieved to collect randomized controlled trials (RCTs) on the efficacy of fish oil or probiotic supplementation in T2DM patients from the database inception to December 13, 2023. Primary outcome indicators encompassed glycated hemoglobin (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR) and blood lipid profile (triglyceride (TG) and total cholesterol (TC). Secondary outcome indicators included inflammatory markers such as tumor necrosis factor -α (TNF-α) and adipocytokine (including leptin and adiponectin). The R software was used for statistical analysis, and GraphPad Prism was used for figure rendering. RESULTS: A total of 60 RCTs involving 3845 T2DM patients were included in the analysis. The results showed that the probiotics (Bifidobacterium, Lactobacillus, Lactococcus, Propionibacterium, etc.) were more effective in reducing HOMA-IR than fish oil (Surca = 0.935). Bifidobacterium demonstrated the highest efficacy in reducing HbA1c levels (Surca = 0.963). Regarding lipid metabolism, fish oil was superior to probiotics in lowering TG and TC levels (Surca values of 0.978 and 0.902, respectively). Furthermore, fish oil outperformed probiotics in reducing TNF-α (Surca = 0.839) and leptin (Surca = 0.712), and increasing adiponectin levels (Surca = 0.742). Node-splitting analysis showed good consistency (P > 0.05 for direct, indirect, and network comparison across various interventions). CONCLUSIONS: In T2DM patients, fish oil was more effective than probiotics in regulating lipid metabolism. Probiotics outperformed fish oil in regulating glucose metabolism particularly; specifically, Bifidobacterium showed higher efficacy in reducing blood glucose.

Rare, late onset of immune checkpoint inhibitor-induced type 1 diabetes mellitus in a patient with small-cell lung cancer treated with serplulimab: a case report and review of the literature.

BACKGROUND: As a newly approved immune checkpoint inhibitor in China, serplulimab has been widely used in the immunotherapy of tumors. However, the immune-related adverse events of immune checkpoint inhibitors should not be ignored. Although immune checkpoint inhibitor-induced type 1 diabetes mellitus is a rare complication, it may cause diabetic ketoacidosis and endanger the lives of patients. CASE PRESENTATION: This case report describes a 55-year-old male of Han nationality from China diagnosed with small-cell lung cancer with multiple metastases who experienced an adverse event of type 1 diabetes mellitus 68 weeks after receiving serplulimab therapy. The patient presented with typical symptoms of diabetic ketoacidosis, including severe thirst, nausea, vomiting, deep respirations, and stupor. Despite the absence of diabetes-related autoantibodies, the patient had extremely low levels of insulin and C-peptide release. Other potential causes of diabetes were ruled out, confirming the condition as serplulimab-induced immune checkpoint inhibitor-induced type 1 diabetes mellitus. After aggressive treatment to correct diabetic ketoacidosis, the patient's blood glucose levels stabilized and symptoms of diabetes improved significantly, although long-term insulin maintenance therapy was necessary. CONCLUSION: This case highlights a rare, late-onset adverse event of immune checkpoint inhibitor-induced type 1 diabetes mellitus that may be overlooked during treatment with serplulimab. The monitoring of blood glucose levels and early signs and symptoms of diabetes cannot be relaxed at the late stage of treatment, even if patients do not have elevated blood glucose levels before and during the middle stage of treatment.

Accumulative prediction values of serum thyroid stimulating hormone and visceral adipose tissue for metabolic syndrome in postmenopausal women: A 10-year follow-up study of Chinese population.

