Search

Genistein (GEN) has been demonstrated to interfere with antitumor effects of cisplatin (CIS) in vitro. To analyze whether these findings are also relevant in vivo, we examined the effects of combined GEN and CIS treatment in an ovariectomized nude mouse breast cancer xenograft model. Tumor growth and markers for antitumor activity were determined after three weeks of treatment. Furthermore, the concentrations of GEN metabolites were measured in serum, liver, and xenograft tumor tissues using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Three weeks’ oral exposure to GEN at a dose of 5 mg kg-1·d-1 resulted in an average concentration of total GEN metabolite equivalent as high as 0.2729 nmol·g-1 wet weight in xenograft tumor tissues. At this dosage, GEN significantly antagonized the antitumor effects of CIS. Mechanistically, GEN blocked both the inhibition of cell proliferation and induction of apoptosis triggered by CIS. Moreover, GEN concentrations in xenograft tumor tissues were found to be significantly higher than in serum and liver. In conclusion, our findings suggested that oral GEN exposure at a level comparable to dietary exposure in humans could interfere with CIS chemotherapy.

ANNEXIN V belongs to a family of phospholipid binding proteins which is able to bind to negatively charged phospholipids such as phosphatidylserine (PS) in the presence of a high affinity Ca2+ ion. When apoptosis occurs, even at early stage, PS will be exposed to the outside of the cell surface from the cytoplasm side of membrane leaflets., Therefore ANNEXIN V has been suggested as a bio-marker for imaging early apoptotic events of various cell death including those in disease conditions. However, most ANNEXIN V-based apoptotic detecting techniques were in vitro approaches. Here, we presented a new BRET (Bioluminescence Resonance Energy Transfer) based genetic coded biosensor by fusing ANNEXIN V and a BRET version of NanoLuc (teLuc) for both in vitro and in vivo apoptosis detection. The BRET feature of this new sensor makes it convenient to be applied to both conventional fluorescent-based in vitro apoptosis detection and bioluminescence-based animal live imaging for in vivo study. Because of its robust bioluminescence signal, it is possible to perform the evaluation of the disease-induced apoptotic damage and recovery process directly at deep tissue level in live animal.

BACKGROUND The long-term survival of patients with solitary hepatocellular carcinoma (HCC) following anatomical resection (AR) vs non-anatomical resection (NAR) is still controversial. It is necessary to investigate which approach is better for patients with solitary HCC. AIM To compare perioperative and long-term survival outcomes of AR and NAR for solitary HCC. METHODS We performed a comprehensive literature search of PubMed, Medline (Ovid), Embase (Ovid), and Cochrane Library. Participants of any age and sex, who underwent liver resection, were considered following the following criteria: (1) Studies reporting AR vs NAR liver resection; (2) Studies focused on primary HCC with a solitary tumor; (3) Studies reporting the long-term survival outcomes (> 5 years); and (4) Studies including patients without history of preoperative treatment. The main results were overall survival (OS) and disease-free survival (DFS). Perioperative outcomes were also compared. RESULTS A total of 14 studies, published between 2001 and 2020, were included in our meta-analysis, including 9444 patients who were mainly from China, Japan, and Korea. AR was performed on 4260 (44.8%) patients. The synthetic results showed that the 5-year OS [odds ratio (OR): 1.19; P < 0.001] and DFS (OR: 1.26; P < 0.001) were significantly better in the AR group than in the NAR group. AR was associated with longer operating time [mean difference (MD): 47.08; P < 0.001], more blood loss (MD: 169.29; P = 0.001), and wider surgical margin (MD = 1.35; P = 0.04) compared to NAR. There was no obvious difference in blood transfusion ratio (OR: 1.16; P = 0.65) or postoperative complications (OR: 1.24, P = 0.18). CONCLUSION AR is superior to NAR in terms of long-term outcomes. Thus, AR can be recommended as a reasonable surgical option in patients with solitary HCC.

Air pollution is a critical risk factor for the prevalence of COVID-19. However, few studies have focused on whether air pollution affects the efficacy of the SARS-CoV-2 vaccine. To better guide the knowledge surrounding this vaccination, we conducted a cross-section study to identify the relationships between air pollutant exposure and plasma neutralizing antibody (NAb) titers of an inactivated SARS-CoV-2 vaccine (Vero cell, CoronaVac, SINOVΛC, China). We recruited 239 healthcare workers aged 21–50 years who worked at Suining Central Hospital. Of these, 207 were included in this study, depending on vaccination date. The data regarding air pollutants were collected to calculate individual daily exposure dose (DED). The geometric mean of all six pollutant DEDs was applied to estimate the combined toxic effects (DEDcomplex). Then, the participants were divided into two groups based on the mean value of DEDcomplex. The median plasma NAb titer was 12.81 AU/mL, with 85.99% vaccine efficacy in healthcare workers against SARS-CoV-2. In exposure group, observations included lower plasma NAb titers (median: 11.13 AU/mL vs. 14.56 AU/mL), more peripheral counts of white blood cells and monocytes (mean: 6.71 × 109/L vs. 6.29 × 109/L and 0.49 × 109/L vs. 0.40 × 109/L, respectively), and a higher peripheral monocyte ratio (7.38% vs. 6.50%) as compared to the reference group. In addition, elevated air pollutant DEDs were associated with decreased plasma NAb titers. To our knowledge, this study is the first to report the relationship between air pollutant exposure and plasma NAb titers of the SARS-CoV-2 vaccine. This suggests that long-term exposure to air pollutants may inhibit plasma NAb expression by inducing chronic inflammation. Therefore, to achieve early herd immunity and hopefully curb the COVID-19 epidemic, vaccinations should be administered promptly to those eligible, and environmental factors should be considered as well. Supplementary Information The online version contains supplementary material available at 10.1007/s11356-021-16786-y.

