Exogenous delivery of microRNA-134 (miR-134) using α-tocopherol-based PEGylated liposome for effective treatment in skin squamous cell carcinoma.

MicroRNAs (miRNAs) are involved in the pathogenesis of several cancers including skin squamous cell carcinoma (sSCC), and miR-134 is reported to possess tumor inhibition properties. The present study is an attempt to study the mechanistic role and antitumor property of miR-134 in sSCC. For this purpose, α-tocopherol PEG 1000 succinate (TPGS)-based PEGylated liposome was formulated and encapsulated with miR-134 (TP-miR-LP). CCK-8 assay results showed that miR-134 exhibited a concentration-dependent decrease in the cell viability of A-431 cells. Importantly, TPGS-based TP-miR-LP showed significantly (p < 0.05) lower cell viability compared with that of miR-134-loaded PEGylated liposome (miR-LP). Western blot analysis clearly indicates the specific targeting ability of miR-134 (TP-miR-LP) towards the Forkhead Box M1 (FOXM1) in the cancer cells. The apoptosis rate of the cells was significantly increased in TP-miR-LP (~ 38%) than that of miR-LP (~ 15%), respectively with significant inhibition of cell migration. Importantly, tumors treated with TP-miR-LP grew significantly slower compared with that of any other formulation group in the xenograft animal model. Present results clearly demonstrate the tumor suppressive effect of miR-134 through the downregulation of FOXM1 which subsequently blocks the downstream signaling pathways. These findings suggest the translational potential of miR-134 towards designing formulation strategies for sSCC treatment. Graphical abstract.

Ruxolitinib in Alleviating the Cytokine Storm of Hemophagocytic Lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening syndrome classified into primary HLH and secondary HLH. Secondary HLH is always caused by autoimmune disease, infections, or cancer. The first-line therapy for secondary HLH is the HLH 2004 protocol, including dexamethasone, etoposide, and supportive therapy. However, up to 30% of patients, especially pediatric patients, remain unresponsive to first-line treatment, and the mortality rate reaches 50% in children with HLH. Furthermore, some children who have special conditions, such as an active virus infection, are not suitable for immunosuppressants treatment. Recently, several HLH-promoting cytokines have been identified, including interferon-γ, interleukin-2, and interleukin-6. Janus kinase 1 and 2 control the signaling of many cytokines, notably interferon-γ, interleukin-2, and interleukin-6. Janus kinase 1 and 2 inhibitors, such as ruxolitinib, have been successfully used to treat HLH in mice. Here, we report that a boy, diagnosed with HLH and high titer of hepatitis B virus-DNA copies, improved quickly, and the cytokine storm of HLH was alleviated after receiving ruxolitinib. Five days after ruxolitinib treatment, entecavir was introduced and serum titer results of hepatitis B virus-DNA returned negative. With 3 months of ruxolitinib treatment and following-up 1 year, the boy's situation maintained sustained remission. In this study, it is suggested that ruxolitinib might be a first-line drug, which could alleviate the cytokine storm of HLH. This treatment may be ushering in the age of glucocorticosteroid-free HLH treatment, which is particularly meaningful for children because it avoids the side effects of glucocorticosteroid.

Altered gut metabolome contributes to depression-like behaviors in rats exposed to chronic unpredictable mild stress.

The gut microbiota has been increasingly correlated with depressive disorder. It was recently shown that the transplantation of the gut microbiota from depressed patients to animals can produce depressive-like behaviors, suggesting that the gut microbiota plays a causal role in the development of depression. In addition, metabolic disorder, which is strongly associated with depression, is exacerbated by changes in the composition of the gut microbiota and is alleviated by treatment with antidepressants. However, the key players and pathways that link the gut microbiota to the pathogenesis of depression remain largely unknown. To evaluate the relationships between depression and metabolic disorders in feces and plasma, we monitored changes in fecal and plasma metabolomes during the development of depressive-like behaviors in rats exposed to chronic unpredictable mild stress (CUMS). In these animals, the fecal metabolome was altered first and subjected to changes in the plasma metabolome. Changes in the abundance of fecal metabolites were associated with depressive-like behaviors and with altered levels of neurotransmitters in the hippocampus. Furthermore, the analysis of the fecal metabolome and the fecal microbiota in CUMS rats demonstrated consistent changes in the levels of several amino acids, including L-threonine, isoleucine, alanine, serine, tyrosine, and oxidized proline. Finally, we observed significant correlations between these amino acids and the altered fecal microbiota. The results of this study suggest that changes in amino acid metabolism by the gut microbiota contribute to changes in circulating amino acids and are associated with the behavior indices of depression.

