Danggui Shaoyao San ameliorates the lipid metabolism via the PPAR signaling pathway in a Danio rerio (zebrafish) model of hyperlipidemia.

The escalating prevalence of hyperlipidemia has a profound impact on individuals' daily physiological well-being. The traditional Chinese medicine (TCM) prescription Danggui Shaoyao San (DSS) has demonstrated significant clinical efficacy and promising prospects for clinical application. Leveraging network pharmacology and bioinformatics, we hypothesize that DSS can ameliorate lipid metabolic disorders in hyperlipidemia by modulating the PPAR signaling pathway. In this study, we employed a zebrafish model to investigate the impact of DSS on lipid metabolism in hyperlipidemia. Body weight alterations were monitored by pre- and postmodeling weight measurements. Behavioral assessments and quantification of liver biochemical markers were conducted using relevant assay kits. Pathways associated with lipid metabolism were identified through network pharmacology and GEO analysis, while PCR was utilized to assess genes linked to lipid metabolism. Western blotting was employed to analyze protein expression levels, and liver tissue underwent Oil Red O and immunofluorescence staining to evaluate liver lipid deposition. Our findings demonstrate that DSS effectively impedes weight gain and reduces liver lipid accumulation in zebrafish models with elevated lipid levels. The therapeutic effects of DSS on lipid metabolism are mediated through its modulation of the PPAR signaling pathway, resulting in a significant reduction in lipid accumulation within the body and alleviation of certain hyperlipidemia-associated symptoms.

Factors influencing the development of bone starvation syndrome after total parathyroidectomy in patients with renal hyperparathyroidism.

Purpose: To investigate the factors affecting the development of bone starvation syndrome (HBS) after total parathyroidectomy in patients with renal hyperparathyroidism (SHPT). Patients and methods: The clinical data and perioperative indices of 141 patients who underwent PTX for SHPT were retrospectively analyzed. The patients were divided into HBS and non-HBS groups based on postoperative minimum blood calcium <1.87 mmol/L. The differences in general clinical data and perioperative related indices between the two groups were compared; logistic regression analysis was performed to analyze the risk factors influencing HBS occurrence after surgery. Multiple linear regression method was used to analyze the factors influencing the maintenance time of intravenous calcium supplementation and total amount of calcium supplementation during intravenous calcium supplementation. The threshold value for the diagnosis of HBS was analyzed using the ROC subjects' working curve. Results: HBS occurred in 46 (32.6%) patients. Univariate analysis showed statistically significant differences in dialysis age, preoperative calcitonin, preoperative parathyroid hormone, preoperative blood phosphorus, and preoperative alkaline phosphatase between both groups (P < 0.05). Logistic regression analysis using stepwise entry method concluded that preoperative alkaline phosphatase was an independent factor for the development of HBS after surgery. Preoperative parathyroid hormone was an independent factor for the duration of intravenous calcium supplementation and total calcium supplementation during intravenous calcium supplementation in the HBS group. Based on the ROC curve, for postoperative HBS, the cut-off ALP value was 199.5 U/L, with a sensitivity of 80.85% and specificity of 82.61%. Conclusion: Preoperative serum ALP may be an independent factor for HBS occurrence after surgery. When preoperative ALP > 199.5 U/L, patients with SHPT are prone to HBS after surgery, and the higher the preoperative ALP, the higher the incidence of HBS, and vice versa. In addition, preoperative PTH may be the factor in the timing of postoperative intravenous calcium supplementation and the total amount of calcium supplementation during intravenous calcium supplementation in patients with HBS.

Predictors of hyperkalemia after total parathyroidectomy in patients with drug-refractory secondary hyperparathyroidism.