BACKGROUND Evidence suggests that intravaginal practices (IVPs) women use to cleanse their vagina or enhance sexual pleasure may be associated with unhealthy changes in the vaginal microbiome (VM). However, the effects of these practices in postmenopausal women are unknown. OBJECTIVES The objective of this pilot study was to characterize the VM communities of postmenopausal women, identify types and frequency of IVPs, and explore associations between the VM and IVPs in postmenopausal women. METHODS We analyzed the VM data of 21 postmenopausal women in Atlanta, Georgia, from vaginal swabs collected at a routine gynecological visit. 16S rRNA gene sequencing in the V3-V4 region was used to characterize the VM. In addition, we described the IVPs of these women, identified by using our newly developed instrument: the Vaginal Cleansing Practices Questionnaire. The associations between the VM and IVPs were explored by comparing the alpha diversities, beta diversities, and the relative abundances at both the community level and individual genus level. RESULTS The most abundant known bacterial genus found in the VM samples was Lactobacillus (35.7%), followed by Prevotella (21.4%). Eleven women (52%) reported using at least one type of IVP since menopause. The most common type of IVP was soap and water to clean inside the vagina. The use of IVPs was not associated with any alpha diversity metric, including Shannon index, inverse Simpson index, and Chao1 index; beta diversity metric, including Bray-Curtis and Jaccard distances; nor relative abundances at the community and individual genus level. Sociodemographic factors were also not associated with any alpha diversity metric. DISCUSSION Clinicians must assess IVPs and other vaginal and sexual hygiene practices of women of all ages to educate and promote healthy behaviors. More than half of the postmenopausal women in this pilot study use IVPs. Understanding the reasoning behind participants' use of IVPs and their perceptions of the possible effects of these practices will require further research. Although the small sample did not show associations with the VM, more extensive studies are warranted.

Receptor activator of NF-κB (RANK) expression is increased in podocytes of patients with diabetic nephropathy. However, the relevance of RANK to diabetic nephropathy pathobiology remains unclear. Here, to evaluate the role of podocyte RANK in the development of diabetic nephropathy, we generated a mouse model of podocyte-specific RANK depletion (RANK-/-Cre T), and a model of podocyte-specific RANK overexpression (RANK TG), and induced diabetes in these mice with streptozotocin. We found that podocyte RANK depletion alleviated albuminuria, mesangial matrix expansion, and basement membrane thickening, while RANK overexpression aggravated these indices in streptozotocin-treated mice. Moreover, streptozotocin-triggered oxidative stress was increased in RANK overexpression but decreased in the RANK depleted mice. Particularly, the expression of NADPH oxidase 4, and its obligate partner, P22phox, were enhanced in RANK overexpression, but reduced in RANK depleted mice. In parallel, the transcription factor p65 was increased in the podocyte nuclei of RANK overexpressing mice but decreased in the RANK depleted mice. The relevant findings were largely replicated with high glucose-treated podocytes in vitro. Mechanistically, p65 could bind to the promoter regions of NADPH oxidase 4 and P22phox, and increased their respective gene promoter activity in podocytes, dependent on the levels of RANK. Taken together, these findings suggested that high glucose induced RANK in podocytes and caused the increase of NADPH oxidase 4 and P22phox via p65, possibly together with the cytokines TNF- α, MAC-2 and IL-1 β, resulting in podocyte injury. Thus, we found that podocyte RANK was induced in the diabetic milieu and RANK mediated the development of diabetic nephropathy, likely by promoting glomerular oxidative stress and proinflammatory cytokine production.

Undifferentiated small round cell sarcoma (USRCS) is a rare malignant tumor. No reports about USRCS of the postcricoid region of the hypopharynx are available, and its clinical features and treatment guidelines remain undefined. We report a case of USRCS of the postcricoid region of the hypopharynx with treatment of surgery and radiotherapy. A 50-year-old man presented with a 4.9 cm x 3.7 cm tumor in the postcricoid region of the hypopharynx. It was diagnosed as USRCS. The tumor showed small round cells and positive immunoexpression of CD56, Cyclin D1, TLE1 and CD99, but no rearrangement or fusion of EWSR1, SS18, CIC, and BCOR. The patient underwent radiotherapy after surgery, without signs of tumor progression and metastasis at the 9-month follow-up. In conclusion, USRCS of postcricoid region of hypopharyngeal is ultra-rare. To make diagnosis, pathological examination is necessary. Surgery followed by radiotherapy might offer an optional treatment for USCRS.

