AIM: To investigate the pharmacokinetic properties of the main active components of Dalitong extract in SD rats after oral administration using UPLC-MS / MS. METHODS: An UPLC-MS / MS method was established to simultaneously detect tetrahydropalmatine, nobiletin and costunolide in the plasma and tissues of SD rats. The method was applied to investigate the pharmacokinetic characteristics and tissue distribution. RESULTS: After a single oral administration, the three active components were rapidly absorbed into the body, with a peak concentration (Cmax) of (13.73 ± 7.50), (27.01 ± 17.69) and (6.73 ± 29.94) ng / mL for tetrahydropalmatine, nobiletin, and costunolide, respectively. The time to reach the peak concentration (Tmax) was (1.40 ± 0.93), (0.63 ± 0.28) and (2.38 ± 8.81) h, respectively. The area under the curve (AUC) was (80.43±40.03), (41.30±28.69) and (303.90 ± 136.69) ng · h · mL

AIM:To explore the therapeutic effect of teprenone(geranylgeranylacetone,GGA)on lipopolysac-charide(LPS)-induced cardiac dysfunction and its mechanism.METHODS:(1)Eight-week-old male C57BL/6 wild-type mice and carboxyl terminus of heat shock protein 70(HSP70)-interacting protein(CHIP)gene knockout mice were randomly divided into control group,LPS group,LPS+GGA group and GGA group,with 8 mice in each group.The model was established by intraperitoneal injection of LPS(25 mg/kg),and 1 h after LPS stimulation,mice were given intraperito-neal injection of GGA(100 mg/kg).The technique of high-resolution ultrasonography system was used to evaluate the car-diac function of mice.The serum of mice from each group were collected to detect the levels of creatine kinase-MB(CK-MB)and lactate dehydrogenase(LDH).HE staining was performed to observe histological changes of cardiac tissues.ELISA was used to detect the levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in cardiac tissues.West-ern blot was used to detect the protein levels of HSP70,CHIP,karyopherin-α 2(KPNA2),myeloperoxidase(MPO),vas-cular cell adhesion molecule(VCAM),intercellular cell adhesion molecule(ICAM),and nuclear factor-κB(NF-κB)in cardiac tissues.(2)In vitro cell inflammation model was established using mouse myocardial cells HL-1 stimulated with LPS.ELISA was used to detect the levels of TNF-α and IL-6 in cell supernatants.Western blot was used to detect the pro-tein expression levels of HSP70,CHIP,and KPNA2 in myocardial cells.Immunofluorescence staining was performed to observe the content of nuclear NF-κB.RESULTS:(1)GGA effectively improved cardiac function of LPS-stimulated mice,significantly increased ejection fraction and left ventricular fractional shortening(P<0.01),reduced serum levels of CK-MB and LDH(P<0.01),and alleviated myocardial injury.(2)GGA significantly reduced the release of TNF-α and IL-6 caused by LPS(P<0.01),as well as nuclear translocation of NF-κB,decreased the levels of KPNA2,MPO,VCAM and ICAM in cardiac tissues,and increased the levels of HSP70 in cardiac tissues and cells(P<0.01).(3)In CHIP knockout myocardial cells and mice,GGA failed to inhibit LPS-induced inflammatory response and lost its effect on im-proving cardiac function.CONCLUSION:The protective effect of GGA against LPS-caused cardiac dysfunction of mice is related to increasing expression of HSP70 and promoting CHIP activation,which inhibits the translocation of NF-κB into nucleus and suppresses inflammatory factor release.CHIP knockout abolishes the effects of GGA on reducing LPS-induced inflammatory response and myocardial injury.