Background: The purpose of this retrospective study was to explore the primary possible risk factors for the development of postoperative hyperkalemia after total parathyroidectomy with autotransplantation (TPTX + AT) in patients with drug-refractory secondary hyperparathyroidism (SHPT). Methods: The clinical data of 149 patients receiving maintenance dialysis for drug-refractory SHPT, who underwent TPTX + AT, were reviewed and analyzed. Demographic data, dialysis status, and laboratory test indices were collected from enrolled patients. According to the postoperative serum potassium level >5.3 mmol/L or not, they were divided into hyperkalemia group and non-hyperkalemia group. The differences in general clinical data and laboratory indicators between the two groups were compared; logistic regression analysis was performed to analyze the risk factors affecting the development of postoperative hyperkalemia in patients; receiver operating characteristic (ROC) subject workup curves were analyzed for the threshold values of postoperative hyperkalemia. Results: Of the 149 participants, 25 (16.78%) developed postoperative hyperkalemia after TPTX + AT. Univariate analysis suggested that dialysis duration, SHPT duration, dialysis modality, and preoperative alkaline phosphatase, blood potassium, and blood calcium levels were independently associated with the development of hyperkalemia after TPTX + AT. Univariate logistic analysis suggested that dialysis duration [odds ratio (OR) 1.18, 95% confidence interval (CI): 1.03, 1.35, P=0.014], preoperative blood potassium (OR 4.95, 95% CI: 2.05, 11.96, P<0.001), and preoperative blood calcium (OR 16.17, 95% CI: 1.36, 191.58, P=0.027) were 3 factors that predicted hyperkalemia after TPTX + AT. According to ROC curve analysis, the optimal cutoff point for dialysis duration was 8.5 years, the optimal cutoff level for preoperative blood potassium was 4.57 mmol/L, and the optimal cutoff level for preoperative blood calcium was 2.31 mmol/L. Of these 3 factors, preoperative blood potassium had a more balanced sensitivity, specificity, and optimal diagnostic efficacy. Conclusions: Patients with drug-refractory SHPT are prone to hyperkalemia after TPTX + AT. Duration of dialysis and preoperative blood potassium and blood calcium levels can help predict the development of postoperative hyperkalemia.

[Baicalin inhibits LPS/IFN-γ-induced inflammation via TREM2/TLR4/NF-κB pathway in BV2 cells].

This study investigated the mechanism of baicalin on lipopolysaccharide(LPS)/interferon γ(IFN-γ)-induced inflammatory microglia based on the triggering receptor expressed on myeloid cells 2(TREM2)/Toll-like receptor 4(TLR4)/nuclear factor kappaB(NF-κB) pathway. Specifically, LPS and IFN-γ were used to induce inflammation in mouse microglia BV2 cells. Then the normal group, model group, low-dose(5 µmol·L~(-1)) baicalin group, medium-dose(10 µmol·L~(-1)) baicalin group, high-dose(20 µmol·L~(-1)) baicalin group, and minocycline(10 µmol·L~(-1)) group were designed. Cell viability was detected by CCK-8 assay and cell morphology was observed under bright field. The expression of interleukin-1ß(IL-1ß), interleukin-4(IL-4), inducible nitric oxide synthase(iNOS), interleukin-6(IL-6), interleukin-10(IL-10), and arginase-1(Arg-1) mRNA was detected by real-time quantitative PCR, the protein expression of tumor necrosis factor-α(TNF-α), IL-1ß, TREM2, TLR4, inhibitor kappaB-alpha(IκBα), p-IκBα, NF-κB p65 and p-NF-κB p65 by Western blot, and transfer of NF-κB p65 from cytoplasm to nucleus by cellular immunofluorescence. Compared with the normal group, most of the BV2 cells in the model group tended to demonstrate the pro-inflammatory M1 amoeba morphology, and the model group showed significant increase in the mRNA levels of IL-1ß, IL-6, and iNOS, decrease in the mRNA levels of IL-4, IL-10, and Arg-1(P<0.01), rise of the protein expression of TNF-α, IL-1ß, TLR4, p-IκBα, and p-NF-κB p65(P<0.01), reduction in TREM2 protein expression, and increase in the expression of NF-κB p65 in nucleus. Compared with the model group, baicalin groups and minocycline group showed the recovery of BV2 cell morphology, significant decrease in the mRNA levels of IL-1ß, IL-6 and iNOS, increase in the mRNA levels of IL-4, IL-10, and Arg-1(P<0.01), reduction in the protein expression of TNF-α, IL-1ß, TLR4, p-IκBα, and p-NF-κB p65(P<0.05), rise of TREM2 protein expression, and decrease in the expression of NF-κB p65 in nucleus. In summary, these results suggest that baicalin can regulate the imbalance between TREM2 and TLR4 of microglia and inhibit the activation of downstream NF-κB, thus promoting the polarization of microglia from pro-inflammatory phenotype to anti-inflammatory phenotype.