Aim Minimal hepatic encephalopathy (MHE) is a common neuropsychiatric complication of liver cirrhosis and portosystemic shunt. The inhibitory control test (ICT) is a novel computerized psychometric test for MHE diagnosis, but its efficiency has yet to be confirmed. This study aimed to systematically review the existing evidence concerning the ICT application and then evaluate the efficiency of ICT for MHE diagnosis in clinical practice. Methods A comprehensive search of published works was carried out to identify reports concerning the ICT for MHE diagnosis between January 2000 and December 2020. The pooled sensitivity, specificity, and diagnostic odds ratio of ICT for MHE diagnosis were calculated using a random or fixed effect model. The summary receiver operator characteristic (sROC) curve was constructed, and the area under the sROC curve was calculated. Metaregression and subgroup analyses were used to identify the source of heterogeneity. Publication bias was evaluated using the Deeks funnel plot asymmetry test. Results Twelve studies were included in this systematic review, and nine studies enrolling 1022 patients were included in the final meta-analysis. The ICT had a pooled sensitivity, specificity, and DOR of 83%, 64%, and 9, respectively. The area under the sROC curve was 0.79. The metaregression analysis indicated that different locations of studies (relative diagnostic odds ratio, 12.65; p = 0.02) were identified as the source of heterogeneity. No significant publication bias was observed. Conclusions The ICT has a high sensitivity and moderate specificity for MHE diagnosis, and it can be used as a primary diagnostic method for MHE.

Smart medical care is user-centric, medical information is the main line, and big data, Internet of Things, cloud computing, artificial intelligence, and other technologies are used to establish scientific and accurate information, as well as an efficient and reasonable medical service system. Smart medical plays an important role in alleviating doctor-patient conflicts caused by information asymmetry, regional health differences caused by irrational allocation of medical resources, and improving medical service levels. This article mainly introduces the remote care assistance system of emergency department based on smart medical and intends to provide some ideas and directions for the technical research of patients in emergency department receiving remote care. This paper proposes a research method for remote care assistance in emergency departments based on smart medical, including an overview of remote care based on smart medical, remote care sensor real-time monitoring algorithms based on smart medical, signal detection algorithms, and signal clustering algorithms for smart medical. Remote care in the emergency department assisted in research experiments. The experimental results show that 86.0% of patients like the remote care system based on smart medical studied in this paper.

Fibrosis serves a critical role in driving atrial remodelling‐mediated atrial fibrillation (AF). Abnormal levels of the transcription factor PU.1, a key regulator of fibrosis, are associated with cardiac injury and dysfunction following acute viral myocarditis. However, the role of PU.1 in atrial fibrosis and vulnerability to AF remain unclear. Here, an in vivo atrial fibrosis model was developed by the continuous infusion of C57 mice with subcutaneous Ang‐II, while the in vitro model comprised atrial fibroblasts that were isolated and cultured. The expression of PU.1 was significantly up‐regulated in the Ang‐II‐induced group compared with the sham/control group in vivo and in vitro. Moreover, protein expression along the TGF‐β1/Smads pathway and the proliferation and differentiation of atrial fibroblasts induced by Ang‐II were significantly higher in the Ang‐II‐induced group than in the sham/control group. These effects were attenuated by exposure to DB1976, a PU.1 inhibitor, both in vivo and in vitro. Importantly, in vitro treatment with small interfering RNA against Smad3 (key protein of TGF‐β1/Smads signalling pathway) diminished these Ang‐II‐mediated effects, and the si‐Smad3‐mediated effects were, in turn, antagonized by the addition of a PU.1‐overexpression adenoviral vector. Finally, PU.1 inhibition reduced the atrial fibrosis induced by Ang‐II and attenuated vulnerability to AF, at least in part through the TGF‐β1/Smads pathway. Overall, the study implicates PU.1 as a potential therapeutic target to inhibit Ang‐II‐induced atrial fibrosis and vulnerability to AF.

