Level and influencing factors of transition shock among new nurses in China: A multicenter cross-sectional study.

Background and Aims: New nurses are an important part of nursing teams. The failure of new nurses to successfully transition seriously affects personal career development and nursing work quality, and important influencing factors deserve the attention of nursing managers. At present, multicenter, large-sample investigations of transition shock among new nurses are lacking in China. This study aims to investigate the current level and influencing factors of transition shock among new nurses in China. Methods: We conducted a multicenter, cross-sectional study with 3414 new nurses from 16 provinces in 7 regions in China from October 22, 2021, to November 8, 2021. We used the snowball sampling method and an online questionnaire produced by the researchers to collect data; the questionnaire included questions on demographic information, a transition shock scale for new nurses and open-ended questions. Data were analyzed using SPSS version 24. Results: The effective response rate of this study was 97.89%, with 3342 effective participants from 189 hospitals in China, most of whom were female (94.88%). The study showed that the transition shock of new nurses in China was at a moderate level, with pre-job anxiety, unsatisfactory welfare treatment, resignation intention, adverse events, poor sleep quality, 1 or fewer exercise sessions per week, inability to balance work and life, and gluttony negatively affecting the transition shock of new nurses in China. Psychological shock was the strongest among the four dimensions of transition shock. Conclusions: The transition shock of new nurses, especially their psychological shock, deserves more attention from international society. Nursing managers should continue to take supportive measures to intervene in the factors influencing transition shock, with the aim of reducing the level of transition for new nurses, promoting their personal thriving, improving the quality of nursing work and increasing the retention rate of nurses.

Single-cell analysis technologies for cancer research: from tumor-specific single cell discovery to cancer therapy.

Single-cell sequencing (SCS) technology is changing our understanding of cellular components, functions, and interactions across organisms, because of its inherent advantage of avoiding noise resulting from genotypic and phenotypic heterogeneity across numerous samples. By directly and individually measuring multiple molecular characteristics of thousands to millions of single cells, SCS technology can characterize multiple cell types and uncover the mechanisms of gene regulatory networks, the dynamics of transcription, and the functional state of proteomic profiling. In this context, we conducted systematic research on SCS techniques, including the fundamental concepts, procedural steps, and applications of scDNA, scRNA, scATAC, scCITE, and scSNARE methods, focusing on the unique clinical advantages of SCS, particularly in cancer therapy. We have explored challenging but critical areas such as circulating tumor cells (CTCs), lineage tracing, tumor heterogeneity, drug resistance, and tumor immunotherapy. Despite challenges in managing and analyzing the large amounts of data that result from SCS, this technique is expected to reveal new horizons in cancer research. This review aims to emphasize the key role of SCS in cancer research and promote the application of single-cell technologies to cancer therapy.

EM-YOLO: An X-ray Prohibited-Item-Detection Method Based on Edge and Material Information Fusion.

Using X-ray imaging in security inspections is common for the detection of objects. X-ray security images have strong texture and RGB features as well as the characteristics of background clutter and object overlap, which makes X-ray imaging very different from other real-world imaging methods. To better detect prohibited items in security X-ray images with these characteristics, we propose EM-YOLOv7, which is composed of both an edge feature extractor (EFE) and a material feature extractor (MFE). We used the Soft-WIoU NMS method to solve the problem of object overlap. To better extract features, the attention mechanism CBAM was added to the backbone. According to the results of several experiments on the SIXray dataset, our EM-YOLOv7 method can better complete prohibited-item-detection tasks during security inspection with detection accuracy that is 4% and 0.9% higher than that of YOLOv5 and YOLOv7, respectively, and other SOTA models.

A Data Enhancement Algorithm for DDoS Attacks Using IoT.

With the rapid development of the Internet of Things (IoT), the frequency of attackers using botnets to control IoT devices in order to perform distributed denial-of-service attacks (DDoS) and other cyber attacks on the internet has significantly increased. In the actual attack process, the small percentage of attack packets in IoT leads to low accuracy of intrusion detection. Based on this problem, the paper proposes an oversampling algorithm, KG-SMOTE, based on Gaussian distribution and K-means clustering, which inserts synthetic samples through Gaussian probability distribution, extends the clustering nodes in minority class samples in the same proportion, increases the density of minority class samples, and improves the amount of minority class sample data in order to provide data support for IoT-based DDoS attack detection. Experiments show that the balanced dataset generated by this method effectively improves the intrusion detection accuracy in each category and effectively solves the data imbalance problem.