Correction: Altered gut metabolome contributes to depression-like behaviors in rats exposed to chronic unpredictable mild stress.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Value of transvaginal ultrasound combined with 3.0T magnetic resonance imaging for the diagnosis of ectopic pregnancy / 中国辐射卫生

Objective To compare the value of transvaginal ultrasound, 3.0T magnetic resonance imaging (MRI) scanning alone and in combination for diagnosis of ectopic pregnancy, so as to provide insights into early screening of ectopic pregnancy. Methods This study enrolled a total of 130 patients with suspected ectopic pregnancy admitted to Dachuan People’s Hospital in Dazhou City, Sichuan Province, China between February 2019 and December 2022. All patients underwent transvaginal ultrasound examination and 3.0T MRI scanning. The consistency of transvaginal ultrasound and 3.0T MRI with clinical diagnostic results was evaluated with surgical pathology or clinical follow-up results as the golden standards. The sensitivity, specificity, and accuracy of transvaginal ultrasound and 3.0T MRI, alone and in combination, were compared for diagnosis of ectopic pregnancy. Results Of the 130 patients with suspected ectopic pregnancy, 108 cases were confirmed with ectopic pregnancy by surgical pathology, and 22 cases were confirmed without ectopic pregnancy by clinical follow-up. The sensitivity, specificity, and accuracy of transvaginal ultrasound were 85.19% (92/108), 54.55% (12/22), and 80.00% (104/130), respectively, with 0.358 consistency with clinical diagnostic results. The sensitivity, specificity, and accuracy of 3.0T MRI were 92.59% (100/108), 81.81% (18/22), and 90.77% (118/130), respectively, with 0.694 consistency with clinical diagnostic results. The sensitivity, specificity, and accuracy of transvaginal ultrasound combined with 3.0T MRI were 98.15% (106/108), 72.73% (16/22), and 93.85% (122/130), respectively, with 0.764 consistency with clinical diagnostic results. In addition, the sensitivity and accuracy of transvaginal ultrasound combined with 3.0T MRI were significantly higher than transvaginal ultrasound alone for diagnosis of ectopic pregnancy (χ2 = 11.88 and 10.96, both P < 0.01). Conclusion Transvaginal ultrasound combined with 3.0T MRI may provide more diagnostic information for ectopic pregnancy, and is highly consistent with the clinical diagnostic results. In addition, transvaginal ultrasound combined with 3.0T MRI improves the diagnostic sensitivity and accuracy for ectopic pregnancy than transvaginal ultrasound alone.

Genetic variation analysis in three cases of piebaldism and analysis of the genotype-phenotype relationship / 中华皮肤科杂志

Objective:To identify pathogenic genes in 3 cases of piebaldism, and to explore the genotype-phenotype relationships in piebaldism.Methods:Clinical data were collected from 3 patients with piebaldism and their parents at the Department of Dermatology, Henan Provincial People′s Hospital from January 2019 to December 2021. Peripheral blood samples were obtained from them and 100 unrelated healthy controls, and DNA was extracted. Whole-exome sequencing technology was used to screen genetic variation sites, and then Sanger sequencing was performed for verification. The deleteriousness of genetic variants was evaluated by using pathogenicity analysis software tools.Results:Case 1: a 23-year-old male patient presented with white patches on the forehead, chest, and abdomen for 23 years, and his parents had no similar symptoms; case 2: a 1-year- and 5-month-old male infant presented with white patches on the forehead and abdomen for 1 year, and his parents had no similar symptoms; case 3: a 6-year-old male child presented with white patches on the forehead and limbs for 6 years, and his parents had no similar clinical manifestations. Genetic testing showed that a missense mutation c.2033T>C (p.L678P) in exon 14 of the KIT gene, a splice site mutation c.2485-1G>C in exon 18 of the KIT gene, and a heterozygous missense mutation c.2346C>G (p.F782L) in exon 16 of the KIT gene were identified in the case 1, 2, 3 respectively, but no above mutations were identified in the patients′ parents or 100 unrelated healthy controls. The 3 genetic variants were all novel pathogenic mutations, and all were deleterious mutations.Conclusions:Three novel pathogenic mutations in the KIT gene were identified in the 3 cases of piebaldism, namely c.2033T>C (p.L678P), c.2485-1G>C, and c.2346C>G (p.F782L). It was further verified that the severity of piebaldism was closely related to the type and location of KIT gene mutations.

