Estrogen receptor-related receptor γ uppresses hypoxia-induced angiogenesis by regulating VEGFA in endometrial cancer.

OBJECTIVE: Estrogen receptor-related receptor γ (ERRγ), is implicated in cancer cell proliferation and metastasis. The function of ERRγ in tumor angiogenesis, however, is to be revealed. This study was designed to elaborate the regulatory effect of ERRγ on angiogenesis in endometrial cancer (EC). METHODS: Immunohistochemistry (IHC) was adopted to determine the protein expression of ERRγ, VEGFA, CD31 and hypoxia-inducible factor-1 (HIF-1) in tumor tissues. HEC-1A cells stably expressing ERRγ were established bytransfection, and then an endothelial cell tube formation assay was performed. CCK-8 assay was employed for cell viability, and wound healing assay for cell migration ability. Besides, western blot, ELISA and qRT-PCR were used to examine the VEGFA expression. After hypoxia treatment of ERRγ overexpressing HEC-1A cells, the ERRγ expression and VEGFA expression were determined by western blot. Finally, EC xenografts in nude mice were constructed by subcutaneous injection of ERRγ stably expressing HEC-1A cells and control HEC-1A cells. RESULTS: IHC results revealed a negative correlation between the expression of ERRγ and VEGFA in EC tissues. ERRγ overexpression significantly decreased the level of HIF-1 in tumor tissue of nude mice. ERRγ overexpression down-regulated inhibited angiogenesis capability and inhibited the proliferation and migration of HEC-1A cells. Furthermore, ERRγ expression was suppressed under the condition of hypoxia while restoration of ERRγ partially inhibited hypoxia-induced VEGFA expression in HEC-1A cells. CONCLUSIONS: ERRγ is an angiogenesis suppressor and involved in hypoxia-induced VEGFA expression in EC. Hence, ERRγ might be a promising antiangiogenic target for human EC.

[Factors influencing the chronic post-surgical pain after laparoscopic surgery for elderly patients with urinary tract tumors].

OBJECTIVE: To investigate the incidence and potential influence factors that contribute to chronic post-surgical pain (CPSP) in elderly patients with urinary tract tumors who underwent laparoscopic procedures. METHODS: A retrospective study was conducted to collect the clinical data of 182 elderly patients with urinary tract tumors who were ≥65 years and underwent laparoscopic surgery from October 2021 to March 2022 in Peking University Third Hospital. The patients'demographic information, medical history and the severity of postoperative pain were collected. Telephone follow-ups were made 6 months after surgery, and the patients' CPSP conditions were recorded. The diagnostic criteria of CPSP were referred to the definition made by the International Association for the Study of Pain (IASP): (1) Pain that developed or increased in intensity after surgical procedure and persisted for at least 3 months after surgery; (2) Pain that localized to the surgical field or projected to the innervation territory of a nerve situated around the surgical area; (3) Pain due to pre-existing pain conditions or infections and malignancy was excluded. The patients were divided into two groups based on CPSP diagnosis. Risk factors that predisposed the patients to CPSP were identified using univariate analysis. A multivariate Logistic regression model using back-forward method was designed, including both variables that significantly associated with CPSP in the univariate analysis (P < 0.1), and the variables that were considered to have significant clinical impact on the outcome. RESULTS: Two hundred and sixteen patients with urinary tract tumors who had undergone laparoscopic surgery were included, of whom, 34 (15.7%) were excluded from the study. For the remaining 182 patients, the average age was (72.6±5.2) years, with 146 males and 36 females. The incidence of CPSP at the end of 6 months was 31.9% (58/182). Multiva-riate regression analysis revealed that age ≥75 years (OR=0.29, 95% CI: 0.12-0.73, P=0.008) was the protecting factors for postoperative chronic pain in the elderly patients with urinary tract tumors undergoing surgical treatment, while renal cancer (compared with other types of urinary tract tumors) (OR=3.68, 95% CI: 1.58-8.58, P=0.003), and the 24 h postoperative moderate to severe pain (OR=2.57, 95% CI: 1.14-5.83, P=0.024) were the independent risk factors affecting CPSP. CONCLUSION: Age < 75 years, renal cancer and the 24 h postoperative moderate to severe pain are influence factors of the occurrence of CPSP after laparoscopic surgery in elderly patients with urinary tract tumors. Optimum postoperative multimodal analgesia strategies are suggested to prevent the occurrence of CPSP.

[Characteristic changes of blood stasis syndrome in rat model of steroid-induced femoral head necrosis based on the combination of disease, syndrome, and symptom].

