ObjectiveTo investigate the effects of dopamine receptor agonist pramipexole and levodopa on emotion and cognition, and mitochondrial membrane potential of rats after global cerebral ischemia-reperfusion injury. MethodsA total of 80 male Sprague-Dawley rats were divided into sham group (n = 20), model group (n = 20), pramipexole group (n = 20) and combined group (n = 20). The latter three groups were used to prepare the model of global cerebral ischemia-reperfusion injury with Pulsinelli's four-vessel occlusion. The pramipexole group was intraperitoneally injected pramipexole 0.5 mg/kg once a day, while the combined group was injected levodopa 50 mg/kg and pramipexole 0.5 mg/kg, for 14 days. Five rats in each group were tested with open field test three, seven and 14 days after modeling; five were tested with Y-maze test seven and 14 days after modeling; five were detected mitochondrial membrane potential three, seven and 14 days after modeling; and five were observed under Nissl's staining14 days after modeling. ResultsCompared with the model group, the number of entries into the central zone (P < 0.05), total distance travelled (P < 0.05) and average velocity (P < 0.05) in the open field test increased in the pramipexole and combined groups seven and 14 days after modeling, duration spent in the central zone increased in the pramipexole and combined groups seven days after modeling (P < 0.05); the rate of spontaneous alternation of Y-maze test increased in the pramipexole and combined groups 14 days after modeling (P < 0.05); mitochondrial membrane potential in hippocampus increased in the pramipexole and combined groups seven and 14 days after modeling (P < 0.05), and it was less in the pramipexole group than in the combined group 14 days after modeling (P < 0.05); and the number of surviving neurons in the hippocampal CA1 increased in the pramipexole and combined groups 14 days after modeling (P < 0.05). ConclusionPramipexole may improve emotion and cognition of rats after global cerebral ischemia-reperfusion injury, and it may be helpful for restoring mitochondrial membrane potential as combining with levodopa.

Objective:To explore the efficacy and safety of camrelizumab combined with apatinib as the second-line treatment for patients with advanced gastric cancer.Methods:The clinical data of 19 patients with advanced gastric cancer in Hebei General Hospital from August 2019 to March 2022 were retrospectively analyzed. All patients received camrelizumab combined with apatinib as the second-line treatment. The treatment efficacy and adverse reactions were evaluated; the survival analysis was performed using Kaplan-Meier method; Cox proportional hazards model was used to analyze the influencing factors for overall survival (OS) of patients.Results:Among 19 patients, no one achieved complete remission, 4 patients (21.1%) achieved partial remission, 9 patients (47.4%) had stable disease. The objective response rate (ORR) and disease control rate (DCR) were 21.1% (4/19) and 68.4% (13/19), respectively. The ORR of patients with deficient mismatch repair (dMMR) was higher than that of patients with proficient mismatch repair (pMMR) [100.0% (2/2) vs. 11.8% (2/17), P < 0.05], and patients with programmed death receptor ligand 1 (PD-L1) combined positive score (CPS) ≥1 had a higher DCR than patients with PD-L1 CPS < 1 [100.0% (5/5) vs. 25.0% (1/4), P < 0.05]. The median follow-up time of 19 patients was 14.7 months (12.0-17.4 months), the median progression-free survival time and OS time were 2.8 months and 5.7 months (95% CI 2.4-8.9 months). Increased lactate dehydrogenase (LDH) was negatively correlated with OS ( χ2 = 10.262, P = 0.001). Multivariate Cox regression analysis showed that LDH was an independent influencing factor for the OS of patients (<250 U/L vs. ≥250 U/L: HR = 0.149, 95% CI 0.039-0.657, P = 0.005). The most common treatment-related adverse reactions were fatigue (52.6%, 10 cases), anemia (47.4%, 9 cases), thrombocytopenia (36.8%, 7 cases), rash (36.8%, 7 cases), and reactive capillary hemangioma (36.8%, 7 cases). Conclusions:Camrelizumab combined with apatinib as the second-line treatment for advanced gastric cancer have good efficacy and safety.

