AIM To study the chemical constituents from the leaves of Citrus reticulata Blanco and their anti-inflammatory activities.METHODS The 85%ethanol extract from the leaves of C.reticulata was isolated and purified by silica gel,D101 macroporous resin,MCI,ODS and Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The Griess method was used to determine their inhibitory activities on lipopolysaccharide-induced NO production in macrophages RAW 264.7 cells.The mice foot swelling inflammation model induced by carrageenan was established,and the levels of IL-1β,TNF-α were detected.RESULTS Twelve compounds were isolated and identified as nobiletin(1),tangeretin(2),5-demethylinoblitin(3),5,4'-dihydroxy-6,7,8,3'-tetramethoxy flavone(4),5-hydroxy-7,8,3',4'-trimethoxyflavanone(5),3,5,6,7,8,3',4'-heptamethoxyflavanone(6),hesperetin(7),5-hydroxy-6,7,3',4'-tetramethoxyphenone(8),β-balsam alcohol(9),stigmaster-5-en-3β-alcohol(10),p-hydroxybenzaldehyde(11),vanillin(12).Compounds 1,4,6,7,10 and 12 had strong inhibitory activites on NO release in LPS-induced RAW 264.7 cells,and the IC50 values were(25.21±2.10),(37.77±0.50),(38.19±1.58),(21.89±1.73),(43.81±1.18),(47.98±2.55),(41.23±1.11),(43.80±1.43)μmol/mL,respectively.Compounds 2-3 reduced IL-1β and TNF-α levels(P＜0.05,P＜0.01).CONCLUSION Compounds 6-7,9 are isolated from this plant for the first time.Compounds 1-4,8 exhibit strong in vitro anti-inflammatory activities,and compounds 2-3 exhibit significant in vivo anti-inflammatory activities.

Objective: To understand the vaccination status of enterovirus type 71 (EV71) inactivated vaccines in China from 2017 to 2021 and provide evidence for making policy on immunization strategy against hand, foot and mouth disease (HFMD). Methods: Using the reported dose number of EV71 vaccination and birth cohort population data collected by the China immunizaiton program information system to estimate the cumulative coverage of EV71 vaccine by the end of 2021 among the birth cohorts since 2012 at national, provincial, and prefecture levels, and analyze the correlation between the vaccination coverage and the potential influencing factors. Results: As of 2021, the estimated cumulative vaccination coverage of the EV71 vaccine was 24.96% in birth cohorts since 2012. The cumulative vaccination coverage was between 3.09% and 56.59% in different provinces, between 0 and 88.17% in different prefectures. There was a statistically significant correlation between vaccination coverage in different regions and the region's previous HFMD prevalence and disposable income per capita. Conclusions: Since 2017, the EV71 vaccines have been widely used nationwide, but the coverage of EV71 vaccination varies greatly among regions. Vaccination coverage is higher in relatively developed regions, and the intensity of previous epidemic of HFMD may have a certain impact on the acceptance of the vaccine and the pattern of immunization service. The impact of EV71 vaccination on the epidemic of HFMD requires further studies.
Humans ; Enterovirus A, Human ; Hand, Foot and Mouth Disease/prevention & control* ; Vaccines, Inactivated ; Viral Vaccines ; Enterovirus ; Vaccination ; China/epidemiology*

This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 μm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 μL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 μmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.
Humans ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Asteraceae/chemistry* ; Lung Neoplasms/drug therapy*

OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.
Caffeine/therapeutic use* ; Citrates ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Respiration, Artificial ; Retrospective Studies

OBJECTIVE: To study the long-term clinical effect of multicenter multidisciplinary treatment (MDT) in children with renal malignant tumors. METHODS: A retrospective analysis was performed on the medical data of 55 children with renal malignant tumors who were diagnosed and treated with MDT in 3 hospitals in Hunan Province from January 2015 to January 2020, with GD-WT-2010 and CCCG-WT-2016 for treatment regimens. A Kaplan-Meier survival analysis was used to analyze the survival of the children. RESULTS: Of the 55 children, 10 had stage I tumor, 14 had stage Ⅱ tumor, 22 had stage Ⅲ tumor, 7 had stage IV tumor, and 2 had stage V tumor. As for pathological type, 47 had FH type and 8 had UFH type. All children underwent complete tumor resection. Of the 55 children, 14 (25%) received preoperative chemotherapy. All children, except 1 child with renal cell carcinoma, received postoperative chemotherapy. Among the 31 children with indication for radiotherapy, 21 (68%) received postoperative radiotherapy. One child died of postoperative metastasis. The incidence rate of FH-type myelosuppression was 94.4%, and the incidence rate of UFH-type myelosuppression was 100%. The median follow-up time was 21 months and the median survival time was 26 months for all children, with an overall survival rate of 98% and an event-free survival rate of 95%. CONCLUSIONS Multicenter MDT has the advantages of high success rate of operation and good therapeutic effect of chemotherapy in the treatment of children with renal malignant tumors, with myelosuppression as the most common side effects, and radiotherapy is safe and effective with few adverse events. Therefore, MDT has good feasibility, safety, and economy.
Child ; Family ; Humans ; Kidney Neoplasms/therapy* ; Progression-Free Survival ; Retrospective Studies