AIMS: We aim to explore the cumulative predictive value of elevated serum thyroid stimulating hormone (TSH) and visceral fat area (VFA) for metabolic syndrome (MS) development in postmenopausal women. METHODS: A total of 1006 postmenopausal females were enrolled in a 10-year prospective longitudinal study from 2011 to 2021 in the community of Banknote Printing Company of Chengdu. The sociodemographic information collection and anthropometric measurements were made by a professional nurse. Fasting blood samples were drawn for chemical analysis of fasting plasma glucose, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and TSH. Magnetic resonance imaging was performed to measure VFA. All the participants were categorized into four groups according to median VFA and serum level of TSH. RESULTS: A total of 793 postmenopausal females without MS underwent a 10-year follow-up study grouping by TSH and VFA: Group 1 (TSH level <4.2 µIU/mL, and VFA < 70 cm2 ), Group 2 (TSH level ≥4.2 µIU/mL, and VFA < 70 cm2 ), Group 3 (TSH level <4.2 µIU/mL, and VFA ≥70 cm2 ) and Group 4 (TSH level ≥4.2 µIU/mL, and VFA ≥70 cm2 ). During the 10-year follow-up, MS was newly developed in 326 (41.1%) subjects. The incidence of MS was 29.8% (n = 53), 35.2% (n = 63), 41% (n = 87), and 55% (n = 123) from Group 1 to Group 4 (Group 4 vs other groups, p < .001). Cox regression analysis for MS prediction demonstrated that both TSH (Model 3, hazard ratio [HR] = 1.07 [95% confidence interval, 1.05-1.09]) and VFA (Model 4, HR = 1.02 [95% confidence interval, 1.01-1.08]) were not only independent predictors of MS but also involved some interaction between each other (p for interaction = .021). CONCLUSION: Our findings suggested that mutual interaction between higher TSH and VFA contributed to the development of MS. Further studies are needed to clarify these contributions.

Triglyceride-Glucose Index as a Predictor of Lower Extremity Arterial Disease in Patients with Diabetes: A Hospitalized Population Retrospective Study.

BACKGROUND: The triglyceride-glucose (TyG) index is a new, simple, and inexpensive marker of insulin resistance that is becoming increasingly important as a promising predictor of diseases such as atherosclerosis. Atherosclerosis is the main cause of lower extremity arterial disease (LEAD). In this study, we investigated the relationship between TyG index values and LEAD risk in patients with diabetes. METHODS: Patients with diabetes hospitalized at the Endocrinology Department of our hospital from June 1, 2021, to May 31, 2022, were retrospectively included. Baseline data, biochemical indicators, and ankle-brachial index values were collected. Statistical methods were used to assess the relationship between TyG index values and the risk of LEAD. RESULTS: A total of 1,040 hospitalized patients with diabetes were included, they were divided into the LEAD group with 168 patients and the no LEAD group with 872 patients. TyG index values in the LEAD group were higher than those in the no LEAD group (9.94 ± 0.78 vs. 9.36 ± 0.70, P < 0.001). TyG index values were independently correlated with LEAD risk in patients with diabetes (odds ratio = 3.92, 95% confidence interval (CI): 2.92-5.26, P < 0.001) in multivariate logistic regression analysis after adjusting for different risk factors (all P < 0.05). The area under the receiver operating characteristic curve was 0.72 (95% CI: 0.68-0.76) when TyG index values were used to diagnose LEAD in patients with diabetes. When Youden's index reached the maximum value of 0.34, the optimal TyG index threshold for predicting the onset of diabetic LEAD was 9.56, sensitivity was 71.1%, and specificity was 63.0%. CONCLUSIONS: Increases in TyG index values were associated with the risk of LEAD in patients with diabetes and, thus, may be used as a predictor of LEAD in this patient population, especially in primary care institutions with relatively few resources.

Comparison of healing effectiveness of different debridement approaches for diabetic foot ulcers: a network meta-analysis of randomized controlled trials.

Objectives: The choice of the debridement method is very important for the healing of diabetic foot ulcers (DFUs), but the relative effectiveness of different debridement methods in the healing of DFUs remains unclear. This study conducted a network meta-analysis of the relative healing effectiveness of different debridement methods in patients with DFUs. Methods: We performed a literature search in PubMed, Embase, and Cochrane Library from database inception up to 30 June 2023 for screening randomized controlled trials on the healing effectiveness of debridement in DFUs. Outcome measures included ulcer healing rate and ulcer area reduction rate. The Cochrane Risk Bias Tool, version 2.0, was used to assess the risk of bias in the included trials. R software was used for performing statistical analysis and GraphPad Prism was used for image plotting. Results: A total of 19 randomized controlled trials were included, and 900 patients with DFUs were assessed in this analysis. The proteolytic fraction from the latex of Vasconcellea cundinamarcensis (P1G10) in enzymatic debridement showed the best ulcer healing rate (SURCA = 0.919) when compared with the standard of care (SOC) group, with a mean difference (MD) and 95% confidence interval (CI) of 1.40 (0.57, 2.36). Kiwifruit extract demonstrated the best effect on the ulcer area reduction rate (SURCA = 0.931), when compared with that in the SOC group, with an MD and 95% CI of 0.47 (0.27, 0.66). Conclusion: Enzymatic debridement was superior to other debridement methods in terms of ulcer healing rate and ulcer area reduction rate in patients with DFUs. However, as the quality of the included trials is low, enzymatic debridement can be used as a candidate debridement method in addition to sharp-based debridement in clinical practice. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023441715.

