Research progress on the application of hydrogel spacer in brachytherapy for gynecological tumors / 中华放射肿瘤学杂志

Radiotherapy is an important treatment of gynecological tumors. Although novel techniques or measures in recemy years have improved the tumor control rate and reduced radiation toxicity, radiation toxicity remains a major problem due to the location of some key organs adjacent to the tumor. A new material-hydrogel, as an organ spacer, provides a new method to reduce the radiotherapy toxicity. In this article, the application of hydrogel as an organ spacer in brachytherapy for gynecological tumors was reviewed from the aspects of hydrogel characteristics, suitable population, mode of injection, interval distance and dose effect, clinical benefits and cost effectiveness, etc.

Impact of lead oxide nanoparticle exposure on the polarization of microglia cells in mouse hippocampus / 中国职业医学

Objective To investigate the effect of exposure to lead oxide nanoparticles (PbO NPs) on the polarization of microglia in mouse hippocampus. Methods i) Specific pathogen-free male C57 mice were randomly divided into control group, low-, medium- and high-dose groups, with 10 mice in each group. Mice in these three dose groups were intraperitoneally injected with PbO NPs suspension at doses of 5, 10 and 20 mg/kg per day, respectively, and mice in the control group were intraperitoneally injected with the same volume of 0.9% sodium chloride solution, five days per week for four weeks. ii) BV-2 cells were treated with PbO NPs at doses of 0.0, 2.5, 5.0 and 10.0 mg/L for 24 hours. iii) BV-2 cells were randomly divided into control group, PbO NPs group and triggering receptor expressed on myeloid cells 2 (TREM2) high expression + PbO NPs group. The cells in the control group received no treatment. The cells in PbO NPs group were exposed to 10.0 mg/L PbO NPs suspension for 24 hours. Cells in TREM2 high expression + PbO NPs group were transfected with Trem2 high expression plasmid, and then exposed to 10.0 mg/L PbO NPs suspension for 24 hours. iv) The mRNA expression of M1 markers ［nitric oxide synthase (iNos), cyclooxygenase 2 (Cox2), chemokine receptor 7 (Ccr7)］, M2 markers ［arginin-1 (Arg-1), transforming growth factor-β (Tgf-β), chemokine receptor 2 (Ccr2)］ and Trem2 of microglia was detected by real-time fluorescent quantitative polymerase chain reaction. The protein expression of iNOS, ARG-1 and TREM2 was detected by Western blotting. Results i) During the experiment, there was no significant difference in body weight of mice among these four groups (P>0.05). The relative expression of Cox2 and Ccr7 mRNA in the hippocampus of the mice increased in the low-dose group and the iNos, Cox2 and Ccr7 mRNA increased in the medium- and high-dose groups, compared with the control group (all P<0.05). The relative mRNA expression of Tgf-β in the hippocampus of the mice of low-dose group and Arg-1, Tgf-β and Ccr2 in the medium- and high-dose groups was decreased compared with the control group (all P<0.05). The mRNA relative expression of iNos, Cox2 and Ccr7 was increased (all P<0.05), while the mRNA relative expression of Arg-1, Tgf-β and Ccr2 was decreased (all P<0.05) in the hippocampus of the mice of high-dose group compared with the low-dose group. The relative expression of Trem2 mRNA and TREM2 protein in the hippocampus of mice of the medium- and high-dose groups was lower than those in the control group (all P<0.05). The relative expression of Trem2 mRNA and TREM2 protein in the hippocampus of mice of the high dose group was lower than those in the low- and the medium-dose groups (all P<0.05). With the increase of PbO NPs exposure dose, the relative expression of iNOS protein in hippocampus tissues of mice increased (P<0.01), and the relative expression of ARG-1 protein decreased (P<0.01). ii) With the increase of PbO NPs exposure dose, the relative expression of iNOS protein increased (P<0.01), and the relative expression of ARG-1 protein decreased (P<0.01) in BV-2 cells. The relative expression of iNOS protein in BV-2 cells of PbO NPs group and TREM2 high expression + PbO NPs group was increased (all P<0.05), and the relative expression of ARG-1 protein decreased (all P<0.05) compared with the control group. The relative expression of iNOS protein decreased (P<0.05), and the relative expression of ARG-1 protein increased (P<0.05) in BV-2 cells of TREM2 high expression + PbO NPs group compared with the PbO NPs group. Conclusion Exposure to PbO NPs could increase the M1 polarization and decrease the M2 polarization of microglia, with a dose-effect relationship. The M1 polarization of microglia decreased and M2 polarization increased after overexpression of Trem2 gene. The regulation of microglia polarization by TREM2 may be involved in the neurotoxic effects of PbO NPs.

Effect of histone H4 on polarization of alveolar macrophages in mice with acute respiratory distress syndrome / 中国职业医学