The approach combining disease, syndrome, and symptom was employed to investigate the characteristic changes of blood stasis syndrome in a rat model of steroid-induced osteonecrosis of the femoral head(SONFH) during disease onset and progression. Seventy-two male SD rats were randomized into a healthy control group and a model group. The rat model of SONFH was established by injection of lipopolysaccharide(LPS) in the tail vein at a dose of 20 µg·kg~(-1)·d~(-1) on days 1 and 2 and gluteal intramuscular injection of methylprednisolone sodium succinate(MPS) at a dose of 40 mg·kg~(-1)·d~(-1) on days 3-5, while the healthy control group received an equal volume of saline. The mechanical pain test, tongue color RGB technique, gait detection, open field test, and inclined plane test were employed to assess hip pain, tongue color, limping, joint activity, and lower limb strength, respectively, at different time points within 21 weeks of modeling. At weeks 2, 4, 8, 12, 16, and 21 after modeling, histopathological changes of the femoral head were observed by hematoxylin-eosin(HE) staining and micro-CT scanning; four coagulation items were measured by rotational thromboelastometry; and enzyme-linked immunosorbent assay(ELISA) was employed to determine the levels of six blood lipids, vascular endothelial growth factor(VEGF), endothelin-1(ET-1), nitric oxide(NO), tissue-type plasminogen activator(t-PA), plasminogen activator inhibitor factor-1(PAI-1), bone gla protein(BGP), alkaline phosphatase(ALP), receptor activator of nuclear factor-κB(RANKL), osteoprotegerin(OPG), and tartrate-resistant acid phosphatase 5b(TRAP5b) in the serum, as well as the levels of 6-keto-prostaglandin 1α(6-keto-PGF1α) and thromboxane B2(TXB2) in the plasma. The results demonstrated that the pathological alterations in the SONFH rats were severer over time. The bone trabecular area ratio, adipocyte number, empty lacuna rate, bone mineral density(BMD), bone volume/tissue volume(BV/TV), trabecular thickness(Tb.Th), trabecular number(Tb.N), bone surface area/bone volume(BS/BV), and trabecular separation(Tb.Sp) all significantly increased or decreased over the modeling time after week 4. Compared with the healthy control group, the mechanical pain threshold, gait swing speed, stride, standing time, and walking cycle of SONFH rats changed significantly within 21 weeks after modeling, with the greatest difference observed 12 weeks after modeling. The time spent in the central zone, rearing score, and maximum tilt angle in the open field test of SONFH rats also changed significantly over the modeling time. Compared with the healthy control group, the R, G, and B values of the tongue color of the model rats decreased significantly, with the greatest difference observed 11 weeks after modeling. The levels of total cholesterol(TC), total triglycerides(TG), low-density lipoprotein-cholesterol(LDL-C), and apoprotein B(ApoB) in the SONFH rats changed significantly 4 and 8 weeks after modeling. The levels of VEGF, ET-1, NO, t-PA, PAI-1, 6-keto-PGF1α, TXB2, four coagulation items, and TXB2/6-keto-PGF1α ratio in the serum of SONFH rats changed significantly 4-16 weeks after modeling, with the greatest differences observed 12 weeks after modeling. The levels of BGP, TRAP5b, RANKL, OPG, and RANKL/OPG ratio in the serum of SONFH rats changed significantly 8-21 weeks after modeling. During the entire onset and progression of SONFH in rats, the blood stasis syndrome characteristics such as hyperalgesia, tongue color darkening, gait abnormalities, platelet, vascular, and coagulation dysfunctions were observed, which gradually worsened and then gradually alleviated in the disease course(2-21 weeks), with the most notable differences occurred around 12 weeks after modeling.

MRCKß links Dasm1 to actin rearrangements to promote dendrite development.

Proper dendrite morphogenesis and synapse formation are essential for neuronal development and function. Dasm1, a member of the immunoglobulin superfamily, is known to promote dendrite outgrowth and excitatory synapse maturation in vitro. However, the in vivo function of Dasm1 in neuronal development and the underlying mechanisms are not well understood. To learn more, Dasm1 knockout mice were constructed and employed to confirm that Dasm1 regulates dendrite arborization and spine formation in vivo. We performed a yeast two-hybrid screen using Dasm1, revealing MRCKß as a putative partner; additional lines of evidence confirmed this interaction and identified cytoplasmic proline-rich region (823-947 aa) of Dasm1 and MRCKß self-activated kinase domain (CC1, 410-744 aa) as necessary and sufficient for binding. Using co-immunoprecipitation assay, autophosphorylation assay, and BS3 cross-linking assay, we show that Dasm1 binding triggers a change in MRCKß's conformation and subsequent dimerization, resulting in autophosphorylation and activation. Activated MRCKß in turn phosphorylates a class 2 regulatory myosin light chain, which leads to enhanced actin rearrangement, causing the dendrite outgrowth and spine formation observed before. Removal of Dasm1 in mice leads to behavioral abnormalities. Together, these results reveal a crucial molecular pathway mediating cell surface and intracellular signaling communication to regulate actin dynamics and neuronal development in the mammalian brain.

