Electroacupuncture attenuates nociceptive behaviors in a mouse model of cancer pain.

Pain is a major symptom in cancer patients, and cancer-induced bone pain (CIBP) is the most common type of moderate and severe cancer-related pain. The current available analgesic treatments for CIBP have adverse effects as well as limited therapeutic effects. Acupuncture is proved effective in pain management as a safe alternative therapy. We evaluated the analgesic effect of acupuncture in treatment of cancer pain and try to explore the underlying analgesic mechanisms. Nude mice were inoculated with cancer cells into the left distal femur to establish cancer pain model. Electroacupuncture (EA) treatment was applied for the xenograft animals. Pain behaviors of mice were evaluated, followed by the detections of neuropeptide-related and inflammation-related indicators in peripheral and central levels. EA treatment alleviated cancer-induced pain behaviors covering mechanical allodynia, thermal hyperalgesia and spontaneous pain, and also down-regulated immunofluorescence expressions of neuropeptide CGRP and p75 in the skin of affected plantar area in xenograft mice, and inhibited expressions of overexpressed neuropeptide-related and inflammation-related protein in the lumbar spinal cord of xenograft mice. Overall, our findings suggest that EA treatment ameliorated cancer-induced pain behaviors in the mouse xenograft model of cancer pain, possibly through inhibiting the expressions of neuropeptide-related and inflammation-related protein in central level following tumor cell xenografts.

Tetrad stage transient cold stress skews auxin-mediated energy metabolism balance in Chinese cabbage pollen.

Changing ambient temperature often impairs plant development and sexual reproduction, particularly pollen ontogenesis. However, mechanisms underlying cold stress-induced male sterility are not well understood. Here, we exposed Chinese cabbage (Brassica campestris) to different cold conditions during flowering and demonstrated that the tetrad stage was the most sensitive. After completion of pollen development at optimal conditions, transient cold stress at the tetrad stage still impacted auxin levels, starch and lipid accumulation, and pollen germination, ultimately resulting in partial male sterility. Transcriptome and metabolome analyses and histochemical staining indicated that the reduced pollen germination rate was due to the imbalance of energy metabolism during pollen maturation. The investigation of ß-glucuronidase (GUS)-overexpressing transgenic plants driven by the promoter of DR5 (DR5::GUS report system) combined with cell tissue staining and metabolome analysis further validated that cold stress during the tetrad stage reduced auxin levels in mature pollen grains. Low-concentration auxin treatment on floral buds at the tetrad stage before cold exposure improved the cold tolerance of mature pollen grains. Artificially changing the content of endogenous auxin during pollen maturation by spraying chemical reagents and loss-of-function investigation of the auxin biosynthesis gene YUCCA6 by artificial microRNA technology showed that starch overaccumulation severely reduced the pollen germination rate. In summary, we revealed that transient cold stress at the tetrad stage of pollen development in Chinese cabbage causes auxin-mediated starch-related energy metabolism imbalance that contributes to the decline in pollen germination rate and ultimately seed set.

Genome-wide identification of U-box gene family and expression analysis in response to saline-alkali stress in foxtail millet (Setaria italica L. Beauv).

E3 ubiquitin ligases are central modifiers of plant signaling pathways that regulate protein function, localization, degradation, and other biological processes by linking ubiquitin to target proteins. E3 ubiquitin ligases include proteins with the U-box domain. However, there has been no report about the foxtail millet (Setaria italica L. Beauv) U-box gene family (SiPUB) to date. To explore the function of SiPUBs, this study performed genome-wide identification of SiPUBs and expression analysis of them in response to saline-alkali stress. A total of 70 SiPUBs were identified, which were unevenly distributed on eight chromosomes. Phylogenetic and conserved motif analysis demonstrated that SiPUBs could be clustered into six subfamilies (I-VI), and most SiPUBs were closely related to the homologues in rice. Twenty-eight types of cis-acting elements were identified in SiPUBs, most of which contained many light-responsive elements and plant hormone-responsive elements. Foxtail millet had 19, 78, 85, 18, and 89 collinear U-box gene pairs with Arabidopsis, rice, sorghum, tomato, and maize, respectively. Tissue specific expression analysis revealed great variations in SiPUB expression among different tissues, and most SiPUBs were relatively highly expressed in roots, indicating that SiPUBs may play important roles in root development or other growth and development processes of foxtail millet. Furthermore, the responses of 15 SiPUBs to saline-alkali stress were detected by qRT-PCR. The results showed that saline-alkali stress led to significantly differential expression of these 15 SiPUBs, and SiPUB20/48/70 may play important roles in the response mechanism against saline-alkali stress. Overall, this study provides important information for further exploration of the biological function of U-box genes.