Clinical Study on Zhuanyaotang Granules for the Treatment of Degenerative Lumbar Spinal Stenosis / 中国中医药信息杂志

Objective To observe the clinical efficacy of Zhuanyaotang Granules for the treatment of degenerative lumbar spinal stenosis(DLSS).Methods Using a randomized double blind controlled design,104 DLSS patients were divided into an experimental group and a control group using a random number table method,with 52 patients in each group.The treatment group took oral Zhuanyaotang Granules,methylcobalamin tablets and celecoxib capsule simulants.The control group used Zhuanyaotang Granules simulants,methylcobalamin tablets and celecoxib capsules.The course of treatment was 3 weeks for both groups.The follow-ups were conducted at 1 month and 3 months after treatment.The intermittent claudication distance,visual analogue scale(VAS)score and JOA efficacy rating criteria for low back pain score were observed in both groups before treatment,1,2,3 weeks of treatment and 1 month after treatment and 3 months after treatment.Adverse reactions during treatment were recorded.Results There were 5 cases of detachment and 2 cases of exclusion in the experimental group,and 5 cases of detachment and 1 case of exclusion in the control group.Compared with before treatment,there were statistically significant differences in intermittent claudication distance,VAS score,and JOA score between the two groups of patients at various time points during treatment and follow-up(P<0.05);there was no statistically significant difference in intermittent claudication distance,VAS score,and JOA score between the experimental group and the control group before treatment and 1 and 2 weeks of treatment(P>0.05);compared with the two groups at 3 weeks of treatment and 1 and 3 months after treatment,the intermittent claudication distance and JOA score in the experimental group were lower than those in the control group(P<0.05);There was no significant difference in VAS score between the two groups and the control group after 3 weeks of treatment(P>0.05).There were 2 adverse reactions(4.4%)in the experimental group and 5 adverse reactions(10.8%)in the control group,without statistical significance(P>0.05).Conclusion Zhuanyaotang Granules can effectively relieve pain and improve lumbar function in patients with DLSS,which is more effective and safer than oral celecoxib capsules and methylcobalamin tablets.

Occupational stress, anxiety, and depression among grassroots disease control and prevention staff in Hebei Province: A qualitative comparative analysis based on fuzzy sets / 环境与职业医学

Background Grassroots center for disease control and prevention (CDC) staff undertake intensive work of disease prevention and control, and may be susceptible to occupational stress, anxiety, depression, and other health problems. Objective To understand the current situation of occupational stress, anxiety, and depression among grassroots CDC staff, and to identify potential risk factor configurations for occupational stress, anxiety, and depression using fuzzy set qualitative comparative analysis (fsQCA), so as to provide a basis for effective intervention. Methods The staff working in county/district-level CDCs in Hebei Province were the target population of the current study. Stratified random cluster sampling method was used to select 1860 staff members of the target population. A questionnaire of general situation, Job Content Scale, 7-item Generalized Anxiety Disorder Scale, and Patient Health Questionnaire-9 were used. Risk factor configurations associated with health outcomes of interest were identified by fsQCA3.0 software. Results The positive rates of occupational stress, anxiety, and depression were 42.69%, 44.25%, and 47.96%, respectively. Marital status was a necessary condition for occupational stress, anxiety, and depression in the grassroots CDC staff (the necessity values were 0.911, 0.939, and 0.933, respectively). There were two types of risk factor configurations for occupational stress: "self-improvement" and "disease burden"; the risk factor configurations for anxiety were "disease burden" and "economic-disease burden"; while the risk factor configurations for depression were "disease burden", "economic-disease burden", and "self-improvement". The overall consistency scores of occupational stress, anxiety, and depression were 0.941, 0.820, and 0.774, respectively. Regarding outstanding components, "self-improvement" included pressure of job requirements and promotion, "disease burden" included impact of chronic illness on psychological state, and "economic-disease burden" included not only impact of chronic illness but also financial support for CDC staff. Conclusion All positive rates of occupational stress, anxiety, and depression are high among grassroots CDC staff in Hebei Province. Occupational stress, anxiety, and depression of grassroots CDC staff are the results of multiple influencing factors, so targeted intervention measures should be formulated.

