Receptors, Purinergic ; Signal Transduction/physiology*

To reveal the pharmacological mechanism of 3-arylcoumarin derivative 3-(4′-hydroxyphenyl)-6-hydroxycoumarin (SJ-6) against vascular calcification, advanced glycation end products (AGEs) were used to induce the calcification of human aortic vascular smooth muscle cells (HCASMCs), and calcification was identified by alizarin red staining and quantification.The effects of SJ-6 on alkaline phosphatase (ALP) activity, cell proliferation rate, calcium content, and total reactive oxygen species (ROS), superoxide dismutase (SOD), AGEs, and tetra methylethlene diamine proteinase factor-α (TNF-α), interleukin-6 (1L-6), interleukin-β (1L-β), runt-related transcription factor 2 mRNA (Runx2 mRNA), the receptor of advanced glycation endproducts (RAGE), nuclear factor kappa-B (NF-κB), napdh oxidase-1 (NoX-1), protein kinase C(PKC), protein kinase b(AKT), p38 mitogen-activated protein kinase (p38 MAPK), and smooth muscle actin-α (SMA-α) protein expression were determined.According to our results, SJ-6 significantly decreased AGEs content, ALP activity, intracellular calcium content, ROS content, Runx2 mRNA and inflammatory factors TNF-α, 1L-6 and 1L-β (P < 0.05) and increased SOD content (P < 0.01), with similar to those of the positive control drug aminoguanidine hydrochloride (AGH).Therefore, we investigated the pharmacological mechanism of compound SJ-6, which was found to significantly inhibit the expression of RAGE, NF-κB, NoX-1, PKC, Akt, p-p38 and other essential signaling proteins in the calcified cell model (P < 0.01) and increas the expression of smooth actin SMA-α (P < 0.01).SJ-6 inhibits vascular calcification by inhibiting oxidative stress and the expression of AGEs/RAGE, Akt/PKC and NF-κB signaling pathways, suggesting that it may be a novel drug for the treatment of vascular calcification.

Background::Urticaria is a common skin disease characterized by episodes of wheals, and it has a negative effect on patients’ quality of life. Large-scale population-based epidemiological studies of urticaria are scarce in China. The aim of this survey was to determine the prevalence, clinical forms, and risk factors of urticaria in the Chinese population.Methods::This survey was conducted in 35 cities from 31 provinces, autonomous regions, and municipalities of China. Two to three communities in each city were selected in this investigation. Participants completed questionnaires and received dermatological examinations. We analyzed the prevalence, clinical forms, and risk factors of urticaria.Results::In total, 44,875 questionnaires were distributed and 41,041 valid questionnaires were collected (17,563 male and 23,478 female participants). The lifetime prevalence of urticaria was 7.30%, with 8.26% in female and 6.34% in male individuals ( P < 0.05). The point prevalence of urticaria was 0.75%, with 0.79% in female and 0.71% in male individuals ( P < 0.05). Concomitant angioedema was found in 6.16% of patients. Adults had a higher prevalence of urticaria than adolescents and children. Living in urban areas, exposure to pollutants, an anxious or depressed psychological status, a personal and family history of allergy, thyroid diseases, and Helicobacter pylori infection were associated with a higher prevalence of urticaria. Smoking was correlated with a reduced risk of urticaria. Conclusion::This study demonstrated that the lifetime prevalence of urticaria was 7.30% and the point prevalence was 0.75% in the Chinese population; women had a higher prevalence of urticaria than men. Various factors were correlated with urticaria.

