AIM To evaluate the value of arsenic trioxide (ATO) in the treatment of systemic lupus erythematosus and to investigate its mechanism. METHODS① Thirty four BXSB lupus mice were averagely and randomly divided into ATO treated group and control group. The mice of ATO treated group were given (ip) ATO 0.4 mg·kg-1 every other day until d 105 and the observation was ended on d 210. The survival rate of mice was recorded, and the levels of serum IgG and anti-dsDNA antibody were measured with enzyme-linked immunosorbent assay. ② Other 20 BXSB lupus mice were also divided into 2 groups and treated as above and sacrificed on d 90. The spleen and kidneys of each mouse were removed and total RNA was extracted. The levels of interferon-γ (IFN-γ) mRNA in renal and spleen tissues were measured by using reverse transcription polymerase chain reaction. RESULTSUp to d 210, 8 mice died in ATO treated group and 13 died in control group. On d 90 and d 105, the average levels of serum anti-dsDNA antibody (A450 nm) were (0.335±0.011) and (0.223±0.017) in ATO treated group, and (0.688±0.016) and (0.683 ±0.014) in control group. On d 90, the expressions of IFN-γ mRNA in spleen and renal tissues of ATO treated group were significantly lower than that of control group. On d 105, the serum level of IgG was much lower in ATO treated group than that in control group, which were (4.9±1.3) and (6.9±1.0)g·L-1, respectively. CONCLUSION ATO elevates the survival rate, lowers the serum levels of IgG and anti-dsDNA antibody, and depresses the expression of IFN-γ mRNA in spleen and kidney tissues of BXSB mice.

Objective To investigate the expression of P16 and CD44 in gastrointestinal stromal tumors (GIST) and their relationship with the prognosis of patients. Methods The GIST specimens of seventy patients who received surgical excision were collected. Tissue microarray of the seventy GIST samples was constructed. The expression of P16 and CD44 were detected by the immunohistochemical staining. The patients were followed up via out-patient examination and telephone. Results All the patients were followed up for 2-212 months, and the median time for follow-up was 68 months. The differences of the expression of P16 in GISTs among NIH risk ranks were insignificant (P > 0.05). The differences of the expression of CD44 in GISTs among NIH risk ranks were statistically significant (P < 0.05). Univariate analysis showed that tumor size, mitotic count, tumor location, NIH risk rank, the expression of P16 and CD44 were related to the prognosis of GIST patients. Multivariate showed that tumor size, mitotic count, tumor location, and the expression of CD44 was independent prognosis factors of GIST patients. Conclusion CD44 could be used as a biomarker in predicting the prognosis of GIST patients.

Objective To study the effective composition of Aster ageratoides Turcz for relieving asthma and its toxicity . Methods Seventy‐two qualified male guinea pigs ,body mass(300 ± 20)g ,were randomly divided into the control group ,aminophyl‐line group(0 .047 g/kg) and different ratio group of total saponins and total flavonoids (8∶1 ,4∶1 ,2∶1 ,1∶1 ,1∶2 ,1∶4 ,1∶8) . Every group received at dose of 0 .38 g/kg once a day for 3 days by intragastric administration .The effect of relieving asthma was taken as the indicators for the optimization of compositions ,which was detected by observing the latent period of asthma induced by acetylcholine‐histamine in guinea rats .The relaxation percentage of smooth muscle retracted by acetylcholine was detected by Pow‐erlab biological signal collecting system when aminophylline(1 .25 mg/mL) and different matching drugs(0 .02 g/mL) were added in Krebs′solution .The acute toxicities of total saponins ,total flavonoids and mixture of total saponins with total flavonoids (ratio of 1∶2) were detected by classical acute toxicity test of mice .Results Compared with the control group ,aminophylline group ,each group latent period of inducing asthma significantly or very significantly prolonged (P<0 .05) ,among them ,1∶1 ,1∶2 ,1∶4 group and other matching group were significantly different(P<0 .05) ,but 1∶2 group cited the longest incubation period .Aminophylline group and the ratio could significantly relaxe guinea pig tracheal smooth muscle retracted by acetylcholine .Aminophylline group di‐astolic percentage was the largest(24 .12 ± 1 .20)% ,all the groups were less than the percentage of diastolic aminophylline group (P<0 .05) ,but in 1∶2 group with the closest .Aster ageratoides Turcz ,tatarian aster total saponins ,total flavonoids and the ratio of 1∶2 to mice maximum tolerance was respectively 300 ,345 ,325 g/kg .Conclusion For the same total dosage ,the relieving asth‐ma effects of proportions of 1∶2 Aster ageratoides Turcz were obvious .There are no abnormal changes in the acute toxicity trila with total flavonoids ,total saponins ,as well as the ratio of 1∶2 ,safety is relatively good .

