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Trimethylamine N-oxide(TMAO), a metabolite of gut microbiota, is closely associated with chronic kidney disease(CKD). It can aggravate the kidney injury and promote the occurrence of complications of CKD mainly by inducing renal fibroblast activation, vascular endothelial inflammation, macrophage foaming, platelet hyperreactivity, and inhibition of reverse cholesterol transport. Thus it is of great significance for clinical treatment of CKD to regulate circulating TMAO and alleviate its induced body damage. Currently, therapeutic strategies for TMAO regulation include dietary structure adjustment, lifestyle intervention, intestinal microflora regulation, and inhibition of intestinal trimethylamine synthesis and liver trimethylamine oxidation. Chinese medicinal herbs have the clinical advantage of multi-component and multi-target effects, and application of traditional Chinese medicine(TCM) to synergistically regulating TMAO and improving CKD via multiple pathways has broad prospects. This study systematically reviewed the clinical relevance and mechanism of TMAO in aggravating CKD renal function deterioration and complication progression. In addition, the effect and mechanism of TCM in improving TMAO-induced kidney injury, cardiovascular disease, hyperlipidemia, thrombosis and osteoporosis were summarized. The results provided a theoretical basis for TCM in attenuating gut microbiota-derived metabolite TMAO and improving CKD, as well as a basis and direction for in-depth clinical development and mechanism research in the future.
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Humans , Gastrointestinal Microbiome , Medicine, Chinese Traditional , Renal Insufficiency, Chronic/drug therapyABSTRACT
In recent years, fibroblast activation protein (FAP) has emerged as an attractive target for the diagnosis and radiotherapy of cancers using FAP-specific radioligands. Herein, we aimed to design a novel 18F-labeled FAP tracer ([18F]AlF-P-FAPI) for FAP imaging and evaluated its potential for clinical application. The [18F]AlF-P-FAPI novel tracer was prepared in an automated manner within 42 min with a non-decay corrected radiochemical yield of 32 ± 6% (n = 8). Among A549-FAP cells, [18F]AlF-P-FAPI demonstrated specific uptake, rapid internalization, and low cellular efflux. Compared to the patent tracer [18F]FAPI-42, [18F]AlF-P-FAPI exhibited lower levels of cellular efflux in the A549-FAP cells and higher stability in vivo. Micro-PET imaging in the A549-FAP tumor model indicated higher specific tumor uptake of [18F]AlF-P-FAPI (7.0 ± 1.0% ID/g) compared to patent tracers [18F]FAPI-42 (3.2 ± 0.6% ID/g) and [68Ga]Ga-FAPI-04 (2.7 ± 0.5% ID/g). Furthermore, in an initial diagnostic application in a patient with nasopharyngeal cancer, [18F]AlF-P-FAPI and [18F]FDG PET/CT showed comparable results for both primary tumors and lymph node metastases. These results suggest that [18F]AlF-P-FAPI can be conveniently prepared, with promising characteristics in the preclinical evaluation. The feasibility of FAP imaging was demonstrated using PET studies.
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OBJECTIVE: To explore the association of serum Apelin level, silicosis stage and lung function in patients with occupational silicosis(hereinafter referred to as silicosis). METHODS: A case-control study was conducted. A total of 85 patients with silicosis were selected as the silicosis group(44, 28 and 13 patients with stage Ⅰ, Ⅱ and Ⅲ silicosis, respectively), and 120 healthy individuals without occupational hazard exposure were selected as the control group. Serum samples were collected from the cases of the two groups and the level of Apelin was determined by enzyme-linked immunosorbent assay. The pulmonary function of the silicosis group was examined. RESULTS: The median and the 25 th and 75 th percentiles \[M(P_(25),P_(75))\] of serum Apelin levels in the control group and silicosis group were 1.29(0.92, 1.77) and 0.80(0.62, 1.04) mg/L, respectively. The level of serum Apelin M(P_(25),P_(75)) in stage Ⅰ, Ⅱ and Ⅲ silicosis patients was 1.03(0.82, 1.31), 0.66(0.60, 0.80) and 0.50(0.30, 0.65) mg/L, respectively. The results of multiple linear regression analysis showed that the level of serum Apelin in the silicosis group was higher than that in the control group after excluding the influence of age and smoking(P<0.01). The level of serum Apelin decreased with the increase of silicosis stage in the silicosis group(P<0.001). Serum Apelin level in silicosis group was positively correlated with lung vital capacity, forced vital capacity, forced expiratory volume in the first second, and forced expiratory flow between 25% and 75%(all P<0.05). CONCLUSION: The lower level of serum Apein in silicosis patients, the more serious the disease and the more serious the damage to lung function. Apelin is of significance in the diagnosis, staging, treatment appraisal and prognostic evaluation of silicosis, and it can be use as a potential therapeutic target for silicosis.
