An allocentric human odometer for perceiving distances on the ground plane.

We reliably judge locations of static objects when we walk despite the retinal images of these objects moving with every step we take. Here, we showed our brains solve this optical illusion by adopting an allocentric spatial reference frame. We measured perceived target location after the observer walked a short distance from the home base. Supporting the allocentric coding scheme, we found the intrinsic bias 1, 2 , which acts as a spatial reference frame for perceiving location of a dimly lit target in the dark, remained grounded at the home base rather than traveled along with the observer. The path-integration mechanism responsible for this can utilize both active and passive (vestibular) translational motion signals, but only along the horizontal direction. This anisotropic path-integration finding in human visual space perception is reminiscent of the anisotropic spatial memory finding in desert ants 3 , pointing to nature's wondrous and logically simple design for terrestrial creatures.

Single-cell RNA sequencing reveals recruitment of the M2-like CCL8high macrophages in Lewis lung carcinoma-bearing mice following hypofractionated radiotherapy.

BACKGROUND: Tumor-associated macrophages (TAMs) play a pivotal role in reshaping the tumor microenvironment following radiotherapy. The mechanisms underlying this reprogramming process remain to be elucidated. METHODS: Subcutaneous Lewis lung carcinoma (LLC) murine model was treated with hypofrationated radiotherapy (8 Gy × 3F). Single-cell RNA sequencing was utilized to identify subclusters and functions of TAMs. Multiplex assay and enzyme-linked immunosorbent assay (ELISA) were employed to measure serum chemokine levels. Bindarit was used to inhibit CCL8, CCL7, and CCL2. The infiltration of TAMs after combination treatment with hypofractionated radiotherapy and Bindarit was quantified with flow cytometry, while the influx of CD206 and CCL8 was assessed by immunostaining. RESULTS: Transcriptome analysis identified a distinct subset of M2-like macrophages characterized by elevated Ccl8 expression level following hypofractionated radiotherapy in LLC-bearing mice. Remarkbly, hypofractionated radiotherapy not only promoted CCL8high macrophages infiltration but also reprogrammed them by upregulating immunosuppressive genes, thereby fostering an immunosuppressive tumor microenvironment. Additioinally, hypofractionated radiotherapy enhanced the CCL signaling pathway, augmenting the pro-tumorigenic functions of CCL8high macrophages and boosting TAMs recruitment. The adjunctive treatment combining hypofractionated radiotherapy with Bindarit effectively reduced M2 macrophages infiltration and prolonged the duration of local tumor control. CONCLUSIONS: Hypofractionated radiotherapy enhances the infiltration of CCL8high macrophages and amplifies their roles in macrophage recruitment through the CCL signaling pathway, leading to an immunosuppressive tumor microenvironment. These findings highlight the potential of targeting TAMs and introduces a novel combination to improve the efficacy of hypofractionated radiotherapy.

Pediatric Pterygopalatine Fossa Schwannoma Presenting as Vision Loss: A Case Report and Literature Review.

Neurosynovial tumors, originating from Schwann cells within nerve sheaths, are benign entities, with 25% to 45% manifesting in the head and neck region. However, occurrences in the pterygopalatine fossa (PPF) are exceptionally rare, and only a handful of cases have been documented. In this report, we present the unique case of a 6-year-old child exhibiting a sizable soft tissue mass in the left PPF, extending into the inferior orbital fissure. The patient underwent successful intranasal endoscopic removal of PPF schwannoma utilizing the prelacrimal recess approach, with postoperative pathology confirming the diagnosis of schwannoma. Schwannomas within the PPF are particularly uncommon, and instances of such tumors in pediatric patients are even more exceptional. This case highlights the diagnostic and therapeutic challenges associated with PPF schwannomas in children, emphasizing the significance of a multidisciplinary approach for optimal management. In addition, a comprehensive literature review is presented to provide insights into the existing knowledge on this rare entity, further contributing to the understanding of pediatric PPF schwannomas.