Aptamer-modified atomically precise gold nanoclusters as targeted nanozymes to scavenge reactive oxygen species in white adipocytes.

Oxidative stress caused by excessive reactive oxygen species (ROS) leads to the dysfunction of white adipocytes and white fat, and also promotes triglyceride storage by inhibiting the respiration of adipocytes directly. Nanozymes, as a new generation of artificial enzymes, have exhibited attractive potential in scavenging ROS and treatment of ROS-related diseases. Herein, aptamer-modified atomically precise gold Au25nanoclusters (Apt-Au25NCs), are employed as targeted nanozymes to scavenge ROS in white adipocytes. Our results show that Apt-Au25NCs have high targeting capability toward white adipocytes with low cytotoxicity. Furthermore, Apt-Au25NCs show high superoxide dismutase (SOD)-like and catalase (CAT)-like activity in a concentration-dependent manner, and also good thermal and pH stability compared with natural SOD and CAT. Finally, the efficiency of ROS scavenging by Apt-Au25NCs in white adipocytes is evaluated. This work demonstrates that Apt-Au25NCs, as targeted nanozymes, are efficient in scavenging ROS in white adipocytes, exhibiting promising potential for the treatment of obesity and related diseases.

Aptamer-functionalized AuNCs nanogel for targeted delivery of docosahexaenoic acid to induce browning of white adipocytes.

Obesity, as a global public health concern, causes a series of metabolic disorders and other diseases. Browning of white fat (white adipocytes transforming to beige adipocytes) offers an attractive approach for obesity treatment. In the present study, aptamer-functionalized nanogel of gold nanoclusters (AuNCs), termed Apt-NG, was developed as the targeted delivery vehicle of browning agent docosahexaenoic acid (DHA). Apt-NG has multiple advantages, including nanoscale size, strong autofluorescence, low toxicity, and excellent targeting capability to white adipocytes. After treatment with DHA@Apt-NG, the morphology of lipid droplets changed evidently; meanwhile the triglyceride level decreased while the mitochondrial activity increased. The DHA@Apt-NG treatment effectively up-regulated the mRNA expression levels of Ucp1, Pgc-1α, Pparg, and Prdm16, which play important roles in browning of white adipocytes. This study provides a feasible strategy to achieve efficient browning of white adipocytes based on targeted delivery nanosystems, inspiring a new idea for obesity treatment.

The Biomechanical Influence of Defected Cartilage on the Progression of Osteochondral Lesions of the Talus: A Three-dimensional Finite Element Analysis.

OBJECTIVES: Osteochondral lesions of the talus (OLTs) are common injuries in the general population. Abnormal mechanical conditions applied to defected cartilage are believed to be the culprits to deteriorating OLTs. This study aims to investigate the biomechanical effects of defect size of talar cartilage on OLTs during ankle movements. METHODS: A finite element model of the ankle joint was created based on the computed tomography images of a healthy male volunteer. Different defect sizes (S = 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, and 2.0 cm2 ) of talar cartilage were modeled to simulate the progression of OLTs. Mechanical moments were applied to the model to generate different ankle movements, including dorsiflexion, plantarflexion, inversion, and eversion. The effects of varying defect sizes on peak stress and its location were evaluated. RESULTS: The maximum stress on the talar cartilage increased as the area of the defect enlarged. Additionally, as the defect size of OLTs increased, the areas with peak stress on talar cartilage tended to move closer to where the injury was located. High stresses were present in the medial and lateral areas of the talus at the neutral position of the ankle joint. The concentrated stresses were mainly located in the anterior and posterior defect areas. The peak stress in the medial region was higher than on the lateral side. The order of peak stress from highest to lowest was dorsiflexion, internal rotation, inversion, external rotation, plantar flexion, and eversion. CONCLUSIONS: Osteochondral defect size and ankle joint movements significantly modulate the biomechanical features of the articular cartilage in osteochondral lesions of the talus. The progression of osteochondral lesions in a talus deteriorates the biomechanical well-being of the bone tissues of the talus.

