ObjectiveTo explore the effect of oleanolic acid （OA） on water metabolism in mice with water-dampness retention caused by spleen deficiency and the mechanism. MethodThe 60 SPF Kunming （KM） mice were randomized into blank group （n=10） and modeling group （n=50）. Through long-term living in damp place and irregular diet， water-dampness retention caused by spleen deficiency was induced in modeling mice. Then the model mice were randomly classified into model group， natural recovery group， and low-dose， medium-dose， and high-dose OA groups. The mice in the blank group， model group， and natural recovery group were given （ig） 10 mL·kg^-1·d^-1 normal saline， and mice in the low-dose， medium-dose， and high-dose OA groups received 50， 100， 200 mg·kg^-1·d^-1 OA， respectively. The intervention lasted 7 days. Before and after modeling and administration， the general conditions of the mice were observed and body weight of mice was measured. The water content in feces and tissues was detected with the oven-drying method， and water load index and organ coefficient were measured with the weighing method. Enzyme-linked immunosorbent assay （ELISA） was employed to detect the urinary D-xylose excretion， serum gastrin （GAS）， total protein （TP）， albumin （ALB）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， interleukin-6 （IL-6）， antidiuretic hormone （AVP）， aquaporin 1 （AQP1） in renal medulla， and liver Na⁺-K⁺-ATPase. At the same time， OA was docked with ALB， IL-6， AQP1， and Na⁺-K⁺-ATPase. ResultCompared with the blank group， the model group showed withered hair， emaciation， laziness， bradykinesia， slow weight growth， infrequent spontaneous activities， high water content in feces and tissues， low weight loss after water loading， high coefficient of each organ （P<0.05， P<0.01）. Moreover， the model group had less urinary D-xylose excretion， lower serum levels of GAS， TP， ALB， and HDL-C， higher levels of TC， LDL-C， AVP， and IL-6， lower expression of Na⁺-K⁺-ATPase in the liver， and higher expression of AQP1 in renal medulla than the blank group （P<0.05， P<0.01）. The three OA groups demonstrated better general conditions， faster weight gain， more frequent spontaneous activities， lower water content in feces and tissues， larger weight loss after water loading， and lower coefficient of each organ than the model group （P<0.05， P<0.01）. Moreover， compared with the model group， the three OA groups had high D-xylose excretion， high serum levels of GAS， TP， ALB， and HDL-C， low serum levels of TC， LDL-C， AVP， and IL-6， high expression of Na⁺-K⁺-ATPase in liver， and low expression of AQP1 in renal medulla （P<0.05， P<0.01）. The recovery in each OA group was better than that in natural recovery group. Molecular docking results also confirmed that OA had high binding affinity with ALB， IL-6， AQP1， and Na⁺-K⁺-ATPase. ConclusionOA can alleviate the abnormal water metabolism in mice with water-dampness retention caused by spleen deficiency， which lays a basis for its potential clinical application.

OBJECTIVE To explore the material basis and mechanism of expectorant and cough relief effects of the fruits of Phellodendron chinense var. glabriusulum Schneid. METHODS The expectorant and cough relief effects of volatile oil and water decoction of the fruits of P. chinense var. glabriusulum Schneid. were studied by ammonia water cough induction and drug expectorant model mice experiments； GC-MS and UPLC-MS technologies were used to identify its volatile oils and non-volatile components of the fruits of P. chinense var. glabriusulum Schneid. The active ingredients， core targets and pathways of expectoration and cough relief were analyzed by network pharmacology. RESULTS The volatile oil （0.8， 0.2 g/kg， calculated by volatile oil） and water decoction （12， 3 g/kg， calculated by crude drug） of the fruits of P. chinense var. glabriusulum Schneid. both had obvious expectorant and cough relief effects， and showed obvious dose-dependent relationship. A total of 38 volatile oil components were identified from the medicinal herbs， and the relative percentage contents of 8 components were greater than 1%， such as α -pinene， myrcene， β -caryophyllene， germanene D， isospathulenol； a total of 69 non-volatile oil components were identified， mainly including phenolic compounds， alkaloids， and flavonoids. The active ingredients screened from the identified components included 13 compounds such as α-pinene， myrcene， chlorogenic acid， luteolin， berberine. There were a total of 55 intersection targets with diseases， and the core targets were tumor necrosis factor （TNF）， epidermal growth factor receptor （EGFR）， vascular endothelial growth factor A （VEGFA）， serine/threonine kinase proteins （AKT1） and Toll-like receptor 4 （TLR4）. The molecular docking results showed that the active ingredients and the core targets had good binding ability. GO functional analysis found that the targets were significantly enriched in biological processes such as the reaction affecting lipopolysaccharides， the positive regulation of peptidyl serine phosphorylation， and the positive regulation of the biosynthesis process of nitric oxide. KEGG pathway enrichment analysis found that the targets were significantly enriched in the signaling pathways such as cancer， non-small cell lung cancer， proteoglycans in cancer. CONCLUSIONS Fruits of P. chinense var. glabriusulum Schneid. have obvious expectorant and cough relief effects， and its material basis may be α-pinene， myrcene， chlorogenic acid， luteolin， berberine， etc.， and mainly act on TNF， EGFR， VEGFA， AKT1， TLR4 and its significantly enriched signaling pathway.