A microwave digestion system was preparation for the digestion of the sediment samples of 16 stations in the Southe mid_Atlantic ridge by using HNO3_H2 O2_HF as the digestion reagent. The rare earth elements ( RE ) in sediments were determined by inductively coupled plasma mass spectrometry, and distribution characteristics of rare earth elements were studied. The microwave digestion_ICP_MS method was used for the determination of rare earth elements with a good linear relationship ( r=0 . 9997-1 . 0000 ) for each element. The detection limit reached ng/L level, the relative standard deviation ( RSD, n=3 ) was less than 3% and the relative error was 6%. The total amount of rare earth elements (ΣRE) in sediment samples from 16 stations varied in the range of 37. 25-134. 77 μg/g, the ratio range of light RE/heavy RE ( LRE/HRE) was 0 . 61-1 . 70 , the average value was 1 . 27 , and the enrichment of light rare earth elements in sediments was slightly obvious. The RE distribution patterns were basically the same in each station with obvious fractionation between LRE and HRE. The RE distribution patterns were also similar in sediments from different sources with slightly difference between terrestrial and marine sediments. The δEu and δCe in the sediments had negative anomaly which showed that the rare earth elements in sediments came from the seawater. This study first analyzed the content and distribution of rare earth elements in the southern Atlantic, providing data and technical support for further study of the distribution of rare earth elements in the Atlantic.

Objective:To explore a new training mode for nursing professionals suitable for the 1+X certificate system, and realize the training goal of "one specialty and multi-ability" compound technical nursing talents.Methods:To take the "1+ X" certificate standard as the basis for the construction of nursing specialty, to reconstruct the talent training program of integration of graduation certificate and certificate. To take the content of "1+X" certificate as the basis for the construction of professional courses, construct the core curriculum system of integration of curriculum and certificate. To build a "new double-qualified" teaching staff and constructing of new double-qualified teachers and accelerate the development of quality resources.Results:The talent training mode of integration of graduation certificate and certificate under the 1+X certificate system was constructed. The curriculum structure has been optimized. The teachers′ability of teaching, training and examination was improved.Conclusions:The new mode of training nursing professionals under the 1+X certificate system meets 1 degree education and X vocational training of nursing students and achieve a "1" and "X" seamless convergence. It provides innovative ideas for the promotion and implementation of 1+X certificate system pilot work in the field of nursing education nationwide.

Objective To investigate the efficacy of different doses of clopidogrel combined with aspirin in the treatment of high-risk non-disabling ischaemic cerebrovascular events(HR-NICE)under the precise guidance of point-of-care testing(POCT)of cy-tochrome P-450 2C19(CYP2C19)genotype.Methods The single-center,randomised,prospective,and blinded endpoint assess-ment was used.HR-NICE patients continuously enrolled in the stroke green channel and neurology ward of Xuzhou Central Hospital from January 2021 to January 2022,and all patients scraping of the buccal mucosa will be screened for CYP2C19 loss-of-function allele car-riers by POCT.According to the random number table method,they were divided into the intensive group(clopidogrel 150mg/d)and the conventional group(clopidogrel 75mg/d)combined with aspirin(100mg/d)dual antiplatelet for 21 days.Baseline information,acute stroke Org 10172 treatment trial(TOAST)staging and 90 days modified Rankin scale(mRS)score and occurrence of adverse events and severe adverse events were collected for the two groups.The primary efficacy outcome was new stroke within 90 days and the primary safety outcome was severe or moderate bleeding within 90 days.Results A total of 1301 patients were screened,of which 727 patients carried CYP2C19 loss-of-function allele,and 476 patients were included:236 patients in the intensive group and 240 patients in the conven-tional group.The differences between the two groups were not statistically significant at baseline(P>0.05);4 cases(1.7%)inthein-tensive group and 26 cases(10.8%)in the conventional group had a new stroke at 90 days.The differences between the two groups were statistically significant(χ2 = 16.827,P<0.001);0 case(0)in the intensive group and1 case(2.5%)in the conventional group had moderate to severe haemorrhage at 90 days.The differences between the two groups was not statistically significant(P>0.05).Conclu-sion In HR-NICE patients with CYP2C19 loss-of-function allele,the enhanced clopidogrel dose was more effective than the conven-tional dose in the treatment with the antiplatelet drug aspirin combined with clopidogrel,and had a consistent safety profile with no more adverse events such as bleeding.

