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.

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.

Reviews on TCM in Reversing Chemotherapy Resistance of Osteosarcoma from ABC Transmembrane Protein / 肿瘤防治研究

Osteosarcoma (OS) is the most common primary malignant bone tumor in clinic. It has high mortality and disability rate. Effective neoadjuvant chemotherapy combined with limb salvage surgery can improve the 5-year survival rate of OS patients. Drug resistance or low sensitivity of tumor cells is the most common cause of postoperative local recurrence and metastasis. Therefore, the sensitivity of OS cells to chemotherapy drugs is of great value to the prognosis of the patients. In recent years, traditional Chinese medicine has been widely used because of high efficiency and low toxicity. A large number of studies have confirmed that part of traditional Chinese medicine can reverse the chemotherapy resistance of OS cells by regulating the ABC transmembrane transport protein system. This article gives an overview of its related mechanisms and latest developments.

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.

Comparison of three TaqMan Real-Time Reverse Transcription-PCR assays in detecting SARS-CoV-2

Quick and accurate detection of SARS-CoV-2 is critical for COVID-19 control. Dozens of real-time reverse transcription PCR (qRT-PCR) assays have been developed to meet the urgent need of COVID-19 control. However, methodological comparisons among the developed qRT-PCR assays are limited. In the present study, we evaluated the sensitivity, specificity, amplification efficiency, and linear detection ranges of three qRT-PCR assays, including the assays developed by our group (IPBCAMS), and the assays recommended by WHO and China CDC (CCDC). The three qRT-PCR assays exhibited similar sensitivities, with the limit of detection (LOD) at about 10 copies per reaction (except the ORF 1b gene assay in CCDC assays with a LOD at about 100 copies per reaction). No cross reaction with other respiratory viruses were observed in all of the three qRT-PCR assays. Wide linear detection ranges from 106 to 101 copies per reaction and acceptable reproducibility were obtained. By using 25 clinical specimens, the N gene assay of IPBCAMS assays and CCDC assays performed better (with detection rates of 92% and 100%, respectively) than that of the WHO assays (with a detection rate of 60%), and the ORF 1b gene assay in IPBCAMS assays performed better (with a detection rate of 64%) than those of the WHO assays and the CCDC assays (with detection rates of 48% and 20%, respectively). In conclusion, the N gene assays of CCDC assays and IPBCAMS assays and the ORF 1b gene assay of IPBCAMS assays were recommended for qRT-PCR screening of SARS-CoV-2.Competing Interest StatementThe authors have declared no competing interest.View Full Text

Clinical features and outcomes of 221 patients with COVID-19 in Wuhan, China

RationaleIn late December 2019, an outbreak of acute respiratory illness, now officially named as COVID-19, or coronavirus disease 2019, emerged in Wuhan, China, now spreading across the whole country and world. More data were needed to understand the clinical characteristics of the disease. ObjectivesTo study the epidemiology, clinical features and outcomes of patients with COVID-19. Methodswe performed a single center, retrospective case series study in 221 patients with laboratory confirmed SARS-CoV-2 pneumonia at a university hospital. Measurements and Main ResultsThe median age was 55.0 years and 48.9% were male and only 8 (3.6%) patients had a history of exposure to the Huanan Seafood Market. Compared to the non-severe pneumonia patients, the median age of the severe patients was significantly older, and they were more likely to have chronic comorbidities. Most common symptoms in severe patients were high fever, anorexia and dyspnea. On admission, 33.0% patients showed leukopenia and 73.8% showed lymphopenia. In addition, the severe patients suffered a higher rate of co-infections with bacteria or fungus and they were more likely to developing complications. As of February 15, 2020, 19.0% patients had been discharged and 5.4% patients died. 80% of severe cases received ICU care, and 52.3% of them transferred to the general wards due to relieved symptoms, and the mortality rate of severe patients in ICU was 20.5%. ConclusionsThe COVID-19 epidemic spreads rapidly by human-to-human transmission. Patients with elder age, chronic comorbidities, blood leukocyte/lymphocyte count, procalcitonin level, co-infection and severe complications might increase the risk of poor clinical outcomes.