Objective:To evaluate the immunogenicity and immune persistence of purified Vero cells rabies vaccine (PVRV) with Zagreb and Essen regimen.Methods:Prospective study: Patients with first Class II exposure to rabies were recruited from the Dog Injury Cinic of Guangxi Center for Disease Control and Prevention (Guangxi CDC) and randomly divided into the Zagreb (2-1-1) and Essen (1-1-1-1-1) regimen group. All patients were inoculated with the vaccines from the same manufacturer and batch, and 3 ml serum was collected at the 45th day and in 1-year, 2-year and 3-year after immunization. Rapid fluorescent inhibition test (RFFIT) was used to detect rabies virus neutralizing antibody (RVNA). The attenuation of RVNA positive rate and geometric mean titer (GMT) with time was analyzed. Retrospective study: The informed consents for rabies vaccine in the Dog Injury Clinic of Guangxi CDC were checked out. The patients who were injected with PVRV (same manufacturer but unlimited batch) but without passive immune agents for the first time within 3 years were selected and divided into 1-year, 2-year and 3-year group. Each group was further divided into Zagreb and Essen regimen group. The serum (3 ml) was collected at 1 year, 2 years and 3 years after immunization and detected the RVNA by RFFIT.Results:Prospective study: The RVNA positive rates on the 45th day and in 1-year, 2-year and 3-year after immunizationin in the Zagreb and Essen regimen group were 100%, 95%, 85%, 80% and 98.25%, 89.47%, 89.47%, 85.96%, respectively. There was no statistically significant difference in the RVNA positive rates at the same time point between the two regimen groups ( P>0.05). The RVNA GMT on the 45th day and in 1-year, 2-year, and 3-year in the Zagreb and Essen regimen group were 11.32 IU/ml, 1.69 IU/ml, 1.30 IU/ml, 1.30 IU/m and 13.18 IU/ml, 2.13 IU/ml, 1.87 IU/ml, 1.84 IU/m, respectively. There was no significant difference in the RVNA GMT levels at the same time point between the two regimen groups ( F=1.971, P=0.164). The RVNA GMT levels in the two regimen groups had the same trend of attenuation over time (time*group F=0.702, P=0.435). Retrospective study: The RVNA positive rates in 1-year, 2-year and 3-year after immunization in the Zagreb and Essen regimen group were 100%, 95%, 91.43%和94.73%, 86.21%, 87.5%, respectively. There was no statistically significant difference in the RVNA positive rates at the same time point between the two regimen groups ( P>0.05). The RVNA GMT in 1-year, 2-year, and 3-year groups after immunization in the Zagreb and Essen regimen group were 2.65 IU/ml, 2.03 IU/ml, 1.57 IU/ml和3.2 IU/ml, 2.58 IU/ml, 2.45 IU/ml, respectively. There was no significant difference in the RVNA GMT levels at the same time point between the two regimen groups ( P>0.05). Conclusions:The PVRV showed the same excellent immunogenicity and immune persistence after the vaccination with the Zagreb and Essen regimens.

