To investigate the therapeutic effect and related mechanisms of hordenine on ovalbumin (OVA)-induced allergic rhinitis (AR) in rats, HE and AB-PAS staining were used to detect the improvement of pathological damage to the nasal mucosa induced by hordenine. ELISA was employed to detect the effect of hordenine on OVA-sIgE in serum and IL-4 in the nasal mucosa supernatant of rats. IHC and Western blot experiments were undertaken to examine the effect of hordenine on Th1/Th2 cell balance. Bioinformatics analysis was performed to predict pathways, which were verified by in vivo and in vitro experiments. The experimental results showed that hordenine could alleviate the behavioral manifestations of OVA-induced AR rats, alleviate nasal mucosal pathological damage caused by AR, and reduce the secretion of OVA-sIgE and IL-4. In addition, hordenine could regulate the Th1/Th2 balance. Bioinformatics analysis results showed that the potential pathway of action of hordenine on AR was the phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway. The in vivo experimental results showed that the expression of PI3K and p-Akt proteins in the nasal mucosa of the model group rats was significantly increased (P < 0.01), and that the protein expression level was significantly decreased after the administration of hordenine, which was also confirmed by an in vitro experiment. This study suggests that hordenine may regulate Th1/Th2 cell balance through the PI3K/Akt signaling pathway, thereby exerting an alleviating effect on OVA-induced AR.

Background::Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) can profoundly affect the mental health of the people living with HIV (PLWH), with higher rates of anxiety, depression, and sleep disturbances. The disparities in neuropsychological problems evaluated by physicians and self-assessed by patients are still unknown.Methods::A total of 5000 PLWH and 500 physicians from 167 hospitals were enrolled in this cross-sectional study from September 2022 to February 2023. 4-Item Patient Health Questionnaire (PHQ-4) was used for the evaluation of depressive issues and anxiety issues by PLWH. Each physician assessed 10 PLWH under their care for the presence of depressive or anxiety issues. The primary outcomes of this study are the concordance rates on the depressive issues and anxiety issues evaluation between physicians and PLWH. The Cohen’s kappa test was used to assess the agreement between physicians and PLWH.Results::The concordance rate for the evaluation of depressive issues is 73.84% (95% confidence interval [CI]: 72.60-75.04%), and it is significantly different from the expected rate of 80% ( P <0.001). Similarly, the concordance rate for the evaluation of anxiety issues is 71.74% (95% CI: 70.47-72.97%), which is significantly different from the expected rate of 80% as per the null hypothesis ( P <0.001). The overestimation rate by physicians on depressive issues is 12.20% (95% CI: 11.32-13.14%), and for anxiety issues is 12.76% (95% CI: 11.86-13.71%). The mismatch rate for depressive issues is 26.16% (95% CI: 24.96-27.40%), and for anxiety issues is 28.26% (95% CI: 27.02-29.53%). The underestimation rate by physicians on depressive issues is 13.96% (95% CI: 13.03-14.95%), and for anxiety issues is 15.50% (95% CI: 14.52-16.53%). For the treatment regiments, PLWH sustained on innovative treatment regimen (IR) related to a lower prevalence of depressive issues (odds ratio [OR] = 0.71, 95% CI: 0.59-0.87, P = 0.003) and a lower prevalence of anxiety issues (OR = 0.63, 95% CI: 0.52-0.76, P <0.001). PLWH switch from conventional treatment regimen (CR) to IR also related to a lower prevalence of depressive issues (OR = 0.79, 95% CI: 0.64-0.98) and a lower prevalence of anxiety issues (OR = 0.81, 95% CI: 0.67-0.99). Conclusion::Nearly one in three PLWH had their condition misjudged by their physicians. The findings underscore the need for improved communication and standardized assessment protocols in the care of PLWH, especially during the acute phase of HIV infection.