KLHL29-mediated DDX3X degradation promotes chemosensitivity by abrogating cell cycle checkpoint in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous breast cancer subtype and accounts for approximately 15-20% of breast cancer cases. In this study, we identified KLHL29, which is an understudied member of the Kelch-like gene family, as a crucial tumor suppressor that regulates chemosensitivity in TNBC. KLHL29 expression was significantly downregulated in breast cancer tissues compared with adjacent normal tissues, and low levels of KLHL29 were associated with unfavorable prognoses. Ectopic KLHL29 suppressed, while depleting KLHL29 promoted, the growth, proliferation, migration, and invasion of TNBC. Mechanistically, KLHL29 recruited the CUL3 E3-ligase to the RNA-binding protein DDX3X, leading to the proteasomal degradation of the latter. This downregulation of DDX3X resulted in the destabilization of CCND1 mRNA and the consequent cell cycle arrest at G0/G1 phase. Remarkably, the DDX3X inhibitor RK33 combined with platinum-based chemotherapy can synergistically suppress TNBC that usually expresses low levels of KLHL29 and high levels of DDX3X using cancer cell-derived xenograft and patient-derived organoids models. Altogether, we uncovered the potential role for the KLHL29-DDX3X signaling cascade in the regulation of TNBC progression, thus providing a promising combination strategy for overcoming TNBC chemoresistance.

High expression of CCDC69 is correlated with immunotherapy response and protective effects on breast cancer.

BACKGROUND: As a molecule controlling the assembly of central spindles and recruitment of midzone component, coiled-coil domain-containing protein 69 (CCDC69) plays an important role in multiple cancers. Currently, the relationships between CCDC69 and immune infiltration or immunotherapy in breast cancer remain unclear. METHODS: The expression and prognostic significance of CCDC69 in breast cancer were comprehensively analyzed by quantitative real-time PCR, immunohistochemical staining and various databases. The data source of differentially expressed genes, gene set enrichment analysis, and immune cell infiltration analysis came from The Cancer Genome Atlas (TCGA) database. Single-cell analysis based on IMMUcan database was used. The protein-protein interaction network was developed applying STRING, Cytoscape, CytoHubba, and GeneMANIA. TISIDB was employed in analyzing the CCDC69 co-expressed immune related genes. The correlations between CCDC69 and immunotherapy or immune-related scores were analyzed by CAMOIP and TISMO. Ctr-db was also used to conduct drug sensitivity analysis. RESULTS: The mRNA of CCDC69 was downregulated in breast cancer tissues compared with normal tissues. Higher CCDC69 expression was associated with a better breast cancer prognosis. Enrichment analysis showed that the co-expression genes of CCDC69 were mainly related to immune-related pathways. The expression of CCDC69 was found to be positively correlated with multiple tumor-suppression immune infiltration cells, especially T cells and dendritic cells. Meanwhile, high CCDC69 expression can predict better immunotherapy responses when compared with low CCDC69 expression. After the interferon-gamma treatment, the CCDC69 expression was elevated in vitro. CCDC69 expression was a reliable predictor for the response status of two therapeutic strategies in breast cancer. CONCLUSIONS: Our research revealed the clinical significance of CCDC69 in breast cancer and validated the critical roles of CCDC69 in the tumor immune infiltration and immunotherapy responses.

PHF23 promotes NSCLC proliferation, metastasis, and chemoresistance via stabilization of ACTN4 and activation of the ERK pathway.

