Retrospective study of 189 cases of acute perforated peptic ulcer: safety and efficacy of over-the-scope-clip based endoscopic closure.

BACKGROUND: To compare the clinical outcomes in patients with acute perforated peptic ulcer (PPU) treated with over-the-scope clip (OTSC), non-surgical, and surgical interventions, and to explore the effectiveness and safety of OTSC closure. METHODS: Hospital stay, antibiotic use, diet resumption time, and mortality rate were analyzed retrospectively. Binary Logistic regression analysis was used to identify the risk factors influencing PPU complicated with sepsis. RESULTS: Patients were divided into three treatment groups: OTSC (n = 62), non-surgical (n = 72), and surgical (n = 55) groups. The median time (IQR) from symptom onset to admission was 9.0 (4-23) h. 88.71% (55/62) of the patients in In the OTSC group underwent OTSC closure within 24 h (median [IQR] time: 14.5 [7.00-30.25] h). The perforation diameters in the OTSC and surgical groups were 9.87 mm ± 5.97 mm and 8.55 mm ± 6.17 mm, respectively. The median (IQR) hospital stays in the OTSC (9.50 [7.00-12.25] days) and non-surgical group (9.00[7.00-13.00]days) were similar (p > 0.05), but shorter than that in surgical group (12.00[10.00-16.00]days), (p < 0.05). The median duration of antibiotic use was shorter in the OTSC group (7.00[3.00-10.00]) than in the non-surgical group (9.00[7.00-11.00]) and surgical group (11.00[9.00-13.00]) ( p < 0.05); and the time to resume oral feeding was shorter in the OTSC group (4.00[2.00-5.25]) than in the non-surgical group (7.00[6.13-9.00]) and surgical group (8.00[6.53-10.00]), respectively ( p < 0.05). No mortality difference among groups (p = 0.109) was found. Lower albumin level at admission, older age, and elevated creatinine levels were associated with increased sepsis risk, with OR(95%CI) of 0.826 (0.687-0.993), 1.077 (1.005-1.154), and 1.025 (1.006-1.043), respectively (all p < 0.05). CONCLUSION: OTSC closure improves clinical outcomes of acute PPU patients without sepsis. Age, hypoalbuminemia, and baseline renal dysfunction increase the risk of sepsis, while mortality was associated with sepsis and multiorgan dysfunction.

Design and synthesis of nano-iron oxyhydroxide-based molecularly imprinted electrochemical sensors for trace-level carbendazim detection in actual samples.

Carbendazim (CBD) is widely used as a fungicide that acts as a pesticide in farming to prevent crop diseases. However, CBD can remain on crops for a long time. When consumed by humans and animals, it produces a range of toxic symptoms and poses a serious threat to their health. Therefore, the detection of CBD is necessary. Traditional assay strategies for CBD detection, although sensitive and practical, can hardly achieve fast, robust monitoring during food processing and daily life. Here, we designed a novel electrochemical sensor for CBD detection. In this method, iron oxyhydroxide nanomaterial (ß-FeOOH) was first prepared by hydrothermal method. Then, a molecularly imprinted polymer (MIP) layer was electropolymerized on the surface using CBD as the template and resorcinol (RC) as the functional monomer. The synergistic interaction between ß-FeOOH and MIP endows the MIP/ß-FeOOH/CC-based electrochemical sensor with high specificity and sensitivity. Under optimal conditions, the MIP/ß-FeOOH/CC-based sensor showed a wide linear range of 39 pM-80 nM for CBD and a detection limit as low as 25 pM. Therefore, the as-prepared sensor can be a practical and effective tool for pesticide residue detection.

Advances in the endoscopic management of gastric varices.