Objective To investigate the role of histone H4 in the polarization of alveolar macrophages (AM) in lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) in mice. Methods i) The specific pathogen free male C57BL/6 mice were randomly divided into control group and 2, 4, 6 and 8 mg/kg LPS groups, with six mice in each group. The mice in the LPS groups were intratracheally administered LPS according to their respective doses, while the mice in the control group received an equivalent volume of 0.9% saline. After 12 hours, the arterial blood gas was analyzed, and the pulmonary edema and histopathological changes in lung tissues of mice in each group were observed. The level of histone H4 in bronchoalveolar lavage fluid (BALF) of mice was detected using enzyme-linked immunosorbent assay , and mice AMs of the five group were isolated using adherent method. ii) AMs from normal mice were isolated using adherent method and randomly divided into control group, histone H4 injury group, BALF injury group and anti-histone H4 antibody (anti-H4) intervention group. In the histone H4 injury group, AMs were treated with histone H4 at a final concentration of 20 mg/L. In the BALF injury group and anti-H4 intervention group, AMs were treated with 200 μL BALF supernatant from mice intratracheally administered 6 mg/kg body weight LPS, with the latter group treated with 25 mg/L anti-H4 antibody. The control group AMs were treated with phosphate-buffered saline. iii) After 12 hours of stimulation, the cells were collected, and the relative expression of tumor necrosis factor-α (Tnfa), interleukin-1β (Il1b), differentiation antigen 206 (Cd206) and arginase 1 (Arg1) in AMs was detected using real-time quantitative polymerase chain reaction. Results i) Compared with the control group, mice in all four LPS groups exhibited rapid breathing, inflammatory reaction and lung edema in lung tissues, which were aggravated in a dose-dependent manner. The ratio of partial pressure of arterial oxygen to fraction of inspired oxygen in mice decreased with the increase of LPS dose (P<0.05). The wet/dry weight ratio of lung, the level of histone H4 in BALF and the relative expression of Tnfa and Il1b mRNA in AMs increased with the increase of LPS dose (all P<0.05). The mice in the 6 and 8 mg/kg LPS groups developed ARDS. The level of histone H4 in BALF and the relative expression of Tnfa and Il1b mRNA in AMs of mice in 6 and 8 mg/kg LPS groups were higher than those in the other three groups (all P<0.05). ii) The relative expression of Tnfa and Il1b mRNA increased (both P<0.05), and the relative expression of Cd206 and Arg1 mRNA decreased (both P<0.05) in AMs of histone H4 injury group and BALF injury group compared with the control group. Compared with BALF injury group, the relative mRNA expression of Tnfa and Il1b in AMs of anti-H4 intervention group decreased (both P<0.05), while the relative expression of Arg1 mRNA increased (P<0.05). Conclusion LPS can induce a dose-dependent increase in histone H4 levels in BALF in mice. Histone H4 drives the development of ARDS by activating AMs to M1 polarization. Antagonizing histone H4 to interfere with AM polarization to M1 could be a target for the treatment of ARDS.

Analyzing the characteristics and influencing factors of high frequency hearing loss among noise-exposed workers in an urban rail transit enterprise / 中国职业医学

{L-End}Objective To analyze the characteristics of hearing loss and the influencing factors of high-frequency hearing loss (HFHL) among noise-exposed workers in an urban rail transit enterprise over five consecutive years. {L-End}Methods A total of 1 268 noise-exposed workers, who exposed to the average noise intensity of <85.0 dB(A), in an urban rail transit enterprise was selected as the research subjects using a judgment sampling method. The pure-tone audiometry results from 2019 to 2023 were collected to analyze the result of hearing loss. The influencing factors of HFHL (average hearing threshold ≥40.0 dB at high frequencies in both ears) were analyzed using the generalized estimating equations (GEE). {L-End}Results The detection rates of threshold elevations at frequencies of 0.5-6.0 kHz increased with increasing frequency from 2019 to 2023 (all P<0.01), with the highest detection rate at 6.0 kHz. The detection rate of speech frequency hearing loss (hearing threshold weighted value≥26.0 dB in the better ear) was 0.1%, 0.0%, 0.4%, 0.2%, and 0.2%, respectively. The detection rate of HFHL from 2019 to 2023 was 2.4%, 2.8%, 2.8%, 2.1%, and 2.8%, respectively. The GEE analysis results showed that the risk of HFHL of the workers in 2022 and 2023 was lower than that in 2019 (all P<0.01), with the odds ratios and 95% confidence intervals ［OR (95%CI)］ of 0.57 (0.41-0.81) and 0.65 (0.48-0.87), respectively. The risk of HFHL was higher among vehicle maintenance worker than train drivers (P<0.05), with OR (95%CI) of 2.37 (1.18-4.77). The risk of HFHL increased with age and length of service among the workers (all P<0.05), with the OR (95%CI) of 2.05 (1.22-3.46) and 1.69 (1.12-2.54), respectively. No interaction was found between type of job and age, type of job and length of service, or age and length of service in the risk of HFHL among the research subjects(all P<0.05). {L-End}Conclusion Noise exposure below the national occupational exposure limits can lead to hearing loss in noise-exposed workers of urban rail transit enterprises, possibly affecting the hearing threshold at 6.0 kHz first. The influencing factors for HFHL in workers of rail transit are age, length of service, and type of job. There is a dose-effect relationship with age and length of service.

Inicio de la Dosimetría Biológica en Costa Rica y su importancia en la atención de poblaciones sobreexpuestas a radiaciones / Beginning of Biological Dosimetry in Costa Rica and its importance in the care of populations overexposed to ionizing radiation

