OBJECTIVETo analyze the relationship between metabolites of polycyclic aromatic hydrocarbons (PAHs) and serum uric acid levels in coke oven workers and to provide new clues to the pathogenic mechanism of PAHs.

METHODSA total of 1302 coke oven workers were divided into four groups, namely control group and low-, intermediate-, and high-dose exposure groups. The concentrations of ambient PAHs at each workplace were determined by high-performance liquid chromatography. The detailed information on the occupational history and health of workers was collected by questionnaire survey and physical examination, and so were their blood and urine samples. Serum uric acid and creatinine levels were measured using a Hitachi 7020 automatic biochemical analyzer. Ten urinary PAH metabolites were detected by gas chromatography-mass spectrometry.

RESULTSSerum uric acid levels were the highest in the high-dose exposure group, followed by the intermediate- and low-dose exposure groups, and were the lowest in the control group. There were significant correlations between serum uric acid levels and the quartiles of 1-hydroxynaphthalene and 1-hydroxyphenanthrene (P < 0.05). After adjustment for PAH metabolite-related relationship, only urinary 1-hydroxyphenanthrene was significantly correlated with serum uric acid levels (P = 0.001). After adjustment for confounding factors and using the 1st quartile of 1-hydroxyphenanthrene as a reference, the odds ratio for hyperuricemia in subjects with the 2nd, 3rd, and 4th quartiles of 1-hydroxyphenanthrene were 1.55, 1.57, and 2.35, respectively.

CONCLUSIONUrinary 1-hydroxyphenanthrene is associated with a dose-response increase in serum uric acid levels in coke oven workers, and exposure to phenanthrene in PAHs may be a risk factor for hyperuricemia.

Adult ; Coke ; Humans ; Male ; Occupational Exposure ; Polycyclic Aromatic Hydrocarbons ; urine ; Uric Acid ; blood

OBJECTIVETo analyze the relationship between metabolites of polycyclic aromatic hydrocarbons (PAHs) and lung function in coke oven workers, and to provide scientific basis for further exploring the potential mechanism and developing the preventing strategies of the workers' early lung damage.

METHODSWe measured carbon monoxide, sulfur dioxide, benzene soluble matter, particulate matters, and PAHs at different workplaces of a coke oven plant. Detailed information on demography and occupational health condition of 912 workers were collected. We divided these workers into control group and coke oven group according to their workplaces and the different concentrations of COEs in the environment. We detected 10 urinary PAH metabolites and lung function using gas chromatography-mass spectrometry and spirometric tests, respectively.

RESULTSFEV(1.0) (91.12 ± 13.31) and FEV(1.0)/FVC (108.61 ± 20.37) of the coke oven group is significantly lower than the control group (94.16 ± 15.57, 113.45 ± 19.70). In the coke oven group, the hydroxyphenanthrene and 1-hydroxypyrene are negatively correlated with FEV(1.0)/FVC (β = -0.136, β = -0.100), Ptrend < 0.05 for all.

CONCLUSIONThe dose response decrease of lung function is associated with the urinary PAH metabolites in coke oven workers. Indicated that the long exposure to PAHs may cause the early lung damage in coke oven workers, phenanthrene and pyrene may be the main factors.

Adult ; Air Pollutants, Occupational ; urine ; Coke ; Humans ; Lung ; physiopathology ; Male ; Middle Aged ; Occupational Exposure ; analysis ; Phenanthrenes ; urine ; Polycyclic Aromatic Hydrocarbons ; urine ; Pyrenes ; urine ; Respiratory Function Tests

BACKGROUNDThe mechanism of the neural injury caused by chronic intermittent hypoxia (CIH) that characterizes obstructive sleep apnea syndrome (OSAS) is not clearly known. The purpose of this study was to investigate whether P2X7 receptor (P2X7R) is responsible for the CIH-induced neural injury and the possible pathway it involves.