Effect and mechanism of NBED on uranium excretion / 中国药理学与毒理学杂志

OBJECTIVE To study the effect and mechanism of N1,N2 bis(2,3-dihydroxy-4,6-disul-fonic acid benzyl)ethylenediamine sodium salt(NBED)on uranium excretion.METHODS ICR mice were divided into the blank control group,uranium exposure group(0.03 mg·mouse-1),uranium expo-sure+diethylenetriamine pentaacetic acid(DTPA-CaNa3)(150 mg·kg-1)group,and the uranium expo-sure+NBED(45,90,180 mg·kg-1)group.After uranyl acetate was injected into the tail vein of mice,appro-priate doses of NBED or DTPA-CaNa3 were injected into the tail vein.After 24 h,the uranium contents in the kidney,bone and liver+spleen+muscle were determined by inductively coupled plasma mass spectrometry(ICP-MS).The dissociation constant of NBED and the complexation constant of NBED with uranyl were determined via potentiometric titration.RESULTS Animal experiments showed that NBED 45,90 and 180 mg·kg-1 could significantly reduce the uranium accumulation in the kidney by 48.2%-66.5%,in the bone by 21.4%-54.8%,and in liver+spleen+muscle by 38.2%(P<0.01),compared to the uranium exposure group,47.8%,21.4%and 22.7%respectively by DTPA-CaNa3(P<0.05),and the effect in the NBED 180 mg·kg-1 group was significantly better than in the DTPA-CaNa3 group(P<0.05).The results of potentiometric titration showed that there was about 22.3%LH5,59.8%LH4 and 17.85%LH3(L means NBED)in NBED at pH 7.4,and the secondary dissociation LH4 was the main form.In the range of pH 3-11,there were four complex compounds of NBED and uranyl,and their step-wise complex cumulative constants were logβ111(12.5),logβ101(9.8),logβ102(15.3),logβ1-12(6.5)respectively.The(UO2)L22-was the main species(75.3%)at physiological pH 7.4,and the-log[UO22+free]value(pUO2)of free uranyl ion in solution was 9.57.CONCLUSION NBED mainly exists in the form of secondary dissociated LH4in vivo,and chelates with uranyl 2:1 to form uranyl complex,which is excreted in vitro.Intravenous administration of NBED can more effectively promote excretion than DTPA-CaNa3.

Risk assessment of occupational noise-induced hearing loss in worker in a metal tool manufacturing enterprise / 中国职业医学

Objective To evaluate the risk of occupational noise-induced hearing loss in workers in a metal tool manufacturing enterprise, and to carry out risk classification and risk management. Methods A total of 91 male noise-exposed workers from a metal tool manufacturing enterprise in Hebei Province were selected as the research subjects using the convenience sampling method. The work site survey on occupational health and the measurement on individual noise exposure level were carried out. The ISO 1999：2013 (E) Acoustics-Estimation of Noise-Induced Hearing Loss was used to predict the risk of high frequency hearing loss (HFHL) and occupational noise-induced deafness (ONID). The risk classification and risk management were conducted using the WS/T 754-2016 Guideline for Risk Management of Occupational Noise Hazard (hereinafter referred to as WS/T 754-2016). Results The individual noise exposure intensity of workers in the six work sites of the enterprise, including blade workers, sheet punching workers, roller forging workers (hoe), hole punching workers, roller forging workers(shovels), and carpenters, exceeded the national occupational exposure limit, with the maximum volume of 91.2-104.1 dB(A). Among these workers, the positions of blade workers, sheet punching workers, and roller forging workers (hoe) were identified as critical control points for noise hazards in the enterprise. The detection rates of HFHL and ONID were 24.2% and 8.8%, respectively. The risk prediction results showed that, based on the actual noise exposure time and age of the study subjects, the risk of HFHL and ONID ranged from 1.7%-48.8% and 0.0%-29.5%, respectively. The risks of HFHL caused solely by occupational noise exposure when working up to 50.0, 55.0, and 60.0 years of age were 11.4% to 64.7%, 16.4% to 65.1%, and 17.2% to 59.4%, respectively. The risks of ONID caused solely by occupational noise exposure were 0.0% to 45.5%, 4.2% to 51.7%, and 5.9% to 57.4%, respectively. Except for the blade workers, the predicted median of potential noise-induced permanent threshold shifts (NIPTS) in the other five positions were lower than the actual values of NIPTS, with the difference ranging from 3.0-28.3 dB, and 73.3% of them underestimated by 10.0 dB or more. Conclusion The outcome of noise exposure on the hearing of workers in this enterprise are severe. Risk management should be conducted according to the WS/T 755-2016.