Specifications for diagnosis and treatment of non-neonatal tetanus / 中华创伤杂志

Tetanus consists of neonatal tetanus and non-neonatal tetanus.Non-neonatal tetanus remains a serious public health problem,although neonatal tetanus has been eliminated in China since 2012.Non-neonatal tetanus is a potential fatal disease.In the absence of medical intervention,the mortality rate of severe cases is almost 100％.Even with vigorous treatment,the mortality rate remains 30％-50％ globally.These specifications aim to regulate non-neonatal tetanus diagnosis and treatment in China,in order to improve medical quality and safety.These specifications introduce the etiology,epidemiology,pathogenesis,clinical manifestations and laboratory tests,diagnosis,differential diagnosis,grading and treatment of non-neonatal tetanus.

Specifications for diagnosis and treatment of non-neonatal tetanus / 中华创伤杂志

Tetanus consists of neonatal tetanus and non-neonatal tetanus. Non-neonatal tetanus remains a serious public health problem, although neonatal tetanus has been eliminated in China since 2012. Non-neonatal tetanus is a potential fatal disease. In the absence of medical intervention, the mortality rate of severe cases is almost 100%. Even with vigorous treatment, the mortality rate remains 30%-50% globally. These specifications aim to regulate non-neonatal tetanus diagnosis and treatment in China, in order to improve medical quality and safety. These specifications introduce the etiology, epidemiology, pathogenesis, clinical manifestations and laboratory tests, diagnosis, differential diagnosis, grading and treatment of non-neonatal tetanus.

Comparison of four scoring systems for predicting ICU mortality in patients with sepsis / 南方医科大学学报

OBJECTIVE@#To evaluate the value of Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score Ⅱ (SAPS-Ⅱ), Oxford Acute Severity of Illness Score (OASIS) and Logistic Organ Dysfunction System (LODS) scoring systems for predicting ICU mortality in patients with sepsis.@*METHODS@#We collected the data of a total of 2470 cases of sepsis recorded in the MIMIC-III database from 2001 to 2012 and retrieved the scores of SOFA, SAPS-Ⅱ, OASIS and LODS of the patients within the first day of ICU admission. We compared with the score between the survivors and the non-survivors and analyzed the differences in the area under the ROC curve (AUC) of the 4 scoring systems. Binomial logistic regression was performed to compare the predictive value of the 4 scoring systems for ICU mortality of the patients.@*RESULTS@#In the 2470 patients with sepsis, 1966 (79.6%) survived and 504 (20.4%) died in the ICU. Compared with the survivors, the non-survivors had a significantly older mean age, higher proportion of patients receiving mechanical ventilation, and higher initial lactate level, creatinine, urea nitrogen, SOFA score, SAPS-Ⅱ score, OASIS score and LODS score ( < 0.05) but with significantly lower body weight and platelet counts ( < 0.05). The AUCs of the SOFA score, SAPS-Ⅱ score, OASIS score, and LODS score were 0.729 ( < 0.001), 0.768 ( < 0.001), 0.757 ( < 0.001), and 0.739 ( < 0.001), respectively. The AUC of SAPS-Ⅱ score was significantly higher than those of SOFA score (=3.679, < 0.001) and LODS score (=3.698, < 0.001) but was comparable with that of OASIS score (=1.102, =0.271); the AUC of OASIS score was significantly higher than that of LODS score (=2.172, =0.030) and comparable with that of SOFA score (=1.709, =0.088). For predicting ICU mortality in patients without septic shock, the AUC of SAPS-Ⅱ score was 0.769 (0.743-0.793), the highest among the 4 scoring systems; in patients with septic shock, the AUCs SAPS-Ⅱ score and OASIS score, 0.768 (0.745-0.791) and 0.762 (0.738-0.785), respectively, were significantly higher than those of the other two scoring systems. Binomial logistic regression showed the corrected SOFA, SAPS-Ⅱ, and OASIS scores, but not LODS scores, were significantly correlated with ICU mortality in patients with sepsis, and their ORs were 1.08 (95% CI: 1.03-1.14, =0.001), 1.04 (95% CI: 1.02-1.05, < 0.001), 1.04 (95% CI: 1.01-1.06, =0.001), 0.96 (95% CI: 0.89-1.04, =0.350), respectively.@*CONCLUSIONS@#The scores of SOFA, SAPS-Ⅱ, OASIS, and LODS can predict ICU mortality in patients with sepsis, but SAPS-Ⅱ and OASIS scores have better predictive value than SOFA and LODS scores.