OBJECTIVES: To investigate the therapeutic mechanism of 2,6-dimethoxy-1,4-benzoquinone (DMQ) for alleviating dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. METHODS: Eighteen male C57BL/6J mice were equally randomized into control group, DSS group and DMQ treatment group. In DSS and DMQ groups, the mice were treated with DSS in drinking water to induce UC, and received intraperitoneal injections of sterile PBS or DMQ (20 mg/kg) during modeling. The changes in body weight, disease activity index (DAI), colon length, spleen weight, and colon histological scores of the mice were examined, and the percentages of Th17 and IFN-γ⁺ CD8⁺ T cells in the mesenteric lymph nodes and spleen were analyzed using flow cytometry. The expressions of tight junction proteins (Occludin and ZO-1), proteins associated with inflammasome activation (caspase-1 and p20), IL-1β and TNF-α in the colon tissues were detected using Western blotting or ELISA. In the cell experiment, mouse bone marrow-derived macrophages (BMDMs) primed with lipopolysaccharide (LPS) were treated with DMQ, followed by stmulation with nigericin to activate the classical NLRP3 inflammasome pathway. In cultured human peripheral blood mononuclear cells (PBMCs) treated with either LPS alone or LPS plus nigericin, the effects of DMQ on inflammasome activation, pyroptosis, and cytokine release were evaluated via Western blotting, ELISA, and flow cytometry. RESULTS: In DSS-treated mice, DMQ treatment significantly alleviated DSS-induced body weight loss, colon shortening, spleen enlargement, and colon inflammation. The DMQ-treated mice showed significantly reduced percentages of Th17 cells and IFN-γ⁺ CD8⁺ T cells in the mesenteric lymph nodes and spleen, with increased occludin and ZO-1 expressions and decreased caspase-1 expression in the colon tissue. DMQ obviously inhibited classical NLRP3 inflammasome activation in mouse BMDMs and both the classical and alternative pathways of NLRP3 activation in human PBMCs, causing also suppression of caspase-1-dependent pyroptosis. CONCLUSIONS DMQ ameliorates DSS-induced UC in mice by inhibiting NLRP3 inflammasome activation.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Mice, Inbred C57BL ; Colitis, Ulcerative/metabolism* ; Dextran Sulfate/adverse effects* ; Male ; Inflammasomes/metabolism* ; Mice ; Benzoquinones/therapeutic use* ; Th17 Cells ; Caspase 1/metabolism*

Objective To investigate the mechanism of 2,6-dimethoxy-1,4-benzoquinone(DMQ),an active ingredients in fermented wheat germ extract,for inhibiting NLRP3 inflammasome activation and alleviating septic shock in mice.Methods Cultured murine bone marrow-derived macrophages(BMDM)stimulated with lipopolysaccharide(LPS)were treated with DMQ,followed by treatment with Nigericin,ATP,and MSU for activating the canonical NLRP3 inflammasome;the non-canonical NLRP3 inflammasome was activated by intracellular transfection of LPS,and AIM2 inflammasome was activated using Poly A:T.In human monocytic THP-1 cells,the effect of Nigericin on inflammasome activation products was examined using Western blotting and ELISA.Co-immunoprecipitation was performed to explore the mechanism of DMQ-induced blocking of NLRP3 inflammasome activation.In a male C57BL/6J mouse model of LPS-induced septic shock treated with 20 and 40 mg/kg DMQ,the levels of IL-1β and TNF-α in the serum and peritoneal lavage fluid were determined using ELISA,and the survival time of the mice within 36 h was observed.Results Treatment with DMQ effectively inhibited LPS-induced activation of canonical NLRP3 inflammasome in mouse BMDM and human THP-1 cells and also inhibited non-canonical NLRP3 inflammasome activation in mouse BMDM,but produced no significant effect on AIM2 inflammasome activation.DMQ significantly blocked the binding between ASC and NLRP3.In the mouse models of septic shock,DMQ treatment significantly reduced the levels of IL-1β in the serum and peritoneal fluid and obviously prolonged survival time of the mice.Conclusion DMQ can effectively block ASC-NLRP3 interaction to inhibit NLRP3 inflammasome activation and alleviate LPS-induced septic shock in mice.