METHODSEight-week-old male C57BL/6 mice were used. For each exposure time point, eight mice divided in room air (RA) and IH group were assigned to the study of P2X7R expression. Whereas in the 21 days-Brilliant Blue G (BBG, a selective P2X7R antagonist) study, 48 mice were randomly divided into CIH group, BBG-treated CIH group, RA group and BBG-treated RA group. The hippocampus P2X7R expression was determined by Western blotting and real-time polymerase chain reaction (PCR). The spatial learning was analyzed by Morris water maze. The nuclear factor kappa B (NFκB) and NADPH oxidase 2 (NOX2) expressions were analyzed by Western blotting. The expressions of tumor necrosis factor α, interleukin 1β (IL-β), IL-18, and IL-6 were measured by real-time PCR. The malondialdehyde and superoxide dismutase levels were detected by colorimetric method. Cell damage was evaluated by Hematoxylin and Eosin staining and Terminal Transferase dUTP Nick-end Labeling method.

RESULTSThe P2X7R mRNA was elevated and sustained after 3-day IH exposure and the P2X7R protein was elevated and sustained after 7-day IH exposure. In the BBG study, the CIH mice showed severer neuronal cell damage and poorer performance in the behavior test. The increased NFκB and NOX2 expressions along with the inflammation injury and oxidative stress were also observed in the CIH group. BBG alleviated CIH-induced neural injury and consequent functional deficits.

CONCLUSIONSThe P2X7R antagonism attenuates the CIH-induced neuroinflammation, oxidative stress, and spatial deficits, demonstrating that the P2X7R is an important therapeutic target in the cognition deficits accompanied OSAS.

Animals ; Disease Models, Animal ; Hypoxia ; Male ; Metabolic Networks and Pathways ; Mice ; Mice, Inbred C57BL ; Purinergic P2 Receptor Antagonists ; pharmacology ; Receptors, Purinergic P2X7 ; analysis ; physiology ; Rosaniline Dyes ; pharmacology ; Sleep Apnea, Obstructive ; metabolism

AIM:To explore the effects of CD38 on lysosome reformation and cholesterol efflux in macro-phages.METHODS:Bone marrow-derived macrophages from low-density lipoprotein(LDL)receptor knockout(LDLr-/-)mice were cultured as cell model.Live cell imaging system was applied to evaluate the effect of nicotinic acid adenine di-nucleotide phosphate(NAADP)on lysosome number.ELISA was conducted to measure NAADP level in macrophages.After the cells were treated with nicotinic acid(NA),RT-qPCR was conducted to detect CD38 mRNA expression,and Western blot was conducted to observe CD38 protein expression and phosphorylated transcription factor EB(TFEB)level.Laser scanning confocal microscopy was applied to evaluate the influence of CD38/NAADP signaling on lysosome number and cholesterol egression.RESULTS:NAADP remarkably increased lysosome number(P<0.05),and this effect was significantly inhibited by NAADP antagonist NED-19,Ca2+ chelator BAPTA,and calcineurin inhibitor CsA(P<0.05).CD38 markedly enhanced NAADP synthesis in macrophages(P<0.05).NAADP synthetic substrate NA prominently ele-vated the expression of CD38 mRNA and protein(P<0.05).NA significantly decreased the phosphorylated TFEB level;this effect was also attenuated by NED-19,BAPTA and CsA(P<0.05).Disrupting CD38/NAADP signaling pathway markedly inhibited NA-induced enhancement of lysosome number,lysosomal free cholesterol and cytosol cholesterol ester efflux in macrophages(P<0.05).NA-induced enhancement of lysosome number,lysosomal free cholesterol and cytosol cholesterol ester efflux abolished in LDLr/CD38 DKO macrophages(P<0.05),whereas these effects induced by NA were recovered after CD38 gene rescue.CONCLUSION:CD38 triggers lysosome reformation via TFEB and consequently pro-motes the efflux of lysosomal free cholesterol and cytosol cholesterol ester.

