OBJECTIVE To investigate the types of neurons that influence the head twitch response(HTR)induced by 5-hydroxytryptaminergic(5-HTergic)psychedelic mescaline in mice.METHODS①Adult male C57BL/6J mice were randomly divided into the normal control group and mescaline(1.56,3.125,6.25,12.5,25 and 50 mg·kg-1)groups,with 15 mice in each group.The drugs of the corresponding groups were ip given,and the HTR frequency of mice was recorded for 30 min.② 5-HT 2A receptor(5-HT2AR)gene bilateral LoxP homozygous mice(5-HT2A flox/flox)were hybridized with calmodulin depen-dent protein kinaseⅡα cyclization recombination enzyme positive(CaMKⅡαcre/+),parvalbumin(PV)cre/+,somatostatin(SOM)cre/+or vasoactive intestinal peptide(VIP)cre/+mice to obtain 5-HT2A R conditional knockout(cKO)mice(5-HT2AΔCaMKⅡα,5-HT2AΔPV,5-HT2AΔSOM and 5-HT2AΔVIP).Each type of cKO mice was randomly divided into the normal control group and mescaline 12.5 mg·kg-1 group,with 15 mice in each group.The drugs of the corresponding groups were ip given before the HTR frequency of mice within 30 min was recorded.③ Each type of cKO mice was randomly divided into the normal control group and mescaline 12.5 mg·kg-1 group,with 12 mice in each group.After receiving the corresponding drug via ip,they were placed in a spontaneous activity test box for 30 minutes and their activity levels were recorded.RESULTS ① Compared with the normal control group,mescaline 3.125,6.25,12.5 and 25 mg·kg-1 significantly increased the HTRs of mice(P<0.05,P<0.01).② Among the different neuronal types of 5-HT2AR cKO mice,only 5-HT2A ΔCaMKⅡα mice had no difference in HTR frequency between the normal control group and the mescaline 12.5 mg·kg-1 group.In 5-HT2AΔPV,5-HT2AΔSOM and 5-HT2AΔVIP mice,the HTRs of mice in the mescaline 12.5 mg·kg-1 group were significantly increased(P<0.01)compared with the normal control group.③ There was no difference in spontaneous activity between the normal control group and the mescaline 12.5 mg·kg-1 group of all cKO mice.CONCLU-SION Pyramidal neurons are involved in mediating the induction of mescaline on HTRs in mice.

OBJECTIVE To establish the cells stably co-expressing α1A-adrenergic receptor(α1A-AR)and enhanced green fluorescent protein(EGFP)tagged nuclear factor of activated T cells 2(NFAT2)(EGFP-NFAT2)in U2OS cells.METHODS ① The pcDNA3.1-α1-AR-3×FLAG recombinant plasmid was transfected into U2OS-EGFP-NFAT2 cells.The transfected cells were selected by hygromycin B(Hygro-B,200 mg·L-1),and screened by EGFP-NFAT2 nuclear translocation assay after α1A-AR agonist norepinephrine(NE)treatment of 30 min.② The mRNA and protein expression levels of α1A-AR in the selected U2OS-EGFP-NFAT2-α1A-AR cells were examined by real-time quantitative PCR(RT-qPCR)and Western blotting.③ U2OS-EGFP-NFAT2-α1A-AR cells were treated with NE(10-8-10-5 mol·L-1)or dexmedetomidine(DMED,10-8.8-10-5 mol·L-1),respectively,for 30 min.EGFP-NFAT2 nuclear translo-cation was detected by high throughout screening assay.④ The U2OS-EGFP-NFAT2-α1A-AR cells were divided into the solvent control group,α1-AR antagonist naftopidill(1 μmol·L-1)group,NE(1 μmol·L-1)group and naftopidill+NE(co-incubation with naftopidill 1 μmol·L-1 and NE 1 μmol·L-1)group,α2-AR antagonist atipamezole(ATI,0.1 μmol·L-1)group,α 2-AR agonist DMED(0.1 μmol·L-1)group,and ATI+DMED(co-incubation with ATI 1 μmol·L-1 and DMED 0.1 μmol·L-1)group.The drug incubation time was 30 min.EGFP-NFAT2 nuclear translocation was abserved via a high throughout screening system to validate the α1A-AR function in U2OS-EGFP-NFAT2-α1A-AR cells.RESULTS ① There were 58 cell strains expressing α1A-AR in U2OS-EGFP-NFAT2 cells by EGFP-NFAT2 nuclear translocation assay.Among these cells,cells No 50 had the highest nuclear translocation function.The α1A-AR mRNA expression of cells No 50 in 5-20 generations were detected by RT-qPCR and were about 500-800 times that of U2OS-EGFP-NFAT2 cells.② The protein band of α1A-AR was also detected in cells No 50,but no band of α1A-AR was detected in U2OS-EGFP-NFAT2 cells by Western blotting.③ NE and DMED increased the relative translocation nuclear index in U2OS-EGFP-NFAT2-α1A-AR cells with ED50 5.94×10-7 and 6.15×10-8 mol·L-1,respectively.④ EGFP-NFAT2 nuclear translocation was significant in U2OS-EGFP-NFAT2-α1A-AR cells after NE addition compared with the solvent control or the naftopidill groups(P<0.01).The EGFP-NFAT2 nuclear translocation in the naftopidill+NE group was significantly decreased compared with the NE group(P<0.01).DMED significantly increased the EGFP-NFAT2 nuclear translocation compared with solvent control or the ATI groups(P<0.01).The EGFP-NFAT2 nuclear translocation in the ATI+DMED group was similar to that of the DMED group.The EGFP-NFAT2 nuclear translocation in the naftopidill+DMED group was decreased significantly compared with the DMED group(P<0.01).CONCLUSION U2OS-EGFP-NFAT2-α1A-AR cells stably co-exrepssing α1A-AR and EGFP-NFAT2 are established,which can be used for high throughout screening of biased chemicals and studies on the mechanism of α1A-AR.