Background: Hepatocellular carcinoma (HCC) is a common type of cancer with a high mortality rate and is usually detected at the middle or late stage, missing the optimal treatment period. The current study aims to identify potential long non-coding RNA (lncRNAs) biomarkers that contribute to the diagnosis and prognosis of HCC. Methods: The differentially expressed lncRNAs (DElncRNAs) in HCC patientsThe differentially expressed lncRNAs (DElncRNAs) in HCC patients were detected from the Cancer Genome Atlas (TCGA) dataset. LncRNAs signature was screened by LASSO regression, univariate, and multivariate Cox regression. The models for predicting diagnosis and prognosis were established, respectively. The prognostic model was evaluated by Kaplan-Meier survival curve receiver operating characteristic (ROC) curve and stratified analysis. The diagnostic model was validated by ROC. The lncRNAs signature was further demonstrated by functional enrichment analysis. were detected from the Cancer Genome Atlas (TCGA) dataset. LncRNAs signature was screened by LASSO regression, univariate and multivariate Cox regression. The models for predicting diagnosis and prognosis were established respectively. The prognostic model was evaluated by Kaplan-Meier survival curve receiver operating characteristic (ROC) curve and stratified analysis. The diagnostic model was validated by ROC. The lncRNAs signature was further demonstrated by functional enrichment analysis. Results: We found the 13-lncRNAs signature that had a good performance in predicting prognosis and could help to improve the value of diagnosis. In the training set, testing set, and entire cohort, the low-risk group had longer survival than the high-risk group (median OS: 3124 vs. 649 days, 2456 vs. 770 days and 3124 vs. 755 days). It performed well in 1-, 3-, and 5-year survival prediction. 13-lncRNAs-based risk score, age, and race were good predictors of prognosis. The AUC of diagnosis was 0.9487, 0.9265, and 0.9376, respectively. Meanwhile, the 13-lncRNAs were involved in important pathways, including the cell cycle and multiple metabolic pathways. Conclusion: In our study, the 13-lncRNAs signature may be a potential marker for the prognosis of HCC and improve the diagnosis.

Background Isocenter deviation, often induced by small displacements of both the device and the patient, is a common error seen in radiotherapy. In this study, we investigated the impact of isocenter deviation on the results of the volumetric modulated arc therapy (VMAT) plan and dosimetric verification gamma passing rate in the treatment of cervical cancer. Methods The clinical data of 15 patients with cervical cancer who were treated with VMAT were retrospectively collected and analyzed. In this study, the isocenter site modification method was adopted. The VMAT plan with isocenter deviation adjustment was set as the experimental group, while the original plan was set as the control group. The impact of isocenter deviation on the results of the VMAT plan and dosimetric verification gamma passing rate was analyzed. Applying gamma analysis with different test criterions, the impact of isocenter deviation on the gamma passing rates was evaluated, and the sensitivity of different test criterions in identifying isocenter deviation was also analyzed. Results There was a significant difference in the average dose in the target area between experimental group and control group (P90%) could also be obtained under the condition of the 3 mm/3% test criterions. It is recommended that the 2 mm/2% test standard should be utilized in clinical practice.

Background &objectives Women with gestational diabetes are at an increased risk of being diagnosed as type 2 diabetes, but the postpartum screening rate is low. To provide evidence-based data for health providers and promote postpartum screening, this systematic review and meta-analysis was conducted to access the risks of type 2 diabetes mellitus (T2DM) diagnosis after gestational diabetes mellitus (GDM) in different demographic and maternal subgroups. Methods MEDLINE, Embase and Cochrane Library were searched systematically. Unadjusted relative risks (RRs) and 95 per cent confidence intervals (CIs) were calculated and pooled using a random-effects model. Heterogeneity was assessed with Cochrane's Q text and by calculating I2 values. Subgroup analyses were conducted to address the disparities of type 2 diabetes conversion after gestational diabetes in different demographic and maternal subgroups. Results 1809 publications were screened and 39 cohort studies including 2,847,596 women were selected. In these studies, 78,893 women were diagnosed as T2DM at six weeks or later after delivery. The unadjusted RRs of women diagnosed T2DM at six weeks or later after delivery ranged from 1.32 (95% CI, 0.46-3.37) to 47.25 (95% CI, 2.95-758.01) with a pooled unadjusted RR of 8.92 (95% CI, 7.84-10.14). Older women, women with a family history of diabetes, Black and non-Hispanic White women and women living in Europe and South-East Asia had a higher risk of developing T2DM after GDM. Interpretation & conclusions It is suggested that healthcare providers may focus on older women with GDM and women with GDM and a family history of diabetes. Black and non-Hispanic White women with GDM may receive more attention, and healthcare providers, especially those in Europe and South-East Asia, may pay more attention to preventive measures for postpartum T2DM.

