Left ventricular strain changes at high altitude in rats: a cardiac magnetic resonance tissue tracking imaging study.

BACKGROUND: Long-term exposure to a high altitude environment with low pressure and low oxygen could cause abnormalities in the structure and function of the heart. Myocardial strain is a sensitive indicator for assessing myocardial dysfunction, monitoring myocardial strain is of great significance for the early diagnosis and treatment of high altitude heart-related diseases. This study applies cardiac magnetic resonance tissue tracking technology (CMR-TT) to evaluate the changes in left ventricular myocardial function and structure in rats in high altitude environment. METHODS: 6-week-old male rats were randomized into plateau hypoxia rats (plateau group, n = 21) as the experimental group and plain rats (plain group, n = 10) as the control group. plateau group rats were transported from Chengdu (altitude: 360 m), a city in a plateau located in southwestern China, to the Qinghai-Tibet Plateau (altitude: 3850 m), Yushu, China, and then fed for 12 weeks there, while plain group rats were fed in Chengdu(altitude: 360 m), China. Using 7.0 T cardiac magnetic resonance (CMR) to evaluate the left ventricular ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV) and stroke volume (SV), as well as myocardial strain parameters including the peak global longitudinal (GLS), radial (GRS), and circumferential strain (GCS). The rats were euthanized and a myocardial biopsy was obtained after the magnetic resonance imaging scan. RESULTS: The plateau rats showed more lower left ventricular GLS and GRS (P < 0.05) than the plain rats. However, there was no statistically significant difference in left ventricular EDV, ESV, SV, EF and GCS compared to the plain rats (P > 0.05). CONCLUSIONS: After 12 weeks of exposure to high altitude low-pressure hypoxia environment, the left ventricular global strain was partially decreased and myocardium is damaged, while the whole heart ejection fraction was still preserved, the myocardial strain was more sensitive than the ejection fraction in monitoring cardiac function.

Triptolide alleviates the development of inflammation in ankylosing spondylitis via the NONHSAT227927.1/JAK2/STAT3 pathway.

Ankylosing spondylitis (AS) is a chronic inflammatory disease that can destroy the affected joints. Triptolide (TPL), a key active ingredient of the traditional Chinese medicine Tripterygium wilfordii exhibits promising efficacy in rheumatic immune disease with its anti-inflammatory effects. The present study aimed to elucidate the mechanism of TPL in treatment of AS by regulating the long non-coding RNA (lncRNA) NONHSAT227927.1. The role and underlying mechanisms of TPL in the development of inflammation in AS were assessed. In vivo, the expression of NONHSAT227927.1 in AS was detected by reverse transcription-quantitative (RT-q)PCR. Correlation analysis and binary logistic regression were performed between immune and inflammatory indicators, perception scale scores of patients and NONHSAT227927.1. In vitro, Cell Counting Kit-8 was used to evaluate the activity of AS-fibroblast-like synoviocytes (FLSs) following TPL exposure. AS-FLS inflammation was assessed by qPCR and ELISA. The interaction between TPL and JAK2 and STAT3 was verified by molecular docking and the JAK2/STAT3 pathway components were detected by western blotting. NONHSAT227927.1 was knocked down by small interfering RNA to determine its role. NONHSAT227927.1 was highly expressed in vivo and positively correlated with disease duration, disease duration, Body mass index (BMI), C-reactive protein (CRP), Visual analog scale (VAS), Visual analog scale (VAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Metrology Index, among which ESR and VAS and BASDAI score were risk factors for NONHSAT227927.1. TPL downregulated pro-inflammatory factors in AS-FLSs and inhibited the JAK2/STAT3 pathway via NONHSAT227927.1. TPL inhibited inflammatory factors in AS-FLSs and alleviated inflammatory responses via the NONHSAT227927.1/JAK2/STAT3 axis.

FSGT capsule inhibits IL-1ß-induced inflammation in chondrocytes and ameliorates osteoarthritis by upregulating LncRNA PACER and downregulating COX2/PGE2.

OBJECTIVE: To explore the efficacy and potential mechanism of Fengshi Gutong capsule (FSGTC) in osteoarthritis (OA) inflammation. METHODS: The impact of FSGTC on laboratory indicators of OA patients was explored using data mining technology and association rule analysis. Then, the OA cell model was constructed by inducing chondrocytes (CHs) with interleukin-1ß (IL-1ß). In the presence of FSGTC intervention, the regulatory mechanism of PACER/COX2/PGE2 in OA-CH viability and inflammatory responses was evaluated. RESULTS: Retrospective data mining showed that FSGTC effectively reduced inflammation indexes (ESR, HCRP) of OA patients. Cell experiments showed that LncRNA PACER (PACER) silencing inhibited the proliferation activity of OA-CHs, increased the level of COX2 protein, elevated the levels of PGE2, TNF-α, and IL-1ß, and decreased the levels of IL-4 and IL-10 (p < .01). On the contrary, FSGTC-containing serum reversed the effect of PACER silencing on OA-CHs (p < .01). After the addition of COX2 pathway inhibitor, the proliferation activity of OA-CHs was enhanced; the levels of PGE2, TNF-α, and IL-1ß were decreased while the levels of IL-4 and IL-10 were increased (p < .01). CONCLUSION: FSGTC inhibits IL-1ß-induced inflammation in CHs and ameliorates OA by upregulating PACER and downregulating COX2/PGE2.