This review provides an overview of the treatment options available for gastric varices (GV) with a focus on endoscopic methods. Various minimally invasive techniques, including endoscopic band ligation, endoscopic cyanoacrylate injection, and transjugular intrahepatic portosystemic shunt, can be applied to the treatment of GV. Endoscopic cyanoacrylate injection is now recognized as a first-line treatment for GV. Endoscopic ultrasound-guided cyanoacrylate injection combined with coils has shown good security and effectiveness. Thrombin injection therapy is a promising treatment, with a similar hemostasis rate to cyanoacrylate injection but with fewer serious complications. With the deepening understanding of the hemodynamics of the GV system, various treatment methods and their combination are gradually evaluated to provide patients with safer and more effective treatment options.

Nanomedicine-mediated regulated cell death in cancer immunotherapy.

Immunotherapy has attracted widespread attention in cancer treatment and has achieved considerable success in the clinical treatment of some tumors, but it has a low response rate in most tumors. To achieve sufficient activation of the immune response, significant efforts using nanotechnology have been made to enhance cancer immune response. In recent years, the induction of various regulated cell death (RCD) has emerged as a potential antitumor immuno-strategy, including processes related to apoptosis, autophagy, necroptosis, pyroptosis, ferroptosis, and cuproptosis. In particular, damage-associated molecular patterns (DAMPs) released from the damaged membrane of dying cells act as in situ adjuvants to trigger antigen-specific immune responses by the exposure of an increased antigenicity. Thus, RCD-based immunotherapy offers a new approach for enhancing cancer treatment efficacy. Furthermore, incorporation with multimodal auxiliary therapies in cell death-based immunotherapy can trigger stronger immune responses, resulting in more efficient therapeutic outcome. This review discusses different RCD modalities and summarizes recent nanotechnology-mediated RCDs in cancer immunotherapy.

Using computer vision and machine learning to identify bus safety risk factors.

In road safety research, bus crashes are particularly noteworthy because of the large number of bus passengers involved and the challenge that it puts to the road network (with the closure of multiple lanes or entire roads for hours) and the public health care system (with multiple injuries that need to be dispatched to public hospitals within a short time). The significance of improving bus safety is high in cities heavily relying on buses as a major means of public transport. The recent paradigm shifts of road design from primarily vehicle-oriented to people-oriented urge us to examine street and pedestrian behavioural factors more closely. Notably, the street environment is highly dynamic, corresponding to different times of the day. To fill this research gap, this study leverages a rich dataset - video data from bus dashcam footage - to identify some high-risk factors for estimating the frequency of bus crashes. This research applies deep learning models and computer vision techniques and constructs a series of behavioural and street factors: pedestrian exposure factors, pedestrian jaywalking, bus stop crowding, sidewalk railing, and sharp turning locations. Important risk factors are identified, and future planning interventions are suggested. In particular, road safety administrations need to devote more efforts to improve bus safety along streets with a high volume of pedestrians, recognise the importance of protection railing in protecting pedestrians during serious bus crashes, and take measures to ease bus stop crowding to prevent slight bus injuries.

Au/Fe3O4-based nanozymes with peroxidase-like activity integrated in immunochromatographic strips for highly-sensitive biomarker detection.

Because of their simplicity, rapidity, and cost-effectiveness, immunochromatographic strips (ICTs) have been widely used as an effective tool in various fields. However, typical strips for the preliminary screening suffer from limited detection sensitivity, particularly in biomarker detection with trace concentration. Herein, to tackle this challenge, we integrated homemade gold-decorated Fe3O4 nanoparticles (Au/Fe3O4 NPs) with flexible strips, exploring the excellent peroxidase-like activity of this labeled material, and then enhancing the detection sensitivity via signal amplification. The limit of detection (LOD) of the strips is as low as 0.05 mIU mL-1 when human chorionic gonadotropin (hCG) is as a biomarker model, which is 500 times lower than that of the traditional color-based strip. Overall, our results demonstrated the potential for Au/Fe3O4 NP based-ICTs for the rapid detection of the biomarker in an instrument-free and point-of-care testing format.

N-3 polyunsaturated fatty acids protect esophageal epithelial cells from acid exposure.