Objective:In order to explore the impact of corona virus disease 2019(COVID-19)on the hospitalization of children with bronchiolitis and to improve clinicians′ understanding of the characteristics of bronchiolitis during the COVID-19 epidemic.Methods:This was a multicenter clinical study, and the data have been collected from 23 children′s medical centers in China.All the clinical data were retrospectively collected from children with bronchiolitis who were hospitalized at each study center from January 1, 2019 to December 31, 2021.The results included gender, age at hospitalization, length of stay, respiratory syncytial virus(RSV) test results, severity rating, ICU treatment, and the total number of children hospitalized with respiratory tract infection during the same period.The clinical data of children with bronchiolitis in 2019 before COVID-19 epidemic and in 2020、2021 during COVID-19 epidemic were statistically analyzed and compared.Results:According to a summary of data provided by 23 children′s medical centers, there were 4 909 cases of bronchiolitis in 2019, 2 654 cases in 2020, and 3 500 cases in 2021.Compared with 2019, the number of bronchiolitis cases decreased by 45.94% in 2020 and 28.70% in 2021.In 2019, 2020 and 2021, there were no significant differences in gender ratio, age, and duration of hospitalization.Compared with 2019, the ratio of bronchiolitis to the total number of hospitalizations for respiratory tract infection decreased significantly in 2020 and 2021( χ2=12.762, P<0.05; χ2=84.845, P<0.05).The proportion of moderate to severe bronchiolitis cases in both 2020 and 2021 was lower than that in 2019, and the difference was statistically significant ( χ2=4.054, P<0.05; χ2=8.109, P<0.05).There was no statistically significant difference in the proportion of bronchiolitis cases requiring ICU treatment between 2019, 2020, and 2021 ( χ2=1.914, P>0.05).In 2019, a total of 52.60%(2 582/4 909) of children with bronchiolitis underwent RSV pathogen testing, and among them, there were 708 cases with RSV positive, accounting for 28.00%.In 2020, 54.14%(1 437/2 654) of children with bronchiolitis underwent RSV pathogen testing, and there were 403 cases with RSV positive, accounting for 28.04%.In 2021, 66.80%(2 238/3 500) of children with bronchiolitis underwent RSV pathogen testing, and there were 935 cases with RSV positive, accounting for 41.78%.Compared with 2019 and 2020, the RSV positive rate in 2021 showed a significant increase( χ2=99.673, P<0.05; χ2=71.292, P<0.05). Conclusion:During the COVID-19 epidemic, the implementation of epidemic prevention and control measures reduced the hospitalization rate and severity of bronchiolitis, but did not reduce the positive rate of RSV detection.

OBJECTIVE To study the unknown impurity in potassium aspartate and magnesium aspartate injection by heart-cutting two-dimensional liquid chromatography coupled with Quadrupole time-of-flight mass spectrometry (2D-LC-Q-TOF-MS). METHODS The Waters ACQUITY UPLC 2D system and Xevo G2-XS QTof-MS system were used. One- dimensional chromatographic conditions were as listed. An Agilent ZORBAX-NH2 column was used, and potassium dihydrogen thophosphate(0.05 mol·L-1)-acetonitrile(37∶63) as the mobile phase, at a flow rate of 1.3 mL·min-1. The detection wavelength was set at 200 nm. Two-dimensional chromatographic conditions were as listed. A Waters ACQUITY UPLC HSS T3 column was used, and 0.1% formic acid solution(ESI+)/5 mmol·L-1 ammonium formate(ESI-) as the mobile phase A, and acetonitrile as the mobile phase B, in gradient mode. The mass spectrometry used an electro spray ionization source(ESI) for positive and negative ion mode detection. RESULTS Combined the high resolution mass, MS2 fragment ions and the UNIFI software, the possible structure of the unknown impurity in potassium aspartate and magnesium aspartate injection was infered. CONCLUSION The 2D-LC-Q-TOF-MS method can be used to identify impurities in potassium aspartate and magnesium aspartate injection, which provides reference for the improvement of quality control and process optimization of potassium aspartate and magnesium aspartate injection.