Genome-wide identification of AAAP gene family and expression analysis in response to saline-alkali stress in foxtail millet (Setaria italica L.).

Amino acid/auxin permease (AAAP) genes encode a large family of protein transporters that play important roles in various aspects of plant growth and development. Here, we performed genome-wide identification of members in the foxtail millet (Setaria italica L.) AAAP family (SiAAAP) and their saline-alkali stress-induced expression patterns, resulting in the identification of 65 SiAAAP genes, which could be divided into eight subfamilies. Except for SiAAAP65, the remaining 64 genes were located on nine chromosomes of foxtail millet. Gene structure and conserved motif analyses indicated that the members in the same subfamily are highly conserved. Gene duplication event analysis suggested that tandem duplication may be the main factor driving the expansion of this gene family, and Ka/Ks analysis indicated that all the duplicated genes have undergone purifying selection. Transcriptome analysis showed differential expression of SiAAAPs in roots, stems, leaves, and tassel inflorescence. Analysis of cis-acting elements in the promoter indicated that SiAAAPs contain stress-responsive cis-acting elements. Under saline-alkali stress, qRT-PCR analysis showed that SiAAP3, SiLHT2, and SiAAP16 were differentially expressed between salt-alkali tolerant millet variety JK3 and salt-alkali sensitive millet variety B175. These results suggest that these genes may be involved in or regulate the response to saline-alkali stress, providing a theoretical basis for further studying the function of SiAAAPs.

[Effect of electroacupuncture on myocardial fibrosis in spontaneously hypertensive rats based on cholinergic anti-inflammatory pathway].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on myocardial fibrosis in spontaneously hypertensive rats (SHR), and explore preliminarily the mediating role of cholinergic anti-inflammatory pathway (CAP) and its downstream nuclear factor κB (NF-κB) signaling pathway. METHODS: Six 12-week-old WKY male rats were employed as the normal group. Eighteen 12-week-old SHR were randomly divided into 3 groups, i.e. a model group, an EA group and a blocking group (EA after blocking α7 nicotinic acetylcholine receptor [α7nAchR]), with 6 rats in each one. In the EA group, EA was delivered at "Neiguan"(PC 6) and the site 0.5 cm from its left side, with disperse-dense wave, 2 Hz/15 Hz in frequency and 1 mA in current intensity. One intervention took 30 min and was given once every 2 days, lasting 8 weeks. In the blocking group, prior to each EA, the α7nAchR specific blocker, α-bungartoxin was injected intravenously in the tails of the rats. After EA intervention, the systolic blood pressure (SBP), the diastolic blood pressure (DBP) and the mean arterial pressure (MAP) were measured with non-invasive blood pressure monitor. Using echocardiogram, the left ventricular (LV) anterior wall end-diastolic thickness (LVAWd) , LV posterior wall end-diastolic thickness (LVPWd) and the LV end-diastolic internal diameter (LVIDd) were measured. The level of hydroxyproline (Hyp) in the myocardial tissue was determined by using alkaline hydrolysis, and that of acetylcholine (Ach) was detected by ELISA. With the real-time PCR adopted, the mRNA expression of NF-κB p65, tumor necrosis factor α (TNF-α), interleukin (IL)-1ß and IL-6 were determined. RESULTS: Compared with the normal group, SBP, DBP, MAP, LVAWd and LVPWd were increased (P<0.01), and LVIDd was decreased (P<0.01) in the rats of the model group. SBP, DBP, MAP and LVAWd were dropped (P<0.01, P<0.05), and LVIDd rose (P<0.01) in the EA group when compared with those in the model group. The differences in the above indexes were not statistically significant between the blocking group and the model group (P>0.05). Compared with the normal group, Hyp level and the mRNA expression of NF-κB p65, TNF-α, IL-1ß and IL-6 in the myocardial tissue increased (P<0.01, P<0.05) and Ach level decreased (P<0.01) in the model group. Hyp level, the mRNA expression of NF-κB p65, TNF-α, IL-1ß and IL-6 in the myocardial tissue were reduced (P<0.05, P<0.01) and Ach level rose (P<0.01) in the EA group when compared with those in the model group. These indexes were not different statistically between the blocking group and the model group (P>0.05). CONCLUSION: CAP may be involved in ameliorating the pathological damage of myocardial fibrosis during EA at "Neiguan"(PC 6). The underlying effect mechanism is associated with up-regulating the neurotransmitter, Ach and down-regulating mRNA expression of NF-κB p65 and pro-inflammatory factors such as TNF-α, IL-1ß and IL-6 in myocardial tissue.