Objective The use of the antifungal agent itraconazole and the calcineurin inhibitor tacrolimus alone, together with the above two drugs, was evaluated in vitro for growth of Candida krusei. Whether or not the combina-tion is more effective than the antifungal alone can inhibit the growth of Candida krusei. Methods According to the guidelines of the American Institute of Clinical and Laboratory Standards, 12 Candida krusei strains were divided into blank control group, itraconazole group, tacrolimus group, and combination group by microdilution method, and then 12 the Candida krusei strain was incubated for 24 h and its growth was observed. Results In comparison with the alone use of isotriconazole in Candida krusei, the combined use of itraconazole,its minimal inhibitory con-centration was much less than that of alone, with a maximum multiple of 32 fold, a minimum multiple up to 4 times; the same, In comparison with the alone use of tacrolimus in Candida krusei, the combined use of tacroli-mus, its maximum multiple of 32 times, the lowest multiple of 2 times. Conclusion The combined use of itracon-azole and tacrolimus in 12 strains of Candida krusei displayed a powerful synergistic effect in vitro.

Objective To analyze the effects of valproic acid(VPA),a histone deacetylase(HDAC)inhibitor,on macrophage polarization in?duced by paraquat(PQ)or lipopolysaccharide(LPS). Methods Mouse RAW264.7 cells were cultured at 37℃with 5%CO2,passaged,and then given one of the following treatments:(1)PQ;(2)PQ+VPA(classⅠandⅡa HDAC inhibitor);(3)PQ+apicidin(classⅠHDAC inhibitor);(4)PQ+MC1568(classⅡa HDAC inhibitor);(5)LPS;(6)LPS+VPA;(7)LPS+apicidin;(8)LPS+MC1568. The cells and culture supernatants were harvested after 8 h of treatment. RT?PCR,ELISA,and flow cytometry were conducted to assess the expression levels of macrophage phenotyp?ic markers. Results Both PQ and LPS skewed the macrophage functional polarity toward proinflammatory phenotype. VPA,apicidin,and MC1568 all inhibited PQ?and LPS?induced macrophages polarizing toward pro?inflammatory phenotype ,but the inhibitory effects were different in some ways. Conclusion VPA inhibits the proinflammatory function of macrophages induced by PQ and LPS ,but the effect of VPA on PQ?and LPS?induced macrophages has its own characteristics.

Objective To investigate whether the effect of transient high glucose on inflammatory factors expression could be continuous in rat glomerular mesangial cell,and its relation with histone methylation modification.Methods Rat glomerular mesangial cells (HBZY-l) were divided into three groups:the high glucose group (25.0 mmol/L glucose),the hypertonic group (MA,5.5 mmol/L glucose+ 19.5 mmol/L mannitol) and the normal-glucose control group (5.5 mmol/L glucose),which were cultured for 24 h respectively.All 3 groups were then changed with normal-glucose medium to culture for 24 h,48 h and 72 h.Their protein,mRNA and supernatant were harvested.The protein expressions of mono-methylation of H3 lysine 4 (H3K4mel) was measured by Western blotting,and the mRNA expressions of NF-κB subunit p65 and set7/9 were determined by real timequantitative PCR.The expression of monocyte chemoattractant protein 1 (MCP-1) and vascular cell adhesion molecule 1 (VCAM-1) were detected by enzyme-linked immunosorbent assay.Results (1)Compared with those in normal control group,the expressions of H3K4mel protein and set7/9 mRNA were first up-regulated in high glucose group,then gradually down-regulated in the following 48 h normal-glucose medium (as compared with those at 0 h,all P ＜ 0.05).At 72 h there was no statistic difference between high glucose group and normal control group (all P ＞ 0.05).(2) Compared with those in normal control group,the up-regulated p65 mRNA,VCAM-1 and MCP-1 sustained at least for 72 h in high glucose group.Conclusions Transient high glucose can induce persistent inflammatory factors expression in rat glomerular mesangial cells,which may via histone modification.

OBJECTIVE:To explore the role of clinical pharmacists providing pharmaceutical care for hemodialysis patients complicated with subacute infective endocarditis(IE). METHODS:Clinical pharmacists participated in the anti-infection treatment for a hemodialysis patients complicated with subacute IE,according to the antimicrobial spectrum,laboratory and imaging find-ings,and patient’s condition changes,assisted physician to optimize the regimen,clinical pharmacists suggested to give imipenem cilastatin sodium after hemodialysis,adjust the initial dose of teicoplanin and give 1 g vancomycin firstly,and maintained 0.5 g af-ter hemodialysis,then adjust its dose based on blood plasma concentration;during treatment,clinical pharmacists closely observed the treatment effect and adverse reactions,providing blood plasma concentration monitoring,medication reminding and medication education. RESULTS:Physicians adopted parts of suggestions of clinical pharmacists,no fever was found,hemogram returned to normal,no abnormal echocardiography,and patient discharged. CONCLUSIONS:Clinical pharmacists guarantee the safety and ef-ficacy of drug use by adopting dose of anti-infection drugs,evaluating efficacy,monitoring adverse reactions and vancomycin plas-ma concentration,and assisting physicians to optimize treatment regimen.