OBJECTIVE To establish a method for the determination of fourteen fluorescent whitening agents in cosmetics by HPLC-MS/MS. METHODS Samples were extracted on a Waters ACQUITY UPLC ®BEH C18(2.1 mm×50 mm, 1.7 μm) column after ultrasonic extracted by DMF with the mobile phase consisted of methanol-0.1% ammonia water solution by gradient elution. The flow rate was 0.3 mL·min-1. The column temperature was 40 ℃. MS was performed using triple quadrupole mass spectrometry. Electrospray ionization source was operated in the positive/negative mode using multiple reaction monitoring scanning mode. RESULTS The results showed that there were good linear relationships for the fluorescent whitening agents in a certain concentration range with correlation coefficients(r) greater than 0.99. The limits of quantification were 0.01-20 μg·g-1 and the limits of detection were 0.004-8 μg·g-1. The average recoveries at three spiked levels were in the range of 85.4%-108.9%, and the relative standard deviation were in the range of 0.3%-7.2%. CONCLUSION The method has high sensitivity, strong specificity, simple and convenient operation, and is suitable for the detection of fourteen fluorescent whitening agents in cosmetics.

Objective:To summarize the evidence of non-drug management of postoperative delirium in neurosurgery patients at home and abroad, so as to provide reference for medical and nursing staff to formulate intervention measures.Methods:This study is a best evidence summary. In view of the problem of non-drug management of postoperative delirium in neurosurgery patients, according to the "6S" pyramid model, the evidence on non-drug management of postoperative delirium in neurosurgery patients was retrieved through computer in domestic and foreign databases, guide websites and professional association websites, including clinical practice guidelines, expert consensus, clinical decision-making, systematic review, evidence summary and so on. The retrieval period was from January 1, 2016 to December 31, 2021. Two researchers independently evaluated the quality of article and extracted evidence, and used the Joanna Briggs Institute (JBI) evidence pre-grading and evidence recommendation grading system (2014 version) to grade and recommend the included evidence.Results:A total of 17 articles were included, including 6 guidelines, 3 expert consensus, 3 systematic reviews, 3 evidence summaries, and 2 clinical decision-makings. Finally, 39 best evidences were summarized in 7 aspects, including risk factor assessment, screening, non-drug prevention, non-drug treatment, information support and health education, follow-up and evaluation, and medical worker training.Conclusions:The best evidence for non-drug management of postoperative delirium in neurosurgical patients is comprehensive. Medical and nursing staff can select evidence according to the clinical situation and the actual situation of patients, and carefully and reasonably transform and apply evidence.

Objective:To evaluate carotid plaque neovascularization and vessel stability using superb microvascular imaging.Methods:Seventy-two patients with carotid atherosclerotic plaques received treatment in The Seventh People's Hospital of Wenzhou from June 2018 to June 2020 and were included in this study. A total of 100 carotid plaques were surgically removed from these patients. These patients were subject to superb microvascular imaging and contrast-enhanced ultrasonography before carotid plaques were removed. Taking pathological results of carotid plaque as a gold standard, we investigated the efficacy of superb microvascular imaging versus contrast-enhanced ultrasonography in detecting carotid plaque neovascularization and vessel stability and evaluated the detection consistency of each imaging method with the gold standard. Results:The sensitivity, specificity, and accuracy of superb microvascular imaging in detecting carotid plaque neovascularization were 93.24%, 92.31%, and 93.00%, and they were 95.96%, 96.15%, and 96.00% for contrast-enhanced ultrasonography. The Kappa values of consistency of agreement on carotid plaque neovascularization identification were 0.825 and 0.923 for superb microvascular imaging and contrast-enhanced ultrasonography, respectively. The sensitivity, specificity, and accuracy of superb microvascular imaging in detecting vessel stability were 94.74%, 95.35%, and 95.00%, respectively and they were 96.49%, 97.67%, and 97.00%, respectively for contrast-enhanced ultrasonography. The Kappa values of consistency of agreement on vessel stability evaluation were 0.898 and 0.939 for superb microvascular imaging and contrast-enhanced ultrasonography, respectively.Conclusion:Superb microvascular imaging has equivalent efficacy in detecting carotid plaque neovascularization and vessel stability to contrast-enhanced ultrasonography. Superb microvascular imaging is non-invasive, provides ease in operation, and is worthy of clinical promotion.