Objective To evaluate the clinical application value of a novel immobilization system in total marrow irradiation ( TMI) with MVCT image. Methods From 2016 to 2017, a retrospective analysis of the setup errors of 22 patients receiving TMI in two groups ( twelve patients were immobilized with the novel immobilization system in group 1, ten patients were immobilized with the combinatorial immobilization devices in group 2) was performed in this study on Zhongnan Hospital of Wuhan University. Two-sample t-test was used to analyze the differences of setup errors and the consistency of setup between two groups. Results In group 1, the setup errors on left-right, superior-inferior, anterior-posterior and rotation directions were ( 1.06±0.79) , ( 1.34±0.66) , ( 2.45±1.48) mm and ( 0.63°±0.65°) for the head and neck position, ( 1.58±1.13) , ( 2.38±1.99) , ( 2.05± 1.68) mm and ( 0.31°± 0.32°) for the chest position, ( 1.67± 1.24) , ( 3.88±2.20) , ( 1.96± 1.32) mm and ( 0.48°± 0.53°) for the pelvis position, and ( 0.95± 0.73) , ( 1.99± 1.35) , ( 3.66±2.13) mm and ( 0.24°±0.31°) for the lower limb, respectively. In group 2, the setup errors were ( 2.59±2.58) , ( 3.28±1.85) , ( 3.71±2.43) mm and ( 1.15°±1.18°) for the head and neck position, ( 4.38±3.69) , ( 5.64±3.78) , ( 2.72± 1.91) mm and ( 1.55°± 0.86°) for the chest position, ( 4.14± 2.97) , ( 6.97±3.68) , ( 2.21±2.26) mm and ( 1.23°±0.74°) for the pelvis position, ( 2.28± 1.15) , ( 5.97± 3.00) , ( 3.44±1.93) mm and ( 1.09°±0.94°) for the lower limb, respectively. The setup errors significantly differed between two groups on the left-right, superior-inferior and rotation directions for all positions ( all P<0.05) . The setup consistency significantly differed between two groups on the left-right, superior-inferior and rotation directions for the chest and pelvis positions ( all P<0.05) . Conclusion The novel immobilization system can significantly improve the setup accuracy and setup consistency, and enhance the precision of treatment for patients.

Objective:To establish the fingerprint of standard decoction of Citri Reticulatae Pericarpium and evaluate its quality. Method:According to the preparation conditions of the standard decoction,15 batches of standard decoction of Citri Reticulatae Pericarpium were prepared.HPLC was employed to determine the content of hesperidin in this standard decoction.Ultraviolet spectroscopy(UV) and infrared spectroscopy(IR) were used to establish the fingerprint of standard decoction of Citri Reticulatae Pericarpium.The correlation coefficient method and double index sequence analysis method were used to compare and analyze the spectra of different batches of this standard decoction. Result:The content of hesperidin in 15 batches of this standard decoction were 0.82%-2.60%,and the measured value of dry extract rate was 32.02%-46.11%.Compared with ultraviolet and infrared control fingerprint,the fingerprint similarities of the standard decoction of each batch were > 0.897 and > 0.942,respectively.The double index analysis results showed that the common peak ratio was more than 62.50%,variation peak ratio was less than 46.67%. Conclusion:The quality evaluation method established in this study can be used for systematic evaluation of standard decoction of Citri Reticulatae Pericarpium,and it can provide theoretical reference for the formulation of quality standard of Citri Reticulatae Pericarpium dispensing granules and other related preparations.

