Right ventricular volume and function by three-dimensional echocardiography: results of the echocardiographic measurements in normal Chinese adults (EMINCA) II.

Three-dimensional (3D) echocardiography is an emerging technique for assessing right ventricular (RV) volume and function, but 3D-RV normal values from a large Chinese population are still lacking. The aim of the present study was to establish normal values of 3D-RV volume and function in healthy Chinese volunteers. A total of 1117 Han Chinese volunteers from 28 laboratories in 20 provinces of China were enrolled, and 3D-RV images of 747 volunteers with optimal image quality were ultimately analyzed by a core laboratory. Both vendor-dependent and vendor-independent software platforms were used to analyze the 3D-RV images. We found that men had larger RV volumes than women did in the whole population, even after indexing to body surface area, and older individuals had smaller RV volumes. The normal RV volume was significantly smaller than that recommended by the American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines in both sexes. There were significant differences in 3D-RV measurements between the two vendor ultrasound systems and the different software platforms. The echocardiographic measurements in normal Chinese adults II study revealed normal 3D-RV volume and function in a large Chinese population, and there were significant differences between the sexes, ages, races, and vendor groups. Thus, normal 3D-RV values should be stratified by sex, age, race, and vendor.

Giant papillary hemangioma-A rare tumor with an exceptional size.

Papillary hemangioma (PH) is a recently described vascular tumor with a predilection for the skin of the head and neck. Histopathologically, it is characterized by a bland endothelial proliferation arranged in a papillary configuration, bearing resemblance to glomeruloid hemangioma seen in the context of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes syndrome. The largest cutaneous PH reported to date measured 1.5 cm in greatest dimension. Here, we report a case of PH with an alarming size of 10 cm. We present this case to add to the limited literature on this rare tumor, highlight the histopathologic differences between PH and its mimics, and emphasize the variable nature of PH tumor size.

MdMYB44-like positively regulates salt and drought tolerance via the MdPYL8-MdPP2CA module in apple.

Abscisic acid (ABA) is involved in salt and drought stress responses, but the underlying molecular mechanism remains unclear. Here, we demonstrated that the overexpression of MdMYB44-like, an R2R3-MYB transcription factor, significantly increases the salt and drought tolerance of transgenic apples and Arabidopsis. MdMYB44-like inhibits the transcription of MdPP2CA, which encodes a type 2C protein phosphatase that acts as a negative regulator in the ABA response, thereby enhancing ABA signaling-mediated salt and drought tolerance. Furthermore, we found that MdMYB44-like and MdPYL8, an ABA receptor, form a protein complex that further enhances the transcriptional inhibition of the MdPP2CA promoter by MdMYB44-like. Significantly, we discovered that MdPP2CA can interfere with the physical association between MdMYB44-like and MdPYL8 in the presence of ABA, partially blocking the inhibitory effect of the MdMYB44-like-MdPYL8 complex on the MdPP2CA promoter. Thus, MdMYB44-like, MdPYL8, and MdPP2CA form a regulatory loop that tightly modulates ABA signaling homeostasis under salt and drought stress. Our data reveal that MdMYB44-like precisely modulates ABA-mediated salt and drought tolerance in apples through the MdPYL8-MdPP2CA module.

Association of serum Asprosin concentrations with heart failure.

BACKGROUND: To analyze the association of serum Asprosin concentrations with heart failure (HF). METHODS: A total of 103 patients with HF were included in the HF group, and 103 patients with health checkups were included in the non-HF group. The serum Asprosin levels of the two groups were measured, and relevant clinical data were collected for statistical analysis. RESULTS: Compared with the non-HF group, the serum Asprosin concentration was significantly higher in the HF group, and the difference was statistically significant (P < 0.001). According to the serum Asprosin levels, we divided all the subjects into three quartiles. We found that the prevalence of HF increased with increasing serum Asprosin levels in the three groups (P < 0.001). Serum Asprosin levels were positively correlated with NT-ProBNP (P < 0.05) and negatively correlated with LVEF (P < 0.001). Dichotomous logistic regression analysis found Asprosin and age to be independent risk factors for HF (OR = 1.010, 95% CI: 1.003-1.018; OR = 1.058, 95% CI:1.004-1.665, respectively). Combining Asprosin and NT-proBNP indicators to draw ROC curves can improve the specificity and sensitivity of HF diagnosis. CONCLUSIONS: Serum Asprosin levels were significantly elevated in HF patients. The serum Asprosin level is an independent risk factor for HF, and the combined detection of Asprosin and NT-proBNP levels can improve the accuracy of HF diagnosis.