AIM: To investigate the characteristics of clinical trials of inhalation in pediatric population in China. METHODS: The pediatric clinical trials of inhaled drugs in China registered on the www.Chinadrugtrials.org.cn and Clinical Trials in USA respectively until November 20, 2021 were reviewed. The characteristics of pediatric clinical trials of inhaled drugs including the clinical trial phases, drug indications and classificatio etc. were analyzed. RESULTS: There were 21 pediatric clinical trials of inhaled drugs registered on the www.Chinadrugtrials.org.cn, accounted for 8.9%(21/235) of inhalation clinical trials in all populations. 47.6% of them were generic drugs, mainly focusing on expectorants for Phlegm symptoms and inhaled preparations for asthma, which accounting for 71.4%(15/21). There were 34 pediatric clinical trials of inhaled drugs registered on the Clinical Trials in USA, the drug indications of which were mainly asthma and anesthesia, accounting for 76.5%(26/34). CONCLUSION: The pediatric clinical trials of inhalations in China started later, and the total number is small compared to adults, mainly focusing on generic drugs. We should pay attention to the research and development of new inhalation drugs, standardizing and promoting the clinical trials of inhaled drugs in pediatric population actively.

Retinal pigment epithelium(RPE)has essential functions,such as nourishing and sup-porting the neural retina,and is of vital importance in the pathogenesis of age-related retinal degen-eration.However,the exact molecular changes of RPE during aging remain poorly understood.Here,we isolated human primary RPE(hRPE)cells from 18 eye donors distributed over a wide age range(10-67 years old).A quantitative proteomic analysis was performed to analyze changes in their intracellular and secreted proteins.Age-group related subtypes and age-associated proteins were revealed and potential age-associated mechanisms were validated in ARPE-19 and hRPE cells.The results of proteomic data analysis and verifications suggest that RNF123-and RNF149-related protein ubiquitination plays an important role in protecting hRPE cells from oxidative damage dur-ing aging.In older hRPE cells,apoptotic signaling-related pathways were up-regulated,and endo-plasmic reticulum organization was down-regulated both in the intracellular and secreted proteomes.Our work paints a detailed molecular picture of hRPE cells during the aging process and provides new insights into the molecular characteristics of RPE during aging and under other related clinical retinal conditions.

Objective To evaluate the effect of dexmedetomidine on postoperative outcomes in pa-tients undergoing off-pump coronary artery bypass grafting ( OPCABG) . Methods One hundred and twen-ty-two patients of both sexes, aged 40-75 yr, with body mass index of 18. 5-32. 0 kg∕m2 , of American So-ciety of Anesthesiologists physical status Ⅲ or Ⅳ, with New York Heart Association Ⅱ or Ⅲ, with lelf ventricular ejection fraction>40％, scheduled for elective OPCABG, were divided into 2 groups ( n=61 each) using a random number table method: dexmedetomidine group ( group D) and control group ( group C) . Dexmedetomidine was intravenously infused in a loading dose of 0. 6μg∕kg at 15 min before anesthesia induction, followed by a continuous infusion of 0. 4 μg · kg-1 · h-1 until the end of surgical procedure in group D. The equal volume of normal saline was given instead in group C. The emergence time, extubation time, length of intensive care unit stay and postoperative length of hospital stay were also recorded. Results Compared with group C, the extubation time, length of intensive care unit stay, and postoperative length of hospital stay were significantly shortened, and the emergence time was prolonged in group D ( P<0. 05) . Conclusion Dexmedetomidine can promote postoperative outcomes in the patients undergoing OPCABG.