BACKGROUND: Epoxyeicosatrienoic acids (EETs), which are metabolites of arachidonic acid catalyzed by cytochrome P450 epoxygenase, are degraded into inactive dihydroxyeicosatrienoic acids by soluble epoxide hydrolase (sEH). Many studies have revealed that sEH gene deletion exerts protective effects against diabetes. Vascular calcification is a common complication of diabetes, but the potential effects of sEH on diabetic vascular calcification are still unknown. METHODS: The level of aortic calcification in wild-type and Ephx2-/- C57BL/6 diabetic mice induced with streptozotocin was evaluated by measuring the aortic calcium content through alizarin red staining, immunohistochemistry staining, and immunofluorescence staining. Mouse vascular smooth muscle cell lines (MOVAS cells) treated with β-glycerol phosphate (0.01 mol/L) plus advanced glycation end products (50 mg/L) were used to investigate the effects of sEH inhibitors or sEH knockdown and EETs on the calcification of vascular smooth muscle cells, which was detected by Western blotting, alizarin red staining, and Von Kossa staining. RESULTS: sEH gene deletion significantly inhibited diabetic vascular calcification by increasing levels of EETs in the aortas of mice. EETs (especially 11,12-EET and 14,15-EET) efficiently prevented the osteogenic transdifferentiation of MOVAS cells by decreasing nidogen-2 (NID2) expression. Interestingly, suppressing sEH activity by small interfering ribonucleic acid or specific inhibitors did not block osteogenic transdifferentiation of MOVAS cells induced by β-glycerol phosphate and advanced glycation end products. NID2 overexpression significantly abolished the inhibitory effect of sEH gene deletion on diabetic vascular calcification. Moreover, NID2 overexpression mediated by adeno-associated virus 9 vectors markedly increased insulin-like growth factor 2 (IGF2) and phospho-ERK1/2 expression in MOVAS cells. Overall, sEH gene knockout inhibited diabetic vascular calcification by decreasing aortic NID2 expression and, then, inactivating the downstream IGF2-ERK1/2 signaling pathway. CONCLUSIONS sEH gene deletion markedly inhibited diabetic vascular calcification through repressed osteogenic transdifferentiation of vascular smooth muscle cells mediated by increased aortic EET levels, which was associated with decreased NID2 expression and inactivation of the downstream IGF2-ERK1/2 signaling pathway.
Animals ; Mice ; Vascular Calcification/metabolism* ; Mice, Inbred C57BL ; Epoxide Hydrolases/metabolism* ; Diabetes Mellitus, Experimental/genetics* ; Male ; Gene Deletion ; MAP Kinase Signaling System/genetics* ; Cell Line ; Immunohistochemistry ; Muscle, Smooth, Vascular/metabolism* ; Signal Transduction/genetics* ; Mice, Knockout

Climate and land use changes may significantly impact the habitat distribution of Gastrodia elata, an endangered traditional medicinal plant. Accurately predicting its future potential suitable habitats is crucial for its conservation and sustainable development. This study integrates current distribution data of G. elata with 56 environmental variables and uses the MaxEnt model to predict changes in its suitable habitats under current climate conditions and four future climate scenarios(SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5). The results show that October precipitation and December minimum temperature are key environmental factors influencing its distribution. Under the current climate, optimal habitats for G. elata are concentrated in montane forest areas in Sichuan, Yunnan, Guizhou, and Hubei, which meet the species' requirements for understory growth. Across all future scenarios, the suitable habitat of G. elata consistently shows a stable northward shift, with a steady increase in suitable areas, extending to the middle and lower reaches of the Yangtze River and the Huang-Huai region, and even expanding into Liaoning, Jilin, and southern Heilongjiang. Land use analysis, taking into account the protection of arable land and the utilization of forest resources, indicates that by 2100, under future climate conditions, arable land in medium-to high-suitability areas is expected to increase by 30%-124%. While the conversion of non-suitable forest land into suitable habitats is projected to increase by 5%-52%, the growth of medium-to high-suitability areas within forests is relatively modest, ranging from 1% to 24%. These findings highlight the need to balance agricultural expansion with forest resource conservation to ensure the long-term sustainability of G. elata and provide scientific guidance for future suitable habitat management.
Ecosystem ; China ; Climate Change ; Gastrodia/growth & development* ; Conservation of Natural Resources ; Plants, Medicinal/growth & development*

Cistanches Herba(CH) is a famous tonic traditional Chinese medicine, with the effects of tonifying kidney Yang, nourishing kidney Yin, replenishing essence and blood, and moistening the intestines to relieve constipation. Modern pharmacological studies have shown that CH has anti-aging, anti-fatigue, immunomodulatory, neuroprotective, and anti-aging activities, serving as an ideal raw material for the development of pharmaceuticals and health products. In 2023, CH was added in the catalog of medicinal and food substances, which provided policy support for its application in conventional food products and expanding pathways for industrial diversification. To comprehensively understand current development status of CH products, this review systematically investigated professional databases including Yaozhi(https://db.yaozh.com), Chinese Pharmacopoeia, Compendium of National Standards for Chinese Patent Medicines, and Kezhuang and collected market survey data to thoroughly review the applications of CH as a primary ingredient in domestic and international Chinese patent medicines, health foods, cosmetics, and common food products. Furthermore, this review points out challenges in the current industrial development and future potential market prospects, aiming to provide guidance for the development and industrialization of CH-based pharmaceuticals and health products, thereby promoting the vigorous growth of the CH industry.
Drugs, Chinese Herbal/pharmacology* ; Humans ; Cistanche/chemistry* ; Animals ; Medicine, Chinese Traditional