Objective:Tumor-treating fields (TTFields) is a kind of non-invasive anti-mitotic tumor therapy, which has been approved for patients with newly diagnosed and recurrent glioblastoma. This study aims to explore the efficacy and safety of TTFields in high-grade gliomas in clinical practice settings.Methods:The clinical data of 15 patients with recurrent glioma and 9 patients with newly diagnosed high-grade glioma admitted to our center from April 2019 to January 2021 were retrospectively analyzed. All patients accepted TTFields≥1 month. Follow-up was performed for 5.3 months (ranged from 2.3 to 10.7 months); Response Assessment in Neuro-Oncology Working Group (RANO) criteria was used to evaluate the glioma responses. The progression-free survival (PFS) and overall survival (OS) were calculated according to Kaplan-Meier method. Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0) and TTFields related skin adverse reaction (dAE) criteria were used to evaluate the adverse events. Quality of life questionnaire-core 30 (QLQ-C30) and QLQ-brain cancer module (QLQ-BN20) questionnaires were used to evaluate the health-related quality of life (HRQoL). Treatment compliance was evaluated by data on the use of NovoTTF-200A devices, and calculated as a percentage of daily TTFields usage.Results:The median duration of TTFields was 4.2 months (ranged from 1.0 to 10.7 months), with a median compliance rate of 91.5% (67.0%-97.0%). TTFields was used alone in 2 patients and used with combination of chemotherapy in 22 patients. From follow-up to April 2021, 14 patients had stable symptoms and 10 had disease progression (8 died). The median PFS and OS of recurrent patients were 5.9 months ( 95%CI: 3.3-8.6 months) and 8.5 months ( 95%CI: 3.2-13.8 months), respectively; and the median PFS and OS of newly diagnosed patients were both 10.7 months (without 95%CI). The common adverse events included grading 1 dAE (58.3%) and grading 2 dAE (12.5%), without grading 3 or 4 dAE, manifested as contact or allergic dermatitis, erosion, folliculitis and ulcers. And 87.5% patients had stable HRQoL. Conclusions:The preliminary results showed that the survival of recurrent high-grade glioma patients treated by TTFields is similar to that reported in foreign literature; and the newly diagnosed patients need further survival follow-up. The patients' treatment compliance and safety are good. The dAE incidence (grading 1-2) is higher than that reported in the literature, and the toxicity was acceptable.

Objective To investigate the relationship between CYP 2C19 gene polymorphisms and clopidogrel efficacy in coronary heart disease patients after percutaneous coronary intervention (PCI).Methods From January 2016 to December 2017,62 patients with acute coronary syndromes and treated with PCI in Guizhou Aerospace Hospital were recruited, CYP2C19 genotype, ADP －induced platelet aggregation rate and myocardial enzymes and other indicators were detected before operation .The myocardial enzymes were measured 24 hours after PCI.According to different metabolic types,the patients were grouped,the above indicators were compared.Results The CYP2C19*1/*1 was 37.10%,CYP2C19*1/*2 was 35.48%,CYP2C19*1/*3 was 11.29%,CYP2C19*2/*2 was 12.90%,CYP2C19*2/*3 was 3.23% and CYP2C19*3/*3 was 0.00%.The LDH,AST,CK,CK－MB and α－HBDH in the PCI patients after operation were significantly higher than those before operation (t＝0.019,0.040, 0.044,0.022,0.014,all P＜0.05).But ADP induced platelet aggregation rate and myocardial enzymes and other indicators among fast metabolism group,intermediate metabolic group and slow metabolic group had no statistically significant differences (all P ＞0.05).Conclusion CYP2C19 mutation frequency in the Chinese population is relatively large,the sample size of this study is less ,the relationship between clopidogrel resistance and the specific genotype can not be obtained ,it need to increase the sample size and comprehensive multi －factor consideration .

Objective To explore the clinical characteristics of patients with thyrotropin-secreting pituitary adenomas ( TSHomas) in China. Methods All the articles related to TSHomas were retrieved from the Chinese journal databases up to July 2017. All reported cases were assessed. Results TSHomas have been diagnosed in all ages (range:12-81 years old, average 41.9 ± 13.8 years old) with no gender difference (male : female=84: 69). The rate of misdiagnosis fell from 84.6％(11/13) to 50.6％(39/77) in the last 10 years. In 92 cases (60.1％), the level of TSH was elevated [median 1.57×ULN (upper limits of normal)]. The most common elevated hormones associated with TSHomas were growth hormone ( GH) and prolactin ( PRL;11.1％and 9.7％, respectively) . 37 cases underwent octreotide suppression test, of which the inhibitory rates ranged from 26. 2％ to 94. 9％ ( median 71.79％). The detection rate of micro-adenoma was 7.7％(1/13)before year 2000, 11.4％(4/35)from 2000 to 2006, and 26.7％(28/105) after 2006. Although TSHomas usually invade surrounding tissues, they hardly cause pituitary apoplexy. Surgery orγ-knife was performed in 132 cases ( 86. 3％) . Immunohistochemistry of tumors showed that 87 (52.9％) of 46 were pure TSH adenomas and 32 (36.8％) cases were mixed ones, while GH and PRL were most common (75.0％and 56.3％respectively) in the mixed adenomas. Negative immunohistochemistry for TSH was found in 9 cases (10.3％). In the follow-up, the restoring rates of thyroid hormone and TSH level were 77.0％(87/113) and 80.0％( 36/45) respectively. Conclusion TSHoma is diagnosed at an earlier age in China than that reported in Europe and America, while at similar age compared with Japan. Macro-adenomas were more common in spite of the increasing detection rate of micro-adenomas. Macro-adenomas are often invasive but less likely to induce pituitary apoplexy. Immunostaining for TSH could be negative. The most common positive immunostaining in mixed adenoma is GH and/or PRL. However, a positive immunostaining for one pituitary hormone does not necessarily correlates with its hypersecretion of that hormone.

