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AIM: To investigate the effect of gastrodin on the expression of brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6) in the striatum of cerebral ischemia rats, and to explore the potential mechanism of gastrodin in treating cerebral ischemia. METHODS: The rats were randomly divided into four groups: normal, sham, model, and gastrodin groups, each consisting of 10 rats. After successful modeling using middle cerebral artery occlusion (MCAO), the gastrodin group received intraperitoneal injection of gastrodin injection at a dose of 10 mg/kg once a day for 14 consecutive days. Pathological changes in striatal neurons were observed using Nissl staining. Immunohistochemistry was utilized to detect positive expression of BDNF and IL-6 proteins in the striatum. Additionally, immunoblot analysis was performed to determine the expression levels of BDNF and IL-6 proteins in the striatum. RESULTS: Nissl staining revealed clear and intact structures of striatal neurons in the normal and sham groups, with tightly arranged cells. In the model group, the number of cells was significantly reduced compared to the sham group (P0.05). Compared to the sham group, the model group showed a decrease in the protein expression level of BDNF in the striatum on the ischemic side (P<0.01) and an increase in the protein expression level of IL-6 (P<0.05, P<0.01). In contrast, the gastrodin group showed an increase in the protein expression level of BDNF in the striatum on the ischemic side (P<0.05, P<0.01) and a decrease in the protein expression level of IL-6 (P< 0.05, P<0.01) compared to the model group. CONCLUSION: Gastrodin has a significant protective effect on striatal injury caused by cerebral ischemia, and its mechanism may be related to the up-regulation of the anti-inflammatory factor BDNF and the down-regulation of the pro-inflammatory factor IL-6.
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Aim To investigate the mechanism of ligu aged 2 months of the same strain were used as the constilide (LIG) in delaying the senescence of auditory trol (Ctrl) group. Auditory brainstem response test was cortex and treating central presbycusis. Methods used to detect the auditory threshold of mice before and Forty C57BL/6J mice aged 13 months were randomly di after treatment. Levels of serum MDA and activity of vided into ligustilide low-dose(L-LIG) group, ligustil serum SOD were detected to display the level of oxidative ide medium-dose (M-LIG) group, ligustilide high-dose stress. The pathological changes of auditory cortex were (H-LIG) group and aging (Age) group, and 10 mice observed by HE staining. Ferroptosis was observed by
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ObjectiveTo investigate the effects of Xinjia Congrong Tusizi decoction （XJCTD） on ovarian functions in the rat model of premature ovarian insufficiency （POI） and decipher the mechanism of regulating the tumor suppressor protein （p53）/nuclear factor E2-related factor 2 （Nrf2） pathway to attenuate granulosa cell ferroptosis. MethodForty-eight SPF-grade female SD rats were randomized into control， model， low-， medium-， and high-dose （1.1， 2.2， 4.4 g·kg-1） XJCTD， and Western medicine （coenzyme Q10， 0.002 7 g·kg-1） groups， with eight rats in each group. The rat model of POI was established by gavage of triptolide （TP）， and after successful modeling， each group was administrated with the corresponding drugs by gavage for 14 d. The body weight and ovarian weight of each rat were weighed and the ovarian index was calculated. The morphology of the ovarian tissue was observed by hematoxylin-eosin staining， and the proportions of growing follicles and atretic follicles were calculated. The serum levels of anti-Müllerian hormone （AMM）， estradiol （E2）， and follicle-stimulating hormone （FSH） were measured by enzyme-linked immunosorbent assay （ELISA）. The DCFH-DA fluorescent probe was used to measure the reactive oxygen species （ROS） content in granulosa cells. The content of cellular Ferrous ion （Fe2+）， lipid peroxide （LPO）， malondialdehyde （MDA）， glutathione （GSH）， and superoxide dismutase （SOD） was detected by colorimetry. The expression of the tumor suppressor protein p53，Nrf2， solute carrier family 7 member 11 （SLC7A11）， and glutathione peroxidase 4 （GPX4） was determined by immunohistochemistry and Western blot. ResultCompared with the control group， the model group showed decreased ovarian weight， body weight， and ovarian index （P<0.01）， reduced ovarian tissue volume and proportion of growing follicles （P<0.01）， increased proportion of atretic follicles （P<0.01）， lowered AMH and E2 levels and elevated FSH level in the serum （P<0.01）， and elevated levels of Fe2+， ROS， LPO， and MDA （P<0.01） and lowered levels of GSH and SOD in granulosa cells （P<0.01）. Moreover， the modeling up-regulated the expression of p53 （P<0.01） and down-regulated the expression of Nrf2， SLC7A11， and GPX4 （P<0.05， P<0.01） in the ovarian tissue. Compared with the model group， XJCTD increased the body weight， ovarian weight， and ovarian index （P<0.01）， alleviated the pathological changes in the ovarian tissue， increased the proportion of growing follicles （P<0.01）， decreased the proportion of atretic follicles （P<0.01）， and reduced the content of ROS in granulosa cells （P<0.05， P<0.01）. In addition， medium- and high-dose XJCTD lowered the FSH level （P<0.01） and raised E2 and AMH levels （P<0.01） in the serum， reduced the Fe2+ content （P<0.05， P<0.01）， and increased the SOD content （P<0.01） in granulosa cells. High-dose XJCTD reduced the LPO and MDA content （P<0.01） and increased the SOD content （P<0.01） in the granulosa cells， down-regulated the expression of p53 （P<0.05）， and up-regulated the expression of Nrf2， SLC7A11， and GPX4 in the ovarian tissue （P<0.05， P<0.01）. ConclusionXJCTD may protect the ovarian function in the rat model of POI by regulating the p53/Nrf2 signaling pathway to attenuate the ferroptosis of ovarian granulosa cells.
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Objective To explore the correlation between the incidence of foodborne diseases and meteorological factors in Jinan, and to provide targeted measures for the prevention and control of foodborne diseases. Methods Data from the reporting systems of two sentinel hospitals for active surveillance of foodborne diseases from 2013 to 2021 in Jinan were collected. The meteorological data in the same period in Jinan were also collected. The generalized additive model was used to explore the nonlinear relationship between meteorological factors and the incidence of foodborne diseases, and threshold function analysis was use to perform subsection regression. Results The incidence of foodborne diseases was positively correlated with daily average temperature (rs=0.23), relative humidity (rs=0.05), and daily average wind speed (rs=0.01), and negatively correlated with daily average air pressure (rs=-0.19). Based on the GAM results and segmented regression analysis of meteorological factors, it was found that when the daily average temperature was below or above the threshold of 24.63°C, for every 1°C increase in daily average temperature, the incidence of foodborne diseases correspondingly increased by 0.04% and 0.18%. When the daily average wind speed was above the threshold of 2.26 m/s, the incidence of foodborne diseases decreased by 0.36% for every 1 m/s increase in the daily average wind speed. Conclusion Nine years of observation and data analysis have shown that meteorological factors such as daily average temperature, relative humidity, air pressure, and wind speed are related to the incidence of foodborne diseases. These findings suggest that meteorological factors may be important factors leading to foodborne diseases, which provides an important scientific basis for formulating effective prevention and control measures.
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AIM: To explore the reasons for screening failure of healthy subjects in clinical trials of orally inhaled drug products (OIDPs). METHODS: Screening data of 1 432 healthy subjects who participated in clinical trials of OIDPs were collected. The main reasons for the screening failure, gender differences in screening failure rate and the correlation between age and screening failure rate were summarized and analyzed. RESULTS: The screening failure rate was 72.4 % and increased with age. The failure rate was slightly higher in females than in males. Besides abnormal vital signs (17.3%), abnormal laboratory test results (16.5%) and withdrawal of consent (7.6%), poor venous condition (13.9%), positive for cigarette test results (12.6%) and failure in inhalation training (7.1%) were also the other three main reasons affecting the screening success rate. Abnormal vital signs and poor venous conditions were the primary screening failure reasons for males and females, respectively. CONCLUSION: The screening success rate could be improved by informing fully and communicating effectively, selecting young subjects with strong understanding abilities, and enhancing the training skills of investigators.