Role of TLR4/NF-κB signaling pathway in hydrogen-rich water improving cognitive impairment induced by ionizing radiation in rats / 环境与职业医学

Background In the process of radiotherapy, when radiation kills tumor cells, it inevitably damages normal tissue cells. Objective To investigate the role of Toll-like receptor 4 (TLR4)/nuclear factor−kappa B (NF-κB) signaling pathway in the improvement of cognitive impairment induced by ionizing radiation by hydrogen-rich water before and after whole brain irradiation in rats. Methods Fifteen male SD rats were randomly divided into three groups: control group, irradiated group (IR group), and hydrogen-rich water intervention group (IR+HRW group), with 5 rats in each group. The control group was not irradiated, but was given purified water (20 mL·kg−1) by gavage every day, while the IR group and the IR+HRW group were irradiated with a single dose of 20 Gy. Three days before, 10 min before, and 30 days after irradiation, purified water/hydrogen-rich water (20 mL·kg−1) was given by continuous gavage every day. The general condition of the rats was observed every day, and the body weight were measured on the 7th, 14th, 21st, and 30th days after irradiation. On the 30th day after irradiation, the learning and memory ability of the rats was tested by Morris water maze; the pathological changes of hippocampus were detected by hematoxylin-eosin (HE) staining after sacrificing the rats; the contents of glutathione (GSH), malondialdehyde (MDA), interleukin-1β (IL-1β), and hydroxyl radicals in brain tissues were detected by enzyme linked immunosorbent assay (ELISA); the mRNA and protein expression levels of TLR4, NF-κB, NOD-like receptor pyrin domain 3 (NLRP3), and cysteinyl aspartate specific proteinase 1 (Caspase 1) were detected by quantitative real-time PCR (qRT-PCR) and Western blotting in the hippocampus of rats. Results After irradiation, the rats in the IR group showed symptoms such as head hair removal and salivation, while the symptoms of the rats in the IR+HRW group were milder. No animal died in the control and the IR+HRW groups, while one rat died in the IR group. From day 14 to day 30 after irradiation, the body weight of the rats in the IR+HRW group tended to be higher than that in the IR group, but the difference was not statistically significant (P>0.05). The Morris water maze results showed that the escape latency of the IR+HRW group was shortened compared with that of IR group from day 1 to day 5 except day 3, but the difference was not statistically significant (P>0.05). For the rats in the IR+HRW group, it took less time to reach the original location of the platform after removing the platform on day 6 and the number of crossing the platform and the residence time in the original platform quadrant increased (P<0.05). The HE staining showed that the number of hippocampal cells in the IR+HRW group was slightly reduced and arranged neatly, without obvious nuclear hyperchromatic and pyknotic phenomenon. The ELISA results showed that the MDA and hydroxyl radical levels were decreased in the IR+HRW group compared with the IR group (P<0.05), the GSH content was increased, and the IL-1β concentration was decreased, but the differences were not statistically significant (P>0.05). The results of qRT-PCR showed that the mRNA expression levels of TLR4 and Caspase 1 in the hippocampus of the IR+HRW group were decreased compared with the IR group (P<0.05), and the mRNA expression levels of NF-κB and NLRP3 were also decreased, but the differences were not statistically significant (P>0.05). The results of Western blotting showed that the expression levels of TLR4 and Caspase 1 protein in the hippocampus of the IR+HRW group were decreased compared with the IR group (P<0.05), and the expression levels of NF-κB p65 and NLRP3 protein were also decreased, but the differences were not statistically significant (P>0.05). Conclusion Hydrogen-rich water can improve cognitive impairment induced by ionizing radiation in rats, and its mechanism may be related to regulating TLR4/NF-κB signaling pathway, inhibiting inflammatory factors, and attenuating oxidative stress.

Detection of ATP2C1 gene mutations in a family with generalized familial benign chronic pemphigus / 中华皮肤科杂志

A 60-year-old female proband presented with recurrent erythema, blisters and erosions all over the body for 30 years, which had been aggravated 10 days prior to the presentation. Skin examination showed erythematous swelling of the bilateral eyelids with scattered dark red crusts, scattered erythema and erosions on the nasolabial folds and chin, large areas of erythema and erosions on the neck, bilateral axillae, left cubital fossa, perineum and perianal area, accompanied by bright red granulation tissues and positive Nikolsky′s sign. The proband had two sons, both of whom occasionally presented with erythema and erosions on the axillae and groin, and had not been diagnosed or treated. Blood samples were collected from the proband and her two sons, and genomic DNA was extracted and subjected to whole-exome sequencing. A heterozygous deletion mutation c.955_957del (p.A319del) was identified in the ATP2C1 gene in the proband and her two sons, which had not been previously reported. The patient was finally diagnosed with generalized familial benign chronic pemphigus.