Objective:To explore the distribution characteristics of brachial-ankle pulse wave velocity (BaPWV) in adolescents.Methods:Cross sectional survey research.A total of 1 607 adolescents aged 12-17 years from 5 middle schools in the Haidian District, Beijing from June 2020 to May 2021 were enrolled for measuring their blood pressure, weight, height and the body mass index (BMI), including 782 males and 825 females.BaPWV was measured using an arteriosclerosis detector.They were divided by the age, sex and obesity.Differences of measurement data among multiple groups were compared by one-way ANOVA, followed by the LSD test, and those between groups were compared by the two-sample t-test.The correlation between BaPWV and other indexes was assessed by the Pearson correlation analysis. Results:The median level of BaPWV in adolescents aged 12-17 years increased with age, which was 982.50 cm/s in adolescents aged 12 years, and maximum 1 113.50 cm/s those aged 17 years.BaPWV in adolescents aged 12-17 years was positively correlated with age ( r=0.936, P=0.006). Subgrouped by the sex, the median BaPWV of male and female adolescents aged 12 years was 962.25 cm/s and 997.50 cm/s, respectively, which reached 1 122.50 cm/s and 1 096.00 cm/s in those aged 17 years, respectively.BaPWV of male and female adolescents was positively correlated with the age ( r=0.903, P=0.014; r=0.945, P=0.004). In male adolescents, BaPWV was positively correlated the systolic and diastolic blood pressure, age, weight, height, BMI( r=0.308, P<0.001; r=0.289, P<0.001; r=0.478, P<0.001; r=0.190, P<0.001; r=0.315, P<0.001; r=0.109, P=0.002). In female adolescents, BaPWV also was positively correlated the systolic and diastolic blood pressure, age, weight, height, BMI( r=0.340, P<0.001; r=0.285, P<0.001; r=0.379, P<0.001; r=0.115, P=0.001; r=0.170, P=0.001; r=0.097, P=0.014). In the overall population, BaPWV was statistically significant between the obese and normal groups ( t=-3.428, P=0.001). No significant difference in BaPWV between male and female adolescents aged 12-13 years was identified ( t=0.123, P=0.902 ), but it was significantly lower in female adolescents aged 14-15 years and 16-17 years than those of age-matched males( t=2.315, P=0.021; t=2.152, P=0.032). Conclusions:The median BaPWV level in adolescents aged 12-17 years, increases with the age.Systolic blood pressure, diastolic blood pressure, body weight, BMI, age and height are positively correlated with BaPWV in adolescents.Obesity can increase the stiffness of blood vessels, which is influenced by the sex.

Objective:To compare the expression level of exosomal miR-503 in peritoneal dialysis effluent (PDE) from patients of different peritoneal transport characteristics, predict the target genes of miR-503 and provide bioinformatic data for researches of peritoneal transport characteristics.Methods:Twenty-four stable peritoneal dialysis (PD) patients were selected and divided into high transport group (H group, n=12) and low transport group (L group, n=12) according to the results of peritoneal equilibration tests (PET). The 500 ml PDE that was left on the patient's abdomen overnight was collected and concentrated using ultrafiltration cell. Exosomes in PDE were resuspended in phosphate buffered saline (PBS) after ultracentrifugation and the characteristics of PDE exosomes were identified by transmission electron microscope (TEM), nanoparticle tracking analysis (NTA), Western blotting and fluorescent staining. MicroRNAs were extracted from PDE exosomes. The expression levels of PDE exosomal miR-503 in the two groups were detected by quantitative real-time PCR. Then the relations between the relative quantity of PDE exosomal miR-503 and PET values or 24 h ultrafiltration volume (UF) were analyzed. Targetscan and miRDB databases were used to predict the target genes of miR-503. Gene ontology (GO) functional enrichment and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analysis were relied on DAVID (https://david.ncifcrf.gov/). Results:The exosomes in PDE showed a round and cup-shaped morphology under TEM, and the diameters were approximately 100 nm measured by NTA. The specific biomarkers of exosomes, CD63, CD81 and heat shock protein -70 (HSP-70) were all detected by Western blotting. The internalization and uptake of the exosomes was observed after fluorescent staining. The relative expression level of PDE exosomal miR-503 in H group was found to be significantly higher than that in L group ( P=0.002), and the relative quantity of PDE exosomal miR-503 was significantly positively correlated with PET values ( r=0.547, P=0.006), but not 24 h UF ( r=-0.297, P=0.159). There were 156 target genes of miR-503 in total that could be predicted by two different databases at the same time. GO analysis of these 156 target genes was mainly focused on kinase binding, regulation of protein modification and catabolic process as well as regulation of epithelial cell proliferation. KEGG enriched many tumor associated or classical signaling pathways, including transforming growth factor-β (TGF-β) signaling pathway and vascular endothelial growth factor (VEGF) signaling pathway. The prediction showed that vascular endothelial growth factor A (VEGFA) was a direct target gene of miR-503 and it was also related to many proteins involved in fibrosis mechanism. Conclusions:The expression level of PDE exosomal miR-503 is significantly higher in H group, and positively correlates with PET values, which may regulate the angiogenesis of peritoneal vessels by targeting VEGFA.