Resumen Introducción: el laboratorio de citogenética del Instituto de Investigaciones en Salud (INISA) de la Universidad de Costa Rica estableció un Servicio de Dosimetría Biológica en enero del 2020 utilizando biomarcadores citogenéticos de exposición a radiaciones ionizantes. Es el primero de su tipo en la región centroamericana. Objetivo: establecer un servicio de dosimetría biológica para Costa Rica, elaborando una curva de calibración dosis-efecto para rayos gamma. Metodología: para la realización de la curva de calibración se irradiaron muestras de sangre periférica in vitro con rayos gamma de dos voluntarios, uno femenino y otro masculino, en 11 puntos de dosis en el rango de 0 a 5 Gy. Se cultivó la sangre acorde a los protocolos internacionales durante 48 horas y se registraron las aberraciones inducidas. Los programas Dose Estimate V5.2 y R versión 4.03 se utilizaron para el cálculo de los coeficientes de la curva de calibración que correlaciona la frecuencia de cromosomas dicéntricos con la dosis. Resultados: los coeficientes de la curva son α: 0.02737±0.00658, ß: 0,05938±0,00450 y C: 0.00129±0.00084. Estos coeficientes tienen valores similares a los reportados internacionalmente. La curva se validó calculando dos dosis incógnitas, en la primera incógnita la dosis suministrada fue de 1,5 Gy y la dosis estimada fue 1,47 Gy y en la segunda la dosis suministrada fue de 4 Gy y la dosis estimada fue 3,616 Gy, para ambos casos no existen diferencias estadísticamente significativas entre las dosis suministradas y las estimadas. Conclusiones: actualmente El Servicio de Dosimetría Biológica del INISA puede estimar dosis absorbida en personas que se sospecha de una sobre exposición a rayos gamma en personal ocupacionalmente expuesto o personas involucradas en un accidente radiológico.

Abstract Introduction. The cytogenetics laboratory of the Health Research Institute (INISA) of the University of Costa Rica established a Biological Dosimetry Service in January 2020 using cytogenetic biomarkers of exposure to ionizing radiation. It is the first of its kind in the Central American region. Objective: establish a biological dosimetry service for Costa Rica, developing a dose-effect calibration curve for gamma rays. Methodology: to carry out the calibration curve, peripheral blood samples from two volunteers, one female and the other male, were irradiated in vitro with gamma rays, at 11 dose points in the range of 0 to 5 Gy. Blood was cultured according to international protocols for 48 hours and induced aberrations were recorded. The Dose Estimate V5.2 and R version 4.03 programs were used to calculate the coefficients of the calibration curve that correlates the frequency of dicentric chromosomes with the dose. Results: the coefficients of the curve are α: 0.02737 ± 0.00658, ß: 0.05938 ± 0.00450 and C: 0.00129 ± 0.00084. These coefficients have values similar to those reported internationally. The curve was validated by calculating two unknown doses, in the first unknown case the delivered dose was 1.5 Gy and the estimated dose was 1.47 Gy and in the second case the delivered dose was 4 Gy and the estimated dose was 3.616 Gy. for both cases there are no statistically significant differences between the delivered and estimated doses. Conclusions: the Biological Dosimetry Service of the INISA can estimate absorbed dose in persons suspected of overexposure to gamma rays in occupationally exposed personnel or persons involved in a radiological accident.Health is loaded with symbolisms and practical manifestations that differ according to social groups and sociocultural contexts. In order to make everyday life and needs visible, the Theoretical Paradigm of Social Representations provides the theoretical-methodological bases necessary to understand the common sense knowledge associated with health among the Nicaraguan migrant population in Costa Rica. Methodology: Qualitative study with ethnographic approach that aimed to identify the social representation of health, through the process of objectification, present among Nicaraguan migrants living in Costa Rica. Data collected through semi-structured interviews, participant observation, and field diaries. Processing according to Content Analysis. Results: The social representation of health found behaves analogously to a formula; where, the search for peaceful environments is added to the achievement of financial stability to result in two interdependent representations: 1) Health as physical-mental strength; and 2) Health as a future and abstract sensation of well-being, happiness and transcendence. The socio-political antecedents in Nicaragua, the migratory process, and the adaptation to Costa Rica play a preponderant role in shaping the representation on health. Conclusion: Social representations about health have direct practical implications on the ways of life and needs of migrant groups. Understanding their common sense knowledge allows to move towards more contextualized public policies. More integration of the thoughts, opinions and feelings of migrants in decision-making platforms is recommended.

First-dose response of part-time versus full-time occlusion therapy for the treatment of amblyopia in children / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the efficacy of the first follow-up visit after daily partial or full-day occlusion of the dominant eye in patients with unilateral amblyopia and assess the maximum efficacy produced by different amounts of occlusion.METHODS: A retrospective clinical study was conducted on 135 cases of unilateral amblyopia cured in our hospital's outpatient clinic from January 2020 to December 2021. They were divided into 2h/d occlusion group, 6h/d occlusion group and all-day occlusion group according to the duration of occlusion, with fine sight training of amblyopic eyes. The effect of the first dose(baseline visual acuity-first review visual acuity), cured visual acuity, stereo vision at the first review and cure time of amblyopic eyes were recorded. The factors affecting the first dose effect in patients with unilateral amblyopia were also analyzed.RESULTS: All patients had a baseline visual acuity of 0.4(0.22, 0.52), a first follow-up visual acuity of 0.22(0.15, 0.3), a first-dose effect of 0.1(0.08, 0.18), and a visual acuity of 0(-0.08, 0.05)when amblyopia cured. The first-dose effects were 0.08(0.07, 0.12)for patients in the 2h/d occlusion group, 0.18(0.08, 0.3)for the 6h/d occlusion group, and 0.10(0.08, 0.18)for the all-day occlusion group. The most significant first-dose effect was the 6h/d occlusion group(P&#x003C;0.05); Analysis of different influencing factors showed that the highest values of the first-dose effect of 6h/d occlusion were in the 3-6 years group, 7-12 years group, female group, strabismic amblyopia group and mild to moderate group(P&#x003C;0.05); Furthermore, the first dose effect of the 6h/d occlusion was positively correlated with cure time of amblyopic eyes(rs=0.334, P=0.038). At the first follow-up, 21 cases(53.8%)had improved Titmus stereo visual acuity in the 6h/d occlusion group, which was higher than that in the 2h/d and all-day occlusion groups [16 cases(41.0%), 13 cases(22.8%), P&#x003C;0.017].CONCLUSIONS: For monocular amblyopia, the first-dose effect of 6h/d occlusion treatment was the most significant, and the recovery of stereopsis was the best.

