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There are many unknown genetic factors that lead to infertility in nonobstructive azoospermia men. Here, we performed whole-exome sequencing in blood samples obtained from 40 azoospermia patients with meiotic arrest and found a novel c.151_154del (p.D51fs) frame-shift mutation in exon 3 of the testis expressed 11 (TEX11) gene in one patient. Sanger sequencing analysis of the patient and 288 fertile men was performed to validate the mutation. Immunohistochemical analysis showed TEX11 expression in late-pachytene spermatocytes and in round spermatids in fertile human testes. In contrast, testes of the patient with TEX11 mutation underwent meiotic arrest and lacked TEX11 expression. Western blotting of human embryonic kidney (HEK293) cells transfected with a vector for the p.D51fs TEX11 variant detected no TEX11 expression. In conclusion, we identified a novel frame-shift mutation in the TEX11 gene in an azoospermia patient, emphasizing that this gene should be included in genetic screening panels for the clinical evaluation of azoospermia patients.
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Objective:To study the protective effect of Euphorbia helioscopia alcohol extract on lipopolysaccharide (LPS) -induced acute lung injury in mice and explore its possible mechanism. Method:The 50 Balb/c male mice were randomly divided into 5 groups, including normal group, model group, dexamethasone group (1.5 mg·kg-1), E. helioscopia alcohol extracts group (7.5，3.75 g·kg-1). Except for the normal group, the other groups used intranasal instillation of LPS to establish a model of acute lung injury in mice. The type and number of inflammatory cells in bronchoalveolar lavage fluid (BALF) were detected by automatic blood analyzer and Wright-Giemsa composite staining. The lung tissue damage was observed by hematoxylin-eosin (HE) staining. The contents of the inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in BALF were detected by flow cytometry. The protein expressions of nuclear factor kappa-B p65(NF-κB p65), phospho-NF-κB p65 (p-NF-κB p65), inhibitor of NF-κBα (IκBα), phospho-IκBα (p-IκBα) in NF-κB pathway and c-Jun N-terminal kinase (JNK), phospho-JNK (p-JNK), p38 protein (p38), phospho-p38 (p-p38), extracellular regulated protein kinases (ERK1/2), phospho-ERK1/2 (p-ERK1/2) in mitogen-activated protein kinase (MAPK) pathway were determined by Western blot. Result:Compared with normal control group, the lung tissue of the model group showed obvious damage, in which a large number of inflammatory cells infiltrated, and the integrity of the alveoli was destroyed. Inflammatory factors TNF-α, IL-6 in BALF and p-NF-κB p65, p-JNK, p-p38, p-ERK protein expression levels in lung tissue were significantly increased (P<0.01). Compared with model group, the pathological damage of lung tissue in mice with high dose of E. helioscopia alcohol extract and dexamethasone positive group was significantly alleviated. The levels of TNF-α and IL-6 in BALF and the expression levels of p-NF-κB p65, p-JNK, p-p38 and p-ERK1/2 protein in lung tissue were significantly down-regulated (P<0.01). Conclusion:The E. helioscopia alcohol extract has a protective effect on LPS-induced acute lung injury in mice, its mechanism may be related to the regulation of the NF-κB/MAPK signaling pathway.
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Objective:To explore the application and value of metagenomic next-generation sequencing (mNGS) in refractory infection after organ transplantation.Methods:A case report discussed about a patient with lumbar spine infection after kidney transplantation and the relevant literature was reviewed. The recipient was a 63-year-old man with low back pain after kidney transplantation. Lumbar spine magnetic resonance imaging showed lumbar spine infection. Multiple operations plus antibacterial and antituberculosis treatments were ineffective. Before and after treatment, numerous tests of traditional pathogenic microorganisms failed to detect any positive bacteria.Results:The detection of lumbar secretion by mNGS suggested aspergillus infection. The symptoms improved after dosing of voriconazole.Conclusions:The incidence of fungal infection of lumbar spine is low. The imaging manifestations are non-typical so that it is easy to misdiagnose. mNGS helps to timely diagnose and guide treatment. With a review of the literature, mNGS has some application value for some difficult and rare infectious diseases.