Saikosaponin D Alleviates DOX-induced Cardiac Injury In Vivo and In Vitro.

ABSTRACT: As a highly efficient anticancer agent, doxorubicin (DOX) is used for treatment of various cancers, but DOX-induced oxidative damages contribute to a degenerative irreversible cardiac toxicity. Saikosaponin D (SSD), which is a triterpenoid saponin with many biological activities including anti-inflammatory effects and antioxidant properties, provides protection against pathologic cardiac remodeling and fibrosis. In the present study, we investigated the work of SSD for DOX-induced cardiotoxicity and the involved mechanisms. We observed that DOX injection induced cardiac injury and malfunction and decreased survival rate. Besides, DOX treatment increased lactate dehydrogenase leakage, cardiomyocyte apoptosis, and myocardium fibrosis and decreased the size of cardiomyocytes. Meanwhile, all the effects were notably attenuated by SSD treatment. In vitro, we found that 1 µM SSD could enhance the proliferation of H9c2 cells and inhibit DOX-induced apoptosis. It was found that the levels of malondialdehyde (MDA) and reactive oxygen species were significantly reduced by improving the activities of the endogenous antioxidative enzymes including catalase and glutathione peroxidase. Furthermore, SSD treatment could downregulate the DOX-induced p38 phosphorylation. Our results suggested that SSD efficiently protected the cardiomyocytes from DOX-induced cardiotoxicity by inhibiting the excessive oxidative stress via p38-MAPK (mitogen-activated protein kinase, MAPK) signaling pathway.

[Effect of Jianpi Huogu Formula on function damage of vascular endothelial cells induced by glucocorticoid].

This study aimed to observe the intervention effect of Jianpi Huogu Formula(JPHGF) on the functional damage of vascular endothelial cells caused by glucocorticoid, and explore its action mechanism from the PI3 K/Akt and mitogen activated protein kinase(MAPK) signaling pathways. The extracted thoracic aorta ring of normal SD rats were intervened first with vascularendothelial growth factor(VEGF, 20 µg·L-1) and/or sodium succinate(MPS, 0. 04 g·L-1) in vitro and then with JPHGF(8, 16, and 32 µg·L-1) for five mcontinuous ethylpdays, rednisolofollowed nebythe statistics of the number, length, and area of microvessels budding fromvascular rings. In addition, the human umbilical vein endothelial cells(HUVECs) induced by VEGF(20 µg·L-1) were added with MPS(0. 04 g·L-1) and then with JPHGF(8, 16, and 32 µg·L-1) for observing the migration, invasion, and luminal formation abilities of HUVECs in the migration, invasion and luminal formation experiments. The protein expression levels of PI3 K, p-Akt, p-JN K, and p-ERK in HUVECs were assayed by Western blot. The results showed that JPHGF dose-dependently improved the num-ber,length, and area of microvessels in MPS-induced rat thoracic aortic ring, reversed the migration, invasion and lumen formation abiliti es of HUVECs reduced by MPS, and up-regulated the protein expression levels of PI3 K, p-Akt, and p-JNK in HUVECs. All thesehave suggested that JPHGF exerts the protective effect against hormone-induced damage to the angiogenesis of vascular endothelial cells by activating the PI3 K/Akt and MAPK signaling pathways, which has provided reference for exploring the mechanism of JPHGF in treating s teroid-induced avascular necrosis of femoral head(SANFH) and also the experimental evidence for enriching the scientific connotationof spleen-invigorating and blood-activating therapy.

[Mechanism of Panlongqi Tablets intervening in vertebral artery type of cervical spondylosis in rats through PI3K/AKT signaling pathway based on network pharmacology and experimental verification].