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OBJECTIVE: To explore the mechanism of bone marrow mesenchymal stem cells(BMSCs) in alleviating silica-induced lung injury in mice. METHODS: Ten specific pathogen free healthy male C57 BL/6 mice were selected for isolating BMSCs and bone marrow macrophages(BMDMs). Transwell chamber was used, BMDMs were inoculated onto the upper chamber and BMSCs in the lower chamber. We divided them into sequencing control group and silica(SiO_2) exposure group. All cells were pre-stimulated with 50 μg/L mass concentration lipopolysaccharide for 4 hours. In the SiO_(2 ) group, 250 mg/L mass concentration SiO_2 was added to the upper chamber of transwell and cultured for 16 hours. Total RNA was extracted from the BMSCs collected from the lower chamber. HiSeq/MiSeq high-throughput sequencing technology was used to detect the BMSCs RNA paired-end sequencing. Transcriptome sequencing data was obtained and bioinformatics analysis was performed. Another 12 specific pathogen free healthy male C57 BL/6 mice were randomly divided into control group and experimental group. All mice received one intra-tracheal injection of 20.0 μL(250 g/L mass concentration) of silica dust suspension. After 6 hours, the mice in the control group was given 500.0 μL of 0.9% sodium chloride solution and mice in the experimental group was given 500.0 μL of BMSCs suspension(cell density 1×10~9/L) by tail vein infusion.Mice were sacrificed 12 hours later. The relative mRNA expression of interleukin(IL)-1 Ra, IL-10, tumor necrosis factor stimulating gene 6(TSG-6) and prostaglandin E2(PGE2) in lung tissues of mice were measured by quantitative real-time PCR(q-PCR). Meanwhile, BMDMs and BMSCs transwell co-culture models were established. The cells were divided into 5 groups: BMSCs group, BMSCs+BMDMs group, BMSCs+BMDMs+ lipopolysaccharide(LPS) group, 50 mg/L SiO_2 group, and 100 mg/L SiO_2 group. After 16 hours of corresponding SiO_2 stimulation, BMSCs of each group were collected and the relative mRNA expression levels of IL-1 Ra, IL-10, TSG-6, and PGE2 in the cells were detected by q-PCR. RESULTS: Compared with sequencing control group, BMSCs co-cultured with SiO_2 had 19 genes up-regulated and 21 genes down-regulated, including 10 genes up-regulated for more than 2.0-fold. The relative mRNA expression of IL-1 Ra, IL-10, PGE2 and TSG-6 in the lung tissue of mice increased in the experimental group than that of the control group(all P<0.05). The relative mRNA expression of TSG-6 increased by 37.5 times higher than that of the control group. Compared with the BMSCs+BMDM+LPS group, the level of TSG-6 mRNA relative expression increased in both the 50 mg/L SiO_2 group and the 100 mg/L SiO_2 group(all P<0.05). CONCLUSION: TSG-6 could be the key factor of BMSCs that can attenuate silica-induced lung injury.
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Pulmonary fibrosis is an interstitial lung disease caused by different pathogenic factors. It has the characteristics of high morbidity and poor prognosis, which seriously affects the quality of life of patients. However, its pathogenesis has not yet been fully elucidated. Surfactant protein(SP)-A and SP-D are lipoprotein complexes distributed at the air-liquid interface of alveoli, synthesized and secreted by alveolar type Ⅱ epithelial cells and bronchiolar cells. They are important parts of the innate immune system, which participate in the host defense process through a variety of regulatory methods, and play an important role in regulating cell apoptosis and lung inflammation, promoting the process of epithelial repair and maintaining the stability of alveolar structure. The disorder and mutation of SP-A and SP-D may be the influencing factors of the pathogenesis of pulmonary fibrosis. Serum SP-A and SP-D levels are differentially expressed in patients with pulmonary fibrosis and normal healthy individuals, and are related to the severity of pulmonary fibrosis. They are considered to be a class of biomarkers that sensitively reflect lung epithelial cell damage and can be used in the diagnosis, treatment and prognostic evaluation of pulmonary fibrosis.
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Acute 1,2-dichloroethane poisoning causes serious illness, deaths and is a social event of great influence. The compilation of Technical Plan for Emergency Treatment of Acute 1,2-Dichloroethane Poisoning provides scientific guidance for effective treatment of 1,2-dichloroethane poisoning events. The plan describes in detail the specific practice and technical requirements of six links in the process of handling emergency of acute 1,2-dichloroethane poisoning, including accident investigation and treatment, risk assessment, collection and testing of samples, medical treatment, health monitoring and emergency response, et al. The key contents of individual protection requirements, investigation content, etiology determination, medical assistance and health education in the disposal of poisoning incidents were clarified, and the procedures and requirements of health education were added. The technical scheme is scientific, objective and operable, which can provide scientific guidance for the effective treatment of 1,2-dichloroethane poisoning accidents.