The relationship between urologic cancer outcomes and national Human Development Index: trend in recent years.

OBJECTIVES: To describe the influence of the socioeconomic development on worldwide age-standardized incidence and mortality rates, as well as mortality-to-incidence ratio (MIR) and 5-year net survival of urologic cancer patients in recent years. METHODS: The Human Development Index (HDI) values were obtained from the United Nations Development Programme, data on age-standardized incidence/mortality rates of prostate, bladder and kidney cancer were retrieved from the GLOBOCAN database, 5-year net survival was provided by the CONCORD-3 program. We then evaluated the association between incidence/MIR/survival and HDI, with a focus on geographic variability as well as temporal patterns during the last 6 years. RESULTS: Urologic cancer incidence rates were positively correlated with HDIs, and MIRs were negatively correlated with HDIs. Prostate cancer survival also correlated positively with HDIs, solidly confirming the interrelation among cancer indicators and socioeconomic factors. Most countries experienced incidence decline over the most recent 6 years, and a substantial reduction in MIR was observed. Survival rates of prostate cancer have simultaneously improved. CONCLUSION: Development has a prominent influence on urologic cancer outcomes. HDI values are significantly correlated with cancer incidence, MIR and survival rates. HDI values have risen along with increased incidence and improved outcomes of urologic caner in recent years.

An Expectation Maximization Based Adaptive Group Testing Method for Improving Efficiency and Sensitivity of Large-Scale Screening of COVID-19.

The pathogen of the ongoing coronavirus disease 2019 (COVID-19) pandemic is a newly discovered virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Testing individuals for SARS-CoV-2 plays a critical role in containing COVID-19. For saving medical personnel and consumables, many countries are implementing group testing against SARS-CoV-2. However, existing group testing methods have the following limitations: (1) The group size is determined without theoretical analysis, and hence is usually not optimal. This adversely impacts the screening efficiency. (2) These methods neglect the fact that mixing samples together usually leads to substantial dilution of the SARS-CoV-2 virus, which seriously impacts the sensitivity of tests. In this paper, we aim to screen individuals infected with COVID-19 with as few tests as possible, under the premise that the sensitivity of tests is high enough. We propose an eXpectation Maximization based Adaptive Group Testing (XMAGT) method. The basic idea is to adaptively adjust its testing strategy between a group testing strategy and an individual testing strategy such that the expected number of samples identified by a single test is larger. During the screening process, the XMAGT method can estimate the ratio of positive samples. With this ratio, the XMAGT method can determine a group size under which the group testing strategy can achieve a maximal expected number of negative samples and the sensitivity of tests is higher than a user-specified threshold. Experimental results show that the XMAGT method outperforms existing methods in terms of both efficiency and sensitivity.

Neuroprotective Effect of Danggui Shaoyao San via the Mitophagy-Apoptosis Pathway in a Rat Model of Alzheimer's Disease.