This study aimed to further explore the relevant mechanism of action by network pharmacology integrated with animal experimental verification based on previous proven effective treatment of vertebral artery type of cervical spondylosis(CSA) by Panlongqi Tablets. Bionetwork analysis was performed to establish drug-disease interaction network, and it was found that the key candidate targets of Panlongqi Tablets were enriched in multiple signaling pathways related to CSA pathological links, among which phosphatidylinositol 3-kinase(PI3 K)/serine-threonine kinase(AKT/PKB) signaling pathway was the most significant. Further, mixed modeling method was used to build the CSA rat model, and the rats were divided into normal, model, Panlongqi Tablets low-, medium-and high-dose(0.16, 0.32, 0.64 g·kg~(-1)) and Jingfukang Granules(positive drug, 1.35 g·kg~(-1)) groups. After successful modeling, the rats were administered for 8 consecutive weeks. Pathological changes of rat cervical muscle tissues were detected by hematoxylin-eosin(HE) staining, and the content of interleukin-1ß(IL-1ß), tumor necrosis factor-α(TNF-α), vascular endothelial cell growth factor(VEGF) and chemokine(C-C motif) ligand 2(CCL2) in rat serum and/or cervical tissues was determined by enzyme-linked immunosorbent assay(ELISA). Western blot was employed to detect the protein expression levels of chemokine(C-C motif) receptor 2(CCR2), PI3 K, AKT, phosphorylated AKT(p-AKT), I-kappa-B-kinase beta(IKK-beta/IKKß), nuclear factor kappa B(NF-κB P65) and phosphorylated nuclear factor kappa B(NF-κB p-P65) in rat cervical tissues, and positive expression of p-NF-κB P65 in rat cervical muscle tissues was detected by immunofluorescence. The results showed that Panlongqi Tablets at different doses improved the degree of muscle fibrosis and inflammation in cervical muscle tissues of CSA rats, and reduced the content of inflammatory factors IL-1ß, TNF-α, VEGF, CCL2 and CCR2 in serum and/or cervical tissues. The protein expression levels of PI3 K, p-AKT, IKKß and p-NF-κB P65 as well as the nuclear entry of p-NF-κB P65 in cervical tissues were down-regulated. These findings suggest that Panlongqi Tablets can significantly inhibit the inflammatory response of CSA rats, and the mechanism of action may be related to the down-regulation of the activation of PI3 K/AKT signaling pathway.

qFIBS: An Automated Technique for Quantitative Evaluation of Fibrosis, Inflammation, Ballooning, and Steatosis in Patients With Nonalcoholic Steatohepatitis.

BACKGROUND AND AIMS: Nonalcoholic steatohepatitis (NASH) is a common cause of chronic liver disease. Clinical trials use the NASH Clinical Research Network (CRN) system for semiquantitative histological assessment of disease severity. Interobserver variability may hamper histological assessment, and diagnostic consensus is not always achieved. We evaluate a second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) imaging-based tool to provide an automated quantitative assessment of histological features pertinent to NASH. APPROACH AND RESULTS: Images were acquired by SHG/TPEF from 219 nonalcoholic fatty liver disease (NAFLD)/NASH liver biopsy samples from seven centers in Asia and Europe. These were used to develop and validate qFIBS, a computational algorithm that quantifies key histological features of NASH. qFIBS was developed based on in silico analysis of selected signature parameters for four cardinal histopathological features, that is, fibrosis (qFibrosis), inflammation (qInflammation), hepatocyte ballooning (qBallooning), and steatosis (qSteatosis), treating each as a continuous rather than categorical variable. Automated qFIBS analysis outputs showed strong correlation with each respective component of the NASH CRN scoring (P < 0.001; qFibrosis [r = 0.776], qInflammation [r = 0.557], qBallooning [r = 0.533], and qSteatosis [r = 0.802]) and high area under the receiver operating characteristic curve values (qFibrosis [0.870-0.951; 95% confidence interval {CI}, 0.787-1.000; P < 0.001], qInflammation [0.820-0.838; 95% CI, 0.726-0.933; P < 0.001), qBallooning [0.813-0.844; 95% CI, 0.708-0.957; P < 0.001], and qSteatosis [0.939-0.986; 95% CI, 0.867-1.000; P < 0.001]) and was able to distinguish differing grades/stages of histological disease. Performance of qFIBS was best when assessing degree of steatosis and fibrosis, but performed less well when distinguishing severe inflammation and higher ballooning grades. CONCLUSIONS: qFIBS is an automated tool that accurately quantifies the critical components of NASH histological assessment. It offers a tool that could potentially aid reproducibility and standardization of liver biopsy assessments required for NASH therapeutic clinical trials.

Bortezomib in combination with fludarabine plus cyclophosphamide for patients with relapsed or refractory mantle-cell lymphoma: results of the LYM-4003 study.