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Objective To investigate the prevalence of osteoarthrosis and the association between hot spring bathing and osteoarthrosis among local adults in typical hot spring areas of Guizhou Province. Methods A face-to-face questionnaire survey was conducted among residents aged from 30 to 65 in five typical hot spring areas, including Xifeng(Xifeng County, Guiyang), Jianhe(Jianhe County, Qiandongnan), Fodingshan(Shiqian County, Tongren), Guiyu(Wudang District, Guiyang)and Huishangu(Suiyang County, Zunyi). Residents' basic information, bone and joint diseases prevalence, hot spring bathing, and other health-related behaviors were investigated in this study. The prevalence of local bone and joint diseases was analyzed, and binary logistic regression was used to calculate OR(95%CI)to analyze the association between hot spring bathing and bone and joint diseases. Results A total of 3 708 adults(1 648 males and 2 060 females)were included as the statistical analysis survey subjects, and 794 people reported bone and joint diseases, accounting for a prevalence rate of 21.41%, 95% CI: 0.201-0.227. The prevalence of females(24.56%)was higher than that of males(17.48%)(P < 0.001). The prevalence rates of diseases increased with age(χtrend2=130.265, P < 0.001). There were also statistically significant differences in the prevalence rate of bone and joint diseases among different genders, age groups, occupations, education levels, and smoking behaviors(P < 0.05). After gender, age, occupation, education and smoking were adjusted for, compared with the group who never took hot spring baths, participants who took hot spring baths occasionally(OR=0.793, 95%CI: 0.631-0.996)and frequently(OR=0.713, 95%CI: 0.536-0.948)were associated with a lower risk of bone and joint diseases. Conclusion The prevalence of osteoarthrosis is 21.41% in the typical hot spring areas of Guizhou Province. Older or females have a higher risk of prevalence of bone and joint diseases. Hot spring bathing may be associated with a lower risk of bone and joint diseases.
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Mesenchymal stem cells(MSCs) have functions such as immune regulation and tissue damage repair, but the specific mechanisms of their effects need to be further studied. Paracrine effect is an important mechanism for MSCs to achieve immune regulation, relieve inflammation and repair tissue damage. Tumor necrosis factor α(TNF-α) stimulated protein 6(TSG-6) is one of the paracrine factors of MSCs, which has significant inflammation inhibitory capability and tissue repair ability. It is an important cytokine of MSCs to exert their anti-inflammatory and anti-fibrotic effects. The MSCs can repair tissue damage in kidney, peritonea, skin, liver, lung, cornea, nervous system, and colon by secreting TSG-6. This powerful repair ability could be attributed to the ability of TSG-6 to inhibit the secretion of pro-inflammatory cytokines and pro-fibrogenic factors, such as TNF-α, interleukin(IL)-6, IL-1β and transforming growth factor-β1, thereby reducing the inflammatory response and fibrosis of the body.
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Objective To study the mechanism of bone marrow mesenchymal stem cell (BMSC)-mediated alleviation of pulmonary alveolitis in mice exposed to silica dust. Methods Thirty mice were randomly divided into 3 groups:control group, and two silica groups with or without BMSCs transplantation.Through the tracheal tube clearance, mice in control group received a single injection 20.0 μL of 0.90% sodium chloride solution by one time.Mice from in silica group and silica/BMSCs transplantation group first received a single injection of 20.0 μL silica dust suspension (mass concentration 250 g/L); followed by either 500.0 μL of 0.90% sodium chloride solution or by 500.0 μL of BMSCs suspension (cell density 1×109/L) through tail vein infusion 6 hours later.Mice were euthanized on the 3th day of the experiments.The levels of NALP3 inflammasome in lungs was determined by Western blot.Transwell system was used for co-culture of BMDM (in upper-chamber) and BMSC (in lower-chamber) co-culture.The level of cytokines IL-1β in BMDM cultural supernatant was detected by enzyme linked immunosorbent assay after stimulated by SiO2 stimulation.The levels of NALP3 inflammasome of in BMDM was determined by Western blot. Results The levels of pro-IL-1β, IL-1β, pro-caspase-1, caspase-1 in lungs of silica/BMSCs transplantation group were lower than that in silica group (P < 0.01).In the experiment in vitro, the concentrations of IL-1β in SiO2 exposed BMSC/BMDM co-culture group were lower than the SiO2 exposure only groups (P < 0.05).Meanwhile, the levels of pro-IL-1β, IL-1β, pro-caspase-1, caspase-1 in BMDM was lower than that in silica group (P < 0.01).The level of these proteins didn′t change while when the cell-free supernatant of BMSC culture was directly added. Conclusion The BMSC could inhibit NALP3 inflammasome of macrophages stimulated by SiO2.