Our previous study showed that n-3 PUFAs inhibited inflammation in rats with esophagitis. This study aimed to observe the protective effect of n-3 PUFAs against acid damage to esophageal epithelial cells (Het-1A cells) and to explore its mechanism. The level of malondialdehyde (MDA) was increased by acid exposure, while that of superoxide dismutase (SOD) was decreased. In groups with different ratios of n-6/n-3 PUFAs, the expression levels of nuclear factor E2 related factor 2 (Nrf2) and SOD were increased with increasing proportions of n-3 PUFAs and were highest in the 1:1 group. Compared with those in the 9:1 group, the expression of NOD like receptor pyrin domain-containing protein 3 (NLRP3) and caspase-1 and the pyroptosis rate in the 1:1 group were decreased. Intervention with an Nrf2 agonist increased the expression of Nrf2 and decreased the expression of NLRP3 and caspase-1 and the pyroptosis rate. However, inhibiting Nrf2 expression led to the opposite result. In conclusion, n-3 PUFAs protected esophageal epithelial cells from acid damage by upregulating Nrf2 expression, which disrupted oxidative stress and NLRP3 inflammasome activation and inhibited pyroptosis.

Scutellaria barbata D. Don inhibits cervical cancer cell proliferation, migration, and invasion via miR-195-5p/LOXL2 axis.

Background: Scutellaria barbata D. Don (SB) is a widely used herbal medicine in China, with various pharmacological effects such as anti-oxidation, anti-inflammation, and anti-cancer. This work is aimed to investigate the tumor-suppressive effect of SB in cervical cancer (CC) and to identify its underlying mechanisms. Methods and materials: CC cell lines (HeLa and HT-3) were treated with different concentrations of SB chloroform extract (ECSB) (0, 0.2, 0.5 mg/ml). MiR-195-5p and LOXL2 mRNA expression in CC cell lines and tissue samples was detected by quantitative real-time polymerase chain reaction. Cell counting kit-8 experiment was utilized to examine cell viability; TUNEL assay and Transwell experiment was executed to examine cell apoptosis, migration, and invasion. Western blotting experiments were implemented to detect LOXL2 protein expression. Bioinformatics and dual-luciferase reporter gene experiment were executed to examine the binding relationship between miR-195-5p and LOXL2. Results: ECSB repressed the viability, migration, and invasion of HeLa and HT-3 cells, and promoted cell apoptosis in a dose-dependent manner. MiR-195-5p was remarkably under-expressed in CC tissues and cells, and ECSB up-regulated miR-195-5p expression. MiR-195-5p inhibitors partially counteracted the suppressive effects of ECSB on the malignant phenotypes of HeLa and HT-3 cells. LOXL2 was a downstream target of miR-195-5p, and ECSB up-modulated LOXL2 expression by specifically repressing miR-195-5p. Conclusion: SB restrains CC cell proliferation and metastasis and promotes cell apoptosis via miR-195-5p/LOXL2, which may be a potential therapeutic agent for CC treatment.

Applying contrast-enhanced ultrasound model to distinguish atypical focal adenomyosis from uterine leiomyomas.