Feasibility study on evaluating right ventricular diastolic function by new Tei'-Index.

Objective: Doppler-derived myocardial performance index (Tei) has been used in the evaluation of right ventricular (RV) function. However, the usage in isolated diastolic dysfunction is limited.We sought to find a new Tei'-index that is more appropriate for evaluating isolated diastolic dysfunction (IDD) based on the symmetry of cardiac structure and function. Methods: 21 patients with impaired RV relaxation were compared to 44 control subjects. Tei and Tei' including their components, isovolumetric relaxation time (IRT), isovolumetric contraction time (ICT), the ejection time (ET), and RV rapid filling time (RFT) were measured from RV outflow and tricuspid inflow Doppler velocity profiles. Results: Tei-index have no change between IDD group and control subjects (0.21 ± 0.08 vs 0.23 ± 0.07 P[bond, double bond]NS). The Tei'-index was significantly shortened in IDD group(0.24 ± 0.09 vs 0.32 ± 0.12,p＜0.05).The decrease in Tei'-index was due to the prolongation of both IRT and RFT, and in the abbreviation of ICT. Tei'-index cutoff value of ≥0.31 identified impaired RV relaxation with a sensitivity of 50 % and specificity of 86 %.We also find that the Tei'-index correlated well with doppler measures of diastolic parameters like E/A, E/e', DT, which suggests its potential use as a noninvasive indicator of the right ventricular (RV) relaxation in patients with heart failure of different causes. Conclusion: New Tei's index is highly effective and specific in the evaluation of early diastolic dysfunction of right ventricle, and can be used as an indicator for the detection of IDD in clinic.

Hepatocyte-specific deletion of small heterodimer partner protects mice against acetaminophen-induced hepatotoxicity via activation of Nrf2.

Acetaminophen (APAP) overdose stands as the primary cause of acute liver failure in the United States. APAP hepatotoxicity involves hepatic glutathione (GSH) depletion and mitochondrial damage. To counteract the toxicity of APAP, the nuclear factor erythroid 2 like 2 (Nrf2) activates the expression of genes responsible for drug detoxification and GSH synthesis. In this study, we present evidence that the elimination of hepatocyte small heterodimer partner, a critical transcriptional repressor for liver metabolism, results in Nrf2 activation and protects mice from APAP-induced acute liver injury. Initial investigations conducted on wildtype (WT) mice revealed a swift downregulation of Shp mRNA within the first 24 h after APAP administration. Subsequent treatment of hepatocyte-specific Shp knockout (ShpHep-/-) mice with 300 mg/kg APAP for 2 h exhibited comparable bioactivation of APAP with that observed in the WT controls. However, a significant reduction in liver injury was observed in ShpHep-/- after APAP treatment for 6 and 24 h. The decreased liver injury correlated with a faster recovery of GSH, attributable to heightened expression of Nrf2 target genes involved in APAP detoxification and GSH synthesis. Moreover, in vitro studies revealed that SHP protein interacted with NRF2 protein, inhibiting the transcription of Nrf2 target genes. These findings hold relevance for humans, as overexpression of SHP hindered APAP-induced NRF2 activation in primary human hepatocytes. In conclusion, our studies have unveiled a novel regulatory axis involving SHP and NRF2 in APAP-induced acute liver injury, emphasizing SHP as a promising therapeutic target in APAP overdose-induced hepatotoxicity.

Seed priming with rutin enhances tomato resistance against the whitefly Bemisia tabaci.