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A large number of experimental and clinical data indicates that tumor-associated macrophages (TAMs) were involved in the whole process of tumor growth, invasion and metastasis. Like macrophages in other tissues, TAMs originate from blood monocytes, which are recruited to the tumor tissues by cytokines and then differentiated into TAMs. It is interesting that the monocytes overexpress siglec receptor in their surface, which has a high binding specificity to sialic acid (SA). From this point of view, we hypothesize that if SA was used as a ligand in the surfaces of drug delivery systems, SA would enhance the targeting efficiency to monocytes, and thus to achieve a higher specificity to TAMs. In our previous study, an SA derivative of SA-octadecylamine (SA-18) was synthesized and was found to enhance cytotoxicity on TAMs in vitro. The chain length is a critical factor for SA efficiency in liposomes and it has a significant influence on the TAM targeting effects of the carriers. So in this study, four kinds of different chain length of SA fatty amine derivatives were synthesized, including SA-18, SA-hexadecylamine (SA-16), SA-tetradecylamine (SA-14) and SA-dodecylamine (SA-12), and were modified on the surfaces of blank liposomes (BLK-SnL, n=18, 16, 14, 12) and pixantrone maleate-loaded liposomes (Pix-SnL, n=18, 16, 14, 12). TAM targeting effects of these SA derivatives were evaluated by acute toxicity and antitumor efficacy in vivo. The results of acute toxicity experiments showed that the toxicities of the SA derivatives deceased gradually with the reduction in the length of lipophilic chain. The in vivo antitumor efficacies of SA-modified blank liposomes showed that these blank formulations had no effect on the tumor inhibition except BLK-S14L (61.4%±18.8%), and BLK-S16L even promoted the tumor growth (-31.7%±13.1%, the 18th day). The in vivo antitumor efficacies of SA-modified Pix liposomes showed that the tumor inhibition effects were Pix-S18L (97.4%±2.1%) > Pix-S14L (73.1%±21.1%) > Pix-S12L (53.9%±17.8%) > Pix-S16L (32.9%). Because of the relatively strong binding ability of SA-18, it was hard to fall off from the liposomes in the transport process, leading to a good TAM targeting ability and less toxicity to the normal tissues. Meanwhile, 50% of the mice in Pix-S18L group showed "tumor shedding" and "wound healing" phenomena without recurrence in two months following the treatment. Therefore, SA-18 is the most potential TAM targeting material among these SA fatty amine derivatives.
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Autophagy is a highly conserved cellular self-digestion pathway, by which intracellular damaged proteins or organelles are delivered to lysosomes for degradation, so as to protect from various dangerous stimuli and maintain cellular homeostasis. Inflammation is a defensive response to injury or pathogens, through which various inflammatory mediators coordinate host defense and repair. However, uncontrolled inflammatory responses can lead to secondary damage and pathogenesis of inflammatory disease. Recent studies indicate that autophagy pathway and related proteins may play important roles in regulating immune response and controlling excessive inflammation. This review introduced research progress in the role of autophagy in regulating excessive inflammation and possible mechanisms.
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Humans , Autophagy , Homeostasis , InflammationABSTRACT
This research aimed to explore the application of autoregressive integrated moving average (ARIMA) model of time series analysis in predicting road traffic injury (RTI) in China and to provide scientific evidence for the prevention and control of RTI.Database was created based on the data collected from monitoring sites in China from 1951 to 2011.The ARIMA model was made.Then it was used to predict RTI in 2012.The ARIMA model of the RTI cases was Yt=eYt-1+0.456▽Yt-1+et (et stands for random error).The residual error with 16 lags was white noise and the Ljung-Box test statistic for the model was no statistical significance.The model fitted the data well.True value of RTI cases in 2011 was within 95％ CI of predicted values obtained from present model.The model was used to predict value of RTI cases in 2012,and the predictor (95％CI) was 207 838 (107 579-401 536).The ARIMA model could fit the trend of RTI in China.
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<p><b>OBJECTIVE</b>To determine the incidence of work-related acute pesticide poisoning among farmers in Jiangsu Province and to identify the risk factors.</p><p><b>METHODS</b>Multi-stage stratified sampling and cluster sampling methods were used to randomly select 1490 farmers from the south (Z village), centre (Y village) and north (X village) of Jiangsu Province. The database was established by EpiData 3.1. SPSS 17.0 and SAS 9.13 were used to do chi-square test, trend chi-square test, single factor and multi-factor logistic regression analysis.</p><p><b>RESULTS</b>Among 1490 farmers, 121 people had work-related acute pesticide poisoning in the past year. The incidence rate in Jiangsu Province was 8.1%. 118 farmers (97.5%) were mild pesticide poisoning.3 farmers (2.5%) were moderate pesticide poisoning. The incidence rate of Work-related acute pesticide poisoning in X village of North Jiangsu Province (13.5%, 68/505) is obviously higher than that in Y village of Central Jiangsu Province (4.8%, 19/399) and Z village of South Jiangsu Province (5.8%, 34/586), and the difference is statistically significant (χ(2) = 29.60, P < 0.01). The incidence rate of Work-related acute pesticide poisoning in female (10.4%, 58/557) is obviously higher than that in male (6.8%, 63/933), and the difference is statistically significant (χ(2) = 6.26, P < 0.05). There are lack of safety guidance, unsafety application methods (without alternate row spraying, without backward application, without down-wind application) and risk behaviors in the spraying (without read labels, preparing pesticides without gloves, wiping sweat with hand (s), equipment leakage, body pollution by pesticide, working when feeling sick, without bath after work). If farmers have risk behaviors above, the incidence rate of Work-related acute pesticide poisoning will be obviously higher than farmers who receive safety guidance and have no such dangerous behaviors, and all the differences are statistically significant (P < 0.05). The group of 24 ∼ 34 years old has the highest risk of work-related acute pesticide poisoning (OR = 7.15).