At present, non-small cell lung cancer (NSCLC) is still one of the leading causes of cancer-related deaths. Chemotherapy remains the standard treatment for NSCLC. However, the emergence of chemoresistance is one of the major obstacles to lung cancer treatment. Plant homologous structural domain finger protein 23 (PHF23) plays crucial roles in multiple cell fates. However, the clinical significance and biological role of PHF23 in NSCLC remain elusive. The Cancer Genome Atlas data mining, NCBI/GEO data mining, and western blotting analysis were employed to characterize the expression of PHF23 in NSCLC cell lines and tissues. Statistical analysis of immunohistochemistry and the Kaplan-Meier Plotter database were used to investigate the clinical significance of PHF23. A series of in vivo and in vitro assays, including assays for colony formation, cell viability, 5-ethynyl-2'-deoxyuridine (EDU incorporation) and Transwell migration, flow cytometry, RT-PCR, gene set enrichment analysis, co-immunoprecipitation analysis, and a xenograft tumor model, were performed to demonstrate the effects of PHF23 on the chemosensitivity of NSCLC cells and to clarify the underlying molecular mechanisms. PHF23 is overexpressed in NSCLC cell lines and tissues. High PHF23 levels correlate with short survival times and a poor response to chemotherapy in NSCLC patients. PHF23 overexpression facilitates cell proliferation, migration and sensitizes NSCLC cells to Cisplatin and Docetaxel by promoting DNA damage repair. Alpha-actinin-4 (ACTN4), as a downstream regulator, interacts with PHD domain of PHF23. Moreover, PHF23 is involved in ACTN4 stabilization by inhibiting its ubiquitination level. These results show that PHF23 plays an important role in the development and progression of NSCLC and suggest that PHF23 may serve as a therapeutic target in NSCLC patients.

ARHGAP39 is a prognostic biomarker involved in immune infiltration in breast cancer.

BACKGROUND: Current studies on the role of ARHGAP39 mainly focused on its effect on neurodevelopment. However, there are few studies on the comprehensive analysis of ARHGAP39 in breast cancer. METHODS: ARHGAP39 expression level was analyzed based on the Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression Project (GTEx), and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database and validated by qPCR in various cell lines and tumor tissues. The prognostic value was analyzed using Kaplan-Meier curve analysis. CCK-8 and transwell assays were conducted to identify the biological function of ARHGAP39 in tumorigenesis. Signaling pathways related to ARHGAP39 expression were identified by the GO and KEGG enrichment analysis and gene set enrichment analysis (GSEA). The correlations between ARHGAP39 and cancer immune infiltrates were investigated via TIMER, CIBERSORT, ESTIMATE and tumor-immune system interactions database (TISIDB). RESULTS: ARHGAP39 was overexpressed in breast cancer and associated with poor survival outcomes. In vitro experiments revealed that ARHGAP39 could facilitate the proliferation, migration, and invasion capability of breast cancer cells. GSEA analysis showed that the main enrichment pathways of ARHGAP39 was immunity-related pathways. Considering the immune infiltration level, ARHGAP39 was negatively associated with infiltrating levels of CD8 + T cell and macrophage, and positively associated with CD4 + T cell. Furthermore, ARHGAP39 was significantly negatively correlated with immune score, stromal score, and ESTIMATE score. CONCLUSIONS: Our findings suggested that ARHGAP39 can be used as a potential therapeutic target and prognostic biomarker in breast cancer. ARHGAP39 was indeed a determinant factor of immune infiltration.

Global Scientific Trends on Healthy Eating from 2002 to 2021: A Bibliometric and Visualized Analysis.