Background: Different from conventional ultrasound, contrast-enhanced ultrasound (CEUS) is better in observing microperfusion. For atypical focal adenomyosis and uterine leiomyomas that are difficult to be distinguished by conventional ultrasound, this study aims to further improve the differential diagnosis performance by using CEUS model. Methods: After screening the cases with difficulties in identifying focal myometrium lesions through conventional ultrasound, the number of cases covered in the focal adenomyosis group and leiomyomas group were 60 and 30 in derivation cohort, 14 and 7 in validation cohort. The qualitative and quantitative characteristics of CEUS were analyzed according to the surgical pathology. The qualitative characteristics include: the enhancement level based on the myometrium, the contrast enhancement pattern, the enhanced time of the lesion based on the myometrium, post-contrast lesion border, the distribution of the contrast agent, and the wash-out time based on the myometrium. The quantitative characteristics include: arrive time (AT), time to peak (TTP), peak intensity (PI), ΔAT, ΔTTP, ΔPI, |ΔAT|, |ΔTTP|, |ΔPI| and lesion temporal variability. Multiple logistic regression analysis was used to screen the independent risk factors, and a risk prediction model for the differential diagnosis of the two diseases was established. The area under the receiver operating characteristic (ROC) curve (AUC) was used to assess the diagnostic performance of the model. The validation cohort was used to further evaluate the diagnostic performance of the model. Results: Through the multivariate analysis, it concluded that short-term vessels first enhanced enhancement mode, unclear boundary, lesion temporal variability under CEUS >9.5 s, uneven contrast agent distribution could be independent risk factors for the diagnosis of adenomyosis [AUC =0.908, 95% confidence interval (CI): 0.833-0.982]. We also determined the sensitivity (98.33%), specificity (70.00%), positive predictive value (PPV) (86.76%), negative predictive value (NPV) (95.45%), and accuracy (87.78%) of this model. Based on pathological diagnosis, the sensitivity and specificity of the model in the validation cohort were both 85.71%, with NPV of 75% and PPV of 92.3%. The area under the ROC curve was 0.898 (95% CI: 0.742-1.000). Conclusions: The establishment of CEUS model has certain clinical application value in differentiating atypical focal adenomyosis from leiomyomas.

Developing Radio-Frequency Roasting Protocols for Almonds Based on Quality Evaluations.

Hot air roasting is a popular method for preparing almonds, but it takes a long time. We roasted almonds via dielectric heating using 5 kW, 40.68 MHz batch radio-frequency (RF) equipment and analyzed their quality and aroma using a gas chromatography/ion mobility spectrometer and sensory evaluation. Almonds with an initial moisture content of 8.47% (w.b.) were heated at an RF electrode gap of 10 cm; the target roasting temperature of 120 °C was achieved at weights of 0.5, 1, 1.5, and 2 kg for 4, 3.5, 7.5, and 11 min, respectively; and the moisture content was reduced to less than 2% (w.b.). For comparison, 1 kg of almonds was roasted in a 105 °C conventional oven for 120 min. The darker color and lower moisture content, water activity, and acid value of the RF-roasted almonds were favorable for preservation. The aroma analysis using gas chromatography/ion mobility spectroscopy (GC-IMS) revealed that the aroma signal after roasting was richer than that of raw almonds, and principal component analysis (PCA) demonstrated that the aromas of roasted and commercial almonds were similar. The RF-roasted almonds presented a better flavor, texture, and overall preferability compared to commercial almonds. RF heating could be used in the food industry to roast nuts.

Dietary restriction and the transcription factor clock delay eye aging to extend lifespan in Drosophila Melanogaster.

Many vital processes in the eye are under circadian regulation, and circadian dysfunction has emerged as a potential driver of eye aging. Dietary restriction is one of the most robust lifespan-extending therapies and amplifies circadian rhythms with age. Herein, we demonstrate that dietary restriction extends lifespan in Drosophila melanogaster by promoting circadian homeostatic processes that protect the visual system from age- and light-associated damage. Altering the positive limb core molecular clock transcription factor, CLOCK, or CLOCK-output genes, accelerates visual senescence, induces a systemic immune response, and shortens lifespan. Flies subjected to dietary restriction are protected from the lifespan-shortening effects of photoreceptor activation. Inversely, photoreceptor inactivation, achieved via mutating rhodopsin or housing flies in constant darkness, primarily extends the lifespan of flies reared on a high-nutrient diet. Our findings establish the eye as a diet-sensitive modulator of lifespan and indicates that vision is an antagonistically pleiotropic process that contributes to organismal aging.

Association Between Self-Perceived Stigma and Quality of Life Among Urban Chinese Older Adults: The Moderating Role of Attitude Toward Own Aging and Traditionality.