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Objective::A multi-organ chip of intestine-liver-breast cancer was constructed based on microfluidic technology and used for pharmacokinetics-pharmacodynamics (PK-PD) study of drugs in vitro. Method::A multi-organ chip comprising a 4-layer polydimethylsiloxane (PDMS) substrate and a 2-layer poly(methyl methacrylate) (PMMA) cover was constructed by microfluidic technology. The connection between cells was investigated by staining the 21-day-grown human colon cancer cell line Caco-2 cell layer and the 3-day-grown human umbilical vein endothelial cell line HUVEC cell layer with CellTracker Red/Green and Hoechst, respectively. The transmission rates of 2 g·L-1 fluorescein sodium and 33.28 mg·L-1 propranolol acrossing the cell layer were employed to verify the function of the constructed intestinal module. The metabolic level of the liver module was investigated by comparing the inhibition rate of 125 μmol·L-1 cyclophosphamide against human breast cancer cell line MCF-7 cells treated with human hepatoma cell line HepG2 cells in a conventional well plate and chip liver module for 48 h. The secretion of albumin by HepG2 cells in the chip was detected to verify the synthesis function of hepatic module. Caco-2 cell layer, HUVEC cell layer, HepG2 cell layer, MCF-7 cell layer and dialysis membrane were assembled on the chip, the culture medium containing 55 mg·L-1 propranolol was injected into the upper channel of the chip for 4 h, and then changed into the normal culture solution. The mass concentration of propranolol in the lower circulating culture medium at each time point within 72 h was determined, and the drug-time curve was drawn. The culture medium containing 125 μmol·L-1 cyclophosphamide, 5 μmol·L-1 paclitaxel, 50 μmol·L-1 capecitabine was injected into the circulating fluid in the upper layer of the chip, in order to study the inhibition rates of the three anti-tumor drugs on the MCF-7 cell layer on the chip within 72 h, and the results were compared with those of the 96-well plate. Result::The constructed chip performed well. The Caco-2 and HUVEC cell layers were tightly connected. The transmission of fluorescein sodium and propranolol between the cell layers demonstrated that the constructed intestinal module had good absorption and transport function. The inhibition rate of MCF-7 by 125 μmol·L-1 cyclophosphamide after metabolism of HepG2 cells on the well plate was 22.12%, and the inhibition rate of MCF-7 by the unmetabolized cyclophosphamide was 1.84%. The inhibition rate of MCF-7 increased to 32.13%after injected 125 μmol·L-1 cyclophosphamide from the upper layer of the chip liver module, and the inhibition rate of MCF-7 after injection from the lower layer of the chip liver module was 7.23%. The mass concentration of propranolol on the chip changed with time, which was basically consistent with that in vivo. The inhibition rate of MCF-7 on the plate with 125 μmol·L-1 cyclophosphamide was lower than that on the chip, and the inhibition rates of MCF-7 on the plate with 5 μmol·L-1 paclitaxel and 50 μmol·L-1 capecitabine were higher than those on the chip. Conclusion::The constructed multi-organ chip of intestine-liver-breast cancer has the absorption and transport function of the intestine and the metabolic function of the liver. The chip can reflect the pharmacokinetic properties of propranolol in vivo, and can be used for pharmacodynamic studies of paclitaxel and capecitabine.
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Objective@#To observe whether the active forced-air warming has the same efficacy on the prevention of perioperative hypothermia in the elderly as compared with young patients.@*Methods@#This was a prospective, randomized, controlled clinical trial.Forty patients scheduled for abdominal surgery under general anesthesia were allocated to two groups: the elderly group and the young group(n=20, each). All patients received active forced-air warming at 20-30 min before induction of anaesthesia till leaving the operation room.Blood products and peritoneal lavage fluids were warmed to 37℃, and other intravenous fluids were at room-temperature.The core temperatures were recorded after entering the operation room(baseline), before induction of anaesthesia, at 15 min intervals after induction of anaesthesia, at the end of surgery and before leaving the operation room.The postoperative shivering and adverse reactions were also recorded.@*Results@#The core temperature was lower in elderly patients than in young patients at baseline and at each time points after 30 min of induction of anaesthesia(P<0.05). In elderly patients, the core temperature was significantly lower before leaving operation room than at the baseline(t=2.353, P=0.03), but in young patients, no significant difference was found in the core temperature between at the baseline and before leaving operation room(t=0.233, P=0.818). The incidence of intra-operative hypothermia was higher in elderly patients than in young patients(40.0% or 8/20 vs.5.0% or 1/20, c2=7.025, P=0.008).@*Conclusions@#During abdominal surgery under general anesthesia, active forced-air warming cannot effectively prevent perioperative hypothermia in elderly patients as compared with young patients.