Advances in dose-effect and biomarker studies of uranium-induced kidney injury / 环境与职业医学

With the development of nuclear energy technology and the use of depleted uranium weapons, the uranium exposed population is gradually expanding and the health effects of uranium exposure are of increasing concern. The toxicity of uranium to kidney, a sensitive organ for uranium to enter the body to produce effects, cannot be ignored. As of now, the effects of uranium exposure on the kidney are still not well understood, the threshold of uranium-induced kidney injury has been controversial, and there is a lack of sensitive and specific biomarkers for the diagnosis of early kindey damage, especially in the context of chronic uranium exposure. For these reasons, this paper reviewed the results of research on dose-effect relationships and biomarkers of uranium-induced kidney injury and provided an outlook on future research directions, with the aim of providing a basis for subsequent study on animal experiments and population health effects related to uranium exposure.

Effects of hydroxyurea on cytotoxicity, inflammation and oxidative stress markers in neutrophils of patients with sickle cell anemia: dose-effect relationship

ABSTRACT Introduction: Although the efficacy of hydroxyurea (HU) in inhibiting erythrocyte sickling has been well demonstrated, the action of this drug on human neutrophils and the mechanism by which it improves the manifestations of the disease have not been studied thoroughly. We aimed to investigate the cell viability, along with inflammatory and oxidative markers in the neutrophils of sickle cell anemia (SCA) patients and the effects of HU therapy on these cells, by evaluating the dose-responsiveness. Methods: In the present study, 101 patients (45 men and 56 women, aged 18-69 years) with SCA were divided into groups according to the use or not of HU: the SS group (without HU treatment, n = 47) and the SSHU group (under HU treatment, n = 54). The SSHU group was further stratified into subgroups according to the daily dose of the drug that patients already used: SSHU - 0.5 g (n = 19); SSHU - 1 g (n = 26) and SSHU - 1.5-2 g (n = 9). A control group (AA) comprised 50 healthy individuals. Neutrophils isolated from whole blood were analyzed using Trypan Blue, monoiodotyrosine (MTT) and lactate dehydrogenase (LDH) toxicity assays. Myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and concentrations of interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-α) and malonaldehyde (MDA) were also measured. Results: Neutrophils from SCA patients showed membrane fragility and a significant decrease in cell viability when analyzed by Trypan Blue (p < 0.05), MTT (p < 0.001) and LDH (p = 0.011), compared to the AA group. Levels of inflammatory (MPO, TNF-α, and IL-10) and oxidative markers (SOD, GSH-Px, and MDA) were also altered (p < 0.05) in these cells, showing a significant difference in the SSHU-1g and SSHU - 1.5-2 g groups, compared to the SS group. Treatment with HU reverted the levels of all markers to concentrations similar to those in healthy individuals in a positive dose-effect relationship. Conclusion: The HU did not generate a cytotoxic effect on neutrophils in SCA patients, but it modulated their oxidative and inflammatory mechanisms, promoting cytoprotection with a positive dose-effect.

Comparative Study of Protective Effects of Atomization Inhalation and Intraperitoneal Injection of Edaravone on Smoke Inhalation Lung Injury Model Rats / 中国药房

OBJECTIVE：To compare the protective effect of atomization inhalation and intraperitoneal injection of edaravone on acute lung injury in smoke inhalation lung injury model rats. METHODS ：Thirty male SD rats were divided into normal control group（group A ），injury group （group B ），intraperitoneal injection group （group C ），low-dose aerosol inhalation group （group D），high-dose aerosol inhalation group （group E ）according to random numble table ，with 6 rats in each group. Group B-E were placed in smoke generator containing pine sawdust to induce smoke inhalation lung injury model. In group A ，the operation was the same as above except that the pine sawdust was not placed. Thirty minutes after modeling ，group C were injected intraperitoneally with edaravone 18 mg/kg（every 70 min，4 times in total ）. Group D and E inhaled edaravone 9，1.8 mg/kg（every 60 min，lasting for 10 min each time ，4 times in total ）. The rats were treated by no means in group A and group B. Six hours after last medication，arterial blood gas analysis was performed ，and the lung wet to dry ratio （W/D）and water content of lung tissue were calculated. The levels of TNF-α，IL-6 and IL- 10 in serum were detected by double antibody ELISA. The contents of MDA ，MPO， SOD and Caspase- 3 in lung tissue were determined by ELISA and other methods. HE staining was used to observe the pathological changes of lung tissue. The apoptotic rate of cells in lung tissue were determined by TUNEL assay. RESULTS ：No abnormality was found in lung tissue of group A ；in group B ，hemorrhage and edema were found in lung tissue ，alveolar structure was difficult to identify，and inflammatory cells and red blood cell infiltration were seen. Above symptoms of rats in group C-E were improved to different extent. Compared with group A ，PaO2/FiO2 and SOD content of lung tissue were decreased significantly in other groups （P＜0.05）；water content of lung tissue ，W/D，serum contents of TNF-α，IL-6 and IL- 10，the contents of MDA ，MPO and Caspase-3 in lung tissue ，apoptotic rate were increased significantly （P＜0.05）. Compared with group B ，PaO2/FiO2 and serum contents of IL- 10 were increased significantly in administration groups （P＜0.05）；water content of lung tissue ，W/D，serum contents of TNF-α and IL-6，the contents of MDA ，MPO and Caspase- 3 in lung tissue ，apoptotic rate were significantly decreased，in dose-dependent manner （P＜0.05）. CONCLUSIONS ：Edaravone has a certain protective effect on smoke inhalation lung injury model rat. It can reduce the production and release of inflammatory mediators and/or cytokines ，reduce the peroxide damage and inhibit cell apoptosis in a dose-dependent manner. The effect of atomization inhalation is more obvious than that of intraperitoneal injection.