IoT Device Identification Using Directional Packet Length Sequences and 1D-CNN.

With the large-scale application of the Internet of Things (IoT), security issues have become increasingly prominent. Device identification is an effective way to secure IoT environment by quickly identifying the category or model of devices in the network. Currently, the passive fingerprinting method used for IoT device identification based on network traffic flow mostly focuses on protocol features in packet headers but does not consider the direction and length of packet sequences. This paper proposes a device identification method for the IoT based on directional packet length sequences in network flows and a deep convolutional neural network. Each value in a packet length sequence represents the size and transmission direction of the corresponding packet. This method constructs device fingerprints from packet length sequences and uses convolutional layers to extract deep features from the device fingerprints. Experimental results show that this method can effectively recognize device identity with accuracy, recall, precision, and f1-score over 99%. Compared with methods using traditional machine learning and feature extraction techniques, our feature representation is more intuitive, and the classification model is effective.

Browning of white adipocytes by gold nanocluster mediated electromagnetic induction heating hyperthermia.

Browning of white adipose tissue (WAT) is becoming an attractive therapeutic target for obesity. Great efforts have been made to develop effective approaches to induce browning. Unfortunately, the current methods suffer from a series of disadvantages, such as low efficiency, unsatisfactory stability, and side effects. Herein, we report a new approach to induce browning of 3T3-L1 white adipocytes based on electromagnetic induction heating (EIH) hyperthermia. In particular, adipocyte-targeting aptamer modified gold nanoclusters (Apt-AuNCs) were employed as the mediators of EIH. Apt-AuNCs had good biocompatibility and excellent targeting performance with white adipocytes. After Apt-AuNCs/EIH treatment, adipocytes with characteristic multilocular and small lipid droplets increased, and the content of triglycerides reduced effectively. Apt-AuNCs/EIH treatment also significantly increased the mitochondrial activity in adipocytes. Meanwhile, the mRNA levels of key genes that are involved in browning, for example UCP1, PRDM16, PPARγ, and PGC-1α, were upregulated. Finally, the induction mechanism of Apt-AuNCs/EIH on browning of white adipocytes was explained by the synergistic effects of EIH hyperthermia and pharmacological action of AuNCs. To the best of our knowledge, this is the first attempt on induction of browning by metal nanocluster-mediated EIH hyperthermia, thus providing an interesting and efficient channel for obesity treatment.

Myrcene exerts anti-asthmatic activity in neonatal rats via modulating the matrix remodeling.

Myrcene (MC), an organic hydrocarbon, was found to exert anti-inflammatory, analgesic, antimutagenic and antioxidant properties. However, the protective role of MC has not been reported against neonatal asthma. Wistar rats induced with asthma were administered with MC; while asthma control and vehicle control were maintained without MC administration. At the end of the experimental period, lung histology, inflammatory cell counts, cytokine analysis, matrix protein expressions were elucidated. Rats administered with MC exerted significant (P < 0.05) defense in protecting the lung tissue with the evidenced restoration of alveolar thickening of the lung tissues. Also, the present study elicited the anti-asthmatic activity of MC, especially via modulating the extracellular matrix protein expression in the asthma-induced animals, while a significant reduction (P < 0.05) in the fibrotic markers were found in MC treated animals. Moreover, the protective effect of MC was evidenced with reduced leukocyte infiltration in BALF, hypersensitive specific IgE levels with a profound decrease in the inflammatory cytokines such as IL-2, IL-4, IL-18, and IL-21 in MC administered animals compared to the asthma-induced group. To an extent, the markers of asthmatic inflammation such as CD14, MCP-1, and TARC were also found to be attenuated in MC exposed animals. The possible application of MC is a promising drug for the treatment of asthma-mediated complications.

Musculoskeletal ultrasonography combined with electromyography in the diagnosis of massage-inducted lateral plantar nerve injury: A case report.