Objective This meta-analysis aimed to identify the risk factors for venous thromboembolism (VTE) in patients with gynecological malignancy during the perioperative period. Methods Studies on the risk factors for VTE in patients with gynecological malignancy during the perioperative period were collected from the Cochrane Library, MEDLINE, EMBASE, Web of Science, EBSCO, and several Chinese databases (from inception to September 2019). Two reviewers independently performed article screening, data extraction, and study quality evaluation. Review Manager 5.3 software was used for data analysis. Results A total of 9555 articles were initially retrieved, including 7498 in Chinese and 1987 in English, and 22 articles were finally included, which were published from 2011 to 2019. The quality scores of the included studies ranged from 5 to 9, suggesting a relatively high quality. A total of 16,318 patients were included for analysis, 922 in the VTE group and 15,396 in the non-VTE group. A total of 20 risk factors related to surgery or with inconsistent conclusions in the current studies were pooled, and the results showed that age, body mass index (BMI > 26 kg/m2), platelet count, D-dimer, duration of surgery, postoperative days in bed, length of hospital stay, intraoperative blood loss, tumor differentiation (GREAD3), tumor staging (stage IV), and operative approach (laparotomy versus laparoscopy) were significant risk factors for VTE in patients with gynecological malignancy during the perioperative period. Conclusion It is important to develop targeted prevention and treatment strategies against these risk factors to reduce the occurrence of VTE in patients with gynecological malignancy during the perioperative period.

Two new compounds (1 and 2), belonging to C-20 oxygenated ent-kauranes-type diterpenoids, were identified from the aerial parts of Isodon serra. Their structures were elucidated by extensive analysis of HRESI-MS and NMR spectroscopic data. Both these two compounds possess a common 7,20-epoxy-ent-kauranes skeleton with a hydroxyl group rarely occurring at C-13. Compounds 1 and 2 were evaluated for their cytotoxic activity against Hela-60 and HepG2 as well as the antibacterial activity against Staphylococcus aureus, Bacillus cereus and Escherichia coli.

Background Although successful ablation of the accessory pathway (AP) eliminates atrial fibrillation (AF) in some of patients with Wolff‐Parkinson‐White (WPW) syndrome and paroxysmal AF, in other patients it can recur. Hypothesis Whether adding pulmonary vein isolation (PVI) after successful AP ablation effectively prevents AF recurrence in patients with WPW syndrome is unknown. Methods We retrospectively studied 160 patients (102 men, 58 women; mean age, 46 ± 14 years) with WPW syndrome and paroxysmal AF who underwent AP ablation, namely 103 (64.4%) undergoing only AP ablation (AP group) and 57 (35.6%) undergoing AP ablation plus PVI (AP + PVI group). Advanced interatrial block (IAB) was defined as a P‐wave duration of >120 ms and biphasic (±) morphology in the inferior leads, using 12‐lead electrocardiography (ECG). Results During the mean follow‐up period of 30.9 ± 9.2 months (range, 3‐36 months), 22 patients (13.8%) developed AF recurrence. The recurrence rate did not differ in patients in the AP + PVI group and AP group (15.5% vs 10.5%, respectively; P = .373). Univariable and multivariable Cox regression analyses showed that PVI was not associated with the risk of AF recurrence (hazard ratio, 0.66; 95% confidence interval, 0.26‐1.68; P = .380). In WPW patients with advanced IAB, the recurrence rate was lower in patients in the AP + PVI group vs the AP group (90% vs 33.3%, respectively; P = .032). Conclusions PVI after successful AP ablation significantly reduced the AF recurrence rate in WPW patients with advanced IAB. Screening of a resting 12‐lead ECG immediately after AP ablation helps identify patients in whom PVI is beneficial.

Setting the stage for good oral health early in life is critical to long-term oral and overall health. This exploratory study aimed to characterize and compare maternal and newborn oral microbiota among mother-infant pairs. Oral samples were collected from 34 pregnant African American women and their infants at 1 to 3 months of age. Extracted 16SrRNA genes were matched to the Human Oral Microbiome Database. Alpha and beta diversity differed significantly between overall maternal and infant microbiomes. Maternal or infant alpha diversity, however, was not differentiated by maternal gingival status. Several demographic and behavioral variables were associated with, but not predictive of, maternal oral microbiome alpha diversity. There was no association, however, among birth mode, feeding mode, and the infant oral microbiome. Megasphaera micronuciformis was the only periodontal pathogen detected among the infants. Notably, maternal gingival status was not associated with the presence/absence of most periodontal pathogens. This study provides an initial description of the maternal and infant oral microbiomes, laying the groundwork for future studies. The perinatal period presents an important opportunity where perinatal nurses and providers can provide oral assessment, education, and referral to quality dental care.

Autophagy, an evolutionarily conserved catabolic process, is the most important pathogenic events in the development and progression of liver diseases. Deregulation of Nrf2 is proposed to play a key pathogenic role in hepatocellular carcinoma (HCC). Under certain pathophysiological conditions, such as oxidative stress, impaired autophagy is accompanied by the Nrf2 activation that leads to the detrimental effects favoring the proliferation and survival of HCC. Elucidating its role and potential mechanism is essential for understanding tumorigenesis and the development of effective clinical application. Nrf2 is participated in HCC proliferation, migration and invasion through autophagy pathways. These includes the negatively regulated-Nrf2 by Keap1 that participates in HCC tumorigenesis via regulating ROS production, in which autophagy may contribute to oxidant metabolic reprogramming of HCC cells. Post-transcriptional modifications, such as phosphorylation and ubiquitination of Nrf2, can be positively or negatively induced by multiple transcription factors. Nrf2 exhibits chemoresistance through its binding sites in the promoter region of the target genes. Nrf2 may be a valuable potential biomarker and therapeutic strategy for diagnostics, prognostics and treatment of HCC.