Intervention Effect and Mechanism of Fufang Huangbaiye Tuji on Skin with Deep Ⅱ Degree Burn Wound / 中国实验方剂学杂志

Objective:To study the intervention effect and underlying mechanism of Fufang Huangbaiye Tuji （FFHBY） on skin with deep Ⅱ degree burn wound. Method:Patients with deep Ⅱ degree burn of fire-toxin injuring fluid syndrome diagnosed in the Affiliated Hospital of Chengde Medical University from June 2019 to June 2020 were randomly divided into a control group （iodophor solution， 35 mL per 1% body surface area）， a low-dose treatment group （FFHBY， 17.5 mL per 1% body surface area）， and a high-dose treatment group （FFHBY， 35 mL per 1% body surface area）， 40 cases in each group. The patients in each group were treated correspondingly with dressing chance once per day. The pathological changes of the wound were observed on the 14th day after treatment. Wound symptoms and signs in each group before treatment and on the 7th， 14th， and 21st days after treatment were quantified， and the clinical efficacy on the 21st day after treatment was evaluated. Wound healing rates in each group were calculated on the 7th， 14th， and 21st days after treatment. The levels of vascular endothelial growth factor （VEGF）， fibroblast growth factor （FGF）-2， FGF-7， epidermal growth factor （EGF）， interleukin （IL）-10， tumor necrosis factor （TNF）-<italic>α</italic>， and Caspase-3 in wound tissues were measured with enzyme-linked immunosorbent assay （ELISA）. Nuclear factor kappa-B （NF-<italic>κ</italic>B） p65 expression in wound surface was detected by immunohistochemistry. The apoptosis rate in wound tissues was determined by the TdT-mediated dUTP-biotin nick end labeding assay （TUNEL） method. Result:There was no significant difference in scores of symptoms and signs among groups before treatment. Compared with the control group， the treatment groups showed no significant difference in wound healing rates on the 7th day after treatment and increased healing rates on the 14th and 21st day after treatment（<italic>P</italic><0.05）. The clinical efficacy in the treatment groups was superior to that in the control group on the 21st day after treatment. Additionally， the treatment groups also showed decreased scores of local symptoms and signs， increased levels of VEGF， FGF-2， FGF-7， EGF， and IL-10， and dwindled apoptosis rate and levels of Caspase-3， TNF-α， and NF-<italic>κ</italic>B p65 expression in wound tissues on the 7th，14th and 21st day after treatment （<italic>P</italic><0.05）. The high-dose treatment group was superior to the low-dose treatment group in the above indicators （<italic>P</italic><0.05）. Histopathological examination showed that inflammatory cell infiltration was relieved in the treatment groups as compared with that in the control group， and the high-dose treatment group exhibited superior efficacy. Conclusion:FFHBY had an obvious therapeutic effect on deep Ⅱ degree burn. It could promote wound healing by up-regulating the level of growth factors， improving inflammatory response， and inhibiting cell apoptosis in a dose-dependent manner.

Efficacy of Fufang Huangbaiye Tuji on Inflammation on Skin with Deep Ⅱ Degree Burn and Its Dose-effect Relationship / 中国实验方剂学杂志

Objective:To observe the effect of different doses of Fufang Huangbaiye Tuji asin the treatment onof the inflammatory response in healing process for of skin with deep Ⅱ degree burn. Methods in healing process. Methods:The 120 cses patients with deep Ⅱ degree burn of fire-toxin injuring fluid syndrome diagnosed in the affiliated hospital of Chengde Medical University between June 2019 and March 2020 were randomly divided into control group，low -dose treatment group and high -dose treatment group，with 40 cases in each group and once. They got a dressing change perevery day. Control group was locally administered with lodophor solution 35 mL per 1% on the body surface area. Low-dose treatment group was locally administered with compound cortex phellodendri fluid 17.5 mL per 1% on the body surface area，while high-dose treatment group was locally administered with compound cortex phellodendri fluid 35 mL per 1% on the body surface area. Observe theThe inflammatory reaction of wound surface in each group onwas observed at admission and after treatment. The pathological changes of each groupsgroup were observed， and determination of nuclear factor kappa-B（NF-<italic>κ</italic>B） p65 expression inon the wound surface was determined by immunohistochemistry on the 4th day after the treatment. The levels of interleukin（IL）-2，IL-8 and tumor necrosis factor（TNF）-α in wound tissue were measured with ELISA and Bacterial culture and count were performed in each group on the 4^th，10^th and 21^st daydays after treatment. The levels of IL-2，IL-8 and TNF-α in wound tissue were measured with ELISA. Results:There was no significant difference in the degree of wound inflammation in each group at admission，and the degree of relief after treatment was positively correlated with the treatment time. At the simultaneous phase point，the inflammatory reaction was severest in control group，which was followed by low-dose treatment group and high-dose treatment group. Bacterial growth were observed on the 4^th day in control group，which was found in low-dose and high-dose treatment groups on the 10^th day，the detection rates of Staphylococcus aureus and Pseudomonas aeruginosa were the highest. Compared with control group，the mean integrated optical density of NF-<italic>κ</italic>B p65 in wound tissue decreased markedly in low-dose and high-dose treatment groups on the 4th day after treatment（<italic>P</italic><0.05），the bacterial count decreased significantly in low-dose and high-dose treatment groups on the 10^th and 21^st days after treatment（<italic>P</italic><0.05），and the levels of IL-2，IL-8 and TNF-<italic>α</italic> in wound tissue decreased markedly in low-dose and high-dose treatment groups on the 4^th，10^th and 21^st days after treatment（<italic>P</italic><0.05），with statistically significant differences between low-dose and high-dose treatment groups（<italic>P</italic><0.05）. Histopathological examination showed that inflammatory granulocytes and edema were improved in low-dose and high-dose treatment groups compared with control group，with a more significant performance in high-dose treatment group. Conclusion:The external application of compound cortex phellodendri fluid can reduce thebacterial growth of bacteria in on the wound surface，which may reduce the inflammatory reaction by inhibiting the production and release of inflammatory mediators，with a certain dose-effcteffect relationship，and is worth clinical promotion.