Objective:To observe the effect of lung distension stabilization formula combined with Liu Zi Jue exercise on the rehabilitation of patients with lung and kidney deficiency syndrome in stable phase of chronic obstructive pulmonary disease (COPD).Methods:Randomized controlled trial. A total of 179 patients with lung and kidney deficiency syndrome in stable COPD (admitted from April 2019 to April 2022) were enrolled in this study. The patients were randomly divided into western medicine conventional treatment group, combined treatment group and Liu Zi Jue group by random number table method. All the patients in the group received conventional western medicine treatment, and 59 patients in the Liu Zi Jue group received Liu Zi Jue treatment. Combined treatment group to take Liu Zi Jue + Lung distension stabilization formula. Data observation: clinical curative effect and TCM syndrome and total integral change before and after the treatment level of interleukin 8 (IL-8), pulmonary function index changes, COPD patients self-assessment scale (CAT) score, st George's hospital respiratory questionnaire (SGRQ) scores change were observed.Results:The total response rate was 66.67% (40/60) in the conventional treatment group, 83.05% (49/59) in the Liu Zi Jue group and 96.67% (58/60) in the combined treatment group. The total response rate in the combined treatment group was significantly higher than that in the conventional treatment group and the Liu Zi Jue group ( Z=3.76, P<0.01). The Liu Zi Jue group was significantly higher than the conventional western medicine group ( χ2=4.24, P=0.040). After treatment, the symptom score of combined treatment group was significantly lower than that of Liu Zi Jue group and conventional treatment group ( F=14.87, P<0.01), and that of Liu Zi Jue group was significantly lower than that of conventional treatment group ( t=5.87, P<0.01). The scores of CAT and SGRQ were significantly lower than those in the Liu Zi Jue group and conventional treatment group ( F values were 76.72 and 312.36, P<0.01), and those in Liu Zi Jue group were significantly lower than that of the conventional treatment group ( t=4.97, P<0.01). After treatment, the serum IL-8 level of the combined treatment group was significantly lower than that of the Liu Zi Jue group and the conventional treatment group ( F=154.64, P<0.01), and the Liu Zi Jue group was significantly lower than that of the conventional treatment group ( t=11.35, P<0.01). FVC [(2.93±0.60) L vs. (2.49±0.65) L, (2.25±0.63) L, F=20.62], FEV1 [(2.20±0.42) L vs. (1.88±0.41) L, (1.72±0.40) L, F=21.30] and FEV1% [(42.34±4.86) % vs. (38.85±5.00) %, (36.95±4.91) %, F=18.49] were significantly higher than those in the Liu Zi Jue group and conventional treatment group ( P<0.01). The Liu Zi Jue group was higher than that of the conventional treatment group ( t values were 3.76, 2.87, 5.15, P<0.01). Conclusion:Lung distension stabilization formula combined with Liu Zi Jue exercisecan promote the rehabilitation of COPD patients with lung and kidney deficiency syndrome in stable phase, improve the curative effect of patients, improve lung function, relieve symptoms, and improve the quality of life.