Objective:To study the prevalence and related factors of apathy in patients with Parkinson's disease (PD)． Methods:From November, 2017 to December, 2019, 254 PD patients in our hospital were included. According to Starkstein Apathy Scale (SAS), they were divided into apathy group and non-apathy group. Clinical data such as demographic data, motor symptoms, non-motor symptoms and motor complications were collected for comparison between two groups. Logistic regression analysis was performed to investigate the risk factors of apathy in PD. Results:Among 254 PD patients, 124 (48.8%) cases were in apathy. Compared with non-apathy group, apathy group was older in age and age of onset, higher in the scores of Movement Disorder Society United Parkinson's Disease Rating Scale part III (MDS-UPDRS Ⅲ), Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA) and Pittsburgh Sleep Quality Index (PSQI) (t > 2.291, P < 0.05), and lower in the scores of Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) (t > 22.424, P < 0.001). There was no statistically significant difference in gender, time of education, body mass index (BMI), disease course, Hoehn-Yahr (H-Y) stage, wearing-off phenomenon, dyskinesia, on-and-off phenomenon, and the scores of Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire (RBDQ) and Epworth Sleeping Scale (ESS) between two groups (P > 0.05). Logistic regression analysis showed that the age of disease onset, MoCA and HAMD scores were correlated with apathy in patients with PD (P < 0.05). Conclusion:The presence of apathy in PD may be associated with older age of disease onset, severity of depression and cognitive impairment.

Adult ; Asymptomatic Diseases/epidemiology* ; Autoimmune Diseases/etiology* ; China/epidemiology* ; Female ; Humans ; Hypothyroidism/etiology* ; Male ; Metabolic Syndrome/epidemiology* ; Middle Aged ; Obesity/epidemiology* ; Risk Factors ; Thyroid Diseases/etiology* ; Young Adult

The components of volatile oils are generally complex, and they often have the functions of divergent dissolving surface, insecticidal and antibacterial. However, there are few reports on bacteriostasis, anti-inflammation and antioxidation roles of volatile oils of Pelargonium graveolens L'Herit. The volatile oil of Pelargonium graveolens L’Herit. was extracted by steam distillation, and GC-MS and peak area normalization analysis showed that it mainly contained 30 compounds, and the identified components accounted for 90.26% of the total peak area. The volatile oil of Pelargonium graveolens L'Herit. has a certain inhibitory effect on Candida albicans and Staphylococcus aureus, especially on Candida albicans. The diameter of the bacteriostatic zone is 15.55±1.53 mm by using the oxford cup method. Dexamethasone and low, middle and high doses of volatile oils of Pelargonium graveolens L'Herit. were given after the RAW264. 7 cell inflammatory model and was induced by lipopolysaccharide (LPS = 10.0 μg/mL). ELISA assays showed that it could effectively reduce the expression of IL-1β and TNF-α in inflammatory cells, and the effect of high doses was similar to that of IL-1β and TNF-α in the dexamethasone group. GC-MS was successfully used to determine and identify the chemical constituents of volatile oils from Pelargonium graveolens L'Herit. in this study. We show that the volatile oil of Pelargonium graveolens L'Herit. had certain bacteriostatic activity and effectively reduces the secretion of IL-1β and TNF-α by inflammatory cells. It provides an experimental basis for the development and utilization of volatile oils from Pelargonium graveolens L'Herit.

Hyperuricemia is a chronic metabolic disease caused by the accumulation of uric acid in the body caused by purine metabolism disorder. In recent years, the incidence of hyperuricemia has increased and the age of onset is showing a younger trend. Finding effective therapeutic targets and treatment methods is a hot spot of current research. The urate transporter ATP-binding cassette subfamily G member 2 (ABCG2) is mainly expressed in the kidney and promotes uric acid excretion. In this study, ABCG2 mRNA was synthesized in vitro and transfected into hyperuricemia model mice to observe its effect on mouse uric acid levels. Firstly, the DNA template of ABCG2 mRNA was chemically synthesized, and then transcribed into mRNA in vitro, followed by modification and transfection into mouse TCMK-1 renal tubular epithelial cells. Finally, the protein expression in the cells was detected by Western blot. The results showed that the amount of protein expression in TCMK-1 cells was positively correlated with the amount of transfected mRNA (P < 0. 01), indicating a successful transfection. In animal experiments, twenty-four SPF mice were randomly divided into four groups (n = 6): control group, hyperuricemia model group, benzbromarone group [20 mg/(kg•d)] and mRNA group [2 mg/(kg•3d)]. The mice have been modeled and treated for 28 days. During this period, the body weight and growth status of the mice were monitored daily. After the treatment, the levels of serum uric acid, urine uric acid, serum creatinine, blood urea nitrogen and liver xanthine oxidase were analyzed. The results showed that compared with the model group of mice, mRNA treatment can significantly reduce the levels of serum uric acid (100. 38 ± 10. 94), blood urea nitrogen (6. 30 ± 1. 10), and serum creatinine (30. 86 ± 5. 78, P<0. 05 or P<0. 01). It can also increase the level of urine uric acid (617. 48 ± 50. 34, P<0. 05) in mice and promote the excretion of uric acid. But it has no significant effect on the activity of xanthine oxidase (26. 19 ± 2. 58) in the liver. The pathological changes of mice kidney were observed by HE staining. The results showed that compared with mice in the model group, pathological damages such as renal tubular cell edema and inflammatory cell infiltration in the mRNA treatment group were significantly improved. The relative expression of mRNA in mice kidney was detected by qRT-PCR, and the protein expression of ABCG2 in mice kidney was detected by immunohistochemistry and Western blot. The results showed that the relative expression of ABCG2 mRNA and its protein were significantly up-regulated in the kidney tissues of mice in the mRNA group (P < 0. 01), indicating that the transfection was successful in vivo. In conclusion, ABCG2 mRNA synthetized and modified in vitro can be successfully expressed in hyperuricemia mice and promote excretion of uric acid and other organic ions, as well as improvement of renal injury in mice. These results provide experimental basis for the clinical application of ABCG2 as a target for the treatment of hyperuricemia related diseases.