STIC-HD live flow technology in the antenatal diagnosis of scimitar syndrome: A case report.

Scimitar syndrome (SS) is a rare entity with an incidence of approximately 1-3 in 200 000 people. It is typically characterized by complete or partial anomalous pulmonary venous drainage from the right lung into the systemic venous circulation, most commonly the inferior vena cava (IVC). For the first time, we report the diagnosis of SS in a fetus in utero using four-dimensional (4D) spatiotemporal image correlation combined with high-definition live flow rendering mode (STIC-HD live flow).

SIRT3-dependent mitochondrial redox homeostasis mitigates CHK1 inhibition combined with gemcitabine treatment induced cardiotoxicity in hiPSC-CMs and mice.

Administration of CHK1-targeted anticancer therapies is associated with an increased cumulative risk of cardiac complications, which is further amplified when combined with gemcitabine. However, the underlying mechanisms remain elusive. In this study, we generated hiPSC-CMs and murine models to elucidate the mechanisms underlying CHK1 inhibition combined with gemcitabine-induced cardiotoxicity and identify potential targets for cardioprotection. Mice were intraperitoneally injected with 25 mg/kg CHK1 inhibitor AZD7762 and 20 mg/kg gemcitabine for 3 weeks. hiPSC-CMs and NMCMs were incubated with 0.5 uM AZD7762 and 0.1 uM gemcitabine for 24 h. Both pharmacological inhibition or genetic deletion of CHK1 and administration of gemcitabine induced mtROS overproduction and pyroptosis in cardiomyocytes by disrupting mitochondrial respiration, ultimately causing heart atrophy and cardiac dysfunction in mice. These toxic effects were further exacerbated with combination administration. Using mitochondria-targeting sequence-directed vectors to overexpress CHK1 in cardiomyocyte (CM) mitochondria, we identified the localization of CHK1 in CM mitochondria and its crucial role in maintaining mitochondrial redox homeostasis for the first time. Mitochondrial CHK1 function loss mediated the cardiotoxicity induced by AZD7762 and CHK1-knockout. Mechanistically, mitochondrial CHK1 directly phosphorylates SIRT3 and promotes its expression within mitochondria. On the contrary, both AZD7762 or CHK1-knockout and gemcitabine decreased mitochondrial SIRT3 abundance, thus resulting in respiration dysfunction. Further hiPSC-CMs and mice experiments demonstrated that SIRT3 overexpression maintained mitochondrial function while alleviating CM pyroptosis, and thereby improving mice cardiac function. In summary, our results suggest that targeting SIRT3 could represent a novel therapeutic approach for clinical prevention and treatment of cardiotoxicity induced by CHK1 inhibition and gemcitabine.

A Rare Case of Sinonasal Pleomorphic Adenoma.

Pleomorphic adenoma (PA) is the most prevalent benign tumor of the salivary glands, characterized by both epithelial and mesenchymal differentiation. It primarily originates within the parotid and submandibular glands, with only rare occurrences in the minor salivary glands. PA in the sinonasal area is extremely rare. Herein, we present a case of a 61-year-old female with a large soft tissue mass in the paranasal sinus and nasal cavity, as evidenced by computed tomography imaging. The patient suffered from repeated nasal congestion for more than 6 months. Eventually, the mass was completely resected using an endoscopic endonasal prelacrimal approach under general anesthesia. Postoperative pathological examination revealed the presence of PA in the nasal sinus.

Expression and Significance of Galectin-1 and Galectin-3 in the Serum and Placental Tissues of Patients with Intrahepatic Cholestasis of Pregnancy.

