Purpose::Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation.Methods::C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference. Results::Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol.Conclusions::Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.

Ligustrum lucidum is a woody perennial plant of genus Ligustrum in family Oleaceae. Its dried fruit has high medicinal value. In this study, the authors evaluated the variability and species identification efficiency of three specific DAN barcodes(rbcL-accD, ycf1a, ycf1b) and four general DAN barcodes(matK, rbcL, trnH-psbA, ITS2) for a rapid and accurate molecular identification of Ligustrum species. The results revealed that matK, rbcL, trnH-psbA, ITS2 and ycf1a were inefficient for identifying the Ligustrum species, and a large number of insertions and deletions were observed in rbcL-accD sequence, which was thus unsuitable for development as specific barcode. The ycf1b-2 barcode had DNA barcoding gap and high success rate of PCR amplification and DNA sequencing, which was the most suitable DNA barcode for L. lucidum identification and achieved an accurate result. In addition, to optimize the DNA extraction experiment, the authors extracted and analyzed the DNA of the exocarp, mesocarp, endocarp and seed of L. lucidum fruit. It was found that seed was the most effective part for DNA extraction, where DNAs of high concentration and quality were obtained, meeting the needs of species identification. In this study, the experimental method for DNA extraction of L. lucidum was optimized, and the seed was determined as the optimal part for DNA extraction and ycf1b-2 was the specific DNA barcode for L. lucidum identification. This study laid a foundation for the market regulation of L. lucidum.
Ligustrum/genetics* ; Seeds ; Fruit ; Polymerase Chain Reaction ; Research Design

This study aims to investigate the therapeutic effects and potential mechanisms of resveratrol(Res) on poor ovarian response(POR) in mice. The common target genes shared by Res and POR were predicted by network pharmacology, used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, and then validated by animal experiments. The mice with regular estrous cycle after screening were randomized into normal, POR, and low-and high-dose(20 and 40 mg·kg~(-1), respectively) Res groups. The normal group was administrated with an equal volume of 0.9% sodium chloride solution by gavage, and the mice in other groups with tripterygium glycosides suspension(50 mg·kg~(-1)) by gavage for 2 weeks. After the modeling, the mice in low-and high-dose Res groups were treated with Res by gavage for 2 weeks, and the mice in normal and POR groups with an equal volume of 0.9% sodium chloride solution by gavage. Ovulation induction and sample collection were carried out on the day following the end of treatment. Vaginal smears were collected for observation of the changes in the estrous cycle, the counting of retrieved oocytes, and the measurement of ovarian wet weight and ovarian index. The enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of anti-mullerian hormone(AMH), follicle-stimulating hormone(FSH), estradiol(E_2), and luteinizing hormone(LH) in the serum. The ovarian tissue morphology and granulosa cell apoptosis were observed by hematoxylin-eosin(HE) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL), respectively. Western blot was employed to determine the protein levels of phosphatidylinositol 3-kinase(PI3K), protein kinase B(AKT), forkhead box O(FOXO) 3a, hypoxia-inducible factor(HIF)-1α, B-cell lymphoma-2(Bcl-2), and Bcl-2-associated X protein(Bax). A total of 222 common targets shared by Res and POR were collected. GO annotation indicated that these targets were mainly involved in oxidative stress response. KEGG enrichment analysis revealed that Res can intervene in POR via PI3K/AKT, HIF-1, and FOXO signaling pathways. Animal experiments showed that the model group had higher rate of estrous cycle disorders, lower number and poorer morphology of normally developed follicles at all levels, more atretic follicles, higher apoptosis of ovarian granulosa cells, lower number of retrieved oocytes, lower ovarian wet weight and ovarian index, higher serum levels of FSH and LH, lower levels of AMH and E_2, higher expression levels of HIF-1α, FOXO3a and Bax, and lower expression levels of PI3K, AKT, and Bcl-2 in the ovarian tissue than the normal group. Compared with the POR group, low-and high-dose Res decreased the rate of estrous cycle disorders, improved the follicle number and morphology, reduced atretic follicles, promoted the apoptosis of ovarian granulosa cells, increased retrieved oocytes, ovarian wet weight and ovarian index, and lowered serum FSH and LH levels. Moreover, Res down-regulated the expression levels of HIF-1α, FOXO3a and Bax, and up-regulated the expression levels of PI3K, AKT and Bcl-2 in the ovarian tissue. In summary, Res can inhibit apoptosis and mitigate poor ovarian response in mice by regulating the PI3K/AKT/FOXO3a and HIF-1α pathways.
Female ; Mice ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Resveratrol/pharmacology* ; bcl-2-Associated X Protein ; Phosphatidylinositol 3-Kinases/metabolism* ; Sodium Chloride ; Follicle Stimulating Hormone ; Proto-Oncogene Proteins c-bcl-2