INTRODUCTION: It is well known that foot massage is a very prevalent stress relief method in China. Literatures have reported various massage-inducted peripheral nerve injuries. However, massage-inducted lateral plantar nerve (LPN) injury is very rare. Here, we represent an unusual case of massage-inducted LPN damage, and we also report the diagnostic method of this patient using musculoskeletal ultrasonography combined with electromyography (EMG). PATIENT CONCERNS: A 21-year-old woman presented symptoms of redness, swelling, pain and numbness in the medial right ankle joint for 2 days. DIAGNOSIS: The results of musculoskeletal ultrasonography and EMG provide great help for doctors to make accurate diagnosis. The patient was eventually diagnosed with LPN injury. INTERVENTIONS: No further foot massage was allowed. Vitamin B12 was taken orally for 2 months. Conservative therapy, including electrical stimulation therapy and infrared therapy, was conducted. Besides, active rehabilitation training was also performed. OUTCOMES: The discomfort symptoms were relieved significantly after 2 months conservative treatment. Clinical symptoms and EMG examination illustrated satisfactory result during follow up time. CONCLUSION: The report showed that the masseur should be very careful when doing foot massage to prevent nerve damage. Besides, musculoskeletal ultrasonography combined with EMG can provide important evidence for accurate and effective diagnosis of LPN injury.

MicroRNA-300 inhibits the growth of hepatocellular carcinoma cells by downregulating CREPT/Wnt/ß-catenin signaling.

A number of studies have demonstrated that altered expression levels of microRNA-300 (miR-300) are associated with tumor progression; however, little is understood regarding the role of miR-300 in hepatocellular carcinoma (HCC). The present study aimed to investigate the expression, biological function and potential regulatory mechanism of miR-300 in HCC. A miR-300 mimic and miR-300 inhibitor were transfected into liver cancer cells using RNAiMAX reagent. The expression levels of miR and mRNA were detected by reverse transcription-quantitative polymerase chain reaction. Protein expression levels were detected by western blot analysis. Cell growth was determined using Cell Counting Kit-8, a colony formation assay and cell cycle assay. miRNA targeting sites were analyzed using bioinformatics analysis and dual-luciferase reporter assay. The results revealed that miR-300 expression was significantly decreased in HCC tissues and cell lines. In vitro experiments demonstrated that overexpression of miR-300 could inhibit cell proliferation, colony formation and cell cycle progression of liver cancer cells. By contrast, inhibition of miR-300 was associated with increased rates of cell proliferation, colony formation and cell cycle progression. Notably, regulation of nuclear pre-mRNA domain-containing protein 1B (CREPT) was identified as a putative target gene of miR-300 by bioinformatics analysis. A luciferase reporter assay revealed that miR-300 directly targets the 3'-untranslated region of CREPT. Further data demonstrated that miR-300 can regulate CREPT expression levels in liver cancer cells. Notably, miR-300 was identified to regulate the Wnt/ß-catenin signaling pathway in liver cancer cells. The restoration of CREPT expression partially reversed the antitumor effect of miR-300. In conclusion, the current results revealed a tumor suppressive role of miR-300 in HCC and indicated that the underlying mechanism was associated with a regulation of CREPT. The present study suggests that miR-300 and CREPT may serve as potential therapeutic targets for liver cancer.

Value of using the international classification of functioning, disability, and health for stroke rehabilitation assessment: A multicenter clinical study.

This study aimed to evaluate the efficiency of the International Classification of Functioning, Disability, and Health (ICF) in stroke rehabilitation assessment in China and to identify correlations between the ICF and several commonly used clinical assessment instruments for stroke.In total, 52 hospitals and 5 premier rehabilitation and neurology research centers participated in this cross-sectional multicenter clinical study. A total of 2822 stroke patients admitted to a neurology or rehabilitation department of a participating medical center between July 2012 and June 2014 were included. The ICF checklist contains 4 parts with 128 two-level items: body functions, body structures, activities and participation, and environmental factors. We analyzed the results of ICF assessments and determined whether correlations existed between the various items of the ICF and several commonly used clinical assessment instruments.In all but 3 instances, the scores for the ICF-b-body function, ICF-s-body structure-degree of impairment, ICF-s-body structure-impairment location, ICF-d-activity performance, ICF-d-ability performance, ICF-e-facilitator, and ICF-e-barrier correlated significantly (P < .05) with the scores for the commonly used clinical assessment instruments.The ICF checklist is a new rehabilitation assessment instrument that is compatible with commonly used clinical assessment scales for stroke and can be used in combination with these scales.