</p><p><b>CONCLUSION</b>The incidence rate of work-related acute pesticide poisoning among farmers in Jiangsu Province was higher. Effective measures are needed to prevent and reduce the occurrence of work-related acute pesticide poisoning. We can teach the farmers who spray pesticides about safety guidance, safety application methods and avoiding risky behaviors.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Agricultural Workers' Diseases , Epidemiology , Agriculture , Methods , Incidence , Occupational Exposure , Pesticides , Poisoning , Risk FactorsABSTRACT
Objective To explore the risk factors on cases regarding work-related acute pesticide poisoning among farmers of Jiangsu province.Methods A population-based,1 ∶ 2 matched case-control study was carried out,with 121 patients as case-group paired by 242 persons with same gender,district and age less then difference of 3 years,as controls.Cases were the ones who had suffered from work-related acute pesticide poisoning.A unified questionnaire was used.Data base was established by EpiData 3.1,and SPSS 16.0 was used for both data single factor and multi-conditional logistics regression analysis.Results Results from the single factor logistic regression analysis showed that the related risk factors were:lack of safety guidance,lack of readable labels befores praying pesticides,no regression during application,using hand to wipe sweat,using leaking knapsack,body contaminated during application and continuing to work when feeling ill after the contact of pesticides.Results from multi-conditional logistic regression analysis indicated that the lack of safety guidance (OR=2.25,95％ CI:1.35-3.74),no readable labels befores praying pesticides (OR=1.95,95％ CI:1.19-3.18),wiping the sweat by hand during application (OR=1.97,95％CI:1.20-3.24)and using leaking knapsack during application (OR=1.82,95％ CI:1.10-3.01) were risk factors for the occurrence of work-related acute pesticide poisoning.Conclusion The lack of safety guidance,no readable labels befores praying pesticides,wiping the sweat by hand or using leaking knapsack during application were correlated to the occurrence of work-related acute pesticide poisoning.
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Objective To explore the characteristics of polysomnography (PSG) of depressed patients and the correlation between rapid eye movement (REM) and severity degree of depression. Methods Polysomnography was used to assess patients'sleep condition and Montgomery-Asberg depression scale (MADRS) was used to assess the severity degree of depression. 90 patients and 30 healthy controls were included. Results Compared to healthy controls,sleep progress of depressed patients changed as follow:prolonged sleep latency((25.2 ±15.25) minutes) ,lowered sleep efficiency(0.853 ±0.11) ;the architecture of sleep also changed:percentage of stage 1 increased( (27.7 ± 16.38) % ),percentage of REM sleep increased( (22. 8 ± 6. 1 ) % ) , percentage of stage 2 decreased ((40.2±11.3)%), percentage of slow wave sleep decreased ((11.8 ±9. 32)%); REM sleep significantly changed; decreased REM latency((79. 27 ±30. 44) minutes) , increased REM activity((129. 0 ±53. 12) u) .increased intensity of REM((36.7 ±14.0)u/min), increased REM density((159.2 ±57.2)u/min) were observed in depressed patients. There was no obvious correlation between the variance of REM and severity degree of depression. Conclusion There are a series of changes in sleep progress, architecture and REM sleep of depression and the change of REM sleep can be specified to diagnose depression. However,there is no causality between REM variance and severity of depression.
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@# ObjectiveTo explore environmental conditions under which bone marrow stromal cells could be induced into osteogenic phenotype.MethodsRat bone marrow stromal cells were isolated and proliferated in vitro, and the 3rd passage was divided into the group A (control group), group B (cells cultured in the medium containing dexamethasone, β-glycerol disodium phosphate salt hydrate, vitamin C and active form of vitamin D3), and group C (on the bases of group B, the cells were cultured additionally with fracture hematoma extract). On the post-induction day 5, 8, and 11, the morphological changes were observed and the osteogenic markers such as alkaline phosphotase (ALP), collagen type Ⅰ (Col Ⅰ) and osteocalcin (OCN) were assayed with immunohistochemical staining, the calcification was manifested with von Kossa staining.ResultsIn the group A, no evident osteogenic effects had been observed. In the group B, on 5th day post-induction, some bone marrow stromal cells underwent a morphological change, and mild expression of ALP and Col Ⅰ was observed but with no calcification effect. On 8th day post-induction, the ratio of morphologically changed cells increased, and the expression of ALP and Col Ⅰ increased still with no evident calcification. On 11th day post-induction, anti-OCN staining was positive and the calcium nodes were showed by von Kossa staining. The phenotype changes in the group C were similar to group B, but were more evident.ConclusionBone marrow stromal cells can be induced into osteogenic phenotype in vitro with small molecular inducers. Fracture hematoma extract can enhance this effect thus might be used as an addictive in osteogeneration.