Objectives This study aimed to determine vestibular involvement in patients with auditory neuropathy (AN) using ocular vestibular evoked myogenic potential (oVEMP), cervical vestibular evoked myogenic potential (cVEMP), caloric tests, video Head Impulse Tests (vHIT), and Suppression Head Impulse Paradigm (SHIMP) tests. Methods Twenty-two patients with AN (study group) and 50 age-and-gender-matched healthy subjects (control group) were enrolled. All patients underwent air-conducted sound oVEMP and cVEMP tests. In the study group, 20 patients underwent a caloric test, 10 patients underwent a video Head Impulse Test (vHIT), and nine patients underwent the Suppression Head Impulse Paradigm (SHIMP) test. Results Significant differences in VEMP abnormalities were found between the two groups. Most AN patients showed no VEMP response, while only a few patients showed VEMP responses with normal parameters. Some AN patients presented abnormal VEMP parameters, including thresholds, latencies, and amplitudes. The abnormal rate (including no response and abnormal parameters) was 91% in the cVEMP test and 86% in the oVEMP test. No significant difference was found between oVEMP and cVEMP abnormalities. AN patients exhibited a 70% abnormal rate in the caloric test. Most AN patients showed normal VOR gains. Most patients showed no overt corrective saccades in vHIT, and exhibited normal anticompensatory saccades in the SHIMP test. Conclusion Many AN patients experience vestibular dysfunction, which may be detected by using a vestibular functional test battery. Significance VEMP abnormalities might reflect the status and degree of vestibular involvement in AN.

Background While the importance of commensal microbes in vaginal health is well appreciated, little is known about the effects of gynecological cancer (GynCa) and radiation therapy (RT) on the vaginal microbiome (VM) of postmenopausal women. Methods We studied women with GynCa, pre‐ (N = 65) and post‐RT (N = 25) and a group of healthy controls (N = 67) by sequencing the V4 region of the 16S rRNA gene from vaginal swabs and compared the diversity and composition of VMs between the three groups accounting for potential confounding factors in multivariate analysis of variance. Results Comparisons of cancer vs healthy groups revealed that Lactobacillus and Bifidobacterium have significantly higher relative abundance in the healthy group, while the cancer group was enriched in 16 phylogroups associated with bacterial vaginosis (BV) and inflammation, including Sneathia, Prevotella, Peptoniphilus, Fusobacterium, Anaerococcus, Dialister, Moryella, and Peptostreptococcus. In our sample, RT affected the α‐diversity and correlated with higher abundance of typically rare VM species, including several members of the Lacnospiraceae family, a taxon previously linked to vaginal dysbiosis. In addition to cancer and treatment modalities, age and vaginal pH were identified as significant parameters that structure the VM. Conclusions This is among the first reports identifying VM changes among postmenopausal women with cancer. RT alone seems to affect several phylogroups (12 bacterial genera), while gynecological cancer and its treatment modalities are associated with even greater significant shifts in the vaginal microbiota including the enrichment of opportunistic bacterial pathogens, which warrants further attention., Vaginal microbial communities in postmenopausal women undergoing gynecologic cancer treatments have small but detectable differences compared to healthy controls, including higher diversity and abundance of opportunistic bacterial pathogens. Radiation therapy alone seems to affect several phylogroups (12 bacterial genera), while gynecological cancer and its treatment modalities (surgery and chemotherapy) are associated with even greater significant shifts in the vaginal microbiota including the enrichment of opportunistic bacterial pathogens, which warrants further attention.

Purpose To analyze the clinical features and risk factors of tigecycline-associated hypofibrinogenaemia and study whether cefoperazone/sulbactam combined with tigecycline aggravates coagulopathy or hypofibrinogenaemia. Methods A retrospective case–control study of patients with severe infection who were treated with tigecycline was conducted. Patients were assigned to the hypofibrinogenaemia group (

Seed aging is a problem during long-term seed storage, affecting the commercial and germplasm value of seeds. In this study, a widely cultivated rice (Oryza sativa L.) cultivar, Huanghuazhan, was used to investigate the effects of exogenous spermidine (Spd) on accelerated aging (AA). The results showed that the speed of germination and the activities of catalase (CAT), ascorbate peroxidase (APX) and β-amylase were reduced by AA, and more H2O2 accumulated in aged seeds than in normal seeds. As compared with aged seeds pretreated with water, seed vigor and the gibberellic acid (GA) content in aged seeds pretreated with Spd were increased by 47% and 17%, respectively. Furthermore, antioxidant enzyme activity and related gene expression were also higher in aged seeds pretreated with Spd. It is speculated that CAT and APX are the two primary enzymes involved in the effects of Spd to AA. These results suggest that the adverse effect of AA stress on seeds may be partially alleviated by the application of exogenous Spd, which may affect the scavenging of reactive oxygen species.