Concomitant Asymptomatic Intracranial Atherosclerotic Stenosis Increase the 30-Day Risk of Stroke in Patients Undergoing Symptomatic Intracranial Atherosclerotic Stenosis Stenting.

BACKGROUND: In the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial, 19.1% of ischemic strokes occurred out of the territory of previously symptomatic stenosis during the mean follow-up period of 23.4 months. However, it is unknown how many ischemic strokes were due to a previously asymptomatic intracranial atherosclerotic stenosis (ICAS). The objective of this study was to investigate whether the concomitant asymptomatic ICAS influences the outcome of patients undergoing symptomatic ICAS stenting. METHODS: We retrospectively reviewed 576 consecutive patients with nondisabling ischemic stroke (modified Rankin scale score of ≤3) who were treated with symptomatic ICAS (≥70% stenosis) stenting with or without concomitant asymptomatic ICAS. The baseline characteristics and the 30-day primary end points (stroke or death after stenting) were compared by bivariate and multivariable logistic analyses. RESULTS: The 30-day rate of primary end points was 5.2%, which was higher in patients with concomitant asymptomatic ICAS (≥50% stenosis) than in those without asymptomatic ICAS (no stenosis or <50% stenosis) (8.9% versus 3.8%, P = .014). In patients with concomitant asymptomatic ICAS, 25% of ischemic strokes occurred out of the territory of the stented artery, whereas in patients without asymptomatic ICAS, no ischemic stroke occurred out of the territory of the stented artery. Multivariable analysis showed that concomitant asymptomatic ICAS was an independent risk factor for 30-day stroke (odds ratio = 2.37, 95% confidence interval, 1.14-5.63; P = .023). CONCLUSIONS: Concomitant asymptomatic ICAS (≥50% stenosis) might increase the 30-day risk of stroke in patients undergoing symptomatic ICAS stenting.

Enhancing Saccharomyces cerevisiae reactive oxygen species and ethanol stress tolerance for high-level production of protopanoxadiol.

Protopanaxadiol (PPD) is an active compound in Panax ginseng. Recently, an optimized PPD synthesis pathway contained a ROS releasing step (a P450-type PPD synthase, PPDS) was introduced into Saccharomyces cerevisiae. Here reported a synergistic effect of PPDS-CPR (CPR, cytochrome P450 reductase) uncoupling and ethanol stress on ROS releasing, which reduced cells viability. To build a robust strain, a cell wall integrity associated gene SSD1 was high-expressed to improve ethanol tolerance, and ROS level decreased for 24.7%. Then, regulating the expression of an oxidative stress regulation gene YBP1 decreased 75.2% of ROS releasing, and improved cells viability from 71.3±1.3% to 88.3±1.4% at 84h. Increased cells viability enables yeast to produce more PPD through feeding additional ethanol. In 5L fermenter, PPD production of W3a-ssPy reached to 4.25±0.18g/L (19.48±0.28mg/L/OD600), which is the highest yield reported so far. This work makes the industrial production of PPD possible by microbial fermentation.

Danshen (Salvia miltiorrhiza) Compounds Improve the Biochemical Indices of the Patients with Coronary Heart Disease.

Danshen was able to reduce the risk of the patients with coronary heart disease (CHD), but the mechanism is still widely unknown. Biochemical indices (lipid profile, markers of renal and liver function, and homocysteine (Hcy)) are closely associated with CHD risk. We aimed to investigate whether the medicine reduces CHD risk by improving these biochemical indices. The patients received 10 Danshen pills (27 mg/pill) in Dashen group, while the control patients received placebo pills, three times daily. The duration of follow-up was three months. The serum biochemical indices were measured, including lipid profiles (LDL cholesterol (LDL-C), HDL-C, total cholesterol (TC), triglycerides (TG), apolipoprotein (Apo) A, ApoB, ApoE, and lipoprotein (a) (Lp(a))); markers of liver function (gamma-glutamyl transpeptidase (GGT), total bilirubin (TBil), indirect bilirubin (IBil), and direct bilirubin (DBil)); marker of renal function (uric acid (UA)) and Hcy. After three-month follow-up, Danshen treatment reduced the levels of TG, TC, LDL-C, Lp(a), GGT, DBil, UA, and Hcy (P < 0.05). In contrast, the treatment increased the levels of HDL-C, ApoA, ApoB, ApoE, TBil, and IBil (P < 0.05). Conclusion. Danshen can reduce the CHD risk by improving the biochemical indices of CHD patients.