Objective:To investigate the effect of hyperbaric oxygen on plasma endothelin-1 (ET-1) and nitric oxide (NO) in patients with intrauterine growth retardation (IUGR) as well as the clinical efficacy.Methods:A total of 90 IUGR patients, treated in the First Affiliated Hospital of Zhengzhou University from January 2018 to May 2019, were selected and divided into the observation group and the control group according to the double-blind lottery method, with 45 patients in each group. The patients in the control group were only given routine treatment, while those in the observation group were treated with hyperbaric oxygen combined with the routine treatment as same as the control group. The therapeutic effects of the two groups were observed and recorded. The level of ET-1 was analyzed by enzyme linked immunosorbent assay, and the level of NO was tested by nitrate reductase colorimetry. The values of peak-to-diastolic ratio (S/D), resistant index (RI), and pulsation index (PI) at the end of umbilical artery vasoconstriction were detected by ultrasonic doppler umbilical cord blood flow analyzer. The levels of plasma TXB2 and 6-Keto-PGF1α were detected by radioimmunoassay.Results:After 3 weeks treatment, the total effective rate of the observation group (95.56%) was significantly higher than that of the control group (77.78%) ( χ2=7.168, P<0.05); compared with those before treatment, the levels of ET-1 and NO of both groups were significantly up-regulated; the ET-1 level of the observation group after treatment was significantly lower than that of the control group, while the NO level was significantly higher ( P<0.05). After treatment, the values of S/D, RI, and PI at the end of umbilical artery vasoconstriction of both the groups after treatment were all lower than those before treatment, especially the values of S/D, RI, and PI of the observation group after treatment were significantly lower than those of the control group ( P<0.05). Compared with those before treatment, the levels of patients′ plasma TXB2 and 6-keto-PGF1α of both the groups were significantly up-regulated; the level of patients′ plasma TXB2 of the observation group after treatment was significantly lower than that of the control group, while the level of 6-keto-PGF1α was significantly increased( P<0.05 or P<0.01). Conclusion:Hyperbaric oxygen could significantly improve the clinical effect on IUGR, and improve the fetal development. This treatment, therefore, is worthy of popularization and application in clinic.

Objective:To investigate the effect of hyperbaric oxygen on plasma endothelin-1 (ET-1) and nitric oxide (NO) in patients with intrauterine growth retardation (IUGR) as well as the clinical efficacy.Methods:A total of 90 IUGR patients, treated in the First Affiliated Hospital of Zhengzhou University from January 2018 to May 2019, were selected and divided into the observation group and the control group according to the double-blind lottery method, with 45 patients in each group. The patients in the control group were only given routine treatment, while those in the observation group were treated with hyperbaric oxygen combined with the routine treatment as same as the control group. The therapeutic effects of the two groups were observed and recorded. The level of ET-1 was analyzed by enzyme linked immunosorbent assay, and the level of NO was tested by nitrate reductase colorimetry. The values of peak-to-diastolic ratio (S/D), resistant index (RI), and pulsation index (PI) at the end of umbilical artery vasoconstriction were detected by ultrasonic doppler umbilical cord blood flow analyzer. The levels of plasma TXB2 and 6-Keto-PGF1α were detected by radioimmunoassay.Results:After 3 weeks treatment, the total effective rate of the observation group (95.56%) was significantly higher than that of the control group (77.78%) ( χ2=7.168, P<0.05); compared with those before treatment, the levels of ET-1 and NO of both groups were significantly up-regulated; the ET-1 level of the observation group after treatment was significantly lower than that of the control group, while the NO level was significantly higher ( P<0.05). After treatment, the values of S/D, RI, and PI at the end of umbilical artery vasoconstriction of both the groups after treatment were all lower than those before treatment, especially the values of S/D, RI, and PI of the observation group after treatment were significantly lower than those of the control group ( P<0.05). Compared with those before treatment, the levels of patients′ plasma TXB2 and 6-keto-PGF1α of both the groups were significantly up-regulated; the level of patients′ plasma TXB2 of the observation group after treatment was significantly lower than that of the control group, while the level of 6-keto-PGF1α was significantly increased( P<0.05 or P<0.01). Conclusion:Hyperbaric oxygen could significantly improve the clinical effect on IUGR, and improve the fetal development. This treatment, therefore, is worthy of popularization and application in clinic.