OBJECTIVE This study aimed to explore the optimal process for preparing long-acting liposomes loaded with cock-roach extract(CE-Lip)and to evaluate their therapeutic efficacy against ulcerative colitis(UC).METHODS The CE-Lip was pre-pared using a thin film dispersion method.Orthogonal experiments were conducted to optimize the formulation and freeze-drying process of CE-Lip.Morphological characterization and in vitro release rate assessment were performed.The therapeutic efficacy of CE-Lip was evaluated using a mouse model of UC.RESULTS The optimal preparation process involved a cholesterol-phospholipid mass ratio of 1∶5,an extract-phospholipid mass ratio of 1∶4,hydration time of 0.75 h,hydration volume of 3 mL,and hydration temperature of 30℃.The optimal freeze-drying process utilized a mixture of 5%mannitol and 10%trehalose as protective agents.The resulting CE-Lip exhibited an average particle size of(276.7±5.6)nm,with a vesicular structure.The stability of CE-Lip after freeze-drying was excellent,and its in vitro release rate was significantly lower than that of the raw material.Pharmacological results demonstrated that CE-Lip significantly reduced DAI scores,colon length,CMDI scores,TNF-α expression,and HS scores in UC mice,while increasing EGF expression and mucin expression in goblet cells.CONCLUSION A simple,stable,and reproducible process for preparing CE-Lip is established.The resulting CE-Lip exhibits uniform size distribution,good stability,and sustained release effects.Compared to conventional formulations,CE-Lip significantly enhanced the therapeutic effect of CE against UC in mice.This study provides a foun-dation for further development and research of CE-Lip.

Houpu Mahuang Decoction,from the Essentials from the golden cabinet,is a commonly used prescription for respiratory diseases.In recent years,research on the pharmacology and mechanism of action of Houpu Mahuang Decoction has received some at-tention.It has been found that Houpu Mahuang Decoction plays a protective role in chronic airway diseases by inhibiting airway inflam-mation,relieving asthma,regulating immunity,and protecting airway barriers.Based on this,it is proposed to strengthen research on material basis,establish quality standards and material benchmarks,explore in-depth mechanisms,reveal the scientific connotation of drug efficacy,improve the quality of clinical research evidence,establish clinical prediction models,and other aspects in the future.This will provide a basis for the research and development of prescription formulations and new drugs,in order to better return to clinical practice,serve clinical practice,and promote the modernization and internationalization of TCM.

OBJECTIVE: Improvement in the quality of life is reflected in the narrowing of the gap between health-adjusted life expectancy (HALE) and life expectancy (LE). The effect of megacity expansion on narrowing the gap is rarely reported. This study aimed to disclose this potential relationship. METHODS: Annual life tables were constructed from identified death records and population counts from multiple administrative sources in Guangzhou, China, from 2010 to 2020. Joinpoint regression was used to evaluate the temporal trend. Generalized principal component analysis and multilevel models were applied to examine the county-level association between the gap and social determinants. RESULTS: Although LE and HALE in megacities are increasing steadily, their gap is widening. Socio-economic and health services are guaranteed to narrow this gap. Increasing personal wealth, a growing number of newborns and healthy immigrants, high urbanization, and healthy aging have helped in narrowing this gap. CONCLUSION In megacities, parallel LE and HALE growth should be highly considered to narrow their gap. Multiple social determinants need to be integrated as a whole to formulate public health plans.
Cities ; Health Status ; Humans ; Infant, Newborn ; Life Expectancy ; Quality of Life ; Social Determinants of Health

An ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) method was established for the determination of active components of Sarcandrae Herba, and applied to the pharmacokinetics study of multiple dosage forms. After SD rats were administered by gavage with three dosage forms [Sarcandrae Herba extract, commercial Sarcandrae Herba Guttate Pills, and polydopamine guttate pills loaded with active components of Sarcandrae Herba(PDA-Sg Guttate Pills)], blood samples were collected from the inner canthus at different time points. After protein precipitation, plasma samples were separated on ACQUITY UPLC C_(18) column(2.1 mm×100 mm, 1.7 μm). The mobile phase consisted of water containing 0.2% formic acid and acetonitrile in gradient elution. The negative ions were measured simultaneously in the multi-reaction monitoring(MRM) mode. The pharmacokinetic parameters were calculated and fitted by DAS 2.0. All four components could be detected in the plasma of rats in each group at each time point except the neochlorogenic acid and cryptochlorogenic acid in the Sarcandrae Herba extract group. The guttate pills group showed a significant increase in drug content at each time point. The exposure of the main components of Sarcandrae Herba in blood was effectively increased by PDA-drug loading effect in PDA-Sg Guttate Pills(The AUC_(0-24 h) of neochlorogenic acid, cryptochlorogenic acid, isaziridin and rosmarinic acid reached 2.45, 32.90, 1.54, 4.81 times that of the commercial guttate pills). This study proves the measurability of the above-mentioned multi-component in vitro-in vivo delivery process. The pharmacokinetic study has shown that PDA-Sg Guttate Pills can effectively delay the elimination time and improve the bioavailability of the four components, which can provide theoretical data for the production of the drug.
Animals ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/pharmacokinetics* ; Indoles ; Polymers ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Tandem Mass Spectrometry/methods*