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AIM: To investigate the safety of bioequivalence (BE) studies of orally inhaled drug products (OIDPs) conducted by Phase I clinical Research Center of our hospital. METHODS: The safety data were collected from 482 healthy subjects enrolled in 20 OIDPs BE studies in Wuxi People's hospital from 2017 to 2022. The difference of adverse events (AEs) between test preparation and reference preparation were compared, as well as the influence of gender, age, mechanism of drug action and device type on AE were analyzed. RESULTS: A total of 102 cases of AEs were occurred in 77 subjects (16.0%, 77/482), 87 cases of AEs were related to experimental drugs, all AEs were mild or moderate, and no serious adverse events occurred. There was no difference in the incidence of AE between test preparation and reference preparation. In addition, gender, age, mechanism of drug action and device type had no significant effects on AEs. CONCLUSION: In 20 bioequivalence studies of OIDPs, OIDPs were safe and well tolerated in healthy subjects after dosing, and safety features of generic OIDPs and original drug were basically similar.
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Aim To explore the mechanism of Polygonum capitatum(PC)in the treatment of Helicobacter Pylori associated gastritis(HAG). Methods The databases were used to identify the target of PC active compounds and HAG-related genes,and the intersection was taken to obtain the potential targets of PC treatment of HAG. The interaction network diagram of “drug-active compound-target-disease” and the protein-protein interaction(PPI)network of potential target protein interaction in HAG treated by PC were constructed by software Cytoscape 3.6.0. The important nodes in the network were screened by several topological indexes,and the GO and KEGG enrichment were analyzed by STRING database to obtain the potential signaling pathway of PC in the treatment of HAG. The binding ability of PC active components with key target proteins was observed by molecular docking method. On this basis,the related targets of PC in the treatment of HAG were verified in vivo and in vitro experiments. Results The PC active compounds and targets were identified through the database,and the “drug-active compound-target-disease” network diagram and the PPI network of potential target proteins were constructed. Combined with several topological indexes,the PPI network of potential target-protein interaction was analyzed,and 52 hub genes were screened. Further bioinformatics analysis and high-throughput sequencing revealed that PC exerted an effect on HAG through the Akt/NF-κB/NLRP3 pathway. Based on this,it was found that PC could reduce IL-18 and IL-1β in HAG GES-1 cells and HAG SD rats,up-regulate Akt and its phosphorylation level and reduce NF-κB expression,inhibit the activation of NLRP3 inflammatory body,so as to improve HAG inflammatory response. Conclusions PC could exert a therapeutic effect on HAG by activating Akt and its phosphorylation level,and inhibiting the expression of NF-κB and NLRP3 inflammasome related factors. This study provides a theoretical basis for explaining the mechanism of PC in the treatment of HAG.
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{L-End}Objective To establish the construction of intelligent management system for equipment and supplies of medical rescue teams for provincial nuclear and radiation accidents, based on modern Internet+ Internet of Things. {L-End}Methods The current status and requirements of emergency equipment and supplies allocation and management of medical emergency teams for provincial nuclear and radiation accidents were analyzed. Utilizing technologies such as Internet of Things, low-power Bluetooth, and radio frequency identification, an intelligent management system for medical rescue teams, its equipment and supplies for provincial nuclear and radiation accidents was designed. {L-End}Results The intelligent management system for medical rescue teams, its equipment and supplies for nuclear and radiation accidents was able to perform the inventory warning, expiration date warning, maintenance alert, and warning for emergency personnel health status, based on dynamic management of rescue personnel, equipment and supplies. It provided an effective support for on-site commanders in making emergency decisions. {L-End}Conclusion The use of Internet+Internet of Things technology can achieve intelligent management for medical rescue teams and its equipment and supplies can effectively improve the level of personnel and equipment support for the rescue of nuclear and radiation accidents at the provincial level.