This study aimed to identify the maximum-tolerated dose (MTD) of cyclophosphamide when combined with bortezomib and fludarabine (B-FC) in a phase 1b trial, and to assess the efficacy and safety of this combination in a phase 2 trial in patients with relapsed or refractory MCL (rrMCL). Forty patients were enrolled between April 8, 2011, and October 10, 2015. The MTD of cyclophosphamide was identified to be 250 mg/m2 days 1-2. At a median follow-up of 31.6 months (13.5-47.4), among 32 patients in phase 2, 10 (31%) had a complete response and 13 (41%) had a partial response. The median progression-free survival was 21 months (95% CI 7.3-34.7), and the median overall survival was 32.4 months (95% CI 17.8-47.0). Grade 3-4 hematologic AEs included neutropenia (27%) and thrombocytopenia (39%). The B-FC regimen has satisfactory responses and manageable toxicities in rrMCL patients (ClinicalTrials.gov NCT01322776).

Therapeutic Effect of an Anti-Human Programmed Death-Ligand 1 (PD-L1) Nanobody on Polymicrobial Sepsis in Humanized Mice.

BACKGROUND Immunosuppression is regarded as the main cause of death induced by sepsis. Anti-programmed death-ligand 1 (PD-L1) therapy is promising in reversing sepsis-induced immunosuppression but no evidence is available on use of commercially available anti-PD-L1 medications for this indication. The present preclinical study was performed to investigate the therapeutic effect of an anti-PD-L1 nanobody (KN035) in sepsis. MATERIAL AND METHODS The level of expression of PD-L1 in PD-L1 humanized mice was confirmed with flow cytometry. Plasma concentrations of KN035 at different dosages at different time points were detected using an enzyme-linked immunosorbent assay. PD-L1 humanized mice were allocated into 4 groups: sham, cecal ligation and puncture (CLP), isotype (isotype+CLP), and PD-L1 (KN035+CLP). The 7-day survival rate was observed to investigate outcomes in CLP mice. Disease severity was assessed with histopathological scoring of mice lungs and livers. Immune status was assessed based on cell apoptosis in the spleen and bacterial clearance. RESULTS PD-L1 levels were significantly elevated in peripheral lymphocytes, monocytes, and neutrophils after CLP surgery. Blood concentrations of KN035 showed that 2.5 mg/kg had potential to be an ideal dosage for KN035 therapy. Survival analysis demonstrated that KN035 was associated with significantly reduced mortality on Day 7 after surgery (P=0.0083). The histopathological tests showed that KN035 alleviated sepsis-induced injury in the lungs and liver. KN035 reduced the number of apoptotic cells in the spleen and almost eliminated bacterial colonies in the peritoneal lavage fluid from the CLP mice. CONCLUSIONS KN035, an anti-PD-L1 antibody, can improve the rate of survival in CLP mice and alleviate sepsis-induced apoptosis in the spleen.

Phylogenomic Analyses of a Clade Within the Family Flavobacteriaceae Suggest Taxonomic Reassignments of Species of the Genera Algibacter, Hyunsoonleella, Jejuia, and Flavivirga, and the Proposal of Pseudalgibacter gen. nov. and Pseudalgibacter alginicilyticus comb. nov.

The family Flavobacteriaceae forms a major branch within the phylum Bacteroidetes. Whole-genome sequence-based analysis could significantly improve the accuracy of taxonomic assignments. In this study, phylogenomic analyses were carried out to revisit the taxonomic status of a clade of the family Flavobacteriaceae. Taking genome-based phylogeny as the primary guideline and average amino acid identity and phenotypic information as supplements, the following taxonomic proposals were put forward: Arenitalea lutea should be reclassified into the genus Algibacter; Algibacter aquaticus should be reclassified into the genus Flavivirga; Jejuia pallidilutea and Algibacter aestuarii should be reclassified into the genus Hyunsoonleella; Algibacter alginicilyticus should be reclassified into the novel genus Pseudalgibacter gen. nov. This study builds up a solid framework for taxonomic decisions of a clade of the family Flavobacteriaceae and will contribute to further insights into the evolution of this family.

Anxiety, depression and cognitive emotion regulation strategies in Chinese nurses during the COVID-19 outbreak.

AIMS: To explore the association between cognitive emotion regulation strategies and anxiety and depression among nurses during the COVID-19 outbreak. BACKGROUND: Nurses play a vital role in responding to the COVID-19 outbreak, but many of them suffer from psychological problems due to the excessive workload and stress. Understanding the correlation between cognitive emotion regulation strategies and anxiety and depression will promote targeted psychosocial interventions for these affected nurses. METHODS: This cross-sectional study of 586 nurses was conducted in Eastern China. Participants completed online questionnaires that investigated anxiety, depression and cognitive emotion regulation strategies. RESULTS: The prevalence of nurses' anxiety and depression was 27.6% and 32.8%, respectively. Lower self-blame, rumination and catastrophizing, as well as greater acceptance and positive refocusing, were related to fewer symptoms of anxiety or depression. CONCLUSION: The cognitive emotion regulation strategies of acceptance and positive refocusing contribute to reducing anxiety or depression. These strategies should be considered when implementing psychotherapeutic interventions to improve nurses' adverse emotional symptoms. IMPLICATIONS FOR NURSING MANAGEMENT: This study highlights the need to assess cognitive emotion regulation strategies use in screening for anxiety and depression. Nurse managers should develop psychosocial interventions including appropriate strategies to help nurses with adverse emotions during a pandemic.