Hyperlipidemia (HPL) characterized by metabolic disorder of lipids and cholesterol is one of the important risk factors for cardiovascular diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a potent circulating regulator of LDL through its ability to induce degradation of the low-density lipoprotein cholesterol receptor (LDLR) in the lysosome of hepatocytes. Aloe-emodin (AE) is one of potentially bioactive components of Chinese traditional medicine Daming capsule. In this study we evaluated the HPL-lowering efficacy of AE in both in vivo and in vitro HPL models. High-fat diet-induced rats were treated with AE (100 mg/kg per day, ig) for 6 weeks. We found that AE administration significantly decreased the levels of total cholesterol (TC) and LDL in the serum and liver tissues. Moreover, AE administration ameliorated HPL-induced hepatic lipid aggregation. But AE administration did not significantly inhibit HMG-CoA reductase activity in the liver of HPL rats. A cellular model of HPL was established in human hepatoma (HepG2) cells treated with cholesterol (20 μg/mL) and 25-hydroxycholesterol (2 μg/mL), which exhibited markedly elevated cholesterol levels. The increased cholesterol levels could be reversed by subsequent treatment with AE (30 μM). In both the in vivo and in vitro HPL models, we revealed that AE selectively suppressed the sterol-regulatory element-binding protein-2 (SREBP-2) and hepatocyte nuclear factor (HNF)1α-mediated PCSK9 signaling, which in turn upregulated LDL receptor (LDLR) and promoted LDL uptake. This study demonstrates that AE reduces cholesterol content in HPL rats by inhibiting the hepatic PCSK9/LDLR pathway.

This study aimed to determine whether and how the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide affects the chemoresistance and chemosensitivity of pancreatic cancer cells to gemcitabine in vitro and in vivo. The GLP-1R and protein kinase A (PKA) levels were compared between the human pancreatic cancer cell line PANC-1 and the gemcitabine-resistant cell line PANC-GR. The in vitro effects of liraglutide on the cell proliferation and apoptosis as well as the nuclear factor-kappa B NF-κB expression levels of PANC-GR cells were evaluated. In addition, a mouse xenograft model of human pancreatic cancer was established by s.c. injection of PANC-1 cells, and the effects of liraglutide on the chemosensitivity were evaluated in vitro and in vivo. In contrast to PANC-1 cells, PANC-GR cells exhibited lower expression levels of GLP-1R and PKA. Incubation with liraglutide dose dependently inhibited the growth, promoted the apoptosis, and increased the expression of GLP-1R and PKA of PANC-GR cells. Similar effects of liraglutide were observed in another human pancreatic cancer cell line MiaPaCa-2/MiaPaCa-2-GR. Either the GLP-1R antagonist Ex-9, the PKA inhibitor H89, or the NF-κB activator lipopolysaccharide (LPS) could abolish the antiproliferative and proapoptotic activities of liraglutide. Additionally, each of these agents could reverse the expression of NF-κB and ABCG2, which was decreased by liraglutide treatment. Furthermore, liraglutide treatment increased the chemosensitivity of pancreatic cancer cells to gemcitabine, as evidenced by in vitro and in vivo experiments. Thus, GLP-1R agonists are safe and beneficial for patients complicated with pancreatic cancer and diabetes, especially for gemcitabine-resistant pancreatic cancer.

Many methods have been used to detect heavy metals in herbal medicines, while few are developed to remove them. In this study, a novel genetically engineered fusion protein composed of metallothionein (MT), cellulose binding module (CBM), and superfolder GFP (sfGFP) was designed to remove heavy metals. MT, a kind of cysteine-rich protein, was used to chelate heavy metals with high specific affinity. The CBM facilitated the fusion protein MT-CBM-sfGFP binding to cellulose specifically, which made the purification and immobilization in one step. The sfGFP was used to detect the fusion protein MT-CBM-sfGFP easily during the process of expression and immobilization. The MT from Cancer pagurus (MTCap) and the CBM from Cellulomonas fimi (CBMCef) were used as an example and the fusion protein (MTCap-CBMCef-sfGFP) was expressed in Escherichia coli. Then, the cell lysates were mechanically mixed with cellulose to create biosorbent MTCap-CBMCef-sfGFP@cellulose. The efficiency of the biosorbent MTCap-CBMCef-sfGFP@cellulose for Pb2+ removal was evaluated using the water decoction of Honeysuckle as a model. Results suggested that MTCap-CBMCef-sfGFP@cellulose had high efficiency for Pb2+ removal from the water decoction of Honeysuckle without affecting its active ingredients. The low-cost, easy production, and high efficiency of the biosorbent enable it to have many applications in heavy metal removal from aqueous solutions of herbal medicines and food.