Background: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease, usually occurring in the third trimester of pregnancy. Its typical clinical manifestations are itching and elevated serum total bile acid levels, which are more harmful to the fetus, and can lead to a variety of adverse pregnancy outcomes. This paper discusses the expressions of galectin -1 and 3 in the serum and placenta of ICP patients and their relationship with the effect of the incidence of ICP. Methods: Galectin-1 and 3 in serum and placenta were detected in 22 pregnant women with ICP and 20 healthy pregnant women admitted to the obstetrics Department of Northern Jiangsu People's Hospital from May 2021 to February 2022. Results: Serum levels of galectin-1 and galectin-3 in ICP pregnant women were significantly higher than those in controls, with significant differences (P<0.05). Placental galectin-1 and 3 were higher in normal pregnant women, and there were statistical differences between groups (P<0.05). Conclusion: In ICP, the maternal serum and placental galectin-1 and 3 levels were significantly increased, both of which may play an important role in the development of ICP, which may be the initiation factor of ICP pathophysiology, a marker of ICP prediction, and a target of ICP prevention strategies.

Short-chain fatty acids (SCFAs) as potential resuscitation factors that promote the isolation and culture of uncultured bacteria in marine sediments.

Many marine bacteria are difficult to culture because they are dormant, rare or found in low-abundances. Enrichment culturing has been widely tested as an important strategy to isolate rare or dormant microbes. However, many more mechanisms remain uncertain. Here, based on 16S rRNA gene high-throughput sequencing and metabolomics technology, it was found that the short-chain fatty acids (SCFAs) in metabolites were significantly correlated with uncultured bacterial groups during enrichment cultures. A pure culture analysis showed that the addition of SCFAs to media also resulted in high efficiency for the isolation of uncultured strains from marine sediments. As a result, 238 strains belonging to 10 phyla, 26 families and 82 species were successfully isolated. Some uncultured rare taxa within Chlorobi and Kiritimatiellaeota were successfully cultured. Amongst the newly isolated uncultured microbes, most genomes, e.g. bacteria, possess SCFA oxidative degradation genes, and these features might aid these microbes in better adapting to the culture media. A further resuscitation analysis of a viable but non-culturable (VBNC) Marinilabiliales strain verified that the addition of SCFAs could break the dormancy of Marinilabiliales in 5 days, and the growth curve test showed that the SCFAs could shorten the lag phase and increase the growth rate. Overall, this study provides new insights into SCFAs, which were first studied as resuscitation factors in uncultured marine bacteria. Thus, this study can help improve the utilisation and excavation of marine microbial resources, especially for the most-wanted or key players. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00187-w.

Glycyrrhizic acid glycosides reduces extensive tripterygium glycosides-induced lipid deposition in hepatocytes.

Aim: Tripterygium glycosides (TG) extracted from the plant Tripterygium wilfordii Hook F has been used to treat chronic kidney diseases for many years. However, hepatotoxicity limits its clinical application. Glycyrrhizic acid glycosides (GA) can reduce TG hepatotoxicity, however, further investigation into the underlying molecular mechanisms by which GA attenuates TG-induced hepatotoxicity is required. Methods: Sprague‒Dawley rats were randomly divided into the control group, the TG groups (TG189 mg/kg group, TG472.5 mg/kg group), and the TG + GA groups (TG189 mg/kg + GA20.25 mg/kg group, TG472.5 mg/kg + GA20.25 mg/kg group). After 21 consecutive days of intragastric administration, structural and molecular changes in hepatocytes were detected. Results: After 21 days of TG treatment, the serum level of the total bilirubin, triglyceride, total cholesterol, and low-density lipoprotein cholesterol increased in the TG189 mg/kg and TG472.5 mg/kg groups when compared to the control group. High-density lipoprotein cholesterol levels were reduced in both TG groups. The ultrastructure of hepatocytes and the structural integrity of the liver were compromised. In addition, the relevant molecular level of the peroxisome proliferators-activated receptor α (PPARα) and acyl-CoA synthetase long-chain family members (ACSLs) pathway was modulated. With the addition of 20.25 mg/kg GA, the serum biochemical indexes and liver tissue structure ultrastructure of hepatocytes were improved, and the PPARα-ACSLs pathway was corrected. Conclusion: The combined application of GA and TG improved abnormal lipid metabolism, repaired liver structure, reduced lipid deposition in hepatocytes, and reduced TG-induced hepatotoxicity.