A Review of Labeling Approaches Used in Small Extracellular Vesicles Tracing and Imaging.

Small extracellular vesicles (sEVs), a subset of extracellular vesicles (EVs) originating from the endosomal compartment, are a kind of lipid bilayer vesicles released by almost all types of cells, serving as natural carriers of nucleic acids, proteins, and lipids for intercellular communication and transfer of bioactive molecules. The current findings suggest their vital role in physiological and pathological processes. Various sEVs labeling techniques have been developed for the more advanced study of the function, mode of action, bio-distribution, and related information of sEVs. In this review, we summarize the existing and emerging sEVs labeling techniques, including fluorescent labeling, radioisotope labeling, nanoparticle labeling, chemical contrast agents labeling, and label-free technique. These approaches will pave the way for an in-depth study of sEVs. We present a systematic and comprehensive review of the principles, advantages, disadvantages, and applications of these techniques, to help promote applications of these labeling approaches in future research on sEVs.

Integrating network pharmacology and experimental validation to decipher the mechanism of the Chinese herbal prescription modified Shen-Yan-Fang-Shuai formula in treating diabetic nephropathy.

CONTEXT: Diabetic nephropathy (DN) is the main cause of end-stage renal disease. Modified Shen-Yan-Fang-Shuai formula (M-SYFSF) has excellent clinical efficacy in treating diabetic kidney disease. However, the potential mechanism of M-SYFSF remains unknown. OBJECTIVE: To investigate the mechanism of M-SYFSF against DN by network pharmacological analysis and biological experiments. MATERIALS AND METHODS: Utilizing a web-based pharmacology database, the potential mechanisms of M-SYFSF against DN were identified. In vivo experiments, male SD rats were injected with streptozotocin (50 mg/kg) and got uninephrectomy to construct a model of DN. M-SYFSF (11.34 g/kg/d) was gavaged once per day for 12 weeks after model establishment. In vitro experiments, human proximal tubular cells (HK-2) were performed with advanced glycation end-products (AGEs) (100 µg/mL), then intervened with M-SYFSF freeze-dried powder. Pathological staining, WB, IHC, ELISA were conducted to explore the mechanism of M-SYFSF against DN. RESULTS: Network pharmacological analysis showed that MAPK pathway was the potential pathway. Results showed that compared with the Model group, M-SYFSF significantly reduced 24h urine albumin, UACR, and serum creatinine levels (54.90 ± 26.67 vs. 111.78 ± 4.28, 8.87 ± 1.69 vs. 53.94 ± 16.01, 11.56 ± 1.70 vs. 118.70 ± 49.57, respectively), and improved renal pathological changes. Furthermore, the intervention of M-SYFSF reduced the expression of pro-inflammatory cytokines and inhibited the activation of MAPK pathway in AGEs-treated HK-2 cells. DISCUSSION AND CONCLUSION: M-SYFSF is likely to reduce inflammation in DN by inhibiting the MAPK pathway. It provides a theoretical basis for the clinical application of M-SYFSF in the treatment of DN.

Roles and mechanisms of exosomal microRNAs in viral infections.