Flavonoids are ubiquitously distributed in plants, showing pleiotropic effects in defense against abiotic and biotic stresses. Although it has been shown that seed priming with flavonoids can enhance plant resistance to abiotic stress, little is known about its potential to enhance plant tolerance to biotic stresses, especially for herbivorous insects. Here, we investigated whether treatment of tomato (Solanum lycopersicum) seeds with rutin improves plant resistance against the whitefly (Bemisia tabaci). Specifically, we measured the effect of rutin seed treatment on tomato seedling vigour, plant growth, feeding behavior and performance of B. tabaci on plants grown from control and rutin-treated seeds, and plant defense responses to B. tabaci attack. We found that seed treatment with different concentrations of rutin (viz 1, 2, 5, 10, and 20 mM) had minimal impact on shoot growth. Furthermore, seed treatment of rutin reduced the developmental rate of nymphs, the fecundity and feeding efficiency of adult females on plants grown from these seeds. The enhanced resistance of tomato against B. tabaci is closely associated with increased flavonoids accumulation, callose deposition and the expression of jasmonic acid (JA)-dependent defense genes. Additionally, callose deposition and expression of JA-dependent genes in tomato plants grown from rutin-treated seeds significantly increased upon B. tabaci infestation. These results suggest that seed treatment with rutin primes tomato resistance against B. tabaci, and are not accompanied by reductions in shoot growth. Defense priming by seed treatments may therefore be suitable for commercial exploitation.

Effects of perioperative use of esketamine on postpartum depression risk in patients undergoing cesarean section: A randomized controlled trial.

BACKGROUND: Postpartum depression (PPD) is a prevalent public health issue. Although ketamine has prophylactic effects on PPD in women undergoing cesarean section, the effects of esketamine on PPD remain unclear. This trial aimed to evaluate the efficacy of perioperative esketamine infusion on PPD risk by assessing Edinburgh Postnatal Depression Scale (EPDS) scores and blood biomarkers. METHODS: A total of 150 participants undergoing elective cesarean section were randomly allocated to receive either esketamine or normal saline. Since 27 participants were excluded due to consent withdrawal or loss to follow-up, 123 patients were included. The primary outcome was the prevalence of PPD risk. Secondary outcomes included the prevalence of postpartum anxiety (PPA) risk, levels of biomarkers, postoperative pain intensity, and cumulative sufentanil consumption. RESULTS: The prevalence of PPD and PPA risk at 3 days, 42 days, 3 months, and 6 months postpartum did not differ between the two groups. Furthermore, EPDS scores, pain intensity at rest, and during coughing on postoperative days (POD) 1 and 2 did not differ between the two groups. Sufentanil consumption during 0-12 h, 12-24 h, 0-24 h, and 0-48 h postoperatively were significantly lower in the esketamine group compared to the control group. Blood biomarkers did not differ between the two groups on POD 3. LIMITATIONS: The sample size was small. PPD risk was simply screened, not diagnosed. CONCLUSIONS: Perioperative administration of esketamine did not decrease the incidence of PPD risk in women after elective cesarean section. However, esketamine reduced opioid consumption.

Salidroside attenuates cerebral ischemia/reperfusion injury by regulating TSC2-induced autophagy.

Salidroside (SAL), an antioxidant derived from Rhodiola rosea, exerts neuroprotective effects in cerebral ischemia/reperfusion (I/R) injury; however, the mechanisms have not been fully elucidated. The present study established a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) and a cellular model of oxygen-glucose deprivation/reoxygenation (OGD/R) to explore the roles and mechanisms of SAL in cerebral I/R injury. The rat model of MCAO/R was established and rats were treated with different doses of SAL. The Zea-Longa scoring system and 2,3,5-triphenyltetrazolium chloride (TTC) staining showed that SAL reduced neurological deficit scores and cerebral infarct volumes in MCAO/R rats. The results of Morris water maze (MWM) test showed that SAL reduced memory impairment in MCAO/R rats. In addition, SAL significantly reduced oxidative stress and suppressed inflammatory response. Next, the OGD/R model was established with PC12 cells and treated with SAL. The results of flow cytometry and 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assays showed that SAL reduced apoptosis, enhanced cell viability and protected neuronal cells from damage by decreasing lactate dehydrogenase (LDH) activity. SAL increased the expression of TSC complex subunit 2 (TSC2), and activated the 5'-AMP-activated protein kinase (AMPK) and inhibited the mammalian target of rapamycin (mTOR) signaling pathways. It was verified that SAL alleviated cerebral I/R injury by regulating the AMPK/TSC2/mTOR pathway to induce autophagy. In conclusion, SAL reduces the inflammatory response and oxidative stress in a concentration-dependent manner, and protects against cerebral I/R injury by modulating TSC2-induced autophagy. These findings suggest SAL may prove to be a potential therapeutic agent for ischemic stroke.