Observation on the curative effect of neck acupuncture and scalp acupuncture in improving cognitive impairment and quality of life after stroke

Objective: To explore the intervention value of needle acupuncture and scalp acupuncture in improving cognitive impairment and life in stroke patients; Methods: A total of 62 stroke patients who were healed in our hospital from August 2019 to October 2021 were retrospectively selected as the research objects, and were divided into a combined healing cluster (Combined healing cluster, CTG, n=31, The patients received conventional healing combined with acupuncture and acupuncture) and the general healing cluster (GTG, n=31). The healing effects of the two clusters were contrast, and the National Institutes of Health Stroke Scale (NIHSS), neurological deficit score before and after healing Table (NDS) and Barthel Index (BI) score changes, the follow-up outcomes of the two clusters of patients were calculated and contrast between the two clusters; Results: (1) The total effective rate of patients in CTG cluster was 96.77%, and the total effective rate of patients in GTG cluster was 80.65%, and the variation in effective rate between the two clusters was notable (P<0.05). The NIHSS and NDS marks of the CTG cluster were notably bottom than those of the GTG cluster, and the variation between the clusters was notable (P<0.05). (3) On the 7th, 15th and 30th days of healing, the BI marks of the CTG cluster were notably upper than those in the GTG cluster, and the variation between the clusters was notable (P<0.05). (4) There were a total of 3 recurrences in the CTG cluster after 6 months of follow-up, with a recurrence rate of 10.00%, and a total of 9 recurrences in the GTG cluster. The recurrence rate of patients in the CTG cluster was notably bottom than that in the GTG cluster (P<0.05) (AU)

Feasibility analysis of combined traditional Chinese medicine fumigation and electromyography biofeedback in injured players with shoulder-hand syndrome after stroke

Objective: Exploring the feasibility of combining herbal fumigation and myoelectric biofeedback therapy in injured players with post-stroke shoulder-hand syndrome. Methods: A total of 80 players with shoulder-hand syndrome after stroke who were healed in our hospital from July 2019 to June 2021 were retrospectively opted as the research subjects, and were divided into a joint intervention cluster (JIG) according to the variations in their healing methods. cluster, n=40, receiving traditional Chinese medicine fumigation and EMG biofeedback healing) and EMG healing cluster (Electromyobiological feedback cluster, EFG cluster, n=40), the healing effect, changes in simplified FMA mark of upper limbs before and after healing, and healing effects were contrasted between the two clusters. The changes of the front and rear shoulder pain and the pain part of the High Coast Shoulder Joint Function Rating Scale were recorded, and the occurrence of adverse reactions in the two clusters of injured players was recorded; Results: The total effective rate of injured players in the JIG cluster was 97.50% (39/40), which was notably upper than 85.00% (34/40) in the EFG cluster, and the variation between the clusters was notable (P<0.05). None notable variation in the simplified FMA mark between the clusters (P>0.05). On the 7th, 14th, and 28th days of healing, the simplified FMA mark of the upper limbs of the JIG cluster was notably upper than that of the EFG cluster, and the variation was notable (P>0.05). P<0.05); before healing, None notable variation between the two clusters in the degree of shoulder pain and the pain part of the Gaoshore Shoulder Joint Function Assessment Scale (P>0.05). After 28 days of healing, the degree of shoulder pain in the JIG cluster was notably bottom In the EFG cluster, the pain mark of the Gaoan Shoulder Joint Function Assessment Scale was notably upper than that in the EFG cluster, and the variation between the two clusters was notable (P<0.05) (AU)

Inhibition of ACSL4 Alleviates Parkinsonism Phenotypes by Reduction of Lipid Reactive Oxygen Species.