Exosomes are small extracellular vesicles with a diameter of 30-150 nm that originate from endosomes and fuse with the plasma membrane. They are secreted by almost all kinds of cells and can stably transfer different kinds of cargo from donor to recipient cells, thereby altering cellular functions for assisting cell-to-cell communication. Exosomes derived from virus-infected cells during viral infections are likely to contain different microRNAs (miRNAs) that can be transferred to recipient cells. Exosomes can either promote or suppress viral infections and therefore play a dual role in viral infection. In this review, we summarize the current knowledge about the role of exosomal miRNAs during infection by six important viruses (hepatitis C virus, enterovirus A71, Epstein-Barr virus, human immunodeficiency virus, severe acute respiratory syndrome coronavirus 2, and Zika virus), each of which causes a significant global public health problem. We describe how these exosomal miRNAs, including both donor-cell-derived and virus-encoded miRNAs, modulate the functions of the recipient cell. Lastly, we briefly discuss their potential value for the diagnosis and treatment of viral infections.

Enterovirus A71 Promotes Exosome Secretion by the Nonstructural Protein 3A Interacting with Rab27a.

Exosomes are small membrane-bound vesicles which are intraluminal vesicles (ILVs) secreted to the extracellular space after multivesicular bodies (MVBs) fuse with the plasma membrane. Although it is known that exosomes play a multitude of roles during viral infection, the mechanism that regulates their secretion during viral infection is unknown. Here, we found that enterovirus A71 (EV-A71) infection increased exosome secretion both in vivo and in vitro. Importantly, the expression of nonstructural protein 3A was sufficient to promote exosome secretion, while a mutation affecting the amino acid 18 position abrogated this effect, without changing the size of exosomes in vivo or in vitro. Transmission electron microscopy (TEM) analysis revealed that 3A decreases the number of MVBs and ILVs in vivo and in vitro, which suggested 3A may boost the fusion between MVBs and the plasma membrane. Furthermore, we demonstrated that an interaction between 3A and the small GTPase protein, Rab27a, protected Rab27a from ubiquitination, resulted in increasing exosome release. Data indicated a novel mechanism by which EV-A71 3A modifies exosome secretion during viral infection. IMPORTANCE Research has shown that viral infection impacts exosome secretion, but its regulation mechanisms remain poorly understood. Nonstructural protein 3A of EV-A71 interacts with many host factors and is involved in the remodeling of cellular membranes. In this investigation, we applied exogenous expression of 3A protein for exploring its regulation on exosome secretion and utilized immunoprecipitation combined with proteomics approaches to identify 3A-interacting factors. Our results demonstrate that 3A protein upregulates the release of the exosomes and that the 3A mutant strain of EV-A71 induce less exosome release compared with the EV-A71 wild type. Viral 3A protein interacts with the host factor Rab27a to prevent it from being ubiquitinated, which in turn improves exosome secretion both in vitro and in vivo. EV-A71 3A protein is a novel viral factor in the control of exosome production.

Involvement of Interleukin-1 ß/Insulin-Like Growth Factor 1 in Ameliorating Effects of Electroacupuncture on Myocardial Fibrosis Induced by Essential Hypertension.