Alzheimer's disease (AD) is a serious neurodegenerative disease. While the main pathological characteristic of AD is widely believed to be the accumulation of amyloid-beta (Aß) in neurons around neurofibrillary plaques, the molecular mechanism of pathological changes is not clear. Traditional Chinese medicine offers many treatments for AD. Among these, Danggui Shaoyao San (DSS) is a classic prescription. In this study, an AD model was established by injecting Aß 1-42 into the brains of rats, which were then treated with different concentrations of Danggui Shaoyao San (sham operation; model; and Danggui Shaoyao San high-dose, medium-dose, and low-dose intervention groups). The Morris water maze test was used to assess the learning and memory abilities of the animals in each group. Nissl staining was used to detect neurons. Mitophagy was evaluated by transmission electron microscopy and immunofluorescence colocalization. Apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The expression levels of autophagy- and apoptosis-related proteins were measured by western blot. Compared to the model group, the groups of AD rats administered medium and high doses of Danggui Shaoyao San showed significantly increased learning and memory abilities (P < 0.05), as well as significantly increased autophagosomes in the hippocampus. Moreover, the expression of PTEN-induced kinase 1 (PINK1), Parkin, and microtubule-associated protein light chain 3 (LC3-I/LC3-II) was increased, while that of p62 was significantly decreased (P < 0.05). The neuronal apoptosis rate was also significantly decreased, the Bcl-2/Bax ratio was significantly increased, and the cleaved caspase-3 protein expression was significantly decreased (P < 0.05). Therefore, Danggui Shaoyao San inhibited neuronal apoptosis in AD rats via a mechanism that may be related to the activation of the PINK1-Parkin-mediated mitophagy signaling pathway.

A novel nomogram for predicting the risk of epilepsy occurrence after operative in gliomas patients without preoperative epilepsy history.

OBJECTIVE: Epilepsy is a common complication in glioma patients after undergoing brain tumor surgery combined with chemotherapy and/or radiotherapy. Whether antiepileptic drug prophylaxis could be used in these patients remains an open question. The purpose of this study was to produce a model for predicting the risk of epilepsy occurrence in such patients. METHODS: The clinicopathologic data of glioma patients after tumor treatment were reviewed in this study. Univariate and multivariate logistic regression analyses were carried out to analyze the correlation between the clinicopathologic data and the risk of epilepsy occurrence. A nomogram was built according to the multivariate logistic regression model results. RESULTS: A total of 219 patients with gliomas were reviewed. Univariate analyses revealed that age, WHO glioma classification, CD34, EGFR, Ki67, MGMT, P53 and VIM were significantly associated with the risk of epilepsy occurrence. Multivariate analyses revealed that age, WHO glioma classification, CD34, EGFR, MGMT, and VIM were predictors of risk of epilepsy occurrence. A nomogram of the risk of epilepsy occurrence was built based on statistically significant variables from the multivariate logistic regression analysis. The c-index of the nomogram was 0.755 (95 % confidence interval (CI), 0.742-0.769). SIGNIFICANCE: This nomogram model provides reliable information about the risk of epilepsy occurrence for oncologists and neurological physicians.

High Mean Corpuscular Volume as a Predictor of Poor Overall Survival in Patients with Esophageal Cancer Receiving Concurrent Chemoradiotherapy.

BACKGROUND: Increasing numbers of recent studies have demonstrated that high mean corpuscular volume (MCV) is a predictor of poor overall survival (OS) and therapeutic response in patients with solid tumors. The aim of the present study was to explore the association between high MCV and OS in patients with advanced esophageal cancer (EC) undergoing concurrent chemoradiotherapy. PATIENTS AND METHODS: Enrolled in this study were 249 patients with advanced EC who underwent concurrent chemoradiotherapy. Pre-treatment MCV values were collected in all patients and their correlations with OS and pathophysiological characteristics were analyzed. The chi-square test was used to explore the correlation between MCV and various clinical pathophysiological characteristics, and the prognostic significance of high MCV using Kaplan-Meier curves and the Cox proportional hazards model. All P-values were two-tailed and a P-value <0.05 was considered statistically significant. RESULTS: According to ROC curve analysis, the optimal cut-off value of MCV was 93.6 fL. The mean OS was 14.7 months in all 249 EC patients, 10.9 months in patients with MCV >93.6 fL, and 18.8 months in patients with MCV <93.6 fL; the difference is statistically significant (P<0.05). Chi-square test showed that the MCV value was correlated with the N stage of the tumor and the therapeutic effect, indicating that the higher the MCV was, the higher the T stage of the tumor and the worse the therapeutic effect would be (p=0.012 and p <0.01). Multivariate analysis showed that MCV (OR = 1.864, 95% CI: 1.439-2.415) was an independent prognostic factor for OS in EC patients. CONCLUSION: High MCV is a poor predictor of OS in patients with advanced EC receiving concurrent chemoradiotherapy.