Effect of Zhuangyao Tongluo Formula（壮腰通络方） Containing Serum on TNF-α-mediated Vicious Circle of Pyroptosis of Nucleus Pulposus Cells / 中医杂志

ObjectiveTo explore the mechanism of Zhuangyao Tongluo Formula（壮腰通络方，ZTF） in delaying intervertebral disc degeneration. MethodsM1 macrophages were induced from THP-1 cells using LPS， IFN-γ and PMA. The induced M1 macrophages were then co-cultured with nucleus pulposus cells in a transwell system. Fetal bovine serum was used as the control serum， and the effects of different concentrations （5%， 10%， 15%， 20%） of serum from rats treated with ZTF on the activity of M1 macrophages and nucleus pulposus cells were analyzed using MTT assay. Experiment 1 was established， including the nucleus pulposus cell control group， M1 macrophage control group， nucleus pulposus cell + ZTF group， nucleus pulposus cell + TNF control group， nucleus pulposus cell + TNF + ZTF group， co-culture group， and co-culture + ZTF group. The levels of IL-1β， and IL-18 in the culture supernatant were detected using ELISA. The mRNA expression of IL-1β and IL-18 in nucleus pulposus cells was detected using qPCR. Additionally， the expression of GSDMD protein in nucleus pulposus cells was detected using cell immunofluorescence. In experiment 2， co-culture groups were constructed using TNF-α overexpression （OE） or empty vector （EV） plasmids， including co-culture group， TNF-EV + co-culture group， TNF-EV co-culture group + ZTF， co-culture + ZTF group， TNF-OE co-culture group + ZTF， and TNF-OE + co-culture group. The mRNA and protein expression of TNF-α in M1 cells in each group were detected using qPCR and WB. ResultsThe ZTF with 10% serum was selected for subsequent experiments. The results of experiment 1 showed that compared to the control group of nucleus pulposus cells， there was no statistically significant difference in the levels of IL-1β， IL-18， mRNA， and GSDMD expression in the nucleus pulposus cells + ZTF group （P＞0.05）. However， the TNF-α + co-culture group showed a significant increase in IL-1β， IL-18 levels， mRNA， and GSDMD expression （P＜0.01）. When compared to the co-culture group， the ZTF+ co-culture group showed a significant decrease in IL-1β， IL-18 levels， mRNA， and GSDMD expression （P＜0.01）. The results of experiment 2 showed that there was no statistically significant difference in TNF-α mRNA and protein expression between the empty vector plasmids + co-culture group and the co-culture group （P＞0.05）. Compared to the empty vector + co-culture group， the expression of TNF-α mRNA and protein was significantly reduced in the empty vector co-culture + ZTF group （P＜0.01）. Compared to the co-culture group and the empty vector + co-culture group， the expression of TNF-α mRNA and protein was significantly reduced in the co-culture + ZTF group （P＜0.01）. Compared to the co-culture + ZTF group， the expression of TNF-α mRNA and protein significantly increased in the overexpression vector co-culture + ZTF group （P＜0.01）. Compared to the overexpression vector co-culture + ZTF group， the expression of TNF-α mRNA and protein significantly increased in the overexpression vector co-culture group （P＜0.01）. ConclusionZTF serum can inhibit the TNF-α-induced apoptosis of nucleus pulposus cells and delay lumbar disc degeneration by reducing the expression of TNF-α in M1 macrophages.

Risk assessment of venous thromboembolism in emergency patients in Beijing / 中华急诊医学杂志

Objective:To assess the risk of venous thromboembolism (VTE) and anticoagulation-related bleeding of acute critical emergency patients staying in the emergency department at least 72 h, so as to improve the ability of emergency physicians to identify risk factors of VTE and their awareness of safety prevention in these patients.Methods:Multicenter emergency internal medicine patients meeting the inclusion criteria at the same time were collected. Padua and Caprini scores were used to evaluate the risk of VTE and the HAS-BLED score was used to assess the risk of anticoagulation-related bleeding.Results:A total of 930 emergency patients from 7 medical centers were enrolled in our study from January 15, 2021 to March 15, 2021. The proportion of high-risk population with VTE was 50.22% with Padua score and 78.49% with Caprini score, respectively. The proportion of high-risk bleeding (HAS-BLED score) was 40.43%.Conclusions:More than half of the acute critical ill patients who stay in emergency department for more than 72 h are at high risk of VTE. This group of patients have a relatively low risk of anticoagulation-related bleeding.