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Objective: To investigate the protective effect of Perillae Folium with aqueous extract (PFAE) on some key factors of Adriamycin (ADR)-induced oxidative injury in human renal tubular epithelial cells(HK-2), including the survival rate, oxidative injury indexes and cell apoptosis,in order to define the underlying mechanism. Method: A model of ADR-induced HK-2 cells oxidative injury was established in vitro, then cell viability was detected by cell counting kit-8 (CCK-8) after intervention with positive reference N-acetylcysteine (NAC) or PFAE (5,15,45 g·L-1) at different concentrations. According to the morphological changes under microscopy, the optimum concentration of PFAE was screened out for the follow-up experiments. Then, the experiments were divided into six groups:blank group, ADR (0.05 g·L-1) group, PFAE (15 g·L-1) group, ADR+PFAE (0.05+15) g·L-1 group, NAC (0.81 g·L-1) group, and ADR+NAC (0.05+81) g·L-1 group. After that, malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity(TAC) were measured in the cell homogenate after 24 h administration. The level of reactive oxygen species (ROS) was detected by 2',7'-dichloroflurescin diacetate (DCFH-DA) fluorescence probe. Flow cytometry and TdT-mediated dUTP Nick-End Labeling (TUNEL) were used to monitor the cell apoptosis. Western blot was used to observed the expressions of mitochondrial apoptosis-associated proteins, like B lymphocyte tumor-2 gene (Bcl-2), Bcl-2 related X protein (Bax), cysteine aspartate protease-9 (Caspase-9), cysteine aspartate protease-3 (Caspase-3) and poly ADP-ribose polymerase (PARP), as well as their shear bodies. In addition, the phosphorylation protein expressions of p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK), c-Jun amino-terminal kinase (JNK) in mitogen-activated protein kinase (MAPK) signaling transduction pathway were detected by Western blot. Result: Compared with blank group, ADR group showed a decreased cell viability (PPPPPPPP-1. The ATC and SOD levels were increased in ADR+PFAE group and ADR+NAC group (PPConclusion: PFAE could alleviate the oxidative injury of HK-2 cells induced by ADR, and have an antioxidant effect, which inhibited cell apoptosis through mitochondrial apoptotic pathway and ERK/p38 MAPK signaling pathway.
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Objective To observe whether the active forced-air warming has the same efficacy on the prevention of perioperative hypothermia in the elderly as compared with young patients.Methods This was a prospective,randomized,controlled clinical trial.Forty patients scheduled for abdominal surgery under general anesthesia were allocated to two groups:the elderly group and the young group (n=20,each).All patients received active forced-air warming at 20-30 min before induction of anaesthesia till leaving the operation room.Blood products and peritoneal lavage fluids were warmed to 37℃,and other intravenous fluids were at room-temperature.The core temperatures were recorded after entering the operation room(baseline),before induction of anaesthesia,at 15 min intervals after induction of anaesthesia,at the end of surgery and before leaving the operation room.The postoperative shivering and adverse reactions were also recorded.Results The core temperature was lower in elderly patients than in young patients at baseline and at each time points after 30 min of induction of anaesthesia (P ＜ 0.05).In elderly patients,the core temperature was significantly lower before leaving operation room than at the baseline(t =2.353,P =0.03),but in young patients,no significant difference was found in the core temperature between at the baseline and before leaving operation room (t =0.233,P =0.818).The incidence of intra-operative hypothermia was higher in elderly patients than in young patients(40.0 ％ or 8/20 vs.5.0 ％ or 1/20,c2 =7.025,P =0.008).Conclusions During abdominal surgery under general anesthesia,active forced-air warming cannot effectively prevent perioperative hypothermia in elderly patients as compared with young patients.
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AIM:To investigate the role of Krüppel-like factor 17(KLF17)in nude mouse xenograft model, and to explore the target genes regulated by KLF 17, the target gene functions and the signaling pathways involved.ME-THODS:The KLF17 was stably up-regulated in human lung adenocarcinoma A 549 cells and down-regulated in human lung adenocarcinoma H322 cells by lentiviral infection.BLAB/c nu/nu nude mice(n=11)were divided into KLF17 up-regual-tion group(n=5)and KLF17 down-regulation group(n=6).The right and left bodies of the nude mice were subcutane-ously injected with KLF17-up-/down-regulating cells and the counterpart empty vectors were used as control cells,respec-tively.The effects of KLF17 on the growth of the cell-derived xenografts in nude mice were analyzed.The mRNA and pro-tein expression levels of KLF17 in xenograft tumor tissues were analyzed by real-time PCR and immunohistochemical stai-ning,respectively.Transcriptome sequencing was used to explore the differentially expressed genes in the xenograft tumors derived from KLF17-up-regulating A549 cells,and the functions of the potential target genes were analyzed using the lung adenocarcinoma data from The Cancer Genome Atlas(TCGA)database.Gene Ontology and KEGG PATHWAY enrichment analyses were performed to analyze the functions of the differentially expressed genes and the involved signal pathways.RE-SULTS:The growth rate of KLF17-up-regulating A549 cell-derived xenograft tumors in the nude mice was significantly lower than that in empty control group(P<0.05),while the growth rate and the weight of KLF 17-down-regulating H322 cell-derived xenograft tumors in nude mice were significantly higher than those in empty control group(P<0.01 and P<0.05,respectively).In the A549 cell-derived xenograft tumor model,the KLF17 mRNA and protein were significantly in-creased in KLF17 up-regualtion group.The transcriptome sequencing showed the potential target genes regulated by KLF 17 were ras homolog family member V(RHOV)and coronin 1C(CORO1C).Ten-year cumulative survival time of the patients with lung adenocarcinoma from TCGA database was significantly different between high and low expression of RHOV and CORO1C at mRNA level.Increased expression levels of RHOV and CORO1C were correlated with short survival time in the patients with lung adnocarcinoma.The results of Gene Ontology and KEGG PATHWAY enrichment analyses indicated that the target genes(differentially expressed genes)regulated by KLF17 were related to the stimulation response,growth and adhesion of tumor cells,and participated in chemotaxis-,adhesion-and extracellular matrix receptor-related signaling path-ways.CONCLUSION:KLF17 inhibits the xenograft tumor growth in nude mice,and inhibits the oncogenes such as RHOV and CORO1C.The target genes regulated by KLF17 participate in the regulation of tumor adhesion-and growth-related sig-naling pathways.