Validation of Jianpi Qingre Tongluo Recipe in Reducing Inflammation and Dyslipidemia in Osteoarthritis via Lnc RNA HOTAIR/APN/PI3K/AKT.

Objective: Jianpi Qingre Tongluo Recipe (JQP) has been widely used in clinical practice, and its anti-Osteoarthritis (OA) effectiveness and specific mechanism have been concerned. This study aims to explore the clinical effect of JQP in reducing inflammation and dyslipidemia in OA and the molecular mechanism. Methods: The clinical efficacy of JQP in OA treatment was assessed through data mining. Through the network pharmacology technology, the interactive network of "active component-target-disease" was developed, the interaction relationship of the related proteins was analyzed, and enrichment analysis of gene pathway biological process was conducted. Molecular docking was carried out with PyMOL and AutodockTools-1.5.7. Finally, cell experiments were used to verify JQP's delay of immune inflammation in OA. Results: We found that JQP could ameliorate the immune inflammatory and lipid metabolism indicators; reduce VAS and SAS score in OA. A total of 98 genes overlapped between target genes of JQP and OA. TNF, IL-6, IL-1ß, and AKT1 shared the highest centrality among all target genes. KEGG analysis unveiled that 98 intersection genes were predominantly enriched in PI3K/AKT pathway in the anti-OA system. In vitro, after peripheral blood mononuclear cell (PBMC) stimulation, inflammatory cytokines imbalances and the expressions of adiponectin (APN) were decreased in osteoarthritis-chondrocytes (OA-CH). Furthermore, JQP-containing serum protected OA-CHs through down-regulating HOTAIR levels, thereby up-regulating APN and depressing PI3K/AKT pathway. Conclusion: This study suggests that JQP might reduce inflammation and improve lipid metabolism of OA by regulating HOTAIR/APN/PI3K/AKT. Our results bring a new solution for OA.

Jianpi Qingre Tongluo Decoction exerted an anti-inflammatory effect on AS by inhibiting the NONHSAT227927.1/JAK2/STAT3 axis.

Purpose: This study aims to determine whether Jianpi Qingre Tongluo Decoction (JQP) alleviates ankylosing spondylitis (AS) inflammation via the NONHSAT227927.1/JAK2/STAT3 axis. Methods: The effect of JQP on immune-inflammatory indicators in AS patients was explored through a combination of data mining, association rule analysis, and random walk model evaluation. Subsequently, network pharmacology and molecular docking were performed to screen out the potential signaling pathway. ELISA, PCR and wb were used to evaluate the effect of JQP on AS-FLS activity and inflammatory factors. The role of NONHSAT227927.1/JAK2/STAT3 combination in inflammation was studied by editing NONHSAT227927.1 and adding the JAK2/STAT3 inhibitor AG490. Involvement of the JAK2/STAT3 pathway was detected by PCR, WB, or immunofluorescence analysis. Results: Retrospective data mining results show that JQP can effectively reduce the immune inflammatory response in AS patients. Through network pharmacology and molecular docking, it is speculated that JQP exerts its effect on AS through the JAK2/STAT3 pathway. Overexpression of NONHSAT227927.1 activated the JAK2/STAT3 pathway and promoted the expression of inflammatory factors, while serum containing JQP reversed the effects of NONHSAT227927.1 overexpression. NONHSAT227927.1 silencing inhibits the proliferation of AS-FLSs, inhibits the levels of inflammatory factors, and reduces the expression of JAK2/STAT3 protein. After adding the pathway blocker AG490, it was observed that the cell viability of AS-FLSs was reduced by inflammatory factors and the levels of JAK2/STAT3 were inhibited. , and overexpression of NONHSAT227927.1 can reverse this trend. Conclusions: JQP exerted an anti-inflammatory effect on AS by inhibiting the NONHSAT227927.1/JAK2/STAT3 axis.

Evaluation of cardiac index and right ventricular hypertrophy index in rats under a chronic hypoxic environment at high altitude.