Diet has been recognized as a vital risk factor for non-communicable diseases (NCDs), climate changes, and increasing population, which has been reflected by a rapidly growing body of the literature related to healthy eating. To reveal a panorama of the topics related to healthy eating, this study aimed to characterize and visualize the knowledge structure, hotspots, and trends in this field over the past two decades through bibliometric analyses. Publications related to healthy eating between 1 January 2002 and 31 December 2021 were retrieved and extracted from the Web of Science database. The characteristics of articles including publication years, journals, authors, institutions, countries/regions, references, and keywords were assessed. The analyses on co-authorship, co-occurrence, and co-citation were performed and network visualization maps were constructed by VOSviewer. Major subdomains identified by bibliometrics were further discussed and analyzed. A total of 12,442 articles on healthy eating were identified. Over the past two decades, the annual global publications increased from 71 to 1764, showing a nearly 25-fold growth. The journal Nutrients published the most articles and The American Journal of Clinical Nutrition possessed the highest citations. The United States, Harvard University, and Hu, Frank B. were identified as the most productive and influential country, institution, and author, respectively. The co-occurrence cluster analysis of the top 100 keywords formed four clusters: (1) the food insecurity environment for youths highlighting the necessity and significance of implementing healthy eating in early life; (2) sustainable advantages of the Mediterranean diet; (3) the importance of an overall healthy lifestyle optimization leveraged by eHealth; (4) the challenges during the course of healthy eating against obesity, which are prominent in reflecting the knowledge structure, hotspots, and trends. Moreover, COVID-19, orthorexia nervosa, sustainability, microbiota, food insecurity, and e-health are identified keywords that represented the latest high-frequency keywords and indicated the emerging frontiers of healthy eating. This study indicates that the number of publications on healthy eating will increase in the future and that healthy dietary patterns and clinical applications of healthy eating will be the next hotspots in this research field.

Efficacy and safety of endocrine therapy after mastectomy in patients with hormone receptor positive breast ductal carcinoma in situ: Retrospective cohort study.

Background: More than half of Chinese patients with hormone receptor positive (HR+) ductal carcinoma in situ (DCIS) are treated with mastectomy, and usually subjected to postoperative endocrine therapy (ET). Given that long-term ET can cause severe adverse effects it is important to determine the beneficial effect and safety of post-mastectomy ET on the disease-free survival (DFS) and adverse events in patients with HR+ DCIS. Methods: To explore beneficial effect and safety of post-mastectomy ET in patients with HR+ DCIS, we performed a multicenter, population-based study. This retrospective study analyzed the DFS and adverse events in 1037 HR+ DCIS Chinese patients with or without post-mastectomy ET from eight breast centers between 2006 and 2016. The median follow-up time period was 86 months. Results: There were 791 DCIS patients receiving ET (ET group). Those patients were followed up for a median of 86 months (range, 60-177 months). There were 23 cases with tumor recurrence or distant metastasis. There were similar 5-year DFS rates and DFS between the ET and non-ET groups, even for those with high-risk factors. Conversely, 37.04% of patients suffered from adverse events after ET, which were significantly higher than those in the non-ET group. Conclusions: ET after mastectomy did not benefit patients with HR+ DCIS for their DFS, rather increased adverse events in those patients. Therefore, ET after mastectomy may not be recommended for patients with HR+ DCIS, even for those with high-risk factors, such as multifocal, microinvasive, and higher T stage. Funding: This study was supported by grants from Outstanding Scientific Fund of Shengjing Hospital (201803) and Outstanding Young Scholars of Liaoning Province (2019-YQ-10).

Platelet-rich plasma for the treatment of diabetic foot ulcer: a systematic review.