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The study aims to explore the active molecules of traditional Chinese medicine that specifically bind to interleukin-15 receptor α (IL-15Rα) using molecular docking and surface plasmon resonance (SPR) technology. AutoDock molecular docking software was used to perform simulated docking of more than 3 000 compounds from 48 traditional Chinese medicines at IL-15Rα and screen the specific binding compounds. Then Biocore T200 biomolecular interaction analysis system of SPR was used to confirm the binding specificity of the selected target compounds. Finally, the biological effects of the target compounds on IL-15Rα were verified by cell biological experiments. The results showed that neoprzewaquinone A (Neo) possessed the highest specific binding affinity among the active molecules from traditional Chinese medicine, and the dissociation constant (KD) value was (0.62 ± 0.20) µmol/L. The results of cell experiment showed that Neo significantly inhibited the proliferation of Mo7e cells induced by IL-15, and the IC50 was 1.075 µmol/L, approximately 1/120 of the IC50 of Cefazolin (IL-15 specific antagonist). These results suggest that Neo is a specific inhibitor of IL-15Rα and may be a potential active drug for the treatment of diseases related to the dysfunction of the IL-15Rα signaling.
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Simulation de docking moléculaire , Interleukine-15/pharmacologie , Résonance plasmonique de surface , Sous-unité alpha du récepteur à l'interleukine-15/métabolisme , Liaison aux protéinesRésumé
BACKGROUND@#The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis.@*METHODS@#In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis.@*RESULTS@#A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP.@*CONCLUSIONS@#Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.
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Humains , Liquide de lavage bronchoalvéolaire , Études prospectives , Alvéolite allergique extrinsèque/diagnostic , Fibrose , GlucidesRésumé
【Objective】 To evaluate the detection and distribution characteristics of anti-P1 in tumor patients, so as to aid in blood screening and transfusion safety. 【Methods】 The clinical data of 112 658 tumor patients who underwent blood preparation and transfusion in our hospital from January 2014 to December 2021 were retrospectively analyzed, and column agglutination technique was used to perform transfusion compatibility test. 【Results】 A total of 1 079 (0.96%, 1 079/112 658) cases were detected with unexpected antibodies, of which 71 (6.58%, 71/1 079) were identified as anti-P1. In anti-P1 cases, 59.15% (42/71) were males; 60.56% had no pregnancy history (P<0.01); 29.58% (21/71), 52.11%(37/71), 12.68%(9/71) and 5.63%(4/71) of anti-P1 patients were with type A, B, O and AB, respectively. 57 cases of anti-P1 patients (80.28%) had difficulty in ABO blood group identification. The incidence of interfering in patients with type B was higher than that of other blood types (P<0.05), as the frequency of w+ in reverse blood typing was higher than other reactive patterns (P<0.05). The incidence of gastric tumor and brain space-occupying lesion in patients with anti-P1 was higher than that in patients with other alloantibodies, while the incidence of gynecological tumors was lower (P<0.05). 【Conclusion】 Anti-P1 affects the ABO blood group identification of tumor patients, and most of them had difficulty in ABO blood group identification. Compared with patients with other alloantibodies, patients with anti-P1 are more likely to be male and suffer from gastric and brain tumors, but less likely from gynecological tumors.