Analysis on exercise capacity of patients with pneumoconiosis and different degrees of pulmonary dysfunction / 中国职业医学

OBJECTIVE: To explore the exercise capacity of patients with occupational pneumoconiosis with varying degrees of pulmonary dysfunction. METHODS: A total of 488 hospitalized occupational pneumoconiosis patients were selected as study subjects using the judgment sampling method and examined for pulmonary function test and cardiopulmonary exercise test(CPET). Among them, 272 patients with normal lung function were assigned as the control group, and 216 patients with abnormal lung function as the case group. The case group was divided into mild, moderate and severe pulmonary dysfunction subgroups according to the forced expiratory volume in one second/predicted value ratio(FEV_1%pred).RESULTS: The FEV_1%pred, maximal voluntary ventilation(MVV), maximum exercise tidal volume(VT_(max)), breathing reserve(BR), maximal Watt(W_(max)), maximum oxygen uptake(VO_(2max)) and anaerobic threshold(AT) in patients of the case group were lower than that in the control group(all P<0.05). The FEV_1%pred, MVV, VT_(max), W_(max), and VO_(2max) in patients in the 3 subgroups of abnormal lung function were decreased(all P<0.05) compared with the control group. The VO_(2max) and AT decreased in the case group with the increase of the degree of pulmonary dysfunction(P<0.05). The FEV1%pred, MVV, maximal exercise minute ventilation and VT_(max) of the study subjects were positively correlated with VO_(2max) and AT(all P<0.01), but the BR had no correlation with VO_(2max) and AT(all P>0.05). CONCLUSION: The more serious the abnormal degree of pulmonary function in the patients with occupational pneumoconiosis, the more obvious the decline of their exercise ability, showing a dose-effect relationship.

Liver inflammation and oxidative damage induced by subchronic crotonaldehyde exposure in male rats / 中国职业医学

OBJECTIVE: To investigate the hepatotoxicity induced by subchronic crotonaldehyde exposure in male rats and analyze its possible mechanism. METHODS: The specific pathogen-free male Wistar rats were randomly divided into control group, low-, medium-and high-dose crotonaldehyde groups, with 10 rats in each group. The crotonaldehyde solution at doses of 0.0, 2.5, 4.5, and 8.5 mg/kg body weight were given by intragastric administration, once a day, 5 days per week, and continuous for 90 days. The body weight of the rats were weighed during the exposure period. After the exposure, the liver organ coefficients and histopathological changes of the rats were observed. The activities of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) and the level of total bilirubin(TBIL) in the serum of rats were determined by colorimetry. The levels of malondialdehyde(MDA) and reduced glutathione(GSH), and the activities of glutathione peroxide(GSH-Px) and superoxide dismutase(SOD) were determined by colorimetry. The levels of interleukin(IL)-1β, IL-6, tumor necrosis factor alpha(TNF-α) and interferon-γ(IFN-γ) was detected by enzyme-linked immunosorbent assay. RESULTS: At the end of exposure, the increment of body mass of rats in the low-, medium-and high-dose crotonaldehyde groups was lower than that in the control group(P<0.05). The organ coefficients of rats in the middle-and high-dose groups were lower than that in the control group(P<0.05). The liver tissues of the three doses crotonaldehyde groups showed varying degrees of inflammatory cell infiltration. The activities of ALT, AST and the level of TBIL in the serum of rats increased with the increase of the crotonaldehyde exposure dose(P<0.01). With the increase of the crotonaldehyde dose, the level of MDA in rat liver tissue increased(P<0.01), and the level of GSH and the activities of GSH-Px and SOD decreased(P<0.01). The levels of IL-1β, IL-6, TNF-α and IFN-γ in rat liver tissues increased(P<0.05). CONCLUSION: Crotonaldehyde exposure can cause liver tissue damage in rats. Its mechanism of action may be related to the changes of oxidative balance and upregulation of the expression of inflammatory factors in liver tissue. These changes have the dose-effect relationship.