MdWRKY120 Enhance Apple Susceptibility to Alternaria alternata.

Alternaria alternata (A. alternata) is a common pathogen that greatly influences apples' quantity and quality. However, chemical treatments produce increased health risks along with decreased food and environmental safety. Advancements in plant molecular biology, such as transgenic technology, have increased apple trees' resistance to pathogens and have therefore attracted widespread attention. WRKY transcription factors are involved in abiotic and biotic stress regulation; however, their biological role in non-model plants such as apple, is still unknown. In this investigation, MdWRKY120 was isolated from the 'GL-3' apple to determine its function during Alternaria alternate infection. The MdWRKY120-GFP fusion protein was located in the nucleus. MdWRKY120 in yeast cells exhibited activating transcriptional activity, meaning it is a transcription activator. MdWRKY120 overexpression transgenic plants were more sensitive to A. alternata, while RNAi transgenic plants showed increased resistance to A. alternata. This investigation demonstrates that MdWRKY120 enhances the susceptibility of apples to A. alternata.

Enhancing Natural Killer Cell-Mediated Cancer Immunotherapy by the Biological Macromolecule Nocardia rubra Cell-Wall Skeleton.

The biological macromolecule Nocardia rubra cell-wall skeleton (Nr-CWS) has well-established immune-stimulating and anti-tumor activities. However, the role of Nr-CWS on natural killer (NK) cells remains unclear. Here, we explore the function and related mechanisms of Nr-CWS on NK cells. Using a tumor-bearing model, we show that Nr-CWS has slightly effect on solid tumor. In addition, using a tumor metastasis model, we show that Nr-CWS suppresses the lung metastasis induced by B16F10 melanoma cells in mice, which indicates that Nr-CWS may up-regulate the function of NK cells. Further investigation demonstrated that Nr-CWS can increase the expression of TRAIL and FasL on spleen NK cells from Nr-CWS treated B16F10 tumor metastasis mice. The spleen index and serum levels of TNF-α, IFN-γ, and IL-2 in B16F10 tumor metastasis mice treated with Nr-CWS were significantly increased. In vitro, the studies using purified or sorted NK cells revealed that Nr-CWS increases the expression of CD69, TRAIL, and FasL, decreases the expression of CD27, and enhances NK cell cytotoxicity. The intracellular expression of IFN-γ, TNF-α, perforin (prf), granzyme-B (GrzB), and secreted TNF-α, IFN-γ, IL-6 of the cultured NK cells were significantly increased after treatment with Nr-CWS. Overall, the findings indicate that Nr-CWS could suppress the lung metastasis induced by B16F10 melanoma cells, which may be exerted through its effect on NK cells by promoting NK cell terminal differentiation (CD27lowCD11bhigh), and up-regulating the production of cytokines and cytotoxic molecules.

PRAME immunohistochemistry for melanoma diagnosis: A STARD-compliant diagnostic accuracy study.

BACKGROUND: Preferentially expressed antigen in melanoma (PRAME) is a tumor-associated antigen that is frequently expressed in cutaneous melanoma and can be evaluated by immunohistochemistry. Earlier studies on PRAME utilized case-control study designs that may misestimate diagnostic accuracy and lack generalizability. METHODS: Using retrospective cohort selection, a cross-sectional study of diagnostic accuracy of PRAME was conducted according to standards for reporting diagnostic accuracy studies requirements. RESULTS: Mean PRAME positive fraction was higher in 42 malignant melanocytic lesions than 101 benign melanocytic lesions (0.71 ± 0.30 vs. 0.13 ± 0.20, p < 0.01). Receiver operating characteristic curve showed the test was effective (area under the curve = 0.90). Global PRAME 4+ scores (>75%) were associated with sensitivity of 0.63, specificity of 0.97, accuracy of 0.87, and excellent interrater concordance (Kappa = 0.83). Lower cutoffs for PRAME of 2+ (>25%) and 3+ (>50%) produced higher joint sensitivity/specificity (Youden index) than PRAME 4+, but lower accuracy. CONCLUSION: PRAME as it is used in clinical practice is an effective test for melanoma. PRAME is best used as an ordinal variable to calculate the posttest probability of melanoma. PRAME ≤25% (0/1+) favors nevus, PRAME 26%-75% (2/3+) is noncontributory, and PRAME >75% (4+) favors melanoma.