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OBJECTIVE: To explore the immune cytotoxic effect and the maximum non-effect dose of trichloroethylene( TCE) on Jurkat T cells in vitro. METHODS: i) Naive and activated Jurkat T cells were treated with different concentrations of TCE( 0. 10, 0. 50, 1. 00, 2. 00, 5. 00, 10. 00 mmol / L). Phorbol-12-myristate-13-acetate and ionomycin were used as agonist. No TCE was used in the control group and dimethyl sulfoxide( DMSO) was used as the solvent group. The morphology of Jurkat T cells was observed using a light microscope and the survival rate of Jurkat T cells was investigated using CCK-8 essay after cells were cultured for 24,48 and 72 hours. ii) Nave and activated Jurkat T cells were treated with different concentrations of TCE( 0. 00,0. 02,0. 20,2. 00 mmol / L). The apoptosis of cells was detected using flow cytometry and the level of interleukin-2( IL-2) in supernatant was detected using enzyme linked immunosorbent assay after cells were cultured for 24,48 and 72 hours. RESULTS: i) Cytotoxic effect was observed after cells were exposed to 10. 00 mmol / L TCE for 24 hours. Cells dispersed,cell volume diminished,cell membrane ruptured,cytoplasm condensed and increased outflow of intercellular organelles. The effect of interaction between exposure dose and exposure time was statistically significant on cell survival rate( P < 0. 01). Compared with the control and DMSO groups at the same time points,there were no significant differences in the 0. 10,0. 50,1. 00 and 2. 00 mmol / L TCE treatment groups in cell survival rates in three different time points( P > 0. 05),while the cell survival rates of 5. 00 and 10. 00 mmol / L TCE treatment groups were significantly decreased( P < 0. 01). ii) When TCE concentration was 0. 00-2. 00 mmol / L,there were no significant differences in the main effect of exposure dose and interactions of between exposure dose and cell type or exposure time on cell apoptosis rate( P > 0. 05). Compared with the same time points and groups of naive Jurkat T cells,the levels of IL-2 of activated Jurkat T cells were significantly increased( P < 0. 01). In the three different time points,the level of IL-2 of activated Jurkat T cells increased in accordance with the TCE exposure dose,showing a dose-effect relationship( P < 0. 01). The level of IL-2 of activated Jurkat T cells increased in accordance with TCE exposure time,showing a time-effect relationship( P < 0. 01). CONCLUSION:s TCE at the level of 2. 00 mmol / L had no observed effect in Jurkat T cells. High doses of TCE( ≥5. 00 mmol / L) showed cytotoxic damages to naive and activated Jurkat T cells and low doses of TCE( ≤2. 00 mmol / L) could stimulate activated Jurkat T cells secrete IL-2 in a dosedependent and time-dependent manner.