Objective To investigate the mechanism of 2,6-dimethoxy-1,4-benzoquinone(DMQ),an active ingredients in fermented wheat germ extract,for inhibiting NLRP3 inflammasome activation and alleviating septic shock in mice.Methods Cultured murine bone marrow-derived macrophages(BMDM)stimulated with lipopolysaccharide(LPS)were treated with DMQ,followed by treatment with Nigericin,ATP,and MSU for activating the canonical NLRP3 inflammasome;the non-canonical NLRP3 inflammasome was activated by intracellular transfection of LPS,and AIM2 inflammasome was activated using Poly A:T.In human monocytic THP-1 cells,the effect of Nigericin on inflammasome activation products was examined using Western blotting and ELISA.Co-immunoprecipitation was performed to explore the mechanism of DMQ-induced blocking of NLRP3 inflammasome activation.In a male C57BL/6J mouse model of LPS-induced septic shock treated with 20 and 40 mg/kg DMQ,the levels of IL-1β and TNF-α in the serum and peritoneal lavage fluid were determined using ELISA,and the survival time of the mice within 36 h was observed.Results Treatment with DMQ effectively inhibited LPS-induced activation of canonical NLRP3 inflammasome in mouse BMDM and human THP-1 cells and also inhibited non-canonical NLRP3 inflammasome activation in mouse BMDM,but produced no significant effect on AIM2 inflammasome activation.DMQ significantly blocked the binding between ASC and NLRP3.In the mouse models of septic shock,DMQ treatment significantly reduced the levels of IL-1β in the serum and peritoneal fluid and obviously prolonged survival time of the mice.Conclusion DMQ can effectively block ASC-NLRP3 interaction to inhibit NLRP3 inflammasome activation and alleviate LPS-induced septic shock in mice.

BACKGROUND: Weather conditions are a possible contributing factor to age-related macular degeneration (AMD), a leading cause of irreversible loss of vision. The present study evaluated the joint effects of meteorological factors and fine particulate matter (PM_2.5) on AMD. METHODS: Data was extracted from a national cross-sectional survey conducted across 10 provinces in rural China. A total of 36,081 participants aged 40 and older were recruited. AMD was diagnosed clinically by slit-lamp ophthalmoscopy, fundus photography, and spectral domain optical coherence tomography (OCT). Meteorological data were calculated by European Centre for Medium-Range Weather Forecasts (ECMWF) reanalysis and were matched to participants' home addresses by latitude and longitude. Participants' individual PM_2.5 exposure concentrations were calculated by a satellite-based model at a 1-km resolution level. Multivariable-adjusted logistic regression models paired with interaction analysis were performed to investigate the joint effects of meteorological factors and PM_2.5 on AMD. RESULTS: The prevalence of AMD in the study population was 2.6% (95% CI 2.42-2.76%). The average annual PM_2.5 level during the study period was 63.1 ± 15.3 µg/m³. A significant positive association was detected between AMD and PM_2.5 level, temperature (T), and relative humidity (RH), in both the independent and the combined effect models. For PM_2.5, compared with the lowest quartile, the odds ratios (ORs) with 95% confidence intervals (CIs) across increasing quartiles were 0.828 (0.674,1.018), 1.105 (0.799,1.528), and 2.602 (1.516,4.468). Positive associations were observed between AMD and temperature, with ORs (95% CI) of 1.625 (1.059,2.494), 1.619 (1.026,2.553), and 3.276 (1.841,5.830), across increasing quartiles. In the interaction analysis, the estimated relative excess risk due to interaction (RERI) and the attributable proportion (AP) for combined atmospheric pressure and PM_2.5 was 0.864 (0.586,1.141) and 1.180 (0.768,1.592), respectively, indicating a synergistic effect between PM_2.5 and atmospheric pressure. CONCLUSIONS This study is among the first to characterize the coordinated effects of meteorological factors and PM_2.5 on AMD. The findings warrant further investigation to elucidate the relationship between ambient environment and AMD.
Humans ; Adult ; Middle Aged ; Cross-Sectional Studies ; Air Pollutants/analysis* ; Particulate Matter/analysis* ; China/epidemiology* ; Macular Degeneration/etiology* ; Meteorological Concepts