Objective: To understand the infectious disease prevention and control among primary and secondary schools in Hebei Province from 2019 to 2021 and to provide a scientific basis for promoting epidemic prevention and control in schools. Methods: Relevant indicators of infectious disease prevention and control in primary and secondary schools were collected and screened from the on site supervision and inspection data uploaded from various places, and analyzed with SPSS 22.0 software. Results: The qualified rates of infectious disease prevention and control in primary and secondary schools in Hebei Province from 2019 to 2021 were 77.11%, 89.74% and 96.24%, respectively, the difference was statistically significant( χ 2=455.45, P <0.01). The qualified rates of infectious disease prevention and control in primary schools, middle schools and high schools from 2019 to 2021 increased by year, the difference was statistically significant( χ 2=319.49, 118.74, 25.73, P <0.05). The qualified rates of six infectious disease prevention and control indicators such as morning inspection record, special person responsible for epidemic report, registration record of absence due to illness increased by year, the difference was statistically significant( χ 2=140.34, 9.10, 113.55 , 163.71 , 286.74, 329.18, P <0.05). Conclusion Steady improvement in school infectious disease prevention and control has been observed, while qualification rate in primary school and rural area still need to be improved, with missing or late report. Government support and talent policy, hardware and sofeware construction, as management level should be strengthened.

Most α2-AR agonists derived from dexme-detomidine have few structure differences between them and have no selectivity for α2A/2B-AR or Gi/Gs,that can lead to the side effect of drugs.To get novel and potent α2A-AR agonists,we built the homology model for human α 2A-AR and α2B-AR to find α2A-AR agonists with higher selectivity.Compound P300-2342 and its 3 analogs sig-nificantly decreased the locomotor activity of mice(P＜0.05).Furthermore,P300-2342 and its 3 analogs inhibited the binding of[3H]rauwolscine to α 2A-AR and α 2B-AR respectively.In α2A-AR-HEK293 cells,P300-2342 decre-ased forskolinstimulatedcAMPpruductionwithoutincreas-ing cAMP pruduction,that indicated the P300-2342 acti-vating α2A-AR coupling with Gαi/o pathway without Gαs coupling.P300-2342 had no agonistic and antagonistic activities on α 2B-AR.Similar results were shown in 3 analogs of P300-2342.The docking results showed that P300-2342 formed the π-hydrogen bonds with Y394,V114 of α2A-AR,and with V93 of α2B-AR.3 analogs of P300-2342 formed several π-hydrogen bonds with V114,Y196,F390 of α 2A-AR and with V93 of α 2B-AR.We believe that these molecules can serve as leads for fur-ther optimization of α2A-AR agonists with potentially few side effects.

Objective:To explore the impact of King's theory of goal attainment combined with goal setting on the effect of standardized training of general practitioners.Methods:A total of 39 general practitioners who underwent the standardized training in The Fifth Affiliated Hospital of Xinjiang Medical University from January 2019 to January 2020 were classified as control group, and traditional teaching was adopted. Another 42 general practitioners who underwent the training in The Sixth Affiliated Hospital of Xinjiang Medical University during the same period were classified as a research group, and the teaching based on King's theory of goal attainment combined with goal setting was adopted. The theoretical knowledge and operational skills scores, changes in clinical comprehensive ability before and after the training, and teaching recognition were compared between the two groups. SPSS 25.0 was used for t test and chi-square test. Results:After the training, the scores of theoretical knowledge and operation skills of the research group were both higher than those of the control group [(92.83±5.62) vs. (85.47±12.11); (90.15±7.22) vs.(83.36±11.24)]. There was no significant difference between the two groups in the scores of inquiry and communication ability, problem-solving ability, general medical thinking ability, interpretation ability of auxiliary examination results, clinical analysis and decision-making ability, team cooperation ability, community common disease diagnosis and treatment ability and humanistic care ability before the training ( P>0.05); the above scores were all improved after the training ( P<0.05), and the above scores of the research group were significantly higher than those of the control group ( P<0.05). The total recognition of teaching in the research group was 95.24%(40/42), which was significantly higher than that 76.92%(30/39) in the control group ( P<0.05). Conclusion:The application of King's theory of goal attainment combined with goal setting in standardized training of general practitioners can effectively improve the level of general practitioners' theoretical knowledge, operational skills, clinical comprehensive ability and recognition of teaching.