Objective: To investigate the protective effect of propofol on neurological function in rats after traumatic brain injury (TBI) and its possible mechanism. Methods: A total of 96 SD rats were randomly divided into sham operation group, sham operation+ propofol group, TBI group and TBI + propofol group, with 24 rats in each group. The TBI model was prepared by modified Feeney method. The sham operation+ propofol group and the TBI+ propofol group were given 50 mg/kg of propofol once daily. The sham operation group and the TBI group were injected with the same amount of normal saline. Modified neurobehavioral functional scores (mNSS) were evaluated at 1, 3, 7 and 14 days after injury; dry-wet specific gravity method was used to detect brain water content in injured area; TUNEL staining was used to detect neuronal apoptosis; chemiluminescence was used to detect activity of Oxygen cluster (ROS) content; Western blot was used to determine the expressions of inositol requirement enzyme 1 (IRE-1), enhancer binding protein homolog protein (CHOP), heme oxygenase 1 (HO-1), quinone oxidoreductase 1 (NQO1) and nuclear factor E2 related factor 2 (Nrf2) protein. Results: Compared with the sham operation group and the sham operation + propofol group, the mNSS, brain tissue water content, apoptosis number and ROS increased at 1, 3, 7 and 14 days after TBI in the TBI group and TBI + propofol group (P<0.05). Compared with TBI group, mNSS in TBI+ propofol group decreased significantly [(9.3±1.4)points ∶(10.9±1.2)points] 7 days after injury (P<0.05); the brain tissue water content decreased significantly [(81.0±0.8)%∶(82.1±0.8)%] 3 days after injury (P<0.05); the number of apoptotic cells decreased significantly 7 days after injury[(14.1±1.4)%∶(15.6±1.6)%], with the most significant decrease at 14 days after injury [( 10.4±1.5)%∶(13.2±1.4)% (P<0.05); and ROS decreased significantly 7 days after injury [(61.5±4.0)RFU∶(77.3±5.5)RFU](P<0.05). Compared with the sham operation group and the sham operation+ propofol group, the expressions of IRE-1 and CHOP were significantly up-regulated in the TBI group and the TBI+ propofol group (P<0.05); the expressions of HO-1, NQO1 and Nrf2 in the TBI group were significantly decreased (P<0.05); the expressions of HO-1 and NQO1 in TBI+ propofol group were increased (P<0.05) while the expression of Nrf2 were decreased slightly (P<0.05). Compared with the TBI group, the expressions of IRE-1 and CHOP in TBI+ propofol group were decreased (P<0.05), while the expressions of HO-1, NQO1 and Nrf2 were significantly increased (P<0.05). Conclusion After TBI in rats, propofol can reduce oxidative stress by activating the Nrf2-antioxidant element (ARE) pathway, reduce brain edema, and inhibit neuronal apoptosis, thus playing a neuro-protective role.