Objective:To explore the clinical effects of combined medial and lateral approaches in treating of calcaneal fractures combined with sustentaculum tali fractures and/or dislocations of sustentaculum tali-talus joint.Methods:Four adult cadaver specimens (8 feet) were selected, of which two (4 feet) were dissected on the medial side of the calcaneus to observe the adjacency and exposure range of sustentaculum tali. The other two specimens were simulated as medial and lateral approaches to reduce and fix calcaneal fractures. Retrospective analysis of 9 cases (9 feet) of Sanders II-IV type calcaneal fractures with combined medial and lateral approaches in the treatment of fractures and/or dislocations of sustentaculum tali-talus joint was performed. The average age was 49.9±11.3 (25-58) years. During the operation, the medial incision was made first, and the sustentaculum tali fracture was temporarily reduced and fixed to the talus. Then the lateral incision was made to expose the lateral side of the calcaneus, and the fracture fragments were reduced and fixed; the sustentaculum tali was fixed laterally with screws, and 2 cases were additionally fixed medially with absorbable rods. At the same time, six cases (8 feet) of calcaneal fractures with sustentaculum tali fractures and/or dislocations of sustentaculum tali-talus were treated with lateral approach as a control group. The lateral sides of both groups were fixed with calcaneal locking plate and implanted with demineralized bone matrix into the cavity after articular surface reduction. The B?hler and Gissane angles of the two groups of patients were measured at 1 year after operation. The American Orthopaedic Foot and Ankle Society (AOFAS) scoring system was used to evaluate the clinical efficacy.Results:The sustentaculum tali-talus joint had a shape of an inverted "V" with two divided parts. The tip of the sustentaculum tali was exposed through the front window of the posterior tibial tendon. The sustentaculum tali and the medial side of the calcaneal body was completely exposed and fixed through the window between the posterior tibial tendon and the flexor digitorum longus tendon. The postoperative incision blood loss in the combined medial and lateral approach group was 73.6±4.3 ml, which was greater than that in the lateral approach group (70.6±7.1 ml) ( t=2.18, P=0.045). The lateral incision healed in both groups. The medial incision healed delayed in 1 patient in the combined medial and lateral approach group. The fractures in the combined medial-lateral approach group and the lateral approach group were both healed. The healing duration was 12.2±2.1 weeks and 12.8±2.8 weeks, respectively, without significant difference ( t=0.50, P=0.622). The B?hler angles of the combined medial-lateral approach group and the lateral approach group were 37.0°±5.7° and 27.9°±4.0° at 1 year after operation, respectively. These values were greater than the preoperative values of 4.7°±3.4° and 3.9°±2.9° ( P<0.05), with significant difference between groups ( t=3.76, P=0.002). The Gissane angles were 133.2°±9.8° and 139.1°±9.4° respectively, which were lower than those of 172°±7.3° and 175.6°±5.6° before operation ( P<0.05). There was no significant difference between the groups ( t=1.26, P=0.226). The AOFAS score of the combined medial and lateral approach group was 93.6±4.0 points, which was higher than that of the lateral approach group (84.3±8.2 points) ( t=3.03, P=0.008). Conclusion:Intra-articular calcaneal fractures combined with a high probability of sustentaculum tali fractures and/or dislocations of sustentaculum tali-talus joint. Compared with the simple lateral approach, the use of the combined medial-lateral approach and the medial-lateral surgical sequence is beneficial to restore the calcaneal alignment and anatomic shape, especially the alignment relationship of the medial calcaneus and talus, so as to obstain better early clinical outcomes.

Objective To explore the new way of administration and clinical effect of botulinum toxin A in the treatment of focal hyperhidrosis.Methods The clinical efficacy was observed in 132 sites of 28 patients with focal hyperhidrosis,and the degree and range of focal hyperhidrosis were determined by the minor iodine-starch test.50 U of botulinum toxin A was injected in unilateral axillary,palms and soles with BellaVita instrument and 30 U for forehead.Each patient was followed-up in 1 week,2 weeks and every month after injection for 8 months.According to the results of the minor iodine-starch test the objective effect and evaluation score were obtained,and the comprehensive effect evaluation score was calculated with the objective effect evaluation score and the subjective effect evaluation score in each follow-up.Results The comprehensive effect evaluation score before injection of botulinum toxin A was 1.34±3.94,and that after injection was 23.21±9.44 for 1 week,92.41±11.95 for 1 month,98.21±5.60 for 2 months,95.98±5.94 for 3 months,and 86.61±10.17 for 4 months,respectively.Compared with that before injection,the difference was statistically significant (P ＜0.05).The effect decreased slowly after 4 months of injection,and the efficacy was maintained for 8 months (4.46±6.98);compared with that before injection,the difference of the clinical efficacy was not statistically significant (P ＞0.05).Based on the comprehensive effect evaluation scores,the differ ence of the clinical efficacy was not statistically significant between 1 week and 6 months after injection (P＞0.05).Conclusions The clinical effect of botulinum toxin A injected by BellaVita is prompt and effective for focal hyperhidrosis.

Objective:To establish a method for the determination of trace nickel in agomelatine. Methods:An inductive coupled plasma atomic emission spectrometry method was applied in the determination at 221. 648 nm. The sample solution was prepared by the ignited residue of agomelatine. The content of nickel was determined using the standard curve. Results:The linear range was 0. 025-1. 000 μg·ml-1(r=0. 999 8). The RSD of precision was 0. 63%. The detection limit was 0. 000 8μg·ml-1. The quantitative limit was 0. 003μg·ml-1 . The average recovery was 99. 4% with RSD of 2. 20%. The RSD of repeatability was 1. 33%. Conclusion:The method is simple, sensitive and accurate in the determination of trace nickel in agomelatine.