BACKGROUND: Ageism is a global challenge, which leads to a range of adverse outcomes for elderly people worldwide, which maybe more severe among urban older adults in a competitive society. However, how self-perceived ageism influences the quality of life in a sample of urban older adults remains inconclusive. OBJECTIVES: The current study aims to assess the status of self-perceived stigma among urban Chinese older adults, identify its relationship with quality of life, and further explore whether both attitude toward own aging and traditionality moderate this relationship. MATERIALS AND METHODS: Primary data were collected through cross-sectional surveys among urban older adults in three provinces of China from October 2019 to December 2020. A total of 764 urban older adults were valid participants (effective response rate = 81.28%) and completed questionnaires via anonymous face-to-face interviews. Socio-demographic factors, self-perceived stigma, attitude toward own aging, traditionality, and quality of life were assessed using questionnaires that included the Self-perceived Stigma, Attitude Toward Own Aging, Traditionality, and SF-8 Scales. RESULTS: For urban Chinese older adults, the average score of self-perceived stigma was 2.041 ± 0.726. Self-perceived stigma (ß = -0.391, p < 0.05) and attitude toward own aging (ß = -0.211, p < 0.05) both influenced quality of life. Additionally, attitude toward own aging (ß = -0.530, p < 0.05) and traditionality (ß = -0.525, p < 0.05) moderated the association between self-perceived stigma and quality of life. Simple slope analysis revealed that when the level of negative attitude toward own aging and traditionality was higher, the strength of the influence of self-perceived stigma on quality of life was stronger. CONCLUSION: Urban Chinese older adults were aware of the self-perceived stigma, which contributes to decreased quality of life. Attitude toward own aging and traditionality could moderate the association between self-perceived stigma and quality of life. When negative attitudes toward own aging and traditionality are higher, self-perceived stigma has a greater effect on the quality of life. More interventions related to relieving self-perceived stigma, traditionality, and negative attitude toward own aging should be considered to build a new modern society that emphasizes health, friendliness, well-being, and dignity for all ages.

Discoidin Domain-Containing Receptor 2 Is Present in Human Atherosclerotic Plaques and Involved in the Expression and Activity of MMP-2.

Discoidin domain-containing receptor 2 (DDR2) has been suggested to be involved in atherosclerotic progression, but its pathological role remains unknown. Using immunochemical staining, we located and compared the expression of DDR2 in the atherosclerotic plaques of humans and various animal models. Then, siRNA was applied to knock down the expression of DDR2 in vascular smooth muscle cells (VSMCs), and the migration, proliferation, and collagen Ι-induced expression of matrix metalloproteinases (MMPs) were evaluated. We found that an abundance of DDR2 was present in the atherosclerotic plaques of humans and various animal models and was distributed around fatty and necrotic cores. After incubation of oxidized low-density lipoprotein (ox-LDL), DDR2 was upregulated in VSMCs in response to such a proatherosclerotic condition. Next, we found that decreased DDR2 expression in VSMCs inhibited the migration, proliferation, and collagen Ι-induced expression of matrix metalloproteinases (MMPs). Moreover, we found that DDR2 is strongly associated with the protein expression and activity of MMP-2, suggesting that DDR2 might play a role in the etiology of unstable plaques. Considering that DDR2 is present in the atherosclerotic plaques of humans and is associated with collagen Ι-induced secretion of MMP-2, the clinical role of DDR2 in cardiovascular disease should be elucidated in further experiments.

Effect of Endoscopic Appendix Intubation and Irrigation on Acute Uncomplicated Appendicitis.