Association of lower extremity work-related musculoskeletal disorders and types of working among manufacturing workers / 中国职业医学

OBJECTIVE: To investigate the prevalence of lower extremity work-related musculoskeletal disorders(WMSDs) among manufacturing workers, and to explore the association of lower extremity WMSDs and different types of working. METHODS: A total of 7 908 workers were selected as study subjects from four manufacturing factories in China using the cluster sampling method. The Musculoskeletal Disorders Investigating Questionnaire was adopted to investigate the prevalence of lower extremity WMSDs and the distribution of types of working. The prevalence ratio(PR) of WMSDs, calculated by log-binomial model, was used to estimate the correlation of WMSDs in different parts of lower extremity. The multi-factor logistic regression was used to analyze the association of lower extremity WMSDs and different types of working. RESULTS: The total annual prevalence of lower extremity WMSDs was 41.0%(3 241/7 908) among manufacturing workers. The annual prevalence of WMSDs of different parts in lower extremity from high to low were knee(29.5%), ankle/foot(23.9%) and hip/thigh(16.7%). The correlation of WMSDs of the three parts in lower extremity was close, and the range of PR values was 2.21-3.88. The result of logistic regression analysis showed that the workers who frequently sat for long periods had higher risk of lower extremity WMSDs than those who never/rarely sat for long periods(odds ratio=1.39, P<0.01). The higher the frequency of standing, kneeling/squatting for long periods, carrying heavy loads ≥5 kg and driving, the higher the risk of lower extremity WMSDs(the odds ratios were 1.33, 1.41, 1.16 and 1.12, respectively, P<0.01). CONCLUSION: The prevalence of lower extremity WMSDs was relatively high among manufacturing workers. There is a dose-effect relationship between the types of working and lower extremity WMSDs.

Effect of bloodletting at tip of ear with different amounts on pain in patients with early-stage stye: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the curative effect between bloodletting at tip of ear with different amounts combined with western medication and western medication alone for early-stage stye.@*METHODS@#A total of 108 patients with early-stage stye were randomly divided into a 50 μL group (36 cases, 4 cases dropped off), a 100 μL group (36 cases, 2 cases dropped off) and a western medication group (36 cases, 5 cases dropped off). The patients in the western medication group were treated with levofloxacin eye drops and levofloxacin hydrochloride eye gel. Based on the treatment of the western medication group, the patients in the 50 μL group were treated with 50 μL bloodletting (about 3 drops) at tip of ear while the patients in the 100 μL group were treated with 100 μL bloodletting (about 6 drops) at tip of ear; the bloodletting was given once a day for 3 days. After treatment, the changes of visual analogue scale (VAS) and clinical effect were observed, and the patients were followed up by telephone on the 8th day.@*RESULTS@#After treatment, the VAS score in each group was reduced (0.05). One week after the onset of the disease, all the patients in the 50 μL group and 100 μL group were cured, and one patient in the western medication group was not cured, and treated with routine surgery.@*CONCLUSION@#Based on the conventional western medication treatment, bloodletting at tip of ear can significantly reduce the pain of stye, and the effect of 100 μL bleeding is better than 50 μL.

Research progress on dose-effect relationship of Chinese materia medica / 中草药

The dose-effect relationship of Chinese materia medica (CMM) is the basis to determine the clinical dosage, as well as the key to ensure the safety and effectiveness in clinic. In this paper, the author reviews and summarizes the research ideas, research status, and research bottlenecks related to the dose-effect relationship of CMM in the past 10 years. It is suggested to introduce the theory of spectrum-effect relationship into the study of dose-effect relationship, so as to provide reference for further research on the dose-effect relationship of CMM.

Study on the Dose-time-effect Relationship of Tibetan Medicine Rannasangpei in Cerebral Ischemia-reperfusion Injury Model Rats with Intragastric Administration / 中国药房

OBJECTIVE： To study the dose-time-effect relationship of Tibetan medicine Rannasangpei in cerebral ischemic- reperfusion injury model rats with intragastric administration. METHODS： The rats were randomly divided into sham operation group （normal saline， 10 mL/kg）， model control group （normal saline， 10 mL/kg）， positive control group （nimodipine， 30      mg/kg）， Rannasangpei different dose groups （0.52， 1.04， 2.08， 4.17， 8.33， 16.67， 33.34， 66.68， 133.36， 266.72 and 533.44    mg/kg）， with 18 rats in each group. Each group was given relevant medicine intragastrically once； 25 min after intragastric administration， cerebral ischemic-reperfusion injury model was established with suture-occluded method in those groups except for sham operation group. 24， 48， 72 h after cerebral ischemia， neuroethology of rats were graded in each group. The rate of cerebral infraction was detected to evaluate the optimal effective time， the optimal dose （Dmax） and maximal effect （the rate of minimum cerebral infraction， Emax） of Ratnasampil at different periods of cerebral ischemia. Dose-time-effect relationship of Rannasangpei dose with the rate of cerebral infraction was fitted with Thermo Kinetica 5.1 software. The area under curve （AUClast） and retention dose （MRTlast） of dose-effect curve were calculated， and detect the levels of SOD and MDA. RESULTS： Compared with sham operation group， the neurobehavior of model group was significantly abnormal （P＜0.05 or P＜0.01）， and the rate of cerebral infarction was significantly increased （P＜0.01）； the level of SOD was decreased significantly （P＜0.01， 48 h）， and the level MDA was increased significantly （P＜0.05， 48 h）. Compared with model control group， there was no significant change in neurobehavioral abnormalities in the nimodipine group （P＞0.05）， and the rate of cerebral infraction was decreased significantly （P＜0.01， 24， 48 h）. The level of SOD in rats were increased significantly （P＜0.01， 48 h）， while the level MDA decreased significantly （P＜0.05， 48 h）. Rannasangpei 2.08-33.34 mg/kg could significantly improved neurobehavioral abnormalities （P＜0.05， 24 h）； 24 h after cerebral ischemia， the rate of cerebral infraction was decreased significantly in Rannasangpei 4.17-133.36 mg/kg group （the lowest is 33.34 mg/kg group， P＜0.05 or P＜0.01）. The level of SOD in rats were increased significantly in 33.34-533.44 mg/kg groups （P＜0.05）. the level MDA was decreased significantly in 0.52-2.08， 8.33， 33.34， 266.72 and 533.44 mg/kg groups （P＜0.05）. Dmax was 33.34 mg/kg， Emax was 3.02％， AUClast was 5 141.76 mg/kg and MRTlast was 329.161 mg/kg. 48 h after cerebral ischemia， the rate of cerebral infraction was decreased significantly in Rannasangpei 2.08-133.36 mg/kg groups （the lowest is 66.68 mg/kg group， P＜0.05 or P＜0.01）， while the level of SOD was increased significantly in 1.04-533.44（except for 4.17）mg/kg groups （P＜0.05）. The level of MDA was decreased significantly in 16.67-66.68， 533.44 mg/kg groups （P＜0.05）， Dmax was 66.68 mg/kg， Emax was 2.13％， AUClast was    5 219.36 mg/kg and MRTlast was 340.521 mg/kg. 72 h after cerebral ischemia， the rate of cerebral infraction and the level of MDA had no significant decreased in Rannasangpei groups （P＞0.05）， and the levels of SOD had no significant increase （except for 0.52 mg/kg group， P＞0.05）. CONCLUSIONS： The optimal effective time of Rannasangpei for the treatment of cerebral ischemia-reperfusion injury in rats is 48 h， and the Dmax is 66.68 mg/kg. The improvement mechanism may be related to increase the level of SOD and decrease the level of MDA.