Research advances in toxicity of uranium in vivo and its new chelators / 中国辐射卫生

Uranium is an important radioactive actinide in nature and an important nuclear material in nuclear industry. After uranium is accidentally released into the environment, it enters the body through the respiratory tract, the digestive tract, and other ways, then enters the circulation system through blood, and is finally mainly deposited in the kidney and bone, causing a certain degree of toxicity. Therefore, efficient low-toxicity chelators are an important way to reduce radionuclide pollution, radiation damage, and chemical toxicity. This article reviews uranium deposition and harm, the detoxification mechanism of uranium chelators, and the research advances in uranium chelators and points out the development trend of uranium chelators.

Establishment and Application of dose evaluation model for typical mammal in dry region in China / 中华放射医学与防护杂志

Objective:To establish a simplified anatomical model with the selected rabbits widely distributed in China′s dry region as the reference species and compare the result of internal exposure dose coefficients based on the present mode and ERICA.Methods:A simplified anatomical model based on anatomy and geometry was established for rabbits. Combined with Monte Carlo program, the deposited energy of radionuclide particles in rabbit tissues/organs was obtained, and the internal and external exposure dose coefficient for rabbits was calculated following the empirical formula.Results:Simplified anatomy model-based dose coefficients were 129I 4.81 × 10 -6, 137Cs 4.34 × 10 -5, and 134Cs 3.81 × 10 -5(μGy·h -1)/(Bq·kg -1) for internal exposure and 129I 3.16 × 10 -7, 137Cs 2.39 × 10 -4 and 134Cs 6.22 × 10 -4(μGy·h -1)/(Bq· kg -1) for external exposure. respectively. ERICA-based dose coefficients were 129I 4.44 × 10 -5, 137Cs 1.94 × 10 -4 and 134Cs 2.34 × 10 -4(μGy·h -1)/(Bq·kg -1) for internal exposure and 129I 2.19 × 10 -6, 137Cs 2.52 × 10 -4 and 134Cs 6.95 × 10 -4(μGy·h -1)/(Bq·kg -1) for external exposure, respectively. Conclusions:The simplified anatomical model established is based on the measured data and focuses on the radiation doses to biological tissues/organs, and the calculated result based on the present model are closer to the actual situation, and can provide reference values for the reference biological evaluation of non-human species.

Quantitative Study on Kinematics of Ankle Rotating-Traction-Poking Manipulation for Treating Acute Lateral Ankle Sprain / 医用生物力学

Objective To quantify operation characteristics of the ankle rotating-traction-poking manipulation (RTPM) for treating acute lateral ankle sprain by using motion capture technology, so as to provide objective references for standardized operation of RTPM and its education inheritance. Methods A professional physiotherapist performed the RTPM on 60 volunteers with acute lateral ankle sprain. Motion capture system was used to acquire effective kinematic data during the RTPM, so as to make analysis and summarize rules. Results The average time of ankle rotating for six circles was 11.36 s and the average time of ankle traction and poking was 3.42 s. The average displacement of ankle traction was 36.94 mm and the average displacement of ankle poking was 22.44 mm. The average angle of ankle traction was 23.27°, and the average angle of ankle poking was 22.76°. During the RTPM for treating acute lateral ankle sprain, the average linear velocity of ankle rotating was 58.28 mm/s, and the average linear velocity of ankle traction and poking was 23.81 mm/s. The linear acceleration of ankle rotating was 0.43 mm/s2, and the linear acceleration of ankle traction and poking was 0.54 mm/s2. Conclusions The RTPM can be applied in clinical practice. During the RTMP, the principle of gentleness, rhythmicity and continuity should be followed. Under the premise of following physiological characteristics of ankle joint, treatment of the sprained ankle should be carried out with slow and uniform speed continuously.

Cellular endocytosis and exocytosis of soluble uranium and its damage to HK-2 cells / 中国辐射卫生

Objective To investigate the endocytosis and exocytosis of soluble uranium in human kidney proximal tubular epithelial (HK-2) cells and the cytotoxicity after uranium exposure. Methods Cell Counting Kit-8 assay was used to determine the cell viability after different concentrations of uranium exposure, and optical microscopy and transmission electron microscopy were used to observe the changes in cells after uranium exposure. Inductively coupled plasma mass spectrometry was used to monitor the endocytosis and exocytosis of uranium over time by cells. Flow cytometry was used to assess the changes in cell cycle and apoptosis after uranium exposure. Results After uranium exposure, HK-2 cells showed dose-dependent damage; cell cycle was arrested in G1 phase; cell apoptosis and necrosis occurred; cell proliferation was inhibited. The content of endocytic uranium increased gradually within 24 h, and there was a threshold for uranium endocytosis, while the fraction of uranium binding to cell surface was low (< 0.2%). Over 40% of the endocytic uranium would be exocytosed within 1 h. Uranium could form needle-like precipitates in both intracellular and extracellular areas after uranium exposure. Conclusion After uranium exposure, cells show decreased viability, cell cycle arrest, and cell apoptosis. The process of endocytosis and exocytosis of soluble uranium is very rapid. HK-2 cells can convert soluble uranium into non-toxic precipitates.