Phosphorylation of JNK Increases in the Cortex of Rat Subjected to Diabetic Cerebral Ischemia.

Previous studies have demonstrated that the c-Jun N-terminal kinase (JNK) pathway plays an important role in inducing neuronal apoptosis following cerebral ischemic injury. JNK signaling pathway in activated during cerebral ischemic injury. It participates in ischemia-induced neuronal apoptosis. However, whether JNK signaling is involved in the process of neuronal apoptosis of diabetes-induced cerebral ischemia is largely unknown. This study was undertaken to evaluate the influence of cerebral ischemia-reperfusion injury on phosphorylation of JNK in diabetic rats. Twenty-four adult streptozotocin induced diabetic and 24 adult non-diabetic rats were randomly subjected to 15 min of forebrain ischemia followed by reperfusion for 0, 1, 3, and 6 h. Sixteen sham-operated diabetic and non-diabetic rats were used as controls. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL). Protein expression of phospho-JNK was examined by immunohistochemistry and Western blot. The numbers of TUNEL-positive cells and phospho-JNK protein expression in the cerebral cortices after 1, 3 and 6 h reperfusion was significantly higher in diabetic rats compared to non-diabetic animals subjected to ischemia and reperfusion (p < 0.05). Western blot analysis showed significantly higher phospho-JNK protein expression in the cerebral cortices of the diabetic rats after 1 and 3 h reperfusion than that was presented in non-diabetic animals subjected to ischemia and reperfusion (p < 0.05). These findings suggest that increased phosphorylation of JNK may be associated with diabetes-enhanced ischemic brain damage.

Coffee and caffeine potentiate the antiamyloidogenic activity of melatonin via inhibition of Aß oligomerization and modulation of the Tau-mediated pathway in N2a/APP cells.

There is an increasing prevalence of Alzheimer's disease (AD), which has become a public health issue. However, the underlying mechanisms for the pathogenesis of AD are not fully understood, and the current therapeutic drugs cannot produce acceptable efficacy in AD patients. Previous animal studies have shown that coffee (Coff), caffeine (Caff), and melatonin (Mel) have beneficial effects on AD. Disturbed circadian rhythms are observed in AD, and chronotherapy has shown promising effects on AD. In this study, we examined whether a combination of Coff or Caff plus Mel produced a synergistic/additive effect on amyloid-ß (Aß) generation in Neuro-2a (N2a)/amyloid precursor protein (APP) cells and the possible mechanisms involved. Cells were treated with Coff or Caff, with or without combined Mel, with three different chronological regimens. In regimen 1, cells were treated with Coff or Caff for 12 hours in the day, followed by Mel for 12 hours in the night. For regimen 2, cells were treated with Coff or Caff plus Mel for 24 hours, from 7 am to 7 am the next day. In regimen 3, cells were treated with Coff or Caff plus Mel with regimen 1 or 2 for 5 consecutive days. The extracellular Aß40/42 and Aß oligomer levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. The expression and/or phosphorylation levels of glycogen synthase kinase 3ß (GSK3ß), Erk1/2, PI3K, Akt, Tau, Wnt3α, ß-catenin, and Nrf2 were detected by Western blot assay. The results showed that regimen 1 produced an additive antiamyloidogenic effect with significantly reduced extracellular levels of Aß40/42 and Aß42 oligomers. Regimen 2 did not result in remarkable effects, and regimen 3 showed a less antiamyloidogenic effect compared to regimen 1. Coff or Caff, plus Mel reduced oxidative stress in N2a/APP cells via the Nrf2 pathway. Coff or Caff, plus Mel inhibited GSK3ß, Akt, PI3K p55, and Tau phosphorylation but enhanced PI3K p85 and Erk1/2 phosphorylation in N2a/APP cells. Coff or Caff, plus Mel downregulated Wnt3α expression but upregulated ß-catenin. However, Coff or Caff plus Mel did not significantly alter the production of T helper cell (Th)1-related interleukin (IL)-12 and interferon (IFN)-γ and Th2-related IL-4 and IL-10 in N2a/APP cells. The autophagy of cells was not affected by the combinations. Taken together, combination of Caff or Coff, before treatment with Mel elicits an additive antiamyloidogenic effects in N2a/APP cells, probably through inhibition of Aß oligomerization and modulation of the Akt/GSK3ß/Tau signaling pathway.