Evaluation of contrast-induced acute kidney injury using IVIM and DKI MRI in a rat model of diabetic nephropathy.

OBJECTIVE: To assess the potential of intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) in monitoring renal changes in a diabetic nephropathy (DN) rat model with acute kidney injury (CI-AKI) induced by iso-osmotic contrast media (IOCM) and low-osmotic contrast media (LOCM). METHODS: A diabetic nephropathy rat model was established, and the animals were randomly split into the LOCM group and IOCM group (n = 13 per group), with iopamidol and iodixanol injection, respectively (4 g iodine/kg). MRI including IVIM and DKI was performed 24 h before contrast medium injections (baseline) and 1, 24, 48, and 72 h after injections. Changes in pure molecular diffusion (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), mean diffusion (MD), mean kurtosis (MK), serum creatinine (SCr) and urea nitrogen (BUN), histopathology alterations, and α-smooth muscle actin (α-SMA) expression were assessed. Inter-observer agreement was evaluated using the intraclass correlation coefficient (ICC). RESULTS: Compared against baseline levels, significant decreases in D, D*, and f were observed in all anatomical kidney compartments after contrast injection (p < 0.05). MD in the cortex (CO) and outer medullary (OM) gradually decreased, and MK in OM gradually increased 24-72 h after injection. D, D*, f, and MD were negatively correlated with the histopathologic findings and α-smooth muscle actin (α-SMA) expression in all anatomical kidney compartments. Inter-observer reproducibility was generally good (ICCs ranging from 0.776 to 0.979). CONCLUSIONS: IVIM and DKI provided noninvasive imaging parameters, which might offer effective detection of CI-AKI in DN.

Kinetic Characterization of the Immune Response to Methicillin-Resistant Staphylococcus aureus Subcutaneous Skin Infection.

Staphylococcus aureus is a leading cause of skin and soft tissue infections (SSTIs). Studies examining the immune response to S. aureus have been conducted, yet our understanding of the kinetic response to S. aureus subcutaneous skin infection remains incomplete. In this study, we used C57BL/6J mice and USA300 S. aureus to examine the host-pathogen interface from 8 h postinfection to 15 days postinfection (dpi), with the following outcomes measured: lesion size, bacterial titers, local cytokine and chemokine levels, phenotype of the responding leukocytes, and histopathology and Gram staining of skin tissue. Lesions were largest at 1 dpi, with peak necrotic tissue areas at 3 dpi, and were largely resolved by 15 dpi. During early infection, bacterial titers were high, neutrophils were the most abundant immune cell type, there was a decrease in most leukocyte populations found in uninfected skin, and many different cytokines were produced. Histopathological analysis demonstrated swift and extensive keratinocyte death and robust and persistent neutrophil infiltration. Gram staining revealed subdermal S. aureus colonization and, later, limited migration into upper skin layers. Interleukin-17A/F (IL-17A/F) was detected only starting at 5 dpi and coincided with an immediate decrease in bacterial numbers in the following days. After 9 days, neutrophils were no longer the most abundant immune cell type present as most other leukocyte subsets returned, and surface wounds resolved coincident with declining bacterial titers. Collectively, these data illustrate a dynamic immune response to S. aureus skin infection and suggest a key role for precisely timed IL-17 production for infection clearance and healthy tissue formation.

Upregulation of Periostin Through CREB Participates in Myocardial Infarction-induced Myocardial Fibrosis.