Mediating role of resilience in relationship between occupational stress and depression of staff of centers for disease control and prevention / 环境与职业医学

Background Since the outbreak of the COVID-19 epidemic, staff of the centers for disease control and prevention (CDC) have been burdened with heavy epidemic prevention control, and excessive occupational stress can cause depression and other psychological problems. Objective To explore the status of occupational stress, resilience, and depression of CDC staff and potential relationships between them. Methods From December 2020 to April 2021, a survey was conducted at provincial and municipal levels, and the stratified cluster sampling method was used at county (district) level to select a total of 3514 samples. Their occupational stress, resilience, and depression status were evaluated using the Chinese Effort-Reward Imbalance Scale (ERI), the Chinese Connor-Davidson Resilience Scale (CD-RISC), and the Patient Health Questionnaire (PHQ-9). Independent sample t test, analysis of variance, χ2 test, Pearson correlation analysis, and mediation test (structural equation model) were conducted. Results The positive rate of occupational stress was 34.29% in the CDC staff, the resilience score was 66.28±15.32, and the positive rate of depression was 48.58%. Significant differences were found in the positive rates of occupational stress among different groups of gender, age, education background, marital status, administrative duty, weekly exercise frequency, chronic disease prevalence, and participation in epidemic control (P<0.05); in the resilience scores among different groups of gender, age, administrative duty, weekly exercise frequency, chronic disease prevalence, and participation in epidemic control (P<0.05); in the positive rates of depression among different groups of gender, age, educational background, personal monthly income, weekly exercise frequency, chronic disease prevalence, and participation in epidemic control (P<0.05). Occupational stress was negatively correlated with resilience (r=−0.165, P<0.01). Resilience was negatively correlated with depression (r=−0.383, P<0.01). Occupational stress was positively correlated with depression (r=0.343, P<0.01). The structural equation embracing a partial mediating effect of resilience on the relationship occupational stress and depression was established, and the partial mediating effect was 0.039, accounting for 10.46% of the total effect. Conclusion High positive rates of occupational stress, reduced resilience, and depression are shown among CDC staff in the context of the COVID-19 epidemic, and resilience partially mediates the effect of occupational stress on depression. The study findings suggest that improving resilience may reduce occupational stress and depression in CDC staff.

Establishment and application of typical insect dose model in northwestern China / 中华放射医学与防护杂志

Objective:To validate the feasibility of establishing a dosimetric model for insect species by investigating the ecological environment of an inland site in the northwestern China.Methods:For Damalacore, a simplified anatomical model based on anatomy and geometry and a model based on CT scan sequence image were established to produce a voxel model. In combination with the Monte Carlo particle transport process, the deposited energy of the radionuclides in the insect tissues/organs was obtained. The dose rate from 90Sr and 137Cs to Damalacore was calculated on the basis of empirical formula. Results:The dose rate from internal exposure to the simplified anatomical model was 8.58×10 -2for 90Sr and 4.25×10 -3μGy/h for 137Cs, whereas the dose rate from external exposure to the simplified anatomy model was 2.81×10 -2for 90Sr and 2.56×10 -1μGy/h for 137Cs, respectively. The internal exposure to the voxel model from 90Sr and 137Cs was 3.91×10 -2and 2.91×10 -3μGy/h, whereas the external exposure to the voxel model from 90Sr and 137Cs was 2.81×10 -2 and 2.56×10 -1μGy/h, respectively. The internal exposure from 90Sr and 137Cs to ERICA model was 1.46×10 -1 and 1.46×10 -2μGy/h, whereas the external exposure to the ERICA model from 90Sr and 137Cs was 5.79×10 -2 and 2.58×10 -1μGy/h, respectively. Conclusions:The calculated results based on the two models are similar to those based on ERICA model and therefore are proved reliable. With improved model accuracy, the calculated result are more close to the practical situation and feasible.