Objective To explore the regular progressive pattern of nontraumatic osteonecrosis of the femoral head (ONFH) in order to establish the reliable and convenient new classification of ONFH.Methods The coronal section of the femoral head was divided into three pillars (medial,central and lateral).The mid-coronal section of the femoral head on MRI was selected.The China-Japan Friendship Hospital (CJFH)classification of ONFH was established according to the site of necrotic focus in three pillars.A total of 153hips with ONFH were classified according to CJFH classification and Japanese Investigation Committee (JIC)classification,respectively.The collapse rate was observed and compared between both classifications of ONFH.Results The CJFH classification for ONFH consists of 3 types:type A,the medial pillar was involved; type B,the medial and central pillars were involved; type C,the lateral pillar was involved.According to site of necrosis focus in the lateral pillar,the type C was divided into 3 types:C1,there pillars were involved but there still was some normal tissue in lateral pillar;,C2,partial central pillar and all lateral pillar were involved; C3,the whole femoral head was involved.The natural history of the ONFH showed the collapse rate of type C2 and C3 in CJFH classification (95.3％) was higher than that (72.3％) of type C2 in JIC classification.Conclusion The CJFH classification of ONFH based on three pillars is more sensitive than JIC classification in predicting collapse of the femoral head.Moreover,the CJFH classification is convenient to use.

OBJECTIVE: To investigate the expression and clinical pathological significance of PDCD4 in laryngocarcinoma tissue and its potential significance to clinic. METHOD: Western-blotting and immunohistochemistry ana lyse to measure the protein expression of PDCD4 in 54 cases of laryngocarcinoma tissues (studying group) and their paraneoplastic normal tissues (control group). The correlations of PDCD4 with clinical pathological parameters were analyzed. RESULT: PDCD4 protein was positively expressed in paraneoplastic normal tissue while which was lost or decreased in laryngocarcinoma tissue by Western blot and immunohistochemistry. Immunohistochemistry assay showed the location of PDCD4 protein in cells was different between the studying group and the control group. The expression level of PDCD4 was related to the pathological grades of the laryngocarcinoma. It's higher in the well-differentiated tumor group than that in the poorly differentiated ones. But the expressions of PDCD4 were no differences among other clinical parameters including sex, age, clinical classification, clinical stage and the cervical lymphonodus who had been metastases or not. CONCLUSION PDCD4 gene is anti-oncogene. It may play an important role in the pathogenesis and development of laryngeal carcinoma and it may be a new target of therapy for laryngo carcinoma.
Adult ; Aged ; Aged, 80 and over ; Apoptosis Regulatory Proteins ; metabolism ; Female ; Genes, Tumor Suppressor ; Humans ; Immunohistochemistry ; Laryngeal Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; RNA-Binding Proteins ; metabolism

Objective To study the developmental process of the region of basal nuclei of postmortem fetuses by 3.0 T and 7.0 T MRI.Methods One hundred and thirty-one postmortem fetuses of 14 to 40 weeks of gestational age(GA)were scanned by 3.0 T MR,of which 11 fetuses of 14-27 weeks of GA were chosen and scanned by 7.0 T MR. The time when the structures in the region of basal nuclei could be detected and the changes of MR signal intensity were analyzed for MRI of different Tesla.Results On 3.0 T MRI.the dorsal thalamus could be delineated as early as 14 weeks of GA. The germinal matrix, caudate nucleus,and putamen could be visualized as early as 15 weeks of GA. The globus pallidus could be described as early as 18 weeks of GA.and the internal capsule and external capsule could be shown as early as 20 weeks of GA. The signal of the caudate nucleus during 15-30 weeks of GA was relatively hypointense on T1WI and hyperintense on T2WI.but during 31-40 weeks of GA, it was relatively hyperintense on T1WI and hypointense on T2WI. The putamen had a relatively high signal intensity on T1WI and low signal intemity on T1WI during 15-17 weeks of GA, and it appeared patchy during 18-25 weeks of GA,then it had a relatively low signal intensity on T1WI and high signal intensity on T2WI during 26-30 weeks of GA, and during 31-40 weeks of GA,its signal intensity was relatively high on T1WI and low on T2WI.The globus pallidus had a relatively high signal intensity on T1WI and low signal intensity on T2WI during 20-40 weeks of GA Compared to the 3.0 T MRI,the T2 images of 7.0 T MRl were more clear,and most structures in the region of basal nuclei could be clearly displayed as early as 16 weeks of GA.such as the germinal matrix,caudate nucleus,dorsal thalamus,putamen,globus pallidus,internal capsule,and external capsule.The claustrum could be delineated as early as 18 weeks of GA on 7.0 T MRI. Conclusions 3.0 T MRI could show the developmental process of the region of basal nuclei well,but the T2 images of 7.0 TMRl were comparatively better.