Ferroptosis is a programmed cell death pathway that is recently linked to Parkinson's disease (PD), where the key genes and molecules involved are still yet to be defined. Acyl-CoA synthetase long-chain family member 4 (ACSL4) esterifies polyunsaturated fatty acids (PUFAs) which is essential to trigger ferroptosis, and is suggested as a key gene in the pathogenesis of several neurological diseases including ischemic stroke and multiple sclerosis. Here, we report that ACSL4 expression in the substantia nigra (SN) was increased in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated model of PD and in dopaminergic neurons in PD patients. Knockdown of ACSL4 in the SN protected against dopaminergic neuronal death and motor deficits in the MPTP mice, while inhibition of ACSL4 activity with Triacsin C similarly ameliorated the parkinsonism phenotypes. Similar effects of ACSL4 reduction were observed in cells treated with 1-methyl-4-phenylpyridinium (MPP+) and it specifically prevented the lipid ROS elevation without affecting the mitochondrial ROS changes. These data support ACSL4 as a therapeutic target associated with lipid peroxidation in PD.

Construction and analysis of a conjunctive diagnostic model of HNSCC with random forest and artificial neural network.

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous tumor that is highly aggressive and ranks fifth among the most common cancers worldwide. Although, the researches that attempted to construct a diagnostic model were deficient in HNSCC. Currently, the gold standard for diagnosing head and neck tumors is pathology, but this requires a traumatic biopsy. There is still a lack of a noninvasive test for such a high-incidence tumor. In order to screen genetic markers and construct diagnostic model, the methods of random forest (RF) and artificial neural network (ANN) were utilized. The data of HNSCC gene expression was accessed from Gene Expression Omnibus (GEO) database; we selected three datasets totally, and we combined 2 datasets (GSE6631 and GSE55547) for screening differentially expressed genes (DEGs) and chose another dataset (GSE13399) for validation. Firstly, the 6 DEGs (CRISP3, SPINK5, KRT4, MMP1, MAL, SPP1) were screened by RF. Subsequently, ANN was applied to calculate the weights of 6 genes. Besides, we created a diagnostic model and nominated it as neuralHNSCC, and the performance of neuralHNSCC by area under curve (AUC) was verified using another dataset. Our model achieved an AUC of 0.998 in the training cohort, and 0.734 in the validation cohort. Furthermore, we used the Cell-type Identification using Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm to investigate the difference in immune cell infiltration between HNSCC and normal tissues initially. The selected 6 DEGs and the constructed novel diagnostic model of HNSCC would make contributions to the diagnosis.

Salivary Duct Carcinoma Originated from the Inferior Turbinate: A Rare Case Report.

Salivary duct carcinoma (SDC) is an uncommon but highly aggressive tumor with a poor prognosis. SDC mainly arises from the major salivary glands, typically the parotid gland. Here, we report a rare case of sinonasal SDC in a 54-year-old male patient that might have originated from the inferior turbinate. The patient presented with left nasal congestion and rhinorrhea. Following an endoscopic intervention, the histopathological examination revealed a diagnosis of SDC, characterized by the formation of solid cancer nests and central comedo-type necrosis. Given the highly aggressive nature and unfavorable prognosis of SDC, it is essential to consider it as a differential diagnosis for unilateral nasal tumors.

Insulin reduces pyroptosis-induced inflammation by PDHA1 dephosphorylation-mediated NLRP3 activation during myocardial ischemia-reperfusion injury.