OBJECTIVE: To investigate the efficacy and safety of endoscopic appendix intubation and irrigation (EAI) on acute uncomplicated appendicitis. METHODS: This prospective non-randomized study examined 169 patients with suspected acute uncomplicated appendicitis at The First Affiliated Hospital of Fujian Medical University from October 2015 to 2017. Patients were divided into three groups: endoscopic appendix intubation and irrigation (EAI, n = 18), laparoscopic appendectomy (LA, n = 87), and antibiotic alone (A, n = 64). The treatment success rate, duration of hospitalization, medical costs, operation time, duration of abdominal pain, fasting time, complications, and recurrence were analyzed. RESULTS: The three groups had no significant differences in baseline characteristics (age, gender, Alvarado score, white blood cell count, and neutrophil count; all P > 0.05). Compared to the LA group, the EAI group had shorter durations of the operation, fasting, and abdominal pain; less use of oral and intravenous antibiotics; and lower medical costs (all P < 0.05). Compared to the A group, the EAI group had shorter durations of abdominal pain and hospitalization, and less use of intravenous antibiotics (all P < 0.05). The EAI group had no complications, but 3 patients (3.4%) in the LA group had surgery-related complications. CONCLUSION: EAI is a safe and effective treatment for acute uncomplicated appendicitis. Patients who received EAI had shorter durations of abdominal pain and hospitalization than those who received LA or conservative antibiotic treatment. TRIAL REGISTRATION NUMBER AND AGENCY: ChiCTR-IPN-15006565, Chinese Clinical Trial Registry.

First report of internal black rot on Carica papaya fruit caused by Fusarium sulawesiense in China.

Papaya (Carica papaya L.) is a tropical fruit consumed worldwide due to its nutritional, medicinal and pharmacological properties. In China, papaya was widely planted in Guangdong, Guangxi, Hainan, Yunnan, Fujian and Taiwan provinces. From September to December in 2015-2020, fruit with internal black rot disease was observed in papaya plantation in Xuwen, Guangdong province (N20°20'9"; E110°14'45"), approximately 5% fruits on about 85% trees were infected every year. The infected fruits showed the symptom of 'false-ripening' and the pericarp color changed from green to yellow earlier than that of normal fruits. In the cavity of diseased fruits, the sarcocarp black rotted and conspicuous mycelia were observed. Mycelia and infected tissues from symptomatic fruits were picked up, placed on potato dextrose agar (PDA) with 50mg/L ampicillin and incubated at 25± 2 ℃ in the dark. The fungus was purified by spore dilution plate method. Fast-growing colonies with dense, floccose, cottony mycelium were initially white gradually becoming buff brown. Macroconidia were falcate, 3-5 septa with foot-shaped cell and 10.35-41.50 (av. 25.41±6.82) ×1.90-5.95 (av. 3.67±0.85) µm (n>140) in size after 7 days of incubation on carnation leaf agar (CLA). There were scarce microconidia. Chlamydospores were intercalary, solitary or in chains, globose or irregular, hyaline to light brown. The morphological characteristics of the fungus were similar to that of Fusarium sulawesiense (Maryani et al. 2019). The internal transcribed spacer region (ITS) (KU881904 and KY436233), translation elongation factor 1-alpha (tef1) (KU894408 and KY436232), and RNA polymerase second largest subunit (rpb2) (KU894409 and KY436231) were sequenced from two isolates to cofirm species identification. Blast analysis in the FUSARIUM-ID and the NCBI databases revealed above 99 to 100% identity match with the F. sulawesiense strains NRRL34056, NRRL34059, NRRL34004 and NRRL43730 (Xia et al 2019). Maximum likelihood (ML) analysis and Bayesian inference (BI) based on the concatenated sequences using RAxML v.1.0.0 and MrBayes v. 3.2.1 software revealed that the isolates were resolved in the same clade with the F. sulawesiense strains. Thus, the fungus was identified as F. sulawesiense based on morphological characteristics and molecular criteria. To confirm pathogenicity, five healthy fruits were injected with 200 µl of spore suspension (approximately 104 spores/ml) in the field and laboratory, and isovolumetric sterile water served as control. Each fruit was sealed with a plastic bag and kept at natural temperature (about 25-30 ℃). All the inoculated fruits developed typical symptoms after 30 days in the field and 15 days in the laboratory, whereas no symptoms were observed on the control fruits. F. sulawesiense was reisolated from inoculated fruits, but not from non-inoculated fruits. F. sulawesiense displayed a broad host which included Oryza sativa, Musa nana, Citrus reticulata, and Colocasia esculenta etc. in China (Wang et al. 2019). To our knowledge, this is the first report of F. sulawesiense causing internal black rot on papaya fruit. This work is important for papaya growers to prevent this disease in time.