ABSTRACT: Myocardial fibrosis after myocardial infarction (MI) leads to heart failure, which has become an important global public health issue. One of the most important features of myocardial fibrosis is the abnormal deposition of extracellular matrix (ECM) proteins. Periostin is one of the ECM proteins. Cyclic AMP response element-binding protein 1 (CREB) is well known for its involvement in multiple signaling in myocardial fibrosis. It has been confirmed that CREB could regulate ECM proteins deposition. However, little is known about the relationship between CREB and periostin post-MI. This study aims to verify the hypothesis that CREB promotes the expression of periostin in MI-induced myocardial fibrosis. To test this hypothesis, primary rat cardiac fibroblasts were cultured and rat model of MI was established. The level of myocardial fibrosis post-MI was identified by histological staining. The expressions of CREB and periostin were detected through western blot and reverse transcription quantity polymerase chain reaction. The upregulation and downregulation of CREB and periostin were established by plasmid, small interfere RNA (siRNA), and lentivirus, respectively. High levels of CREB and periostin were found post-MI in our study. Meanwhile, the expression of periostin was decreased after CREB downregulation both in vivo and in vitro. Finally, with the treatment of pAV-CREB and si-periostin, the expressions of collagen Ⅰ and Ⅲ were attenuated. The expression of periostin was elevated post-MI and participated in MI-induced myocardial fibrosis, which was regulated through CREB. This study provides a novel idea and potential intervention target for MI-induced myocardial fibrosis.

Malignancy-associated acquired vulvar lymphangioma circumscriptum: A clinicopathologic study of 71 cases.

BACKGROUND: Acquired lymphangioma circumscriptum of the vulva is rare and can occur subsequent to malignancies of the anogenital and pelvic region. We sought to investigate the clinicopathologic characteristics of malignancy-associated acquired vulvar lymphangioma circumscriptum (AVLC). METHODS: We identified all cases of AVLC within our institution with history of prior malignancy between 2005 and 2021. A similar search was performed in the PubMed database to identify published cases to date. The clinical and histopathologic information was recorded. RESULTS: A total of 71 cases were identified. The most common preceding malignancy was cervical carcinoma (71.8%, 51/71). Radiation therapy was given to 91.4% (64/70) of the patients and lymph node dissection was made on 70.2% (40/57). Median interval between the diagnosis of malignancy and the AVLC was 10 years (range 0-32 years). AVLC frequently presented as vesicular (31.6%, 18/57) or verrucous (28.1%, 16/57) lesions clinically. Common treatments for AVLC included excision (53.1%, 26/49) and laser therapy (16.3%, 8/49), with an overall recurrence rate of 42.9% (24/56) at a median follow-up interval of 1.8 years (range 0.04-32.3 years). CONCLUSION: AVLC is a rare, late complication of anogenital and pelvic malignancies causing debilitating physical symptoms and psychological stress. Further studies are warranted to determine the most effective treatment modalities to mitigate recurrence.

Novel insights into negative pressure wound healing from an in situ porcine perspective.

Negative pressure wound therapy (NPWT) is used clinically to promote tissue formation and wound closure. In this study, a porcine wound model was used to further investigate the mechanisms as to how NPWT modulates wound healing via utilization of a form of NPWT called the vacuum-assisted closure. To observe the effect of NPWT more accurately, non-NPWT control wounds containing GranuFoam™ dressings, without vacuum exposure, were utilized. In situ histological analysis revealed that NPWT enhanced plasma protein adsorption throughout the GranuFoam™, resulting in increased cellular colonization and tissue ingrowth. Gram staining revealed that NPWT decreased bacterial dissemination to adjacent tissue with greater bacterial localization within the GranuFoam™. Genomic analysis demonstrated the significant changes in gene expression across a number of genes between wounds treated with non-NPWT and NPWT when compared against baseline tissue. However, minimal differences were noted between non-NPWT and NPWT wounds, including no significant differences in expression of collagen, angiogenic, or key inflammatory genes. Similarly, significant increases in immune cell populations were observed from day 0 to day 9 for both non-NPWT and NPWT wounds, though no differences were noted between non-NPWT and NPWT wounds. Furthermore, histological analysis demonstrated the presence of a foreign body response (FBR), with giant cell formation and encapsulation of GranuFoam™ particles. The unique in situ histological evaluation and genomic comparison of non-NPWT and NPWT wounds in this pilot study provided a never-before-shown perspective, offering novel insights into the physiological processes of NPWT and the potential role of a FBR in NPWT clinical outcomes.