The purpose of this study is to investigate the performance of dual-layer detector spectral CT for iron deposition compared to magnetic resonance imaging (MRI) T2* imaging. Thirty-one patients with a clinical history of myelodysplastic syndromes and aplastic anemia underwent liver and cardiac T2*-weighted unenhanced MRI on a three-tesla MRI scanner, and underwent unenhanced CT scan laterally on a 128-row spectral detector CT. R2* values of the liver, septal muscle, and paraspinal muscle were calculated. Attenuation differences (ΔH) in the liver and myocardium were calculated between the lower (50 keV) and higher (120 keV) energy levels. The liver and cardiac T2* values were 9.54 ± 5.63 ms and 21.41 ± 2.44 ms, respectively. The liver-to-muscle and myocardium-to-muscle T2* value ratios were 0.37 ± 0.23 and 0.79 ± 0.19, respectively. The liver and cardiac ΔH were − 1.13 ± 4.24 HU and 2.22 ± 4.41 HU, respectively. There was a strong linear correlation between the liver R2* and ΔH (r = − 0.832, P

Brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway is associated with ischemic heart diseases (IHD). 7,8-dihydroxyflavone (7,8-DHF), BDNF mimetic, is a potent agonist of TrkB. We aimed to investigate the effects and the underlying mechanisms of 7,8-DHF on cardiac ischemia. Myocardial ischemic mouse model was induced by ligation of left anterior descending coronary artery. 7,8-DHF (5 mg/kg) was administered intraperitoneally two days after ischemia for four weeks. Echocardiography, HE staining and transmission electron microscope were used to examine the function, histology and ultrastructure of the heart. H9c2 cells were treated with hydrogen peroxide (H2O2), 7,8-DHF or TrkB inhibitor ANA-12. The effects of 7,8-DHF on cell viability, mitochondrial membrane potential (MMP) and mitochondrial superoxide generation were examined. Furthermore, mitochondrial fission and protein expression of mitochondrial dynamics (Mfn2 [mitofusin 2], OPA1 [optic atrophy 1], Drp1 [dynamin-related protein 1] and Fis-1 [fission 1]) was detected by mitotracker green staining and western blot, respectively. 7,8-DHF attenuated cardiac dysfunction and cardiomyocyte abnormality of myocardial ischemic mice. Moreover, 7,8-DHF increased cell viability and reduced cell death accompanied by improving MMP, inhibiting mitochondrial superoxide and preventing excessive mitochondrial fission of H2O2-treated H9c2 cells. The cytoprotective effects of 7,8-DHF were antagonized by ANA-12. Mechanistically, 7,8-DHF repressed OMA1-dependent conversion of L-OPA1 into S-OPA1, which was abolished by Akt inhibitor. In conclusion, 7,8-DHF protects against cardiac ischemic injury by inhibiting the proteolytic cleavage of OPA1. These findings provide a novel pharmacological effect of 7,8-DHF on mitochondrial dynamics and a new potential target for IHD.

Background: The vestibular function in patients of large vestibular aqueduct syndrome (LVAS) has not been clarified yet.Aims/objectives: To investigate the characteristic of otolithic organ in LVAS patients, we accessed their ocular and cervical vestibular evoked myogenic potentials (oVEMPs and cVEMPs).Material and methods: This study was carried out between 29 bilateral LVAS patients and 35 healthy controls. Parameters of VEMPs were analyzed.Result: In children patients, response rate for oVEMP was 93.47% and 86.95% for cVEMP. No statistical significance was found compared to their controls. In adult patients, response rate for oVEMP was 83.33% and 75% for cVEMP, which were statistically lower than their controls. In comparison to parameters of VEMPs, no statistical significance were found in children group. Amplitude of oVEMP was significantly higher and that of cVEMP was lower in LVAS adults. N1 latencies were significantly longer and P1 latencies were shorter in adult patients than in controls of cVEMP. Thresholds and N1-P1 intervals of VEMP were found no statistical significance in adult group.Conclusions and significance: We discovered a severer otolithic dysfunction in adults than in children patients. We recommend cVEMP a more effective and sensitive method than oVEMP in assessment of LAVS adult patients.

One new 3,24-dinor-2,4-seco-ursane triterpene, rosanortriterpene C (1), together with four known compounds including 24-norursane-type nortriterpenes (2-3), 24-noroleanane-type nortriterpene (4), ursane-type triterpene (5), was isolated from the fruits of Rosa laevigata var. leiocapus. The new structure was elucidated through comprehensive spectroscopic analysis, including one dimensional (1D) and 2D NMR data, as well as electrospray ionization high resolution (HR-ESI) MS and IR spectrometry. Compounds 1-5 showed moderate anti-inflammatory activities against the production of nitric oxide (NO) in RAW264.7 cells stimulated by lipopolysaccharide (LPS) with IC50 values of 10.35 ± 0.92, 14.28 ± 1.20, 5.04 ± 1.43, 29.29 ± 3.64, and 14.37 ± 0.59 µM, respectively.