Objective To comparatively analyze the clinical characteristics of thyrotropin-secreting pituitary adenomas (TSH-omas).Methods The clinical features, laboratory variables, imaging and pathological Results were retrospectively compared and analyzed of 26 cases with TSH-omas admitted in Chinese PLA General Hospital from Feb. 2006 to Oct. 2016 and 20 cases with TSH-omas admitted in Shanghai Huashan Hospital from Apr. 2006 to Apr. 2013.Results The female ratio was slightly higher in patients of Chinese PLA General Hospital than in Huashan Hospital [(57.7%(15/26)vs. 45.0%(9/20)], while the mean age was similar [39.5±14.1(18-67 years)vs. 40.0±14.5(17-74 years)]. The most common chief complaint was thyrotoxicosis [73.1%(19/26)vs. 55.0%(11/20)], and mild-to-moderate goiter was the most common symptom. The mean serum TSH levels in Chinese PLA General Hospital and in Huashan Hospital were 5.06(2.97-6.27)mU/L and 6.16(3.76-10.91)mU/L respectively, and patients with normal serum TSH levels were more common in Chinese PLA General Hospital than in Huashan Hospital [57.7%(15/26)vs. 40.0%(8/20)]. Microadenoma was more common in Chinese PLA General Hospital than in Huashan Hospital [34.62%(9/26)vs. 20.0%(4/20)], while macroadenoma was more common in Huashan Hospital than in Chinese PLA General Hospital [20.0%(4/20)vs. 7.7%(2/26)]. Microadenoma was more common in female patients of the both groups [66.7%(6/9)vs. 75.0%(3/4)], while macroadenoma was all found in male patients. Tumor invasion of surrounding tissue and structure was often found in macroadenoma. In terms of octreotide inhibition test, the range of 24h TSH inhibition rate was roughly the same in the two groups (37.4%-91.8% and 46.5%-94.1%, respectively). Mixed adenoma was rare among all the pathologically confirmed cases. In Chinese PLA General Hospitals, TSH immunoreactive negative neoplastic cells were found in 3 of 8 cases, and octreotide scanning showed negative in 2 of 12 cases.Conclusions Patients with TSH-omas in the two hospitals show similarities but also some significant differences in the clinical features. Overall, the domestic patients with TSH-omas are diagnosed without gender difference according to the reports in China. The mean age at diagnosis is significantly younger than that in foreign data. Microadenoma is more common in females, while macroadenoma is more common in males. Serum TSH levels can be normal in patients with TSH-omas. Immunostaining and/or octreotide scanning for TSH can be negative.