Objective: To analyze the spatiotemporal distribution of life expectancy (LE) and health-adjusted life expectancy (HALE) in Guangzhou from 2010 to 2019, and quantize the comprehensive impact of different causes and sequelae on health. Methods: The LE, HALE, and cause-excluded health adjusted life expectancy (CEHALE) were estimated using cause-of-death surveillance datasets from Guangzhou Municipal Center for Disease Control and Prevention from 2010 to 2019 and open data from the Global Burden of Disease Study. Joinpoint log-linear regression model was used to analyze the temporal trend and described spatial distribution. Results: In 2019, the LE in residents in Guangzhou was 82.9 years (80.1 years in men and 85.9 years in women), and the HALE was 75.6 years (74.0 years in men and 77.3 years in women). Compared with the urban fringe, the central urban area had higher LE and HALE, and the differences between LE and HALE were small. The LE and HALE in Guangzhou showed an increasing trend from 2010 to 2019. The LE increased by 2.8 years (AAPC=0.4, 95%CI: 0.3-0.4), with the increase of 2.8 years in men and 2.9 years in women. The HALE increased by 2.4 years (AAPC=0.3, 95%CI: 0.3-0.4), with the increase of 2.5 years in men and 2.2 years in women. The median healthy life lost due to communicable, maternal, neonatal, and nutritional diseases was 6.2 years (AAPC=-4.2, 95%CI: -5.3--3.1), while the median healthy life lost due to non-communicable diseases was 14.7 years (AAPC=1.6, 95%CI: 0.9-2.3), the median healthy life expectancy reduced by injury was 6.3 years (AAPC=-3.5, 95%CI: -4.5--2.6). Musculoskeletal disorders, skin and subcutaneous diseases, cardiovascular diseases, nutritional deficiencies, diabetes and kidney diseases were the top five diseases causing healthy life expectancy loss. Conclusion: The LE and HALE in residents in Guangzhou increased steadily from 2010 to 2019, but the quality of life in the urban fringe was lower than that of the central urban area. Non-communicable diseases were the leading causes of healthy life expectancy loss. Health policies and prevention measures should be developed according to area specific characteristics, and social medical resources should be rationally allocated to key diseases to reduce their disease burden.
Cost of Illness ; Female ; Health Status ; Humans ; Infant, Newborn ; Life Expectancy ; Male ; Noncommunicable Diseases ; Quality of Life

As the detection rate of pancreatic cystic neoplasms (PCN) increases,recommendations or guidelines for the diagnosis and treatment of PCN have been released from professional organizations.From the perspective of radiology,we compared seven guidelines in terms of general introduction,preoperative monitoring methods and strategies,stratification of risk factors,surgical indications,and postoperative follow-ups,aiming to provide references for the evaluation of images and the formulation of individualized approach for the treatment of PCN.
Humans ; Pancreatic Cyst/therapy* ; Pancreatic Neoplasms/therapy* ; Pregnenolone Carbonitrile ; Radiography ; Radiology

Ligustri Lucidi Fructus, the sun-dried mature fruit of Ligustrum lucidum, is cool, plain, sweet, and bitter, which can be used as both food and medicine, with the effects of improving vision, blacking hair, and tonifying liver and kidney. It takes effect slowly. However, little is known about the genetic information of the medicinal plant and it is still a challenge to distinguish Ligustrum species. In this study, the complete chloroplast genome of L. lucidum was obtained by genome skimming and then compared with that of five other Ligustrum species, which had been reported. This study aims to evaluate the interspecific variation of chloroplast genome within the genus and develop molecular markers for species identification of the genus. The result showed that the chloroplast genome of L. lucidum was 162 162 bp with a circular quadripartite structure of two single-copy regions separated by a pair of inverted repeats. The Ligustrum chloroplast genomes were conserved with small interspecific difference. Comparative analysis of six Ligustrum chloroplast genomes revealed three variable regions(rbcL-accD, ycf1a, and ycf1b), and ycf1a and ycf1b can be used as the species-specific DNA barcode for Ligustrum. Phylogeny analysis provided the best resolution of Ligustrum and supported that L. lucidum was sister to L. gracile. This study clarified the genetic diversity of L. lucidum from provenance, which can serve as a reference for further analysis of pharmacological differences and breeding of excellent varieties with stable drug effects.
Fruit ; Genome, Chloroplast ; Ligustrum/genetics* ; Phylogeny ; Plant Breeding