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OBJECTIVE: To analyze the usage of glucocorticoid in patients who were treated with occupational medicamentose-like dermatitis due to trichloroethylene( OMDT),in order to provide a reference for regulating the glucocorticoid treatment of the disease. METHODS: Using a retrospective survey method,144 OMDT cases of patients who were diagnosed and cured by Guangdong Province Hospital for Occupational Disease Prevention and Treatment from 2001 to2013 were selected. The general information,clinical data and the use of glucocorticoid were collected and analyzed.RESULTS: i) The usage of glucocorticoid. The median and the 0th to 100 th percentile [M( P_0-P_(100)) ] of first dose of methylprednisolone was 100. 00( 40. 00-1 000. 00) mg / d; 58 patients( 40. 3%) using the first dose of treatment were ineffective. The dosage of glucocorticoid was increased one week after admission,the M( P_0-P_(100)) to an initial dose of120. 00( 40. 00-1 000. 00) mg / d; The M( P_0-P_(100)) of maintenance time of initial dose was 5. 5( 1. 0-14. 0) days. After treating effectively,should the decrement to stop using gradually the first glucocorticoid. The dose was gradually cut down to 20-50 mg every 1 to 3 days if the glucocorticoid dose was more than 100 mg / d; it was cut down to 10 mg every 2 to 3days if the glucocorticoid dose was less than 100 mg / d. The M( P_0-P_(100)) of glucocorticoid using time was 66. 0( 22. 0-229. 0) days. The M( P_0-P_(100)) of total amount of glucocorticoid was 3 510. 0( 420. 0 ~ 27 336. 3) mg. ii) The first dose of glucocorticoid in patients of erythema multiforme group were less than those of exfoliative dermatitis group and bullous epidermal necrolysis group( P < 0. 05),the initial dose and total amount of glucocorticoid were less than the other 3 types of rash( P < 0. 05). iii) Compared with the patients with severe impaired liver function,the first dose,the initial dose and the total amount of glucocorticoid were significantly higher than those in mild impaired liver function( P < 0. 05),and the time of using glucocorticoid was longer than that in mild impaired liver function( P < 0. 05). iv) The first dose and the initial dose of glucocorticoid in patients were positively correlated with the total amount of glucocorticoid [Spearmen correlation coefficient( r_S) were 0. 73 and 0. 78 respectively,P < 0. 01). The maintenance time of the initial dose of glucocorticoid was not correlation with the time of patients who were out of contact with trichloroethylene or the urinary level of trichloroacetic acid at admission( r_Swere- 0. 14 and 0. 10 respectively,P > 0. 05). v) Binary Logistic regression analysis showed that,if the patients who had no erythema multiforme,the more severe the degree of liver dysfunction or the white blood cell count higher than 9. 5 × 10~9/ L,the first dose of glucocorticoid used should be more than 120 mg / d( P <0. 05). CONCLUSION: Liver function and type of rash are important factors that affect the usage of glucocorticoid in patients with OMDT. Glucocorticoid therapy should be prescribed in reference to the liver function and skin lesion of patients with OMDT.
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OBJECTIVE: To establish the clinical pathway of chronic mild occupational cadmium poisoning,and to promote the application of clinical pathway in the treatment of occupational diseases. METHODS: Chronic mild occupational cadmium poisoning was selected as a disease for a pilot study based on GBZ 17-2015 Diagnosis of Occupational Cadmium Poisoning. The diagnosis and treatment scheme and the clinical pathway were developed based on the theory of evidencebased medicine and expert consultation. It was then used and evaluated in clinical practice in several hospitals. RESULTS: The content of clinical pathway of chronic mild occupational cadmium poisoning included the standard in-hospital treatment process protocol,the clinical pathway forms and the consent document for patients. The clinical application of the pathway significantly improved the outcome of treatment,shortened hospital stays and effectively control hospitalization expenses.CONCLUSION: The clinical pathway for chronic mild occupational cadmium poisoning is rational and feasible. The result confirms that the clinical pathway may have good application prospect for the treatment of occupational diseases.
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OBJECTIVE: To analyze the clinical features of occupational chronic toxic peripheral neuropathy caused by1-bromopropan( 1-BP). METHODS: Clinical data of 4 patients who suffered from occupational chronic toxic peripheral neuropathy caused by 1-BP were collected for retrospective analysis. RESULTS: The 4 male patients were ultrasonic cleaning operation workers in a hardware vacuum coating enterprise. They were exposed to high levels of 1-BP for 9-11 months. The main clinical manifestations were varying degrees of sensory disorder and dyskinesia. The main symptoms were progressive increase of numbness and fatigue in the lower extremities. These symptoms might be accompanied by unsteady gait.Physical examination showed muscle strength weakness in the double lower limbs. The hypalgesia,pselaphesia,topesthesia and pallesthesia decreased in the double lower limbs or 4 limbs. The bilateral achilles tendon reflex mainly showed reduced or disappeared. One case had sensory ataxia. Electroneuromyography examination showed different levels of peripheral nerve damage among the cases. The motor nerve conduction velocity and sensory nerve conduction velocity reduced commonly. The axon and myelin sheath damage were visible. On the basis of GBZ / T 247-2013 Diagnosis of Occupational Chronic Toxic Peripheral Neuropathy Caused by Chemicals,these cases were diagnosed as occupational chronic toxic peripheral neuropathy caused by 1-BP. CONCLUSION: Long-term exposure to high level 1-BP can lead to chronic poisoning with peripheral nervous system damage. The diagnosis can be made based on the 1-BP exposure history,clinical features and the neurogenic damage found in electroneuromyography examination.