Predictive value of neuron-specific enolase, neutrophil-to-lymphocyte-ratio and lymph node metastasis for distant metastasis in small cell lung cancer.

OBJECTIVE: To investigate the value of neuron-specific enolase (NSE), neutrophil-to-lymphocyte ratio (NLR) and lymph node metastasis in predicating distant metastasis in patients with limited-stage small cell lung cancer (LD-SCLC). METHODS: Clinical pathological data of LD-SCLC patients in the First Affiliated Hospital of Wenzhou Medical University between August 2009 and October 2017 were retrospectively analyzed. The age, gender, smoking, TNM, NSE, NLR, chemotherapy cycle, radiotherapy, surgery and new metastasis of lymph nodes of 47 cases with distant metastasis and 47 cases without distant metastasis in 1 year were compared. Finally, factors influencing distant metastasis were determined as the predictors. The receiver operating characteristic (ROC) curve model was established based on logistic regression analysis of the factors obtained. RESULTS: Distant metastasis mainly involved brain (17/47), liver (17/47) and bone (17/47). Univariate analysis showed that patients with new lymph node metastasis, high NSE, pretreatment hilar lymph node metastasis and NLR were more prone to have distant metastasis. Multivariate analysis showed that new lymph node metastasis, high NSE, NLR and pretreatment hilar lymph node metastasis were independent predictors. The predictive model established using these predictors had an AUC of 0.872 (95%CI: 0.803-0.941), a sensitivity of 76.60% and a speciality of 80.85%. CONCLUSION: The new lymph node metastasis, NLR and NSE are predictors of distant metastasis, and thus, may have a profound impact on treatment decision making. Patients with lower NLR and NSE expression levels and less new metastasis of lymph nodes have a lower distant metastasis rate.

Predictive value of lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) in patients with oesophageal cancer undergoing concurrent chemoradiotherapy.

BACKGROUND AND OBJECTIVES: The survival rate of patients with advanced oesophageal cancer is very low and can vary significantly, even among patients with the same TNM stage. It is important to look for indicators that are economical and readily available to predict overall survival. The aim of this study was to determine whether lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) could be potential predictors of survival in patients with advanced oesophageal squamous cell carcinoma (ESCC) undergoing concurrent chemoradiotherapy. METHODS: Differences in survival among 204 patients with advanced oesophageal cancer who underwent concurrent chemoradiotherapy were collected and analysed. Univariate and multivariate COX regression analyses were used to investigate the association between blood inflammatory markers and patient survival before treatment. RESULTS: Univariate COX regression analyses showed that a history of alcohol use, neutrophil count, LMR, NLR, tumour length, and N stage were significantly associated with the survival of tumour patients receiving concurrent chemoradiotherapy. Multivariate COX regression analysis showed that NLR and LMR were predictors of outcome in tumour patients receiving chemoradiotherapy. According to receiver operating characteristic (ROC) curve analysis, the AUC of LMR and NLR was 0.734 and 0.749, and the best cutoff point for LMR and NLR was 3.03 and 2.64, respectively. CONCLUSIONS: LMR and NLR can be used to predict the survival of patients with advanced oesophageal cancer receiving concurrent chemoradiotherapy, thereby providing clinicians with suggestions for further treatment options.

Development of a contouring guide for three different types of optic chiasm: A practical approach.