Administration, Oral ; Anticoagulants ; adverse effects ; Aspirin ; adverse effects ; Epistaxis ; chemically induced ; Humans

OBJECTIVE To explore the molecular mechanism for a blood sample with mixed-field hemagglutination upon determination of ABO blood group. METHODS Serological techniques were employed to identify the erythrocyte phenotype. The A and B antigens were detected by flow cytometry. The preliminary genotype of ABO gene was assayed with sequence-specific primer-polymerase chain reaction (PCR-SSP). Exons 6 and 7 of the ABO gene were amplified with PCR and analyzed by direct sequencing. Haplotypes of the ABO gene were analyzed by cloning sequencing as well. RESULTS The serological reaction pattern has supported an O phenotype when all the tubes were centrifuged for the first time. However, a mixed-field hemagglutination of red blood cells (RBCs) with anti-A antibodies was present after the tube was centrifuged five times later. A antigens were detected on the surface of partial red blood cells of the sample by flow cytometry. PCR- SSP results have shown that the preliminary ABO genotype was A/O. Analysis of the fragments of exons 6 and 7 of the ABO gene has indicated that heterozygosis lied as follows: 261G/A, 425T/T, 467C/T, 646A/T, 681A/G, 745C/T, 771C/T, 829A/G, conjecturing the genotype to be A307/O02, which was confirmed by haplotype sequence analysis. Compared with A101 allele, A307 allele has two missense mutations, 467C> T and 745C> T, which have resulted in substitutions Pro156Leu and Arg249Trp in the A glycosyltransferase polypeptide chain. CONCLUSION A variant allele (A307) has been identified for the first time in mainland China, which is responsible for the formation of A3 phenotype.
ABO Blood-Group System ; genetics ; Adult ; Genotype ; Humans ; Male ; Phenotype

OBJECTIVETo screen rare blood groups Fy(a-), s-, k-, Di(b-) and Js(b-) in an ethnic Zhuang population.

METHODSSequence-specific primers were designed based on single nucleotide polymorphism (SNP) sites of blood group antigens Fy(b) and s. A specific multiplex PCR system I was established. Multiplex PCR system II was applied to detect alleles antigens Di(b), k, Js(b)1910 and Js(b) 2019 at the same time. The two systems was were used to screen for rare blood group antigens in 4490 randomly selected healthy donors of Guangxi Zhuang ethnic origin.

RESULTSWe successfully made the multiplex PCR system I. We detected the rare blood group antigens using the two PCR system. There are five Fy(a-), three s(-), two Di(b-) in 4490 Guangxi zhuang random samples. The multiplex PCR system I has achieved good accuracy and stability. With multiplex PCR systems I and II, 4490 samples were screened. Five Fy(a-), three s(-) and two Di(b-) samples were discovered.

CONCLUSIONMultiplex PCR is an effective methods, which can be used for high throughput screening of rare blood groups. The rare blood types of Guangxi Zhuang ethnic origin obtained through the screening can provide valuable information for compatible blood transfusion. Through screening we obtained precious rare blood type materials which can be used to improve the capability of compatible infusion and reduce the transfusion reactions.

Blood Group Antigens ; genetics ; Duffy Blood-Group System ; genetics ; Genotype ; Humans ; Multiplex Polymerase Chain Reaction ; methods ; Receptors, Cell Surface ; genetics

Objective To analyze the results of sputum culture from smear-positive pulmonary tuberculosis cases after treatment for 2 months.Methods Sputum specimens from newly diagnosed 147 smear-positive pulmonary tuberculosis cases after treatment for 2 months were fast cultured by BacT/ALERT 3D.Poeitive cultures were further detected by HAIN test in Zhejiang Provincial Center for Disease Control and prevention and compared with L-J meditun.Results Mycobacteria were found in 45 specimens by Bact/ALERT 3D in contrast to 22 by Lonswtein-Jenson method.The median time was 19.3 days for the whole Bact/ALERT 3D test while the whole procedure would cost 3 months for traditional L-J test.Conclusion Results from sputum smear could not reflect tuberculosis progress properly while BacT/ALERT 3D fast culture would help to find drug resistant patients promptly and accurately.