Characterization of the complete mitogenomes of Baillon's Crake Porzana pusilla and phylogenetic analysis.

The complete mitochondrial genome of the Baillon's Crake Porzana pusilla (Gruiformes: Rallidae) are sequenced and annotated, which contained 37 typical genes. The length of the complete mitochondrial genome is 16,966 bp (GenBank No. MW043485), with As, Ts, Cs, Gs, and AT content of the mitochondrial genome is 32.1, 23.2, 30.9, 13.8, and 55.3%, respectively. All protein-coding genes started with ATN except COX1 and ND5, which start with GTG, and all protein-coding genes end with a complete triplet codon (TAA, AGG, AGA, and TAG), except COX3, which ends with an incomplete T. The ND3 gene of P. pusilla with an extra C nucleotide in 174 site. Phylogenetic analysis revealed that the new sequenced species of P. pusilla was closer to the clade of Porzana fusca and Porzana paykullii, and all three Porzana are clustered into one branch.

Expression of transient receptor potential vanilloid genes and proteins in diabetic rat heart.

Cardiac complications are leading causes of death in diabetic patients. Imbalance of Ca2+ homeostasis is a hallmark of cardiac dysfunction in diabetes, while TRPV channels are non-selective for cations and are permeable to Ca2+. Our aim was to evaluate the expression levels of TRPV1, TRPV2, TRPV3, TRPV4, TRPV5, and TRPV6 genes and proteins in cardiac tissue at 3 days and 4, 8, and 12 weeks after induction of diabetes. Sprague-Dawley rats were assigned to control and DM groups. DM was induced by intraperitoneal injection of streptozotocin (60 mg/kg). The expression levels of TRPV genes were analyzed by the quantitative reverse transcription polymerase chain reaction, and TRPV proteins were determined by western blotting. Compared to controls, the expression levels of TRPV2, TRPV3, and TRPV6 in diabetic myocardium did not change, while TRPV1 decreased at 4, 8, and 12 weeks, TRPV4 was upregulated at 3 days and 4, 8, and 12 weeks, TRPV5 mRNA increased at 8 and 12 weeks, and TRPV5 protein increased at 4, 8, and 12 weeks. Our findings showed that TRPV1, TRPV4, and TRPV5 are associated with the diabetic heart.

Protection of nuclear DNA by lifespan-extending compounds in the yeast Saccharomyces cerevisiae.

DNA damage has been hypothesized to be a driving force of the aging process. At the same time, there exists multiple compounds that can extend lifespan in model organisms, such as yeast, worms, flies, and mice. One possible mechanism of action for these compounds is a protective effect against DNA damage. We investigated whether five of these lifespan-extending compounds, dinitrophenol, metformin, rapamycin, resveratrol, and spermidine, could protect nuclear DNA in the yeast Saccharomyces cerevisiae at the same doses under which they confer lifespan extension. We found that rapamycin and spermidine were able to decrease the spontaneous mutation rate at the CAN1 locus, whereas dinitrophenol, metformin, and resveratrol were able to protect yeast against CAN1 mutations induced by ethyl methanesulfonate (EMS). We also tested whether these compounds could enhance survival against EMS, ultraviolet (UV) light, or hydrogen peroxide (H2O2) insult. All five compounds conferred a protective effect against EMS, while metformin and spermidine protected yeast against UV light. Somewhat surprisingly, none of the compounds were able to afford a significant protection against H2O2, with spermidine dramatically sensitizing cells. We also examined the ability of these compounds to increase lifespan when growth-arrested by hydroxyurea; only spermidine was found to have a positive effect. Overall, our results suggest that lifespan-extending compounds may act in part by protecting nuclear DNA.