OBJECTIVE: To investigate the therapeutic effects of total saponins from Panax notognseng (PNS) combined with cyclophosphamide (CTX) in mice bearing hepatocellular carcinoma H₂₂ cell xenograft. METHODS: We examined the effects of treatment with different concentrations of PNS on H₂₂ cell proliferation for 24 to 72 h in vitro using CCK8 colorimetric assay. Annexin V/PI double fluorescence staining was used to detect the effect of PNS on apoptosis of H₂₂ cells. Mouse models bearing H₂₂ cell xenograft were established and treated with CTX (25 mg/kg), PNS (120, 240 or 480 mg/kg), alone or in combinations. After treatments for consecutive 10 days, the mice were euthanized for examinations of carbon clearance ability of the monocytes and macrophages, splenic lymphocyte proliferation, tumor necrosis factor (TNF-α), interleukin-2 (IL-2), serum hemolysin antibody level, blood indicators, and the tumor inhibition rate. RESULTS: Treatment with PNS concentration-dependently inhibited the proliferation and significantly promoted apoptosis of cultured H₂₂ cells (P < 0.01). In the tumor-bearing mouse models, PNS alone and its combination with CTX both resulted in obvious enhancement of phagocytosis of the monocyte-macrophages, stimulated the proliferation of splenic lymphocytes, promoted the release of TNF-α and IL-2 and the production of serum hemolysin antibody, and increased the number of white blood cells, red blood cells and lymphocytes in the peripheral blood. Treatment with 480 mg/kg PNS combined with CTX resulted in a tumor inhibition rate of 83.28% (P < 0.01) and a life prolonging rate of 131.25% in the mouse models (P < 0.05). CONCLUSION PNS alone or in combination with CTX can improve the immunity and tumor inhibition rate and prolong the survival time of H₂₂ tumor-bearing mice.
Animals ; Carcinoma, Hepatocellular/pathology* ; Cyclophosphamide/therapeutic use* ; Hemolysin Proteins ; Heterografts ; Humans ; Interleukin-2 ; Liver Neoplasms/pathology* ; Mice ; Panax notoginseng ; Saponins/therapeutic use* ; Tumor Necrosis Factor-alpha

Numerous randomised controlled trials have suggested the positive effects of acupuncture on chronic obstructive pulmonary disease (COPD). However, the underlying therapeutic mechanisms of acupuncture for COPD have not been clearly summarized yet. Inflammation is central to the development of COPD. In this review, we elucidate the effects and underlying mechanisms of acupuncture from an anti-inflammatory perspective based on animal studies. Cigarette smoke combined with lipopolysaccharide is often used to establish animal models of COPD. Electroacupuncture can be an effective intervention to improve inflammation in COPD, and Feishu (BL13) and Zusanli (ST36) can be used as basic acupoints in COPD animal models. Different acupuncture types can regulate different types of inflammatory cytokines; meanwhile, different acupuncture types and acupoint options have similar effects on modulating the level of inflammatory cytokines. In particular, acupuncture exerts anti-inflammatory effects by inhibiting the release of inflammatory cells, inflammasomes and inflammatory cytokines. The main underlying mechanism through which acupuncture improves inflammation in COPD is the modulation of relevant signalling pathways: nuclear factor-κB (NF-κB) (e.g., myeloid differentiation primary response 88/NF-κB, toll-like receptor-4/NF-κB, silent information regulator transcript-1/NF-κB), mitogen-activated protein kinase signalling pathways (extracellular signal-regulated kinase 1/2, p38 and c-Jun NH2-terminal kinase), cholinergic anti-inflammatory pathway, and dopamine D2 receptor pathway. The current synthesis will be beneficial for further research on the effect of acupuncture on COPD inflammation. Please cite this article as: Jiang LH, Li PJ, Wang YQ, Jiang ML, Han XY, Bao YD, Deng XL, Wu WB, Liu XD. Anti-inflammatory effects of acupuncture in the treatment of chronic obstructive pulmonary disease. J Integr Med. 2023; 21(6): 518-527.
Animals ; NF-kappa B/metabolism* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Acupuncture Therapy ; Cytokines ; Disease Models, Animal ; Inflammation/therapy*

Aim To use microdialysis technology combined with ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) technology to study the effect of Achyranthes bidentata saponins (ABS) on rheumatoid arthritis (RA) and its mechanisms. Methods SD rats were randomly divided into adjuvant arthritis (AA) model group, blank control group and ABS administration group. AA rat model was induced by Freund's complete adjuvant. UPLC-Q-TOF/MS was used to collect joint cavity microdialysis fluid sample information of each group of rats. Results On 6th day after administration of ABS, an inhibitory effect on the paw swelling, improved the arthritis score (P < 0. 05), and better the pathological morphology of the synovial tissues were found in AA rats. Nineteen potential biomarkers were discovered and identified. Pathway enrichment analysis revealed that they mainly involved purine metabolism, pyrimidine metabolism, fatty acid biosynthesis and steroid hormone biosynthesis pathway. Conclusions Microdialysis combined with metabolomics can reveal the metabolic mechanism of ABS intervention on RA, laying a foundation for further study of the mechanism of ABS.