INTRODUCTION: Sparing of the organs at risk (OARs) is a crucial task in daily radiotherapy practice. Irradiation of the optic chiasm (OC) results in radiation-induced optic neuropathy (RION). The structure of the OC is complex, and OC morphology can vary in axial images. Therefore, a standard atlas can result in inaccurate descriptions of OC morphology in different patients. The aim of our study was to provide a guide based on computed tomography (CT) for the delineation of different types of OC. METHODS: Thirty-six patients were selected to participate in our study. These patients underwent CT analysis of the brain, head and neck regions in a supine position. Axial images 3 mm in thickness were obtained at 3-mm intervals. A magnetic resonance imaging (MRI) study was also performed using the same set-up. The OC was then delineated. The contours were revised by three neuroradiologists and nine radiation oncologists with > 5 years of expertise. RESULTS: Three types of OC were distinguished by magnetic resonance (MR). The location and boundaries of normal, prefixed and postfixed chiasms were developed with a CT-based atlas. Discrepancies were observed in the delineation of the prefixed and postfixed OC. CONCLUSIONS: Our guide allows improved definitions of the anatomical boundaries for different types of OC. Our experience could provide useful information for radiation oncologists in daily practice.

PD-L1 Induces Epithelial-Mesenchymal Transition in Nasopharyngeal Carcinoma Cells Through Activation of the PI3K/AKT Pathway.

Nasopharyngeal cancer (NPC) is a malignant epithelial carcinoma of the head and neck. Cancer therapy targeting programmed cell death protein-1 (PD-1) or programmed death ligand-1 (PD-L1) is revolutionary. However, the tumorigenic mechanism of PD-L1 is not yet clear in NPC. Here we demonstrated an oncogenic role of PD-L1 via activating PI3K/AKT in NPC cells. PD-L1 overexpression was frequently detected in NPC biopsies and cell lines by qRT-PCR. PD-L1 overexpression and knockdown demonstrated that PD-L1 promoted NPC cell invasion and metastasis in vitro and in vivo. Mechanistically, PD-L1 prominently activated the epithelial-mesenchymal transition (EMT) process in a PI3K/AKT-dependent manner. Taken together, we found that PD-L1 overexpression confers NPC cell malignancy and aggressiveness via activating the downstream PI3K/AKT signaling. Thus, these results provide a basis for diagnosis and treatment of NPC.

Hyperprogressive disease in cancer patients with immune checkpoint inhibitor therapy and its coping strategies / 中国肿瘤生物治疗杂志

@#Successful targeting and inhibition of the programmed cell death-1/ programmed cell death-ligand 1 immune checkpoint pathways by monoclonal antibody stimulates an immune response against tumors, has led to a rapidly expanding repertoire of immune checkpoint inhibitors (ICIs) for the treatment of various cancers. Immune checkpoint therapy has dramatically changed the therapeutic landscape of certain types of cancers. However, hyperprogressive disease (HPD) is emerging as a new pattern of progression in cancer patients treated with ICIs, characterized as an absolute increase in the tumor growth rate exceeding 50% per month. This article discusses the concept of HPD, hypotheses as to the underlying biology, and what needs to be done to better understand and identify strategies to prevent or overcome HPD related to checkpoint blockade therapy.

AKT/mTOR signaling pathway is involved in salvianolic acid B-induced autophagy and apoptosis in hepatocellular carcinoma cells.

Chinese medicines are emerging as an attractive new generation of anticancer drugs. Here, we explored the impact of salvianolic acid B (Sal B), the major water-soluble compounds of Danshen, on apoptosis and autophagy of human hepatocellular carcinoma cells (HCC). We also investigated the related molecular mechanisms. We found that Sal B exhibits potent ability to inhibit HCC cells viability in a concentration-dependent manner, and to induce apoptosis via the mitochondrial apoptosis pathway. Additionally, Sal B could also induce autophagy. Furthermore, pretreatment with the autophagy inhibitor chloroquine or 3-methyladenine showed the potential in attenuating the apoptosis rate induced by Sal B. Mechanistically, Sal B treatment inhibited the AKT/mTOR signaling cascade in vitro. Overexpression of AKT abolished the effects of Sal B on HCC cells, suggesting a critical role of the AKT/mTOR signaling pathway in Sal B-induced biological effects. Our results indicated that the mitochondrial pathway was involved in Sal B-induced apoptosis of HCC cells. Moreover, the AKT/mTOR signaling pathway was involved in Sal B-induced autophagy, which promoted apoptosis. This study may provide a promising strategy for using Sal B as a chemotherapeutic agent for patients with HCC.