OBJECTIVE: To investigate the effect of electroacupuncture (EA) at Neiguan (PC 6) on myocardial fibrosis in spontaneously hypertensive rats (SHRs), and to explore the contribution of interleukin-1 ß (IL-1 ß), insulin-like growth factor 1 (IGF-1), and transforming growth factor ß 1 (TGF- ß 1) to the effects. METHODS: Nine 12-weeks-old Wistar Kyoto (WKY) male rats were employed as the normal group. Twenty-seven SHRs were equally randomized into SHR, SHR+EA, and SHR + sham groups. EA was applied at bilateral PC 6 once a day 30 min per day in 8 consecutive weeks. After 8-weeks EA treatment at PC 6, histopathologic changes of collagen type I (Col I), collagen type 1 (Col 1) and the levels of IGF-1, 1L-1 ß, TGF- ß 1, matrix metalloproteinase (MMP)-2 and MMP-9 were examined in myocardial tissure respectively. RESULTS: After 8-weeks EA treatment at PC 6, the enhanced myocardial fibrosis in SHRs were characterized by the increased mean fluorescence intensity of Col I and Col 1 in myocardium tissue (P<0.01). All these abnormal alterations above in SHR + EA group was significantly lower compared with the SHR group (P<0.01). Meanwhile, the increased levels of IL-1 ß, IGF-1, TGF-ß 1 in serum or myocardial tissue of SHRs, diminished MMP 9 mRNA expression in SHRs were also markedly inhibited after 8 weeks of EA treatment (P<0.05 or P<0.01). Furthermore, the contents of IL-1 ß, IGF-1, TGF-ß 1 in myocardial tissue were positively correlated with the systolic blood pressure and hydroxyproline respectively (P<0.01). CONCLUSION: EA at bilateral PC 6 could ameliorate cardiac fibrosis in SHRs, which might be mediated by regulation of 1L-1 ß/IGF-1-TGF- ß 1-MMP9 pathway.

Enterovirus-71 utilizes small extracellular vesicles to cross the blood-brain barrier for infecting the central nervous system via transcytosis.

BACKGROUND: Central nervous system (CNS) infections caused by Enterovirus 71 (EV71) pose a serious threat to children, causing severe neurogenic complications and even fatality in some patients. However, the pathogenesis of EV71 infections in the CNS remains unclear. METHODS: An in vitro blood-brain barrier (BBB) model was constructed by coculturing brain microvascular endothelial cells (BMECs) and astrocytes in transwell inserts for simulating CNS infections. EV71 virions and small extracellular vesicles (sEVs) derived from EV71-infected cells (EV71-sEVs) were isolated from the cell culture supernatant by density gradient centrifugation. The BBB model was separately infected with EV71 virions and EV71-sEVs. The mechanism of crossing the BBB was determined by inhibiting the different endocytic modes. A murine model of EV71 infection was constructed for confirming the results of in vitro experiments. RESULTS: The EV71-sEVs containing viral components were endocytosed by BMECs and released on the abluminal side of the BBB model, where they infected the astrocytes without disrupting the BBB in the early stages of infection. The integrity of the tight junctions (TJs) between BMECs was breached via downregulation of PI3K/Akt signaling in the late stages of infection. CONCLUSIONS: EV71 utilized the circulating sEVs for infecting the CNS by crossing the BBB.

Dual roles and potential applications of exosomes in HCV infections.

The hepatitis C virus (HCV) causes severe liver diseases, including hepatitis, liver cirrhosis, and hepatocellular carcinoma, which have high morbidity and mortality. Antibody targeting receptor-mediated HCV infections have limited therapeutic benefits, suggesting that the transmission of HCV infections is possibly mediated via receptor-independent mechanisms. Exosomes are membrane-enclosed vesicles with a diameter of 30-200 nm, which originate from the fusion of endosomal multivesicular bodies with the plasma membrane. Accumulating evidence suggests that exosomes have a pivotal role in HCV infections. Exosomes can transfer viral and cellular bioactive substances, including nucleic acids and proteins, to uninfected cells, thus spreading the infection by masking these materials from immunological recognition. In addition, exosomes originating from some cells can deliver antiviral molecules or prompt the immune response to inhibit HCV infection. Exosomes can be used for the diagnosis of HCV-related diseases, and are being presently evaluated as therapeutic tools for anti-HCV drug delivery. This review summarizes the current knowledge on the dual roles and potential clinical applications of exosomes in HCV infections.

The complete chloroplast genome of Sloanea hemsleyana.

Sloanea hemsleyana is a potential commercial and oil tree species. This study is the first to report and analyze complete chloroplast genome sequences of S. hemsleyana as a genomic resource for conservation purposes. The chloroplast genome is 158,085 bp in length and consisted of a large single-copy (LSC) region (88,446 bp), and a small single-copy (SSC) region (17,659 bp), separated by a pair of inverted repeats (IR) regions (25,990 bp). It contains 108 genes, with 74 protein-coding genes, 30 tRNA genes, and 4 rRNA genes. Phylogenetic analysis revealed that S. hemsleyana was most closely related to S. sinensis.