Objective To explore the effect of giving sedatives according to the circadian rhythm in prevention of occurrence of delirium and the prognosis of patients undergoing mechanical ventilation in intensive care unit (ICU). Methods A prospective double-blinded randomized controlled trial (RCT) was conducted. The patients admitted to Department of Critical Care Medicine of the Second Hospital of Lanzhou University from July 2014 to February 2015, undergoing invasive mechanical ventilation over 12 hours were enrolled. All the patients were given fentanyl for analgesia, and they were randomly divided into simulated circadian clock group (study group, n = 35) and non-simulated circadian clock group (control group, n = 35). The patients in each group were subdivided into three subgroups according to the kinds of sedative drugs, namely dexmedetomidine group (n = 8), propofol group (n = 14), and dexmedetomidine combined with propofol group (combination group, n = 13). Visual analogue scale (VAS) standard and Richmond agitation-sedation scale (RASS) were used to control the analgesic and to quantify the depth of sedation by titrating the dose of sedative drugs, the simulated circadian clock was set to control the RASS score at 0-1 during the day, and -1 to -2 at night in study group. The RASS score in the control group was set at -1 to -2 day and night. The urine 6-hydroxy acid melatonin (aMT6s) levels at different time points in the first diurnal rhythm (06:00, 12:00, 18:00, 24:00) were determined by enzyme linked immunosorbent assay (ELISA). The incidence of delirium, severe hypotension, severe bradycardia and other adverse reactions, duration of mechanical ventilation and the time of extubation, length of ICU stay, amount of sedative and analgesic drugs used were recorded. The correlation between delirium and other indexes was analyzed by using Spearman correlation analysis. Results ① There were no significant differences in gender, age, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score among groups. ② Urine aMT6s levels did not show circadian rhythm in both groups, aMT6s level at 06:00 in study group showed an increasing tendency as compared with the control group, but the difference was not statistically significant. ③ Compared with the control group, the incidence of delirium was significantly lowered in the study group (14.3% vs. 37.1%, P = 0.029), but no significant differences were found in the incidence of severe hypotension or severe bradycardia (20.0% vs. 25.7%, 11.4% vs. 20.0%, both P > 0.05). In simulated circadian clock group, the incidence of delirium in dexmedetomidine group was significantly lower than that of the propofol group (6.3% vs. 32.1%, P < 0.05). ④ Compared with control group with the same sedative, the duration of mechanical ventilation, extubation time, length of ICU stay were significantly shortened, and the dosage of sedative drugs used was reduced in study group (all P < 0.05). In simulated circadian clock group, the duration of mechanical ventilation in dexmedetomidine group was significantly shorter than that of propofol group and combination group (hours: 75.75±26.78 vs. 102.00±26.31 and 100.31±25.38, both P < 0.05), and the length of ICU stay was significantly shorter than that of propofol group (days: 5.75±1.04 vs. 7.00±1.52, P < 0.05). ⑤ The occurrence of delirium was positively correlated with duration of mechanical ventilation (r = 0.705), extubation time (r = 0.704), length of ICU stay (r = 0.666, all P = 0.000), and no correlation was found between the occurrence of delirium and aMT6s level at 06:00, 12:00, 18:00, and 24:00 (r = -0.135, r = 0.163, r = 0.269, r = -0.077, all P > 0.05). Conclusions Administration of sedatives according to simulating circadian time could decrease the duration of mechanical ventilation, extubation time, and the length of ICU stay, decrease the dosage of sedative drugs, and reduce the incidence of delirium. Dexmedetomidine could reduce the incidence of delirium, and improve the prognosis of patients. Trial registration Registration of clinical trials in China, ChiCTR-IPR-15006644.

Objective To establish blood purification system for rats and provide a safe and reliable experimental platform for further research of blood purification. Methods The right carotid artery and the contralateral jugular vein of adult male Sprague?Dawley rats were cannulated to creat vascular access for blood purification, by which continuous arteriovenous hemofiltration blood purification system was established. Blood flow, substitution fluid flow and ultrafiltration rate were regulated by rotary mini?pumps. Blood purification therapy continued for 4 hours on the basis of maintained anesthesia and effective anticoagulation. The safety of continuous arteriovenous hemofiltration blood purification systems was evaluated by comparing the arterial blood gas, electrolyte indexes and blood glucose during the blood purification therapy. Closely monitoring the vital signs of rats, such as blood pressure and heart rate, and observing whether there were any side effects, such as massive haemorrhage, thrombogenesis and gas embolism in the therapeutic process. Results There were no obvious changes of arterial blood gas, electrolyte indexes and blood glucose during the blood purification therapy (P>0.05). The vital signs did not fluctuate acutely before and after the blood purification therapy (P>0.05). The incidence rate of side effects was very low. Conclusions
Continuous arteriovenous hemofiltration blood purification system had no obvious adverse effects on healthy rats. Our blood purification system for rats appears to be safe and reliable.