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Objective To analyze result of the external quality assessment for laboratories of toxicological pathology diagnosis in organizations in China. Methods A total of 86 organizations that participated in the 2020-2021 external quality assessment in laboratory of toxicological pathology diagnosis (hereinafter referred to as "reference units") were selected as research subjects using convenient sampling method, and the assessment results were analyzed. Results The median of total score was 92, and the 0-100 percentiles were 64-100 in these 86 reference units. Among these reference units, 76 were rated as excellent, 10 as qualified, with the excellent and the qualified rate of 88.4% and 11.6%, respectively. No reference unit was rated as unqualified. The rates of excellence of the reference units in public health institutions, pharmaceutical research institutions, drug safety evaluation centers and testing companies were 95.7%, 84.2%, 85.7% and 86.7%, and the qualified rates were 4.3%, 15.8%, 14.3% and 13.3%, respectively. The distribution of excellence and qualification among the four types of reference units showed no statistical difference (P>0.05). The distribution of sample scores according to the three grades of poor, good, and excellent were 4.9%, 20.7%, and 74.5% in public health institutions, 8.6%, 23.7%, and 67.8% in pharmaceutical research institutions, 12.5%, 25.0%, and 62.5% in drug safety evaluation centers, and 5.4%, 17.5%, and 77.1% in testing companies. The proportion of excellence unit in public health institutions was higher than that in pharmaceutical research institutions (P<0.05). Conclusion The overall toxicological pathology diagnostic capabilities in China are good, and various types of reference units demonstrate comparable technical capabilities. However, there is a need for standardization of diagnostic terminology.
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Objective To analyze the timeline of occupational disease online reporting and reviewing in Guangdong Province from 2014 to 2022. Methods Data and review information from the Occupational Diseases and Hazards Monitoring Information System under China Disease Prevention and Control Information System were collected to analyze the reporting timeline, review status, and timeline of review of "Occupational Disease Report Cards" for the years 2014 to 2022 in enterprises located in Guangdong Province. Results A total of 9 929 occupational disease report cards were recorded in Guangdong Province from 2014 to 2022, and the timely reporting rate of occupational diseases was 84.10%, with an overall upward trend. There was a statistically significant difference in the reporting time among different years (P<0.05), and the reporting time showed a downward trend. In 2022, the timely reporting rate of all cities reached over 80.00%. The final review rate of occupational disease report cards was 85.02%, and the review rate and timely review rate at the county level showed an increasing trend. The occupational disease report card audit timeliness rate from high to low was provincial, district county and city level (61.26% vs 43.87% vs 36.72%, all P<0.05). Conclusion The timeline of occupational disease reporting in Guangdong Province is relatively high, and the review at all levels is generally good. However, further improvement is needed for timely review at the municipal and county levels.
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OBJECTIVE@#To observe the immediate analgesic effect of electroacupuncture (EA) combined with diclofenac sodium on acute gouty arthritis (AGA).@*METHODS@#A total of 90 patients with AGA were randomly divided into a low-dose medication (LM) group (30 cases, 1 case was eliminated, 1 case dropped off), a conventional medication (CM) group (30 cases, 1 case dropped off) and a combination of acupuncture and medication (AM) group (30 cases ). The LM group was given oral administration of 50 mg diclofenac sodium sustained-release capsule; the CM group was given oral administration of 100 mg diclofenac sodium sustained-release capsule; on the basis of the treatment of LM group, the AM group was treated with electroacupuncture at ashi points, Dadu (SP 2), Taichong (LR 3), Taibai (SP 3), Neiting (ST 44), Sanyinjiao (SP 6), Zusanli (ST 36) and Yinlingquan (SP 9) on the affected side, and Taichong (LR 3) and Zusanli (ST 36), Sanyinjiao (SP 6) and Yinlingquan (SP 9) were connected to electroacupuncture respectively, continuous wave, 2 Hz in frequency. The visual analogue scale (VAS) scores of pain before treatment and after 10 min, 2 h, 4 h and 6 h of treatment completion, joint tenderness and swelling scores before treatment and after 10 min and 6 h of treatment completion were compared, and the rate of diclofenac sodium addition within 24 h after treatment completion was recorded among the three groups.@*RESULTS@#After 10 min of treatment completion, the scores of VAS, joint tenderness and joint swelling in the AM group were lower than those before treatment (P<0.05), and the VAS score in the AM group was lower than that in the other two groups (P<0.05). After 2, 4 and 6 h of treatment completion, the VAS scores of the three groups were lower than those before treatment (P<0.05), and the scores in the AM group were lower than those in the LM group (P<0.05). After 6 h of treatment completion, the joint tenderness scores of the three groups and the joint swelling scores of the AM group and the CM group were lower than those before treatment (P<0.05), and the joint tenderness and swelling scores of the AM group were lower than those of the LM group (P<0.05). The rate of diclofenac sodium addition was 3.3 % (1/30) and 3.4 % (1/29) in the AM group and the CM group, respectively, which were lower than 17.9% (5/28) in the LM group (P<0.05).@*CONCLUSION@#Electroacupuncture combined with diclofenac sodium have a good immediate analgesic effect in the treatment of AGA, and have the advantages of small dosage of analgesic drugs and less adverse reactions.