BACKGROUND: Previous studies proved that pyrin domain-containing protein 3 (NLRP3)-induced pyroptosis plays an important role in Myocardial ischemia-reperfusion injury (MIRI). Insulin can inhibit the activation of NLRP3 inflammasome, although the exact mechanism remains unclear. The aim of this study was to determine whether insulin reduces NLRP3-induced pyroptosis by regulating pyruvate dehydrogenase E1alpha subunit (PDHA1) dephosphorylation during MIRI. METHODS: Rat hearts were subject to 30 min global ischemia followed by 60 min reperfusion, with or without 0.5 IU/L insulin. Myocardial ischemia-reperfusion injury was evaluated by measuring myocardial enzymes release, Cardiac hemodynamics, pathological changes, infarct size, and apoptosis rate. Cardiac aerobic glycolysis was evaluated by measuring ATP, lactic acid content, and pyruvate dehydrogenase complex (PDHc) activity in myocardial tissue. Recombinant adenoviral vectors for PDHA1 knockdown were constructed. Pyroptosis-related proteins were measured by Western blotting analysis, immunohistochemistry staining, and ELISA assay, respectively. RESULTS: It was found that insulin significantly reduced the area of myocardial infarction, apoptosis rate, and improved cardiac hemodynamics, pathological changes, energy metabolism. Insulin inhibits pyroptosis-induced inflammation during MIRI. Subsequently, Adeno-associated virus was used to knock down cardiac PDHA1 expression. Knockdown PDHA1 not only promoted the expression of NLRP3 but also blocked the inhibitory effect of insulin on NLRP3-mediated pyroptosis in MIRI. CONCLUSIONS: Results suggest that insulin protects against MIRI by regulating PDHA1 dephosphorylation, its mechanism is not only to improve myocardial energy metabolism but also to reduce the NLRP3-induced pyroptosis.

Evaluation of sulfone-labeled amino acid derivatives as potential PET agents for cancer imaging.

INTRODUCTION: As one of the most important and frequently used molecular imaging techniques in the clinic, positron emission tomography (PET) features high sensitivity and specificity, which generally involves the use of PET contrast agents. Despite the exceptional promise, the availability of novel PET agents could limit its application and there is a clear need to develop new PET agents to improve our understanding of targets of interest and increase the diagnostic specificity. METHODS: Based on the fact that amino acid transport and protein anabolism are increased in tumor tissues, a series of 18F-labeled amino acid analog was labeled with 18F by using [18F]fluoro-4-(vinylsulfonyl)benzene as the radionuclide linker. The obtained probes were subjected to in vitro and in vivo evaluation, including stability, cell line transport channel specificity, PET/CT imaging on tumor and inflammation bearing mice, and biodistribution. RESULTS: Our data shows that [18F]2a had moderate decay corrected labeling yield (>42 %) and high radiochemical purity (>99 %). When tested in vivo, the uptake of [18F]2a was 1.5 ± 0.2%ID/g in NCI-H1975 tumors and 1.1 ± 0.2%ID/g in inflammatory tissues. In contrast, the values for [18F]FDG were 5.7 ± 0.2%ID/g and 4.8 ± 0.1%ID/g, respectively. The inflammatory lesion-to-muscle contrast is 2.4 for [18F]2a, which is 3.0 for [18F]FDG. CONCLUSION: Clearly, [18F]2a hold the great potential for cancer imaging. Its application in distinguishing tumor from inflammatory lesion would still need to be investigated further.

Quality analysis of non-contrast-enhanced CT images synthesized from contrast-enhanced CT images by deep learning model / 中华放射医学与防护杂志