The immune injury effects and clinical significance of eosinophils in auto-immune-related hematocytopenia.

Eosinophils (EOS) quantity, active state, peroxidase activity (POX), and HLA-DR expression in bone marrow of 176 Auto-Immune-Related Hematocytopenia (AIRH) patients were analyzed. Immunofluorescent staining (IF) is performed to observe the expression of immunizing molecules on EOS. In serum of AIRH patients the levels of IL-4, IL-5, IL-6, IL-12, IL-17, and IFN- γ were increased but there was no significance on IL-2 level. In marrow of AIRH, activated EOS expressed POX, and other molecules, it played various cell-mediated immunity injury roles to hemocyte. EOS might be possessed with multiple immunological fuctions, it playes an important immune effect in AIRH autoimmune pathological processes.

[Immune mechanism and clinical significance of infection immunity activation for medullary hematopoietic injury of immune-related hematocytopenia syndrome].

OBJECTIVE: To observe the pathologic effects of marrow hematopoietic cell with immunologic injury induced by infection immunity activation in patients with immune related hematocytopenia syndrome (IRHS) and elucidate its immunologic mechanism and clinical significance. METHODS: A total of 276 IRHS patients with acute and chronic infections were recruited from 2008 to 2013. ELISA was used to detect the levels of interleukin-6 (IL-6), IL-12, IL-17 and interferon gamma (IFN-γ) in peripheral blood sera of IRHS patients before and after therapy. Flow cytometry was performed to detect the proportion of lymphocyte subgroups in peripheral blood. Immunochemical staining was used to analyze the expressive states of peroxydase (POX), HLA-DR in bone marrow and non-specific esterase. The expressive states of CD4, CD8, CD56, IFN-γ, porforin, granzyme, FcγRII, anti-human IgG, mannose receptor (MR), IL-12 and IL-17A in bone marrow cells and hematopoietic microenvironment were analyzed with immunofluorescence (IF). According to the above immunological indices, antibiotics were prescribed along with medaron and ciclosporin A (CsA). RESULTS: Among 276 patients, the levels of IL-6, IL-12, IL-17 and IFN-γ were higher than those in control group (all P < 0.05) . After treatment, the cytokine levels above decreased to normal gradually. The levels of CD3(+) CD4(+) T and NK cells increased respectively in those with concurrent viral or mycoplasma infection(54.23% ± 3.07% and 50.11% ± 3.09% vs 35.25% ± 5.16%, 22.71% ± 2.26% and 19.49% ± 2.07% vs 14.91% ± 4.87%) . The proportions of CD3(+) CD4(+) T and CD19(+) B cells increased in sera of patients with bacterial infection (40.22% ± 4.31% vs 35.25% ± 5.16%, 29.01% ± 4.32% vs 11.56% ± 2.54%) . But the proportion of CD3(+) CD8(+) T cells increased in patients with viral infection of type B hepatitis(32.51% ± 3.44% vs 25.08% ± 4.43%) (all P < 0.05). In patient marrow samples, dendritic cell, T lymphocyte, eosinophilic granulocyte and macrophage were activated to express many above mentioned immunological molecules. Both the destructive pattern of hemocyte and the degree of pathological lesion induced by these immunocytes were related with the cause of infection immunity activation and morbid state of patients. After individualized treatment, 264 patients showed elevated hemogram at 4-8 weeks while the relapse of 12 patients persisted until an initiation of cytotoxic drug and a gradual restoration of hemogram. CONCLUSIONS: Infection is one of the most important factors of IRHS. Excessive activation of infection immunity may induce the disorder of immune system. Then immunocytes destroy or damage those hemocytes with pathological changes through different immunological pathways. The pathogenetic condition and outcome is related with infected pathogen and intrasubject immune state. Control of pathogenic microorganism infection and glucocorticoid treatment may suppress the excessive activation of immunocytes so as to become important preventive and curing measures of IRHS.