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Humains , Diclofenac , Électroacupuncture , Goutte articulaire/traitement médicamenteux , Préparations à action retardée , Thérapie par acupuncture , ArthralgieRésumé
ObjectiveTo investigate the mRNA expression levels of various aquaporins （AQPs） in luteinized granulosa cells from follicles of different diameters. MethodsFrom March 25， 2022 to September 23， 2022 in our reproductive medicine center， 48 women undergoing in-vitro fertilization （IVF） were enrolled and divided into the antagonist group and the agonist group according to the ovarian stimulation protocol. Follicular fluid samples were collected on the day of oocyte pick-up and granulosa cells were extracted from follicles of different diameters： small （<13 mm）， medium （13~18 mm） and large （≥18 mm）. After RNA quantification， 22 cases （66 samples） were included for analysis and mRNA expression levels of AQPs were compared among the three follicle groups. ResultsThe mRNA expression of aquaporin 2 （AQP2） in luteinized granulosa cells increased with the increase of follicle diameter （linear trend P = 0.004） and the difference was statistically significant between two groups of large and small follicles （P = 0.017）. Statistical difference was found in the antagonist group （P = 0.049 6）， but not in the agonist group （P = 0.108）. ConclusionThe mRNA level of AQP2 in luteinized granulosa cells increases with the increase of follicle diameter and its expression is related to the ovarian stimulation protocol， suggesting that AQP2 may play a role in follicle growth and follicular fluid formation， and its mRNA expression level may be regulated by follicle stimulating hormone （FSH） and luteinizing hormone （LH）.
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OBJECTIVE@#To investigate and reveal the underlying mechanism of the effect of total saponins from Dioscoreae nipponica Makino (TSDN) on the arachidonic acid pathway in monosodium urate (MSU) crystal-induced M1-polarized macrophages.@*METHODS@#M1 polarization of RAW264.7 cells were induced by 1 µ g/mL lipopolysaccharide (LPS). The methylthiazolyldiphenyl-tetrazolium bromide method was then used to screen the concentration of TSDN. MSU (500 µ g/mL) was used to induce the gouty arthritis model. Afterwards, 10 µ g/L TSDN and 8 µ mol/L celecoxib, which was used as a positive control, were added to the above LPS and MSU-induced cells for 24 h. The mRNA and protein expressions of cyclooxygenase (COX) 2, 5-lipoxygenase (5-LOX), microsomal prostaglandin E synthase derived eicosanoids (mPGES)-1, leukotriene B (LTB)4, cytochrome P450 (CYP) 4A, and prostaglandin E2 (PGE2) were tested by real-time polymerase chain reaction and Western blotting, respectively. The enzyme-linked immunosorbent assay was used to test the contents of M1 markers, including inducible nitric oxid synthase (NOS) 2, CD80, and CD86.@*RESULTS@#TSDN inhibited the proliferation of M1 macrophages and decreased both the mRNA and protein expressions of COX2, 5-LOX, CYP4A, LTB4, and PGE2 (P<0.01) while increased the mRNA and protein expression of mPGES-1 (P<0.05 or P<0.01). TSDN could also significantly decrease the contents of NOS2, CD80, and CD86 (P<0.01).@*CONCLUSION@#TSDN has an anti-inflammation effect on gouty arthritis in an in vitro model by regulating arachidonic acid signaling pathway.