Synergistic and Attenuating Effect of Electroacupuncture on Aconitine in Improving Heart Failure and Its Calcium Regulation Mechanism.

Objective: The objective is to observe the synergistic and attenuating effect of electroacupuncture (EA) on aconitine (ACO) in improving heart failure (HF) and to explore its underlying mechanism for calcium regulation. Methods: Twenty-four male Sprague-Dawley rats were randomly divided into four groups: normal control (NC) (n = 6), HF(n = 6), ACO (n = 6), and ACO + EA (n = 6). The maximum rates of left ventricular pressure rising and declining (±dp/dtmax), arrhythmia, the left ventricular systolic pressure (LVSP), ejection fraction (LVEF), and fractional shortening (LVFS) were measured by physiological recorder and ultrasound, respectively. Protein expressions of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA2a), phospholamban (PLB), and Na+-Ca2+ exchange (NCX1) in the left ventricle tissue were detected by fluorescence immunoblotting. Results: Compared with the NC group, LVSP, ±dp/dtmax, LVEF, and LVFS were decreased in the HF group; compared with the HF group, LVSP, ±dp/dtmax, LVEF, and LVFS were significantly increased in the ACO + EA group. Compared with the ACO group, the incidence and the degree of arrhythmia were significantly reduced in the ACO + EA group. Compared with the NC group, the activity of SERCA2a was decreased, and the expression of PLB and NCX1 was enhanced in the HF group; compared with the HF group and ACO group, the activity of SERCA2a was increased, and the expression of PLB and NCX1 was significantly attenuated in the ACO + EA group. Conclusions: EA plays a synergistic and attenuated role in ACO improving HF, and the mechanism may be related to the enhancement of the SERCA2a activity and the decrease of the expression of PLB and NCX1 in cardiomyocytes.

[Involvement of ET-1/eNOS in the ameliorating effect of electroacupuncture on cardiac dysfunction in rats with spontaneously hypertensive].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on cardiac function of ventriculus sinister in rats with spontaneously hypertensive (SHR), and to explore the mediation effect of endothelin-1 (ET-1)/endothelial nitric oxide synthase (eNOS). METHODS: Six 12-week-old male Wistar Kyoto (WKY) rats were taken as the normal group. Eighteen 12-week-old SHR were randomly divided into a model group, an EA group and a sham EA group, 6 rats in each group. The rats in the EA group were treated with EA (disperse-dense wave, 2 Hz/15 Hz in frequency, 1 mA in current intensity) at "Neiguan" (PC 6), 30 min each time, once a day for 8 weeks. The rats in the sham EA group were treated with superficial needling at "Neiguan" (PC 6) with no electrical stimulation applied. After treatment, the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were tested by echocardiographic analysis. The left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), heart rate (HR), the maximum rate of increase/decrease of left ventricular pressure (±dp/dtmax) were detected. The serum content of ET-1 was detected by ELISA. Western blot was used to evaluate the expression of ETAR, eNOS in myocardial tissue of left ventricular. RESULTS: Compared with the normal group, LVEF, LVFS, +dp/dtmax/LVSP and -dp/dtmax/LVSP were decreased (P<0.01, P<0.05), while LVSP, LVEDP, +dp/dtmax and -dp/dtmax were increased (P<0.01) in the model group. Compared with the model group, LVEF, LVFS, +dp/dtmax/LVSP and -dp/dtmax/LVSP were increased (P<0.01, P<0.05), and LVSP and LVEDP were decreased (P<0.01) in the EA group. Compared with the normal group, the serum content of ET-1 and the expression of ETAR in myocardial tissue were increased (P<0.01), whereas expression of eNOS was decreased (P<0.01) in the model group. Compared with the model group, the serum content of ET-1 and the expression of ETAR in myocardial tissue were decreased (P<0.05), whereas expression of eNOS was increased (P<0.05) in the EA group. CONCLUSION: EA intervention may alleviate hypertensive cardiac function damage by up-regulating the expression of eNOS protein in myocardial tissue, down-regulating the serum content of ET-1 and the expression of ETAR protein in myocardial tissue.