High-altitude areas are characterized by low pressure and hypoxia, which have a significant impact on various body systems. This study aimed to investigate the alterations in cardiac index and right ventricular hypertrophy index(RVHI) in rats at different altitudes.Twenty-one male Sprague-Dawley (SD) rats aged 4 weeks were randomly divided into three groups based on altitude. The rats were raised for 28 weeks and then transferred to Qinghai University Plateau Medicine Laboratory. Body weight was measured, heart organs were isolated and weighed, and cardiac index and right ventricular hypertrophy index were determined. Statistical analysis was performed on the data from the three groups. Compared with the plain group, the body weight of the middle-altitude group was significantly decreased (P < 0.05), and cardiac index, RVHI-1, RVHI-2 increased significantly ((P < 0.05). The body weight, whole heart mass, right ventricular mass were significantly decreased in high-altitude group (P < 0.05), RVHI-1 and RVHI-2 were significantly increased (P < 0.05). Compared with the middle-altitude group, the body weight, whole heart mass and right ventricular mass of the high-altitude group were significantly decreased (P < 0.05), and RVHI-1 and RVHI-2 were significantly increased (P < 0.05). Increasing altitude led to a decrease in body weight, whole heart mass, and right ventricular mass in rats, indicating structural changes in the right heart. Additionally, the proportion of right heart to body weight and whole heart increased with altitude.

Organic iontronic memristors for artificial synapses and bionic neuromorphic computing.

To tackle the current crisis of Moore's law, a sophisticated strategy entails the development of multistable memristors, bionic artificial synapses, logic circuits and brain-inspired neuromorphic computing. In comparison with conventional electronic systems, iontronic memristors offer greater potential for the manifestation of artificial intelligence and brain-machine interaction. Organic iontronic memristive materials (OIMs), which possess an organic backbone and exhibit stoichiometric ionic states, have emerged as pivotal contenders for the realization of high-performance bionic iontronic memristors. In this review, a comprehensive analysis of the progress and prospects of OIMs is presented, encompassing their inherent advantages, diverse types, synthesis methodologies, and wide-ranging applications in memristive devices. Predictably, the field of OIMs, as a rapidly developing research subject, presents an exciting opportunity for the development of highly efficient neuro-iontronic systems in areas such as in-sensor computing devices, artificial synapses, and human perception.

Dual-layer spectral-detector CT for detecting liver steatosis by using proton density fat fraction as reference.

OBJECTIVES: To evaluate the diagnostic accuracy of liver dual-layer spectral-detector CT (SDCT) derived parameters of liver parenchyma for grading steatosis with reference to magnetic resonance imaging-based proton density fat fraction (MRI-PDFF). METHODS: Altogether, 320 consecutive subjects who underwent MRI-PDFF and liver SDCT examinations were recruited and prospectively enrolled from four Chinese hospital centers. Participants were classified into normal (n = 152), mild steatosis (n = 110), and moderate/severe(mod/sev) steatosis (n = 58) groups based on MRI-PDFF. SDCT liver parameters were evaluated using conventional polychromatic CT images (CTpoly), virtual mono-energetic images at 40 keV (CT40kev), the slope of the spectral attenuation curve (λ), the effective atomic number (Zeff), and liver to spleen attenuation ratio (L/S ratio). Linearity between SDCT liver parameters and MRI-PDFF was examined using Spearman correlation. Cutoff values for SDCT liver parameters in determining steatosis grades were identified using the area under the receiver-operating characteristic curve analyses. RESULTS: SDCT liver parameters demonstrated a strong correlation with PDFF, particularly Zeff (rs = -0.856; p < 0.001). Zeff achieved an area under the curve (AUC) of 0.930 for detecting the presence of steatosis with a sensitivity of 89.4%, a specificity of 82.4%, and an AUC of 0.983 for detecting mod/sev steatosis with a sensitivity of 93.1%, a specificity of 93.5%, the corresponding cutoff values were 7.12 and 6.94, respectively. Zeff also exhibited good diagnostic performance for liver steatosis grading in subgroups, independent of body mass index. CONCLUSION: SDCT liver parameters, particularly Zeff, exhibit excellent diagnostic accuracy for grading steatosis. CRITICAL RELEVANCE STATEMENT: Dual-layer SDCT parameter, Zeff, as a more convenient and accurate imaging biomarker may serve as an alternative indicator for MRI-based proton density fat fraction, exploring the stage and prognosis of liver steatosis, and even metabolic risk assessment. KEY POINTS: Liver biopsy is the standard for grading liver steatosis, but is limited by its invasive nature. The diagnostic performance of liver steatosis using SDCT-Zeff outperforms conventional CT parameters. SDCT-Zeff accurately and noninvasively assessed the grade of liver steatosis.