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Acide urique/métabolisme , Acide arachidonique/métabolisme , Dioscorea , Goutte articulaire , Lipopolysaccharides , Saponines/pharmacologie , Macrophages , Transduction du signal , ARN messager/métabolismeRésumé
OBJECTIVE@#To investigate the effect of midazolam on pain in lumbar disc herniation model rats based on p38 MAPK signaling pathway.@*METHODS@#Fifty SPF-grade Sprague-Dawley healthy rats, half male and half female, were selected and randomly divided into normal group, model group, and low-dose, medium-dose, high-dose groups. Model group and low-dose, medium-dose, high-dose groups were initially modeled for lumbar disc herniation. Intraperitoneal injection of saline was performed in rats of normal and model groups; and in the low-dose, medium-dose, and high-dose groups, intraperitoneal injection of midazolam was performed with doses of 30, 60, and 90 mg/kg, respectively. Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), 5-hydroxytryptamine (5-HT), β-endorphin (β-EP), substance P (SP), neuropeptide Y (NPY) were detected in the serum of rats by enzyme-linked immunoassay. The expression of p38 MAPK and matrix metalloproteinase-3(MMP-3) protein were detected by Western blot in the tissues of rats of each group.@*RESULTS@#The levels of TNF-α, IL-1β and β-EP were higher and the level of 5-HT was lower in the model group than in the normal group(P<0.05);the levels of TNF-α, IL-1β and β-EP were lower and the level of 5-HT was higher in the low-dose, medium-dose and high-dose groups than in the model group(P<0.05). The levels of SP and NPY increased in the model group compared with the normal group (P<0.05) and the levels of SP and NPY decreased in the low-dose, medium-dose and high-dose groups compared with the model group (P<0.05). The expression of p38 MAPK and MMP-3 increased in the model group compared with the normal group (P<0.05); the expression of p38 MAPK and MMP-3 decreased in the low-dose, medium-dose and high-dose compared with the model group(P<0.05).@*CONCLUSION@#Midazolam may ameliorate the immune inflammatory response in rats with a model of lumbar disc herniation, possibly regulated through the p38MAPK signaling pathway.
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Rats , Mâle , Femelle , Animaux , Déplacement de disque intervertébral/anatomopathologie , Rat Sprague-Dawley , Matrix metalloproteinase 3/métabolisme , Midazolam , Facteur de nécrose tumorale alpha/métabolisme , Sérotonine/métabolisme , Système de signalisation des MAP kinases/physiologie , Douleur , p38 Mitogen-Activated Protein Kinases/métabolismeRésumé
Objective: To explore the value of paraquat (PQ) intake, urine protein and myocardial enzyme indexes in judging the prognosis of patients with acute PQ poisoning. Methods: From September to December 2021, all 201 patients with acute PQ poisoning admitted to Guangzhou Twelfth People's Hospital from January 2010 to December 2019 were selected as the research objects. Based on follow-up results 60 days after poisoning, the research objects were divided into survival group (n=78) and death group (n=123) . The differences in information about poisoning, treatment plan, PQ intake, urine protein, creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase between the two groups of patients were compared and analyzed. Logistic regression and Cox regression were used to analyze the correlation between poisoning outcome and PQ intake, urine protein and myocardial enzymes. ROC curve and principal component analysis were used to explore high-efficiency indicators for predicting the outcome of acute PQ poisoning. Results: The PQ intake[50 (20, 100) ml], urine protein (total rank 15570.50) , creatine kinase[ (336.36±261.96) U/L], creatine kinase isoenzyme[ (43.91±43.74) U/L], lactate dehydrogenase [ (346.01±196.50) U/L], α-hydroxybutyrate dehydrogenase content[ (271.23±11.92) U/L] of patients in the death group were all higher than the survival group[15 (10, 20) ml, 4730.50, (187.78±178.06) U/L, (18.88±15.50) U/L, (190.92±60.50) U/L, (152.60±48.34) U/L, respectively] (P<0.05) . The outcome of acute PQ poisoning was positively correlated with PQ intake, urine protein, creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase (P<0.05) . Multivariate logistic regression and multivariate Cox regression analysis showed that creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase and α-hydroxybutyrate dehydrogenase was positively correlated with the prognosis of patients with acute PQ poisoning (P<0.05) . ROC curve analysis and principal component analysis showed that the combined indexes of PQ intake, urine protein and myocardial enzymes had the highest efficacy and weight in judging the prognosis of patients (AUC=0.91, weight coefficient=0.19, sensitivity=0.76, specificity=0.89) . When the combined score was ≥4, the probability of accurately predicting the death of patients was as high as 91% (positive predictive value=0.91) . Conclusion: PQ intake, urine protein combined with creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase has high value in predicting the prognosis of patients with acute PQ poisoning.