Tripartite motif 10 regulates cardiac hypertrophy by targeting the PTEN/AKT pathway.

The pathogenesis of cardiac hypertrophy is tightly associated with activation of intracellular hypertrophic signalling pathways, which leads to the synthesis of various proteins. Tripartite motif 10 (TRIM10) is an E3 ligase with important functions in protein quality control. However, its role in cardiac hypertrophy was unclear. In this study, neonatal rat cardiomyocytes (NRCMs) and TRIM10-knockout mice were subjected to phenylephrine (PE) stimulation or transverse aortic constriction (TAC) to induce cardiac hypertrophy in vitro and in vivo, respectively. Trim10 expression was significantly increased in hypertrophied murine hearts and PE-stimulated NRCMs. Knockdown of TRIM10 in NRCMs alleviated PE-induced changes in the size of cardiomyocytes and hypertrophy gene expression, whereas TRIM10 overexpression aggravated these changes. These results were further verified in TRIM10-knockout mice. Mechanistically, we found that TRIM10 knockout or knockdown decreased AKT phosphorylation. Furthermore, we found that TRIM10 knockout or knockdown increased ubiquitination of phosphatase and tensin homolog (PTEN), which negatively regulated AKT activation. The results of this study reveal the involvement of TRIM10 in pathological cardiac hypertrophy, which may occur by prompting of PTEN ubiquitination and subsequent activation of AKT signalling. Therefore, TRIM10 may be a promising target for treatment of cardiac hypertrophy.

Validation of the Prognostic Significance of the Prognostic Stage Group According to the Eighth Edition of American Cancer Joint Committee on Cancer Staging System in Triple-Negative Breast Cancer: An Analysis From Surveillance, Epidemiology, and End Results 18 Database.

BACKGROUND: The eighth edition of the American Cancer Joint Committee on Cancer (AJCC) staging system for breast cancer put forward the prognostic stage groups for the first time based on the traditional anatomic tumor-node-metastasis staging system. Our study intends to validate the predictive significance of the eighth edition staging system in triple-negative breast cancer (TNBC) patients. MATERIALS AND METHODS: We collected and accessed 26,589 eligible cases of TNBC from the Surveillance, Epidemiology, and End Results database (2010-2015) and reclassified the patient cohort according to the eighth edition of the AJCC staging system into anatomic and prognostic stages. RESULTS: The results showed that more than half of the patients upstaged in the prognostic stage when compared with the anatomic stage. By comparing with the anatomic stage, the prognostic stage had a higher likelihood ratio and linear trend χ2 values. The prognostic stage group also had higher Akaike information criterion and Bayesian information criterion values than the anatomic stage group. CONCLUSIONS: The prognostic staging system in TNBC patients performs more optimistic prognostic stratification and predictability than the anatomic staging system. Moreover, the latest AJCC staging system has a milestone importance to the history of breast cancer staging system.

Public awareness and knowledge of factors associated with dementia in China.

BACKGROUND: Dementia is a global public health priority. Many modifiable factors have been shown to influence the development of dementia, but these factors are not adequately known by the general public. This study aimed to assess public awareness of the factors that are associated with dementia in China. METHODS: A cross-sectional study was conducted from May to October 2019 using an Internet-based questionnaire. Data on basic sociodemographic characteristics were collected, and the knowledge of risk and protective factors for dementia was investigated. Logistic regression analysis was performed to compare levels of the knowledge of factors associated with dementia across populations with different demographic characteristics. RESULTS: Data from 3338 respondents were analyzed. The percentages of participants who accurately identified the risk factors of dementia were follows: 84.24% for negative affect, 65.07% for alcohol use, 56.68% for smoking, 48.74% for hypertension, and 42.66% for diabetes. The percentages of participants who accurately identified the protective factors for dementia were follows: 90.00% for exercise, 84.69% for social activity, 80.92% for intelligence games, 74.45% for reading, and 6.14% for antihypertensive or hypolipidemic drugs. The majority of Chinese people correctly recognized the role of lifestyle factors in the development of dementia but not medical factors. The levels of knowledge of the factors associated with dementia were significantly distinct across populations with different characteristics. The following sociodemographic characteristics were associated with more comprehensive knowledge of dementia risk and protective factors: women, young age, high education levels, nonmanual jobs, and contact with patients with dementia. CONCLUSIONS: Public awareness and knowledge of risk and protective factors for dementia in China are still insufficient. More efforts are needed to publicize information to reduce the risk of dementia.