Objective:To synthesize non-contrast-enhanced CT images from enhanced CT images using deep learning method based on convolutional neural network, and to evaluate the similarity between synthesized non-contrast-enhanced CT images by deep learning(DL-SNCT) and plain CT images considered as gold standard subjectively and objectively, as well as to explore their potential clinical value.Methods:Thirty-four patients who underwent conventional plain scan and enhanced CT scan at the same time were enrolled. Using deep learning model, DL-SNCT images were generated from the enhanced CT images for each patient. With plain CT images as gold standard, the image quality of DL-SNCT images was evaluated subjectively. The evaluation indices included anatomical structure clarity, artifacts, noise level, image structure integrity and image deformation using a 4-point system). Paired t-test was used to compare the difference in CT values of different anatomical parts with different hemodynamics (aorta, kidney, liver parenchyma, gluteus maximus) and different liver diseases with distinct enhancement patterns (liver cancer, liver hemangioma, liver metastasis and liver cyst) between DL-SNCT images and plain CT images. Results:In subjective evaluation, the average scores of DL-SNCT images in artifact, noise, image structure integrity and image distortion were all 4 points, which were consistent with those of plain CT images ( P>0.05). However, the average score of anatomical clarity was slightly lower than that of plain CT images (3.59±0.70 vs. 4) with significant difference ( Z = -2.89, P<0.05). For different anatomical parts, the CT values of aorta and kidney in DL-SNCT images were significantly higher than those in plain CT images ( t=-12.89, -9.58, P<0.05). There was no statistical difference in the CT values of liver parenchyma and gluteus maximus between DL-SNCT images and plain CT images ( P>0.05). For liver lesions with different enhancement patterns, the CT values of liver cancer, liver hemangioma and liver metastasis in DL-SNCT images were significantly higher than those in plain CT images( t=-10.84, -3.42, -3.98, P<0.05). There was no statistical difference in the CT values of liver cysts between DL-SNCT iamges and plain CT images ( P>0.05). Conclusions:The DL-SNCT image quality as well as the CT values of some anatomical structures with simple enhancement patterns is comparable to those of plain CT images considered as gold-standard. For those anatomical structures with variable enhancement and those liver lesions with complex enhancement patterns, there is still vast space for DL-SNCT images to be improved before it can be readily used in clinical practice.

Protective effect and mechanism of AKAP1 on myocardial injury induced by highland hypobaric hypoxia / 中华劳动卫生职业病杂志