Background: With the increasing incidence of diabetes, diabetic foot ulcer(DFU) has become one of the most common and serious complications in people with diabetes. DFU is associated with significant morbidity and mortality, and can also result in significant economic, social and public health burdens. Due to peripheral neuropathy, peripheral vascular disease, hyperglycemic environment, inflammatory disorders and other factors, the healing of DFU is impaired or delayed, resulting in the formation of diabetic chronic refractory ulcer. Because of these pathological abnormalities in DFU, it may be difficult to promote wound healing with conventional therapies or antibiotics, whereas platelet-rich plasma(PRP) can promote wound healing by releasing various bioactive molecules stored in platelets, making it more promising than traditional antibiotics. Therefore, the purpose of this systematic review is to summarize and analyze the efficacy of PRP in the treatment of DFU. Methods: A literature search was undertaken in PubMed, CNKI, EMB-ASE, the Cochrane Library, the WanFang Database and the WeiPu Database by computer. Included controlled studies evaluating the efficacy of PRP in the treatment of diabetic foot ulcers. The data extraction and assessment are on the basis of PRISMA. Results: Twenty studies were evaluated, and nineteen measures for the evaluation of the efficacy of PRP in DFU treatment were introduced by eliminating relevant duplicate measures. The efficacy measures that were repeated in various studies mainly included the rate of complete ulcer healing, the percentage of ulcer area reduction, the time required for ulcer healing, wound complications (including infection rate, amputation rate, and degree of amputation), the rate of ulcer recurrence, and the cost and duration of hospitalization for DFU, as well as subsequent survival and quality of life scores. One of the most important indicators were healing rate, ulcer area reduction and healing time. The meta-analysis found that PRP was significantly improve the healing rate(OR = 4.37, 95% CI 3.02-6.33, P < 0.001) and shorten the healing time(MD = -3.21, 95% CI -3.83 to -2.59,P < 0.001)of patients with DFU when compared to the conventional treatment, but there was no significant difference in reducing the of ulcer area(MD = 5.67, 95% CI -0.77 to 12.11,P =0.08>0.05 ). Conclusion: The application of PRP to DFU can improve ulcer healing rate and shorten ulcer healing time, but more clinical data are needed to clarify some efficacy measures. At the same time, a standardized preparation process for PRP is essential.

The Platelet-to-Lymphocyte Ratio Predicts Diabetic Retinopathy in Type 2 Diabetes Mellitus.

Introduction: As a severe and specific neurovascular complication of type 2 diabetes mellitus (T2DM), diabetic retinopathy (DR) remains the leading cause of vision loss and preventable blindness in adults aged 20 to 74. The pathogenesis of DR is not completely understood, however, studies indicate that chronic inflammation plays a significant role. Emerging evidence suggests that the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the monocyte-to-lymphocyte ratio (MLR) are novel potential inflammatory response markers. The purpose of this study was to investigate the relationships between the NLR, PLR, MLR, and DR. Patients and Methods: 290 patients who had been diagnosed with T2DM participated in the study. Patients were categorized into three groups: 142 control subjects with T2DM, 124 subjects with nonproliferative diabetic retinopathy (NPDR), and 24 patients with proliferative diabetic retinopathy (PDR). Characteristics, laboratory data, as well as NLR, PLR and MLR levels of the study groups were compared. Results: In patients with DR, the median NLR, PLR, and MLR were significantly higher than in patients without DR (p = 0.012, p < 0.001, and p = 0.043, respectively). In the post hoc analysis, there was no correlation between the severity of retinopathy and the increase in NLR or PLR. Multiple logistic regression revealed that the PLR was an independent risk factor for DR (odds ratio [OR]: 1.020, 95% confidence interval [CI]: 1.010-1.029 p = 0.026). Based on the receiver operating characteristic (ROC) curve, the cutoff value of PLR as an indicator for diagnosing DR was estimated to be 129.65, with a sensitivity and specificity of 53.4% and 76.1%, respectively, and an area under the curve of 0.668 (95% CI: 0.605-0.730, p < 0.001). Conclusion: Our findings suggest that PLR may be an independent risk factor for evaluating DR in type 2 diabetes patients.

Mitophagy: A potential therapeutic target for insulin resistance.

Glucose and lipid metabolism disorders caused by insulin resistance (IR) can lead to metabolic disorders such as diabetes, obesity, and the metabolic syndrome. Early and targeted intervention of IR is beneficial for the treatment of various metabolic disorders. Although significant progress has been made in the development of IR drug therapies, the state of the condition has not improved significantly. There is a critical need to identify novel therapeutic targets. Mitophagy is a type of selective autophagy quality control system that is activated to clear damaged and dysfunctional mitochondria. Mitophagy is highly regulated by various signaling pathways, such as the AMPK/mTOR pathway which is involved in the initiation of mitophagy, and the PINK1/Parkin, BNIP3/Nix, and FUNDC1 pathways, which are involved in mitophagosome formation. Mitophagy is involved in numerous human diseases such as neurological disorders, cardiovascular diseases, cancer, and aging. However, recently, there has been an increasing interest in the role of mitophagy in metabolic disorders. There is emerging evidence that normal mitophagy can improve IR. Unfortunately, few studies have investigated the relationship between mitophagy and IR. Therefore, we set out to review the role of mitophagy in IR and explore whether mitophagy may be a potential new target for IR therapy. We hope that this effort serves to stimulate further research in this area.