Objective:To explore the efficacy and safety of different anti-platelet regimens in the treatment of high-risk non-disabling ischemic cerebrovascular events (HR-NICE) guided by point-of-care testing of CYP2C19 gene. Methods:A single-centre, prospective, randomised, open-label, and blinded endpoint design was uesd in the study. From July 2020 to January 2022, HR-NICE patients were enrolled in the Stroke Green Channel and Department of Neurology of Xuzhou Central Hospital, and all patients were scraped the buccal mucosa for screening for CYP2C19 loss-of-function allele carriers by point-of-care testing . Patients with intermediate metabolism were defined as those who carried 1 loss-of-function allele and patients with poor metabolism were those who carried 2 loss-of-function alleles. This study reduced the test turnaround time to 1 hour by using a fully automated medical polymerase chain reaction analyzer for a point-of-care test of CYP2C19 genotype. CYP2C19 loss-of-function allele carriers were divided according to the random number table method into the conventional treatment group (clopidogrel 75 mg, once a day), the ticagrelor group (ticagrelor 90 mg, twice a day) and the intensive dose group (clopidogrel 150 mg, once a day) separately combined with aspirin (100 mg, once a day) dual antiplatelet for 21 days. Baseline information, Acute Stroke Org 10172 Treatment Trial staging, 90-day modified Rankin Scale score, occurrence of adverse events and severe adverse events were collected for all the 3 groups. The primary efficacy outcome was new stroke within 90 days, and the primary safety outcome was severe or moderate bleeding within 90 days. Results:A total of 716 patients were included: 240 in the conventional treatment group, 240 in the ticagrelor group and 236 in the intensive dose group. There was no statistically significant difference between the 3 groups at baseline (all P>0.05). There were 26 cases (10.8%) with new stroke events in the conventional treatment group, 11 cases (4.6%) in the ticagrelor group and 4 cases (1.7%) in the intensive dose group, with statistically significant differences among the 3 groups (χ 2=19.28, P<0.05), and the differences between the conventional treatment group and the ticagrelor group (χ 2=6.59, P=0.010) and between the conventional treatment group and the intensive dose group (χ 2=16.83, P<0.001) were statistically significant, whereas the difference between the ticagrelor group and the intensive dose group was not statistically significant ( P>0.05). In the 3 groups, there was 1 case (0.4%) of severe bleeding in the conventional treatment group, 6 cases (2.5%) in the ticagrelor group and none in the intensive dose group, which showed statistically significant differences (χ 2=7.23, P<0.05), and there was statistically significant difference between the ticagrelor group and the intensive dose group ( P=0.030). Among the patients with intermediate CYP2C19 metabolism, there were 13 cases (13/158, 8.2%) with 90-day recurrent stroke in the conventional treatment group, 4 cases (4/153, 2.6%) in the ticagrelor group, and 0 case (0/159) in the intensive dose group, with statistically significant difference (χ 2=16.04, P<0.001), and the differences between the intensive dose group and the conventional treatment group were statistically significant (χ 2=13.64, P<0.001), whereas there was no statistically significant difference between the intensive dose group and the ticagrelor group ( P>0.05). In the patients with 90-day recurrent stroke in the intensive dose group, there was 0 case (0/159) with intermediate metabolism and 4 cases (4/77,5.2%) with poor metabolism, with statistically significant differences ( P=0.011), whereas there were no statistically significant differences in the conventional treatment group and the ticagrelor group ( P>0.05). Conclusions:Screening carriers of CYP2C19 loss-of-function alleles by point-of-care testing can quickly and precisely guide the treatment of patients with non-cardiogenic HR-NICE. An intensive clopidogrel dose of 150 mg, once a day combined with aspirin was effective in reducing stroke recurrence with less occurrence of any bleeding and adverse events, and patients with intermediate CYP2C19 metabolism may be the best population to benefit.

ObjectiveTo investigate the effects of Jiaohong pills （JHP） and its prescription， Pericarpium Zanthoxyli （PZ） and Rehmanniae Radix （RR） cognitive dysfunction in scopolamine-induced Alzheimer's disease （AD） mice and its mechanism through pharmacodynamic and metabolomics study. MethodThe animal model of AD induced by scopolamine was established and treated with PZ， RG and JHP， respectively. The effects of JHP and its formulations were investigated by open field test， water maze test， object recognition test， avoidance test， cholinergic system and oxidative stress related biochemical test. Untargeted metabolomics analysis of cerebral cortex was performed by ultra-performance liquid chromatography-Quadrupole/Orbitrap high resolution mass spectrometry （UPLC Q-Exactive Orbitrap MS）. ResultThe behavioral data showed that， compared with the model group， the discrimination indexes of the high dose of JHP， PZ and RR groups was significantly increased （P<0.05）. The staging rate of Morris water maze test in the PZ， RR， high and low dose groups of JHP was significantly increased （P<0.05， P<0.01）， the crossing numbers in the PZ， JHP high and low dose groups were significantly increased （P<0.05， P<0.01）； the number of errors in the avoidance test were significantly reduced in the PZ and high-dose JHP groups （P<0.01）， and the error latencies were significantly increased in the JHP and its prescription drug groups （P<0.01）. Compared with the model group， the activities of acetylcholinesterase in the cerebral cortex of the two doses of JHP group and the PZ group were significantly increased （P<0.05， P<0.01）， and the activity of acetylcholinesterase in the high-dose JHP group was significantly decreased （P<0.05）， and the level of acetylcholine was significantly increased （P<0.01）. At the same time， the contents of malondialdehyde in the serum of the two dose groups of JHP decreased significantly （P<0.05， P<0.01）. The results of metabolomics study of cerebral cortex showed that 149 differential metabolites were identified between the JHP group and the model group， which were involved in neurotransmitter metabolism， energy metabolism， oxidative stress and amino acid metabolism. ConclusionJHP and its prescription can antagonize scopolamine-induced cognitive dysfunction， regulate cholinergic system， and reduce oxidative stress damage. The mechanism of its therapeutic effect on AD is related to the regulation of neurotransmitter， energy， amino acid metabolism， and improvement of oxidative stress.