Objective: To investigate the protective effect and its possible mechanism of A-kinase anchored protein 1 (AKAP1) on the myocardial injury induced by highland hypobaric hypoxia. Methods: From January 2021 to May 2022, male C57BL/6 SPF grade mice were divided into wild type control (WT) group and highland hypobaric hypoxia (HH) group with 6 mice in each group. HH group simulated 6000 m altitude with low pressure oxygen chamber for 4 weeks to build the model. Primary myocardial cells of SD rats were divided into normoxia control group and hypoxia experimental group (n=3). Cell models were constructed in a three-gas hypoxia incubator with 1% oxygen concentration for 24 h. AKAP1 protein and mRNA expression in myocardial tissue and cells were detected by western blotting, immunohistochemistry and quantitative real-time polymerase chain reaction (qPCR). After myocardial point injection of the AKAP1 or the control adenovirus, the mice were divided into 3 groups (n=6) : WT group, highland hypobaric hypoxia overexpression control group (HH+Ad-Ctrl group) and highland hypobaric hypoxia overexpression experimental group (HH+Ad-AKAP1 group). The cardiac function of mice was detected by noninvasive M-type ultrasonic cardiomotive, myocardial fibrosis was detected by Masson and Sirius Red staining, and cardiomyocyte hypertrophy was detected by wheat germ agglutinin. After the expression of AKAP1 in primary cardiomyocytes was downregulated by siRNA and upregulated by adenovirus, the cells were divided into three groups (n=3) : normoxia control group, hypoxia interference control group (hypoxia+siCtrl group), hypoxia AKAP1 knockdown group (hypoxia+siAKAP1 group) ; normoxia control group, hypoxia overexpression control group (hypoxia+Ad-Ctrl group), hypoxia AKAP1 overexpression group (hypoxia+Ad-AKAP1 group). Apoptosis was detected by flow cytometry, AKAP1, apoptosis-related protein and mRNA expression levels were detected by western blotting and qPCR, mitochondrial membrane potential was detected by JC-1 staining, and mitochondrial reactive oxygen specie (ROS) level was detected by MitoSOX. Results: The expression of AKAP1 in cardiac muscle of HH group was lower than that in the WT group, and the expression of AKAP1 in hypoxia experimental group was lower than that in normoxia control group (P<0.01). Compared with WT group, the left ventricular ejection fraction and fraction shortening of left ventricle in HH+Ad-Ctrl group were decreased (P<0.01), myocardial fibrosis and hypertrophy were aggravated (P<0.01), and the expression of B-cell lymphoma-2 (BCL-2) was decreased, the expressions of BCL-2-associated X protein (BAX), Caspase 3 and Caspase 9 were increased (P<0.01). After AKAP1 overexpression, compared with HH+Ad-Ctrl group, the left ventricular ejection fraction and left ventricular fraction shortening were increased in HH+Ad-AKAP1 group (P<0.01), myocardial fibrosis and hypertrophy were reduced (P<0.01), and the expression of BCL-2 was increased, the expressions of BAX, Caspase 3 and Caspase 9 were decreased (P<0.01). Compared with normoxia control group, the expression of BCL-2 in hypoxia+siCtrl group was decreased, the expressions of BAX, Caspase 3, Caspase 9 were increased, the apoptosis level was increased (P<0.01), the mitochondrial membrane potential was decreased and the production of ROS was increased (P<0.01). After AKAP1 knockdown, compared with hypoxia+siCtrl group, the expression of BCL-2 in hypoxia+siAKAP1 group was decreased, the expressions of BAX, Caspase 3, Caspase 9 were increased, the apoptosis level was increased (P<0.01), mitochondrial membrane potential was decreased, and the production of ROS was increased (P<0.01). After AKAP1 overexpression, compared with hypoxia+Ad-Ctrl group, the expression of BCL-2 in hypoxia+Ad-AKAP1 group was increased, the expressions of BAX, Caspase 3 and Caspase 9 were decreased (P<0.05), the apoptosis level was decreased (P<0.01), and the mitochondrial membrane potential was enhanced, and the production of ROS was decreased (P<0.01) . Conclusion: The downregulation of AKAP1 in cardiomyocytes under highland hypobaric hypoxia may lead to the decrease of mitochondrial membrane potential and the increase of ROS generation, leading to the apoptosis of cardiomyocytes, and thus aggravating the myocardial injury at highland hypobaric hypoxia.

Association between muscle mass and quality of life in Shaanxi adults / 中华流行病学杂志

Objective: To investigate the association between muscle mass and quality of life in adults in Shaanxi adults. Methods: The data in this analysis were part of the baseline survey of the Regional Ethnic Cohort Study in Northwest China from June 2018 to May 2019 in Shaanxi Province. The participants' quality of life, including physical component summary (PCS) and mental component summary (MCS), was assessed by the 12-Item Short Form Survey, and the Body Fat Determination System measured muscle mass. A logistic regression model with adjustment for confounding factors was established to analyze the association between muscle mass and quality of life in different genders. Further, sensitivity and subgroup analyses were conducted to explore its stability. Finally, a restricted cubic spline was employed to investigate the dose-response relationship between muscle mass and quality of life in different genders. Results: A total of 20 595 participants were included, with an average age of 55.0, and 33.4% were male. After controlling for potential confounders, compared with the Q1 group, the risk of low PCS was reduced by 20.6% (OR=0.794, 95%CI: 0.681-0.925) and the risk of low MCS was lower reduced by 20.1% (OR=0.799, 95%CI: 0.689-0.926) in female Q5 groups. Compared with the Q1 group, the risk of low PCS was reduced by 24.4% (OR=0.756, 95%CI: 0.644-0.888) in the male Q2 group. However, no significant association between muscle mass and MCS in males has been found. In females, restricted cubic spline analysis showed a significant linear dose-response relationship between muscle mass and PCS and MCS. Conclusions: There is a positive association between muscle mass and quality of life in Shaanxi adults, especially females. With the increase in muscle mass, the physical and mental functions of the population continue to improve.