Objective: To investigate the infectious status, gene type transition and epidemiological features of rotavirus A isolated from infants and children (<59 months-of-age) in sentinel hospitals from 2008 to 2015 in Henan province, China. Methods: In total, 2 541 stool samples (each 3- 5 ml) were collected from infants and children aged less than five years in two sentinel hospitals and group A rotavirus was detected by a double antibody sandwich ELISA. Viral RNA was extracted from positive samples and G/P gene typing was performed using a two-step nested multiplex RT-PCR. Epidemiological information (including demographic information such as age, sex and clinical symptoms) was also collected from the patients and analyzed. Results: Group A rotavirus was detected in 30.9% (785/2 541) of diarrhea samples from children. The detection rate was higher in October (54.8%, 345/629) and lower in July (5%, 5/101) each year from 2008 to 2015. The group A rotavirus infection rate was higher in boys (30.6%, 451/1 476) than in girls (31.4%, 334/1 065) (χ²=0.18, P=0.664). Infection mainly occurred in 4-12 months old patients (61.3%, 481/785) (χ²=196.69, P<0.001), and the infection rate was lower in cities (26%, 258/992) compared with rural areas (34.0%, 527/1 549) (χ²=18.19, P<0.001). G typing of 785 strains of group A rotavirus revealed the following types: G1 (13.5%, 106 strains), G2 (11.1%, 87 strains), G3 (29.7%, 233 strains), and G9 (57.5%, 451 strains); P typing revealed the predominance of P[4] (11.3%, 89 strains) and P[8] (84.7%, 665 strains); gene type combinations comprised mainly G9P[8], G2P[4], G3P[8], G1P[8], respectively accounted for 52.9% (415), 9.7% (76), 17.3% (136), 11.3% (89). Gene type combinations G1 [8] and G3P[8] have been decreasing in prevalence since 2008 and G9P[8] has become the dominant gene type of group A rotavirus in Henan province. Among the group A rotavirus infection samples, the male:female infection ratio was 1.4∶1 (451/334), with no significant difference in the infection rate (χ²=0.18, P=0.664); the infection rate was higher in 4- 12 months old patients (61.3%, 481/785), with a significant difference detected between age groups (χ²=196.69, P<0.001). The rate of detection was lower in cities (26.0%, 258/992) than in rural areas (34.0%, 527/1 549) (χ²=18.19, P<0.001). Clinical analysis revealed a body temperature of below 37 degrees in 75.7% of positive cases (594 patients), 37.0- 37.5 degrees in 17.2% of cases (135 patients), 37.6-38.0 degrees in 2.0% of cases (16 patients), and above 38 degrees in 5.1% of cases (40 patients), with most cases showing no fever or a mild fever. The frequency of episodes of diarrhea among the patients was 0- 3 times (21.1%, 166 cases), 4- 6 times (65.6%, 515 cases), 7- 9 times (8.0%, 63 cases), or 10- 15 times (5.2%, 41 cases), mainly showing mild and moderate diarrhea. Vomiting also varied in frequency among the patients from no vomiting (86.9%, 682 cases), 1-2 times (11.8%, 92 cases), 3 times (6.0%, 47 cases), and more than 3 times (0.4%, 3 cases). The occurrence of dehydration varied from no dehydration (86.9%, 682 cases), mild dehydration of 1%- 5% (12.1%, 95 cases), to severe dehydration of ≥5% (1.0%, 8 cases). Conclusion A higher infection rate of group A rotavirus was detected in children younger than five years of age with acute diarrhea in sentinel hospitals in Henan province, including part-mixed infection cases. A predominance of cases was detected in the autumn, and secondly the spring of each year. Gene type G9P[8] was most frequently isolated. The majority of patients displayed no fever, vomiting or dehydration. The cases with clinical symptoms of fever, diarrhea, vomiting and dehydration often showed mild disease.

OBJECTIVE:To improve the dispersion stability in water of Tussilago farfara powder,and to improve compliance of Xiao’er feike granules. METHODS:The effects of 4 kinds of dispersion stabilizer (sodium hexametaphosphate, dextrin, PEG4000 and lecithin) on dispersion stability of suspension in water were investigated during the grinding of T. farfara using rate of absorbance change(β)and Zeta potential as index;IR spectrum of samples were characterized. Using original formulation with-out dispersion stabilizer as control,the dispersion stability of new formulation granules in water were analyzed comparatively after adding dispersion stabilizer. RESULTS:Among 4 kinds of dispersion stabilizer,β of sample prepared by sodium hexametaphos-phate was the lowest,while Zeta potential of it was the highest;compared with original T. farfara,β of T. farfara grinded with 2.5% sodium hexametaphosphate decreased by 16.8%,and Zeta potential absolute value increased by 29.4%;no new peak was found in IR spectrum. Compared with control granules,granules suspension prepared by new formulation had lower β and higher Zeta potential absolute value (P<0.01);particle size was 30 μm and no large particle aggregation was found;β was less than 5.0% within 20 s sedimentation. CONCLUSIONS:During the preparation of Xiao’er feike granules,the application of sodium hexametaphosphate in the grinding of T. farfara powder can improve the dispersion stability of granules in water and the compliance of the preparation.

Molecularly imprinted polymers for dimethoate recognition were synthesized by the precipitation polymerization technique using methyl methacrylate (MMA) as the functional monomer and ethylene glycol dimethacrylate (EGDMA) as the cross-linker. The morphology, adsorption and recognition properties were investigated by scanning electron microscopy (SEM), static adsorption test, and competitive adsorption test. To obtain the best selectivity and binding performance, the synthesis and adsorption conditions of MIPs were optimized through single factor experiments. Under the optimized conditions, the resultant polymers exhibited uniform size, satisfactory binding capacity and significant selectivity. Furthermore, the imprinted polymers were successfully applied as a specific solid-phase extractants combined with high performance liquid chromatography (HPLC) for determination of dimethoate residues in the cucumber samples. The average recoveries of three spiked samples ranged from 78.5% to 87.9% with the relative standard deviations (RSDs) less than 4.4% and the limit of detection (LOD) obtained for dimethoate as low as 2.3μg/mL.