Identification of gastric cancer with convolutional neural networks: a systematic review.

The identification of diseases is inseparable from artificial intelligence. As an important branch of artificial intelligence, convolutional neural networks play an important role in the identification of gastric cancer. We conducted a systematic review to summarize the current applications of convolutional neural networks in the gastric cancer identification. The original articles published in Embase, Cochrane Library, PubMed and Web of Science database were systematically retrieved according to relevant keywords. Data were extracted from published papers. A total of 27 articles were retrieved for the identification of gastric cancer using medical images. Among them, 19 articles were applied in endoscopic images and 8 articles were applied in pathological images. 16 studies explored the performance of gastric cancer detection, 7 studies explored the performance of gastric cancer classification, 2 studies reported the performance of gastric cancer segmentation and 2 studies analyzed the performance of gastric cancer delineating margins. The convolutional neural network structures involved in the research included AlexNet, ResNet, VGG, Inception, DenseNet and Deeplab, etc. The accuracy of studies was 77.3 - 98.7%. Good performances of the systems based on convolutional neural networks have been showed in the identification of gastric cancer. Artificial intelligence is expected to provide more accurate information and efficient judgments for doctors to diagnose diseases in clinical work.

Social support and sleep quality in patients with stroke: The mediating roles of depression and anxiety symptoms.

BACKGROUND: Research has demonstrated that higher social support is associated with better psychological health, quality of life, cognition, activities of daily living and social participation, but the relationship between social support and sleep quality remains unknown. AIMS: This study aimed to assess the incidence of poor sleep quality, clarify the relationship between social support and sleep quality amongst stroke patients and determine whether anxiety and depression symptoms mediate this relationship. METHODS: We conducted a quantitative, cross-sectional study involving 238 patients with stroke (median age of 61 [range 29-87] years, 68.1% male) recruited from a comprehensive tertiary care hospital between September 2019 and January 2020. A self-administered, structured questionnaire was used for the survey. The mediating effect of anxiety and depression symptoms was assessed using the bootstrap method via Model 4 (parallel mediation) of the SPSS PROCESS macro. RESULTS: Results showed that the incidence of poor sleep quality amongst stroke patients was 65%. Mediation analysis showed that social support exerted significant direct effects on sleep quality, and anxiety and depression symptoms mediated the relationship between social support and sleep quality. CONCLUSION: Measures should be taken to enhance social support to improve the sleep quality of stroke patients.

Applications of System Dynamics Models in Chronic Disease Prevention: A Systematic Review.

INTRODUCTION: Chronic disease is a serious health problem worldwide. Given that health care resources are limited, a comprehensive, effective, and affordable way is needed to provide insights to prevent chronic diseases. System dynamics models provide a comprehensive and systematic method that can predict results over time. These models can simulate and predict appropriate prevention measures for chronic diseases to determine the best practice. METHODS: Two researchers (Y.W., B.H.) independently searched databases (PubMed, Web of Science, Scopus, and Embase) for full-text articles published from January 2000 through February 2021. A PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) 2020-compliant search was carried out to review system dynamics models of chronic disease prevention. A total of 34 articles were included in our study. RESULTS: We divided the prevention measures of system dynamics models into 2 main categories: upstream prevention and downstream prevention. Upstream prevention measures include lifestyle (eg, tobacco control, balanced diet, mental health, moderate exercise), obesity prevention, and social factors. Downstream prevention measures include clinical treatment of chronic diseases. Results showed that effective upstream prevention measures could reduce the prevalence of chronic diseases, and downstream prevention measures could reduce the incidence of complications, improve quality of life, prolong life, save medical costs, and reduce mortality. CONCLUSION: To our knowledge, our systematic review is the first to evaluate the application of system dynamics models in preventing chronic diseases. Such models can provide effective simulations. Hence, we can use system dynamics models to design and implement effective prevention measures for people with chronic diseases.

Mechanism of cargo sorting into small extracellular vesicles.