Sorafenib not only impairs endothelium-dependent relaxation but also promotes vasoconstriction through the upregulation of vasoconstrictive endothelin type B receptors.

As a VEGF-targeting agent, sorafenib has been used to treat a number of solid tumors but can easily lead to adverse vascular effects. To elucidate the underlying mechanism, rat mesenteric arteries were subjected to organ cultured in the presence of different concentrations of sorafenib (0, 3, 6 and 9 mg/L) with or without inhibitors (U0126, 10-5 M; SB203580, 10-5 M; SP200126, 10-5 M) of MAPK kinases, and then acetylcholine- or sodium nitroprusside-induced vasodilation and sarafotoxin 6c-induced vasoconstriction were monitored by a sensitive myograph. The NO synthetases, the nitrite levels, the endothelial marker CD31,the ETB and ETA receptors and the phosphorylation of MAPK kinases were studied. Next, rats were orally administrated by sorafenib for 4 weeks (7.5 and 15 mg/kg/day), and their blood pressure, plasma ET-1, the ETB and ETA receptors and the phosphorylation of MAPK kinases in the mesenteric arteries were investigated. The results showed that sorafenib impairs endothelium-dependent vasodilation due to decreased NO levels and the low expression of eNOS and iNOS. Weak staining for CD31 indicated that sorafenib induced endothelial damage. Moreover, sorafenib caused the upregulation of vasoconstrictive ETB receptors, the enhancement of ETB receptor-mediated vasoconstriction and the activation of JNK/MAPK. Blocking the JNK, ERK1/2 and p38/MAPK signaling pathways by using the inhibitors significantly abolished ETB receptor-mediated vasoconstriction. Furthermore, it was observed that the oral administration of sorafenib caused an increase in blood pressure and plasma ET-1, upregulation of the ETB receptor and the activation of JNK in the mesenteric arteries. In conclusion, sorafenib not only impairs endothelium-dependent vasodilatation but also enhances ETB receptor-mediated vasoconstriction, which may be the causal factors for hypertension and other adverse vascular effects in patients treated with sorafenib.

Effects of Primary Decompressive Craniectomy on the Outcomes of Serious Traumatic Brain Injury with Mass Lesions, and Independent Predictors of Operation Decision.

BACKGROUND: Although operative indications for traumatic brain injury (TBI) are known, neurosurgeons are unsure whether to remove the bone flap after mass lesion extraction, and an efficient scoring system for predicting which patients should undergo decompressive craniectomy (DC) does not exist. METHODS: Nine parameters were assessed. In total, 245 patients with severe TBI were retrospectively assessed from June 2015 to May 2019, who underwent DC or craniotomy to remove mass lesions. The 6-month mortality and Extended Glasgow Outcome Scale scores were compared between the DC and craniotomy groups. Using univariable and multivariable logistic regression equations, receiver operating characteristic curves were obtained for predicting the decision for DC. RESULTS: The overall 6-month mortality in the entire cohort was 11.43% (28/245). Patients undergoing DC had lower mean preoperative Glasgow Coma Scale scores (P = 0.01), and higher amounts of individuals with a Glasgow Coma Scale score of 6 (P = 0.007), unresponsive pupillary light reflex (P < 0.001), closed basal cisterns (P < 0.001), and diffuse injury (P = 0.025), compared with the craniotomy group. Because of high disease severity, individuals administered primary DC showed increased 6-month mortality compared with the craniotomy group. However, in surviving patients, favorable Extended Glasgow Outcome Scale rates were similar in both groups. Pupillary light reflex and basal cisterns were independent predictors of the DC decision. Based on receiver operating characteristic curves, the model had sensitivity and specificity of 81.6% and 84.9%, respectively, in predicting the probability of DC. CONCLUSIONS: These preliminary data showed that primary DC may benefit some patients with severe TBI with mass lesions. In addition, unresponsive preoperative pupil reaction and closed basal cistern could predict the DC decision.