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OBJECTIVE: To observe whether bone marrow mesenchymal stem cell( BMMSC) could be induced by alveolar epithelial cell( AEC) of rats exposed to silica dust or not. METHODS: BMMSCs were isolated and cultivated from 6specific pathogen free healthy male SD rats through bone marrow adherent method. The AECs from other 6 rats randomly selected from the same batch were cultivated by immune adherent purification method. Three rats were treated with 1. 0 m L( 40 g/L mass concentration) of silicosis dust suspension by one time intratracheal injection as silicosis dust exposure model,and the other 3 rats were given 0. 9% sodium chloride solution as normal. Experimental group was the co-culture of BMMSCs and AECs from silicosis dust exposure rats. Control group A was the co-culture of BMMSCs and AECs from normal rats. Control group B was the culture of BMMSCs alone. The morphology changes were observed by the inverted phase contrast microscope at the time points of the 4th and the 8th day. Double immunofluorescence staining using aquaporin 5( AQP5) and surfactant protein C( SP-C) was performed on the treated BMMSCs. The fluorescence staining was observed using the inverted fluorescence microscope( IFM) and laser scanning confocal microscope( LSCM). Integral optical density( IOD) analysis was conducted on fluorescence of 2 kinds of proteins by Image-pro plus 6. 0 graphic analysis software. RESULTS: After the co-culture,the BMMSCs in experimental group and control group A changed from long spindle shape to cubic and polygonal shape,the variation of morphology on day 8 was more obvious than that on day 4,and the change in control group A was less obvious than that of experimental group. There was no obvious morphology change in BMMSCs of control group B. By IFM and LSCM,on day 4 and day 8,the expression of green fluorescence AQP5 and red fluorescence SP-C were all observed in BMMSCs of experimental group and control group A. The BMMSCs of control group B only showed a little green fluorescence expression of AQP5,no expression of red SP-C fluorescence was seen. Both by IFM and LSCM,on day 4 and day 8,the 2 kinds of IOD of BMMSCs in experiment group were higher than those of control group A and B at the same time points( P < 0. 01); the IOD of control group A was higher than that of control group B at the same time point( P < 0. 01). The IOD of experiment group and control group A on day 8 were higher than those on day4 in the same group( P < 0. 01). CONCLUSION: AEC of rats exposed to silica dust can effectively induce BMMSC to be differentiated into AEC.
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Objective To evaluate the intraoperative opioid-sparing effect of different frequency transcutaneous electrical acupoint stimulation (TEAS) in the patients undergoing video-assisted thoracoscopic pneumonectomy.Methods Eighty patients,aged 40-64 yr,weighing 50-90 kg,of ASA physical status Ⅰ-Ⅲ,scheduled for elective thoracoscopic pneumonectomy under general anesthesia,were randomly divided into 4 groups (n =20 each) using a random number table:control group (group Con),stimulation on Lieque (LU7)-Quchi (LI11)-Neiguan (PC6)-Hegu (LI4) at 2/100 Hz group (group 2/100 Hz),stimulation on LU7-LI11-PC6-LI4 at 2 Hz group (group 2 Hz),and stimulation on LU7-LI1 1-PC6-LI4 at 100 Hz group (group 100 Hz).The patients in group Con had the electrodes applied,but received no stimulation.In 2/100 Hz,2 Hz and 100 Hz groups,the patients received 2/100,2 and 100 Hz TEAS on LU7-LI11-PC6-LI4 acupoints ipsilateral to the surgery site,respectively,starting from 30 min before induction of anesthesia until the end of surgery,and the intensity was the maximum current that could be tolerated.Anesthesia was induced with iv midazolam,propofol,sufentanil and cisatracurim,and maintained with target-controlled infusion of remifentanil and propofol,continuous infusion of cisatracurim,and iv boluses of sufentanil when necessary.The target plasma concentration of propofol was adjusted to maintain BIS value at 40-60 during operation.The initial target effect-site concentration of remifentanil was 1 ng/ml,and adjusted to 4 ng/ml at skin incision.The concentration of remifentanil and consumption of sufentanil were adjusted to maintain Analgesia Nociception Index (ANI) at 50-70.When the concentration of remifentanil was increased to 4 ng/ml,ANI was still less than 50,and then 0.1 μg/kg sufentanil was given.The duration of operation and intraoperative consumption of remifentanil and sufentanil (the consumption of sufentanil was converted to the consumption of remifentanil producing the equivalent effect by 1:10) were recorded.Results The intraoperative consumption of remifentanil was significantly reduced in 2/100 Hz group as compared with Con,2 Hz and 100 Hz groups.There was no significant difference in the intraoperative consumption of remifentanil between Con group,2 Hz group and 100 Hz group.Conclusion The use of 2/100 Hz but not 2 and 100 Hz TEAS on LU7-LI11-PC6-LI4 significantly reduces intraoperative opioid consumption in the patients undergoing video-assisted thoracoscopic pneumonectomy.