Dose-effect relationship in treatment of chronic neck pain with the direct moxibustion of small moxa cone / 中国针灸

OBJECTIVE@#To evaluate the effectiveness in treatment of chronic neck pain with the direct moxibustion of small moxa cone and explore the dose-effect relationship in treatment of chronic neck pain with different small moxa cones.@*METHODS@#A total of 120 patients with chronic neck pain were randomized into a 3-moxa-cone group, a 5-moxa-cone group, a 7-moxa-cone group and a sham-moxibustion group, 30 cases in each one. Fengchi (GB 20), Tianzhu (BL 10), Jingbailao (EX-HN 15), Jianzhongshu (SI 15) and Jianjing (GB 21) were selected in each of the groups. The direct moxibustion with 3, 5 and 7 moxa cones as well as the sham-moxibustion therapy were provided successively in each of the above groups. In the sham-moxibustion group, the lower 1/3 section of moxa cone (about 1.5 mm in length) was soaked in oil before used in treatment. In each group, the treatment was given twice a week, for 10 treatments totally. Separately, before treatment, after treatment and in 1-month follow-up, the scores of the Northwick Park neck pain questionnaire (NPQ), the scores of McGill pain questionnaire (MPQ) and the local pressure pain threshold (PPT) were observed in each group. After treatment and in 1-month follow-up, the therapeutic effects were evaluated in each group.@*RESULTS@#After treatment and in 1-month follow-up, NPQ scores and MPQ scores in the 3-moxa-cone group, the 5-moxa-cone group and the 7-moxa-cone group were reduced as compared with those before treatment separately (all 0.05). After treatment and in 1-month follow-up, NPQ scores and MPQ scores in the 3-moxa-cone group, the 5-moxa-cone group and the 7-moxa-cone group were lower as compared with the sham-moxibustion group separately (all 0.05).@*CONCLUSION@#The direct moxibustion therapy with different small-moxa-cones effectively relieves chronic neck pain. There is a trend of improvement of the therapeutic effects with increase of the numbers of moxa cones.

Effects of mental workload on work-related musculoskeletal disorders in railway vehicle manufacturing workers / 中国职业医学

OBJECTIVE: To investigate the correlation of mental workload and prevalence of work-related musculoskeletal disorders musculoskeletal disorders( WMSDs) in railway vehicle manufacturing workers.METHODS: A total of 362 male workers in assembling and welding workshop from a railway vehicle manufacturing enterprise were selected as study subjects by cluster sampling method.The level of mental workload and prevalence of WMSDs were investigated using a revised Subjective Workload Assessment Technique and China Musculoskeletal Questionnaire.RESULTS: The median score of mental workload was 67 and the prevalence rate of WMSDs was 56.9%.The multivariate logistic regression analysis results indicated that the higher the mental workload of railway vehicle manufacturers,the higher their risk for WMSDs after excluding the influence of confounding factors( P < 0.05).Workers in welding work showed a higher risk than those in assembling work( P < 0.01).Workers with fast work rhythm showed higher risk of WMSDs than those with regular working rhythm( P < 0.01).Workers with comfortable working environment and temperature showed lower risk of WMSDs than those with uncomfortable working environment and temperature( P < 0.01).CONCLUSION: The mental workload can increase the risk of WMSDs,with a dose-effect relationship in railway vehicle manufacturing workers.The type of work,work frequency and the temperature in working environment are also influencing factors of WMSDs.

Effect of cumulative noise exposure on hypertension in automotive manufacturing workers / 中国职业医学

OBJECTIVE: To analyze the relationship between the cumulative noise exposure( CNE) and prevalence of hypertension in automotive manufacturing workers. METHODS: A total of 1 535 noise-exposed male workers with length of service ≥ 1. 0 year from automobile manufacturing industries in Guangzhou City was chosen as study subjects by convenience sampling method. The noise intensity in the workplace was measured, the CNE calculated, and the occupational health examination conducted. RESULTS: The prevalence of hypertension of the study subjects was 8. 1%( 125/1 535). The prevalence of hypertension showed an upward trend with the increase of CNE( P < 0. 01). The multivariate logistic regression analysis showed that the prevalence risk of hypertension increased with the increase of CNE after adjusting for confounding factors such as body mass index,smoking and wearing personal protective equipment in automobile manufacturing workers( P < 0. 01). CONCLUSION: There is a dose-effect relationship between prevalence of hypertension and CNE in automobile manufacturing workers who exposed to noise.