[Iodine Nutritional Status and Prevalence of Thyroid Disorders among Adults in Chengdu].

Objective: To investigate the prevalence of thyroid disorders, iodine nutritional status and relevant risk factors among adults in Chengdu city on the basis of two population-based surveys, one conducted between 2016 and 2017 and the other, between 2019 and 2020, and to provide references for making health-related administrative decisions. Methods: Two population-based sampling surveys were conducted. The first one was done between October 2016 and December 2017, using stratified cluster random sampling to select subjects from 2 urban and 2 rural communities in Chengdu. Then, between December 2019 and February 2020, sequential cluster sampling was used to select subjects from communities in the peripheral regions of Longquanyi District, Chengdu. Both surveys covered natural populations of people who were 18 or older and who met the inclusion criteria. In the first survey, questionnaires, physical examination, thyroid ultrasound, and examinations of serum thyroid biochemical markers and urine iodine were performed, while in the second survey, only questionnaire concerning thyroid disorders and physical examination were performed. Statistical analysis of the nutritional status of iodine, the prevalence of thyroid disorders, and potential risk factor was conducted. Results: A total of 1859 subjects were enrolled for the first survey and 16152 for the second. According to the results of the first survey, the median urine iodine concentration was 172.10 µg/L, and the group with adequate or more than adequate iodine accounted for more than 60% of the surveyed population. The prevalence of thyroid disorders was found to be 0.48% for overt hyperthyroidism, 0.43% for subclinical hyperthyroidism, 0.43% for Grave's disease, 1.34% for overt hypothyroidism, 16.62% for subclinical hypothyroidism, 16.73% for positive thyroid antibody, 12.96% for TPOAb positive, 10.06% for TGAb positive, 0.81% for goiter, 14.85% for single nodule, 14.42% for multi-nodules, and 29.26% for thyroid nodules. Excess iodine is a risk factor for subclinical hypothyroidism ( OR=1.50, 95% confidence interval [ CI]: 1.07-2.10, P<0.05), and iodine deficiency is a risk factor for multiple thyroid nodules ( OR=1.45, 95% CI: 1.02-2.05, P<0.05). The total prevalence of hyperthyroidism, hypothyroidism and Hashimoto's thyroiditis in the two surveys was 6.58% and 5.95%, respectively, showing no significant difference. The second survey lacked accurate data on thyroid nodules. Conclusion: The iodine nutritional status of adults in Chengdu in recent years was appropriate. The total prevalence of hyperthyroidism, hypothyroidism and Hashimoto's thyroiditis remained stable, while that of thyroid nodule increased in recent years. We should continue with the implementation of the universal salt iodization policy and reinforce efforts in monitoring. Furthermore, we should make an active effort to look into the etiology of thyroid nodules.

The prognostic impact of myosteatosis on overall survival in gynecological cancer patients: A meta-analysis and trial sequential analysis.

Myosteatosis is a novel imaging biomarker for survival in gynecological cancer patients; however, the evidence is inconsistent. This meta-analysis aims to investigate the impact of myosteatosis on overall survival in the gynecological oncology setting. Three databases (PubMed, EMBASE and Web of Science) were systematically searched for relevant literature up to October 30, 2021. A random-effects model was used to evaluate the predictive effect of myosteatosis on overall survival in the gynecological cancer population. The Newcastle-Ottawa Scale was used to assess the methodological quality of the included studies. Trial sequential analysis was used to control the risk of random errors. Twelve studies with a total of 2519 patients were included. Myosteatosis was associated with a 50% increased mortality risk (HR 1.50, 95% CI 1.24-1.82, P < .001) in gynecological cancer patients. Subgroup analyses stratified by study design, statistical model, treatment, sample size and stage confirmed the predictive value of myosteatosis on survival. However, the prognostic ability of myosteatosis only was held in the American and European populations but lost in Asians. Additionally, myosteatosis was not associated with the increased mortality in endometrial and cervical cancers, except for ovarian cancers. Overall, myosteatosis is a powerful predictor of reduced overall survival in gynecological cancer patients.