AIM:To observe the influence of Lycium barbarum polysaccharide (LBP) on the PI3K/Akt/eNOS signaling pathways in ovariectomized rat myocardium .METHODS:Female SD rats (n=30) were divided into sham oper-ation group , ovariectomized group , progynova group , high-dose LBP group and low-dose LBP group .The serum levels of estradiol, lactate dehydrogenase (LDH) and creatine kinase (CK) were measured by ELISA.The myocardial contents of H2 S and oxidative stress injury-related indicators were also detected .The morphological changes of the myocardium were observed with HE staining.The expression of eNOS and PI3K/Akt pathway-related proteins in the myocardium was deter-mined by Western blot .RESULTS: Compared with sham operation group , the serum level of estradiol , the content of H2 S, the activity of GSH-Px, and the expression of eNOS and PI3K/Akt pathway-related proteins in the myocardium in ovariectomized group were all decreased , and the levels of ROS and MDA in the myocardium were increased (P<0.05). The serum levels of LDH and CK were also increased .The arrangement of the myocardial cells was disordered , and the in-tercellular space was also increased in the ovariectomized group .Compared with ovariectomized group , the serum level of estradiol, the myocardial levels of H2S and GSH-Px, and the protein levels of eNOS and phosphorylated Akt were all in-creased in high dose group, while the levels of ROS and MDA in the myocardium were decreased (P<0.05).The serum levels of LDH and CK were also decreased .The morphological changes of the rat myocardium were improved in high dose group.CONCLUSION: LBP prevents and treats postmenopausal cardiovascular lesions through regulating PI 3K/Akt/eNOS signaling pathways in ovariectomized rats .

Objective:To investigate the expressions and clinical significances of SMO , STAT3 and MMP-9 in triple negative breast cancer ( TNBC) .Methods:The expressions of SMO , STAT3 and MMP-9 were immunohistochemically detected in 33 cases of TNBC, 30 cases of mammary hyperplasia and 18 cases of normal breast tissue , and the relationships among SMO , STAT3 and MMP-9 and clinicopathological parameters and prognosis of TNBC patients were analyzed .Results:In TNBC and mammary hyperplasia tissue , the positive expression rates of SMO were 90.9%and 60.0%,the positive expression rates of STAT3 were 96.9% and 73.3%, the positive expression rates of MMP-9 were 90.9% and 36.7%, respectively, however, expressions of them were completely absent in normal breast tissue .The significant correlations were observed between expressions of SMO , STAT3 and MMP-9 in TNBC, mammary hyperplasia and normal breast tissue (P<0.05).The expression of SMO and STAT3 was correlated with superior histologic grade and tumor stage .The expression of MMP-9 was correlated with metastasis of lymph node .The positive correlation was manifested between SMO and STAT3(r=0.361,P<0.05),between SMO and MMP-9 (r=0.633,P<0.01),between MMP-9 and STAT3 (r=0.803,P<0.01) in TNBC.The survival time of TNBC patients was correlated with SMO expression and pTNM (P<0.05).Conclusion:SMO, STAT3 and MMP-9 may play important roles in development of TNBC and may be an important therapeutic target in TNBC .

ObjectiveTo understand the characteristics of mutations in BCR-ABL1 kinase domain mutation,these chronic myeloid leukemia (CML) and Ph positive acute lymphoblastic leukemia (ALL)patients who got imatinib treatment had poor effect.MethodsTotally 177 CML patients and 33 Ph( + )ALL patients were selected at Beijing Dao-Pei Hospital from Sep.2007 to Dec.2010.All of them were Chinese patients.Totally 243 bone marrow or peripheral blood specimens were collected from the patients,who had early effect,then resistance emergenced,or for more than 3 months of poor efficacy.Extracted total RNA from the specimens' nuclear cells,reversed transcription to cDNA.Amplified the whole span of BCRABL1 fusion kinase gene by nest PCR (from 242 to 493 amino acid coding sequence),used the type AB3130XL gene sequencing instrument determinate the gene sequence of ABL1 kinase region and then used the Variant Reporter V1.0 software to analyze the results of gene mutations.ResultsThirty-two kinds of different mutations were detected of ABL1 gene mutations,accounting for 34.2％ (83/243 cases).Among them,the T315I was 12％ (10/83),mutation rate was the highest,followed by Y253H was 11％ (9/83),G250E was 7％ (6/83),E255K was 7％ (6/83),M351T was 6％ (5/83),E459K was 5％ (4/83) ;Q252H,D276G,F317L,E355G,F359V,H396R were all 4％ (3/83).Three cases of insertion mutations were found,including 2 cases of 357-358insk,1 case of V304RfsX17.Seven patients had found existence two or more point mutations.The multiple drug resistance mutations might exist in the same leukemia clone.The same individual was not only contain common resistance mutations,but also rare point mutations,insertion mutations.The mutations might be lead to loss of kinase activity.ConclusionsUnder the imatinib drugs pressure,the ABL1 gene mutation in leukemia cells appears randomly,and results in different resistant clones.Different resistant clones can coexist in the same patients in vivo; resistant clones not only contain point mutations,but also contain inserted deletion mutations.