Sujets)
Humains , Créatine , Creatine kinase , Isoenzymes , Lactate dehydrogenases , Paraquat/intoxication , Pronostic , Études rétrospectives , Myocarde/enzymologie , Urine/composition chimiqueRésumé
Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) has a wide range of symptoms, and it is difficult for clinicians to make a quick and correct diagnosis. On November 11, 2021, a 36-year-old male patient with AAV was admitted to the emergency and critical care department of Yichang Central People's Hospital. He was admitted to the emergency intensive care unit (EICU) with gastrointestinal symptoms (abdominal pain, black stool) as the main physical signs, and was initially diagnosed as AAV with gastrointestinal hemorrhage (GIH). No bleeding point was found after repeated gastroscopy and colonoscopy. Abdominal emission CT (ECT) showed diffuse hemorrhage in the ileum, ascending colon and transverse colon. Multi-disciplinary consultation in the whole hospital considered the diffuse hemorrhage caused by small vascular lesions in the digestive tract caused by AAV. Pulse therapy with methylprednisolone 1 000 mg/d and immunosuppressive therapy with cyclophosphamide (CTX) 0.2 g/d were administered. The patient's symptoms quickly relieved and transferred out of the EICU. After 17 days of treatment, the patient finally died of massive gastrointestinal bleeding. A systematic review of relevant literatures combined with the case diagnosis and treatment process found that only a minority of AAV patients present with gastrointestinal symptoms as their first symptoms, and patients with GIH were very rare. Such patients had a poor prognosis. This patient delayed the use of induced remission and immunosuppressive agents due to the treatment of gastrointestinal bleeding, which may be the main cause of life-threatening GIH secondary to AAV. Gastrointestinal bleeding is a rare and fatal complication of vasculitis. Timely and effective induction and remission treatment is the key to survival. Whether patients should receive maintenance therapy, the duration of maintenance therapy, and the search for markers of disease diagnosis and treatment response are directions and challenges for further research.
Sujets)
Mâle , Humains , Adulte , Hémorragie gastro-intestinale , Vascularites associées aux anticorps anti-cytoplasme des neutrophiles , Soins de réanimation , Cyclophosphamide , MortRésumé
OBJECTIVE@#To analyze the global epidemic status of the Ebola virus disease (EVD) and assess the importation risk into China.@*METHODS@#Data from World Health Organization reports were used. We described the global epidemic status of EVD from 1976-2021, and assessed and ranked the importation risk of EVD from the disease-outbreaking countries into China using the risk matrix and Borda count methods, respectively.@*RESULTS@#From 1976-2021, EVD mainly occurred in western and central Africa, with the highest cumulative number of cases (14,124 cases) in Sierra Leone, and the highest cumulative fatality rate (85%) in the Congo. Outbreaks of EVD have occurred in the Democratic Republic of the Congo and Guinea since 2018. The importation risk into China varies across countries with outbreaks of disease. The Democratic Republic of the Congo had an extremely high risk (23 Borda points), followed by Guinea and Liberia. Countries with a moderate importation risk were Nigeria, Uganda, Congo, Sierra Leone, Mali, and Gabon, while countries with a low importation risk included Sudan, Senegal, and Co