[Literature research and status analysis on clinical application of Guizhi Fuling Formula].

Guizhi Fuling Formula was first seen in Synopsis of Golden Chamber by ZHANG Zhongjing. It is composed of Cinnamomi Ramulus, Poria, Moutan Cortex, Persicae Semen, Peony and other drugs, commonly used in the treatment of gynecological diseases such as hysteromyoma, ovarian cyst, endometriosis, pelvic inflammation, dysmenorrhea, etc. In addition, it is also used in internal medicine and urology. This reflects the modern doctors' recognition of the famous prescriptions in ancient books. However, whether Guizhi Fuling Formula is really suitable for these diseases still needs further study for verification. The author systematically searched CNKI, Wanfang, SinoMed, PubMed, EMbase, Cochrane Library database: 2 304 papers on clinical research of Guizhi Fuling, covering 13 systems and 128 diseases. Combined with the questionnaire of experts, we investigated the knowledge of experts of traditional Chinese medicine, Western medicine and combination of Chinese and Western medicine on the applicable indications of Guizhi Fuling Formula in this paper, systematically elaborated the clinical applications of Guizhi Fuling Formula, and summarized the applicable indications of Guizhi Fuling Formula, in order to provide a reference for the clinical rational application of Guizhi Fuling Formula, and provide a reference also for clinical medication.

Phenanthrene, but not its isomer anthracene, effectively activates both human and mouse nuclear receptor constitutive androstane receptor (CAR) and induces hepatotoxicity in mice.

Polycyclic aromatic hydrocarbons (PAHs) are a class of pervasive global environmental pollutants and adversely affect human health. Among PAHs, phenanthrene and anthracene are isomers consisting of three benzene rings. In the present study, we have made comparisons of constitutive androstane receptor (CAR) activation and toxic effects on the liver between these two isomers. Phenanthrene, but not anthracene, significantly induced promoter activity and gene expression of human drug metabolizing enzyme CYP2B6 in HepG2 cells and human primary hepatocytes, respectively. Phenanthrene, but not anthracene, significantly increased CYP2B10 expression levels and caused hepatotoxicity in mice. Phenanthrene induced the nuclear accumulation of CAR in the liver of wild-type mice, but not CAR-/- mice. Hepatocellular necrosis, elevated expression levels of some CAR-related genes such as CYP2B10, CYP3A11, UGT1A1, SULT2A1 and GSTM3, and lower hepatic glutathione levels were found in phenanthrene-exposed wild-type mice but not CAR-/- mice. Additionally, phenanthrene and anthracene were detected in both raw and grilled lamb samples. The average concentrations of phenanthrene were much higher than those of anthracene in these samples. This study is the first to demonstrate that phenanthrene, but not its isomer anthracene, effectively activates both human and mouse nuclear receptor CAR, and CAR plays a crucial role in phenanthrene-induced mouse hepatotoxicity. Compared with anthracene, K region may be an important electronic structure of phenanthrene for activation of CAR. Dietary consumption of PAHs-contaminated food is an important exposure route for humans. Exposure to phenanthrene may affect human health especially associated with liver.

The effect of cyclic knee motion on the elongation of four-strand hamstring autograft in anterior cruciate ligament reconstruction: an in-situ pilot study.