Objective To investigate the function and molecular mechanism of tacrolimus in podocyte injury and restoration.Methods Cultured podocytes were stimulated by Angiotensin Ⅱ (Ang Ⅱ) or Ang Ⅱ plus tacrolimus.Cells were collected at different time points (0 h,12 h and 24 h).The distribution of F-actin was observed after immunofluorescence staining,and the protein expression of nephrin and podocin were detected by Western Blot (WB).Results In normal control podocytes,F-actin was arranged in cytoplasm powerfully.Ang Ⅱ induced the disruption and discontinuity of F-actin.Tacrolimus inhibited the effect of Ang Ⅱ,stabilized the regular arrangement the F-actin.Compared to normal cells,the protein expression of nephrin in Ang Ⅱ group significantly decreased at 24 h after stimulation (0.76 ± 0.32 in AngⅡ group vs.1.18 ± 0.40 in normal group,P ＜ 0.05).And tacrolimus stabilized the expression of nephrin protein (1.00 ± 0.19 in treatment group vs.0.76 ± 0.32 in Ang Ⅱ group,P ＜ 0.05).Ang Ⅱ and tacrolimus did not affect the expression of podocin protein.Conclusion Tacrolimus inhibits podocyte injury induced by Ang Ⅱ,stabilizes the regular arrangement of cytoskeleton and protein expression of nephrin.

Objective To investigate the role of Calcineurin binding protein 1(Cabin1)in renal tubular epithelial cells(RTECs)injury. Methods The male Sprague-Dawley rats were randomly divided into Sham-oper-ated and 5/6 nephrectomized group. Nephrectomized rats were further divided into two groups ,which were 4 and 8 weeks after operation,including 6 rats in each group. Rats were sacrificed at 4 or 8 weeks after nephrectomy,then control or remnant kidneys were harvested. 2μm sections of kidney tissues were collected and stained with Masson's trichrome and were graded for tubulointerstitial lesion score (TILS). RTECs mitochondrial morphology changes were detected by electron microscope. Western blot was applied to detect Cabin1 protein level in the renal tissue. Results At 8 weeks after the operation,plenty of RTECs fell off from the basement membrane,accompanied with interstitial fibrosis and the infiltration of inflammatory cells. Moreover ,TILS were significantly increased in rats at 8 weeks after operation while compared to sham-operated rats(7.16 ± 0.52 vs. 0.00 ± 0.00,P<0.05). RTECs mi-tochondria begun to swell at 4 weeks after 5/6 nephrectomy,while the disruption of cristae could be found in rats at 8 weeks. Cabin1 protein expression apparently increased in the remnant kidney. Cabin1 protein obviously increased in rats at 8 weeks after the surgery compared to sham-operated rats(0.97 ± 0.09 vs. 0.22 ± 0.07,P<0.05)and rats at 4 weeks after nephrectomy(0.97 ± 0.09 vs. 0.45 ± 0.03,P<0.05). Conclusions Cabin1 is overexpressed during RTECs injury in 5/6 nephrectomized rats. It can be a crucial factor regulating the damage of RTECs.

Objective To explore the impact of intensive follow-up visit in patients with nonvalvular atrial fibrillation taking Warfarin in process of anticoagulant therapy. Methods A total of 100 patients with persistent nonvalvular atrial fibrillation were randomly divided them into intensive follow-up group and regular follow-up group on average. We compared the treatment compliance, INR value, embolism and hemorrhage between two groups. Results The INR qualified rate was 86. 0% after 6 months taking medication in the intensive follow-up group and 72. 0% in the regular follow-up group (χ2 =4. 570,P<0. 05). The incidence rate of hemorrhage was 12% in the intensive follow-up group and 28% in the regular follow-up group (χ2 =4. 000,P<0. 05). Conclusions With the function of propaganda, education, supervision, promotion and attention on patients, follow-up visit makes patients taking Warfarin receive normative, effective anticoagulant treatment and improves the safety of medicine use, thus the effect of preventing stroke can be achieved.

Objective To explore the key points of preoperative emergency nursing in the patients with mechanical pros thetic valve dysfunction .Methods The clinical data from five patients with mechanical prosthetic valve dysfunction from March 2010 to November 2012 were retrospectively analyzed , and the key points of preoperative emergency nursing were summarized in the course of the disease .Results Four patients were recovered and discharged after they got the positive and effective rescue and accepted the valve replacement operation;one patient gave up further treatment because of serious condition .Conclusions The mechanical prosthetic valve dysfunction can lead to acute hemodynamic instability and eventually cause death of patients , and the valve replacement operation as the effective treatment should be carried out as early as possible .The preoperative intensive monitor and targeted emergency nursing can help patients to win the operative time and increase the chance of survival .