Extracellular vesicles (EVs) are special membranous structures released by almost every cell type that carry and protect some biomolecules from being degraded. They transport important signaling molecules involved in cell communication, migration, and numerous physiological processes. EVs can be categorized into two main types according to their size: i) small extracellular vesicles (sEVs), such as exosomes (30-150 nm), released from the fusion of multivesicular bodies (MVBs) with the plasma membrane, and ii) large EVs, such as microvesicles (100-1000 nm). These are no longer considered a waste product of cells, but regulators of intercellular communication, as they can transport specific repertoires of cargos, such as proteins, lipids, and nucleic acids to receptor cells to achieve cell-to-cell communication. This indicates the existence of different mechanisms, which controls the cargos sorting into EVs. This review mainly gives a description about the biological roles of the cargo and the sorting mechanisms of sEVs, especially exosomes.

[Preliminary study on mechanism of electroacupuncture with the involvement of SERCA2a/PLB on the synergistic and attenuated effect of aconitine in treatment of heart failure].

OBJECTIVE: To investigate the mechanism of electroacupuncture (EA) with the involvement of sarcoplasmic reticulum Ca2+-ATPase2a (SERCA2a)/phospholamban (PLB) on the synergistic and attenuated effect of aconitine for heart failure. METHODS: Thirty SPF-ranked SD rats were randomly divided into a control group, a model group, an EA group, an aconitine group and an EA plus aconitine group, with 6 rats in each group. The rat model of acute heart failure was established by infusion of high-dose propranolol hydrochloride solution into the right femoral vein. After stabilized for 10 min in the modeled rats, EA was exerted at "Neiguan" (PC 6), with disperse-dense wave, 2 Hz/15 Hz in frequency, 3 mA in intensity, for 30 min in the EA group and the EA plus aconitine group; aconitine solution (10 µg/kg) was injected from the left femoral veins in the rats in the aconitine group and the EA plus aconitine group. Hemodynamic indexes such as the left ventricular systolic pressure (LVSP) and the maximum rate of increase/decrease of left ventricular pressure (±dp/dtmax) were detected and arrhythmia types were observed and scored. SERCA2a protein and PLB protein expressions in left ventricular myocardial tissue of rats were detected by multiplex fluorescence Western blot. RESULTS: Compared with the control group, LVSP and ±dp/dtmax all were decreased after modeling and at each time point after intervention in the model group (P<0.01). Compared with the model group, ±dp/dtmax was increased in the aconitine group and the EA group at 1 min after intervention (P<0.01, P<0.05), +dp/dtmax was increased at 10 to 60 min after intervention in the aconitine group and at 20 to 60 min after intervention in the EA group (P<0.01, P<0.05), LVSP was increased at 1 min after intervention in the EA group (P<0.01), while LVSP and ±dp/dtmax were all increased at 1 to 60 min after intervention in the EA plus aconitine group (P<0.01, P<0.05). Compared with the aconitine group, LVSP and +dp/dtmax were increased at 1 min after intervention in the EA group (P<0.01, P<0.05), LVSP and ±dp/dtmax at 1 min after intervention while +dp/dtmax at 20 to 60 min after intervention were all increased in the EA plus aconitine group (P<0.01, P<0.05). Compared with the EA group, +dp/dtmax was higher at 10 to 60 min after intervention in the EA plus aconitine group (P<0.01). Compared with the model group, arrhythmia score was higher in the aconitine group (P<0.01). Compared with the aconitine group, arrhythmia score was lower in the EA group and the EA plus aconitine group (P<0.01). As compared with the control group, the expression of SERCA2a protein in the left ventricular cardiomyocytes was decreased (P<0.01), while the expression of PLB protein was increased in the model group (P<0.01). Compared with the model group, the expression of SERCA2a protein was increased in both the EA group and the EA plus aconitine group (P<0.05, P<0.01), and PLB protein expression was decreased in each intervention group respectively (P<0.01, P<0.05). As compared with the EA group and the aconitine group, the expression of SERCA2a protein was increased and the expression of PLB protein was decreased in the EA plus aconitine group separately (P<0.05, P<0.01). CONCLUSION: The intervention with electroacupuncture achieves the synergism/ attenuation effect of aconitine for the improvements in heart failure probably by up-regulating the expression of SERCA2a and down-regulating the expression of PLB in myocardial tissue.