BACKGROUND: Pretension of the viscoelastic graft by cyclic knee motion has been confirmed to decrease the graft creep and improve the outcome of anterior cruciate ligament (ACL) reconstruction. The purpose of the present study was to investigate the effect of cyclic knee motion on the elongation of the four-strand hamstring tendon autograft in situ and to explore the stable level cycle, in which the tendon length achieved a stable level. METHODS: The study was performed with 53 consecutive patients undergoing transtibial ACL reconstruction with four strand hamstring tendon from Aug 2013 to Apr 2015. 43 males and 10 females were included with mean age of 29 ± 10 years. The pretension of the tendons was operated by cyclical knee motion ranging from 0 to 110°after the femoral fixation with Endo-button. The tendon length after 10, 20, 30 and 40 cycles was measured respectively and compared by repeated measure ANOVA. Then multivariate logistic regression was used to investigate the effect of the patients' parameters (age, gender, height, body weight, tendon length, etc.) on the elongation of the graft and the stable level cycle. RESULTS: The mean lengthening of the graft at 10, 20, 30 and 40 times was 3.0 ± 1.4 mm, 4.3 ± 1.5 mm, 4.8 ± 1.7 mm and 4.8 ± 1.8 mm respectively. No significant correlation was found between the elongation and the patients' parameters. There was significant difference of the tendon length from 0 to 30 cycles (F = 264.8, df = 1.95, p<0.001). However, the tendon length achieved a stable level after 30 cycles and the median elongation from 30 cycles to 40 cycles was 0 (0-1) mm with no significant difference (F = 2.039, p = 0.159). The male and female tendon length achieved to a stable level at 20 cycles and 30 cycles respectively but with no significant difference (p = 0.074). CONCLUSIONS: The four-strand hamstring tendon was elongated after cyclic knee motion and the elongation achieved a stable level after 30 cycles for the transtibial technique. Both of the tendon elongation and the stable level cycle were not correlated with patients' gender, age, preoperative duration, graft diameter and length.

The association between obesity indices and hypertension: Which index is the most notable indicator of hypertension in different age groups stratified by sex?

OBJECTIVE: This study aimed to investigate the most notable obesity index and its optimal cut-off point of hypertension in different age groups stratified by sexes among community residents in southern China. METHODS: In this cross-sectional study, 620 men and 631 women aged 18-59 years were enrolled. The independent-samples t-test and chi-square test were conducted to analyze continuous and categorical variables, respectively. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis assessed the association between the obesity indices and hypertension risk. RESULTS: Waist-stature ratio (WSR) and waist-hip ratio (WHR) were the most notable risk factors for hypertension in young men and women, respectively. The odds ratios (ORs) of hypertension risk increased with per standard deviation (SD) in WSR and WHR (WSR: OR = 2.877, 95% confidence interval [CI] = 1.602 to 5.167; WHR: OR = 10.683, 95%CI = 2.179 to 52.376). In the middle-aged group of both sexes, body mass index (BMI) was the most distinctive risk factor for hypertension, the ORs of hypertension risk increased with per SD in BMI (men: OR = 2.297, 95%CI = 1.683 to 3.136; women: OR = 1.810, 95%CI = 1.338 to 2.450). ROC curve analysis demonstrated WSR and PI were better indicators than other indices among young men, and WSR was the best marker among young women. However, BMI and WC were the most sensitive markers in middle-aged men and women, respectively. CONCLUSIONS: In this Chinese population, the association of obesity indices and hypertension is inconsistent in different age groups and sexes. It is important to choose appropriate indicators for specific groups of people.

Irisin alleviates pressure overload-induced cardiac hypertrophy by inducing protective autophagy via mTOR-independent activation of the AMPK-ULK1 pathway.

In hypertrophic hearts, autophagic flux insufficiency is recognized as a key pathology leading to maladaptive cardiac remodeling and heart failure. This study aimed to illuminate the cardioprotective role and mechanisms of a new myokine and adipokine, irisin, in cardiac hypertrophy and remodeling. Adult male wild-type, mouse-FNDC5 (irisin-precursor)-knockout and FNDC5 transgenic mice received 4 weeks of transverse aortic constriction (TAC) alone or combined with intraperitoneal injection of chloroquine diphosphate (CQ). Endogenous FNDC5 ablation aggravated and exogenous FNDC5 overexpression attenuated the TAC-induced hypertrophic damage in the heart, which was comparable to the protection of irisin against cardiomyocyte hypertrophy induced by angiotensin II (Ang II) or phenylephrine (PE). Accumulated autophagosome and impaired autophagy flux occurred in the TAC-treated myocardium and Ang II- or PE-insulted cardiomyocytes. Irisin deficiency caused reduced autophagy and aggravated autophagy flux failure, whereas irisin overexpression or supplementation induced protective autophagy and improved autophagy flux, which were reversed by autophagy inhibitors Atg5 siRNA, 3-MA and CQ. Irisin boosted the activity of only AMPK but not Akt and MAPK family members in hypertrophic hearts and cultured cardiomyocytes and further activated ULK1 at Ser555 but not Ser757 and did not affect the mTOR-S6K axis. Blockage of AMPK and ULK1 with compund C and SBI-0206965, respectively, both abrogated irisin's protection against cardiomyocyte hypertrophic injury and reversed its induction of both autophagy and autophagy flux. Our results suggest that irisin protects against pressure overload-induced cardiac hypertrophy by inducing protective autophagy and autophagy flux via activating AMPK-ULK1 signaling.