Ropeginterferon α-2b (Ropeg), a novel, long-acting pegylated prolene alpha interferon, is the first interferon specifically approved for the treatment of patients with polycythemia vera (PV), and has been found in clinical trials and experience to induce hematologic remission, control disease-related symptoms, and reduce JAK2V617F allelic burden in patients with myeloproliferative neoplasms (MPNs). It has a lower incidence and severity of adverse drug reactions than pegylated interferon alpha and hydroxyurea and a longer dosing interval. Some patients with lowrisk PV and myelofibrosis can benefit from it. This article reviews the latest progress of Ropeg in MPN.
Humans ; Interferon-alpha/therapeutic use* ; Myeloproliferative Disorders/drug therapy* ; Polyethylene Glycols/therapeutic use* ; Recombinant Proteins/therapeutic use* ; Interferon alpha-2 ; Polycythemia Vera/drug therapy*

Objective:This article explores the diagnosis and treatment of a special type of laryngeal foreign body with granuloma in children, providing a clinical reference for standardized diagnosis and treatment. Methods:This article retrospectively analyzes one case admitted to our department and five other cases reported in relevant literature involving a special type of laryngeal foreign body with granuloma in children. It summarizes the clinical characteristics of this disease and explores its diagnosis and treatment. Results:①A total of 6 cases were misdiagnosed and had a long course of illness. Five cases had no clear history of foreign body at the first visit. One case had foreign body history but no foreign body was found. ②The clinical symptoms were diverse, which could be hoarseness, cough, wheezing, dyspnea, or no symptoms. ③A total of 3 cases were diagnosed by laryngoscopy, and 3 cases were diagnosed by laryngoscopy and imaging examination. ④Foreign bodies that were not wrapped in granulomas, were removed first and then the granulomas were treated; foreign bodies wrapped in granulomas were removed after the removal of granulomas. Conclusion:A special type of laryngeal foreign body with granuloma may lack of accurate foreign body history, resulting in long-term retention of foreign bodies, leading to granuloma formation and misdiagnosis. Electronic laryngoscopy combined with CT examination contribute to early diagnosis. Low temperature plasma under endoscope and anesthetic laryngoscope is conducive to the exposure and precise removal of foreign bodies and avoids tracheotomy to a certain extent.
Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Foreign Bodies/surgery* ; Granuloma, Foreign-Body/therapy* ; Larynx/pathology* ; Retrospective Studies

Objective To determine the median effective concentration(EC50)of ropivacaine at the volume of 0.5 mL/kg for ultrasound-guided interscalene brachial plexus block in children aged 6 to 10 years.Methods A prospective dose-finding trial was conducted based a sequential Dixon up-and-down allocation.We recruited children aged 6 to 10 years who were scheduled for unilateral surgery on upper extremity regions in our hospital from April to December 2022.All of them were subjected to general intravenous anaesthesia combined with ultrasound-guided interscalene brachial plexus block.The ropivacaine volume for each patient was 0.5 mL/kg.The concentration of 0.2%for the first patient,subsequent concentrations were adjusted based on the block effect of previous patient,increase or decrease by 0.02%.The trial was stopped when there were 7 turning points.Isotonic regression and Bootstrap were used to calculate the values of EC50 and 95%effective concentration(EC95),along with their 95%confidence intervals(CI).General data,incidence of adverse events,and score of postoperative pain were recorded.Results A total of 26 children aged 6 to 10 years were included.The EC50 of ultrasound-guided interscalene brachial plexus block was determined to be 0.091%(95%CI:0.077%～0.105%),and the EC95 was estimated to be 0.117%(95%CI:0.110%～0.118%).Successful blockade was achieved in 16 cases(61.5%),while 10 cases(38.5%)failed.No statistical differences existed between successful and failed cases regarding sex,age,body weight,surgical site,surgical laterality,operative time,or anesthesia duration.None of the patients experienced adverse events such as pneumothorax,vascular injury,or Horner's syndrome,and the score of postoperative pain were all<6 by modified Children's Hospital of Eastern Ontario Pain Scale.Conclusion In children aged 6 to 10 years,the EC50 of ropivacaine is 0.091%at a volume of 0.5 mL/kg for ultrasound-guided interscalene brachial plexus block,and this low dose of regional anesthetic can reduce the risks such as systemic toxicity and direct neurotoxicity.

This article reported the diagnosis and treatment of a boy with Dent disease presenting with massive proteinuria.He was 3 years old and found to have massive proteinuria during routine physical examination without hypoalbuminemia, urine protein electrophoresis indicated mainly low molecular weight proteins, with hypercalciuria, and metabolic acidosis, no diabetes, no amino acid urine, and renal ultrasound showed no renal calcium deposition, He had no mental and physical developmental delay and no abnormal family history. Gene detection revealed one missense mutation in exon 15 of the OCRL1 gene, c.1477C > T (p.Arg493Trp). After the diagnosis was confirmed, restrictions in dietary intake of calcium, sodium, and oxalate was restricted and oral potassium citrate and hydrochlorothiazide was prescribed. During two months of follow-up, we observed a decrease in urinary calcium levels and normal renal function. This article aims to improve the understanding of this disease among physicians and provide reference for the diagnosis and treatment of this disease through typical case report and review of previous literatures.

Objective To establish and validate a method for simultaneous determination of 9 sedative-hypnotics in human plasma,and to explore the preliminary clinical application.Methods Plasma samples were precipitated with acetonitrile and determined by high performance liquid chromatography tandem mass spectrometry.The column was Agilent Poroshell 120 EC-C18(2.1 mm × 50.0 mm,2.7μm)and eluted with acetonitrile water containing 0.1％formic acid in an equal degree program at a flow rate of 0.3 mL·min-1.The column temperature was 20 ℃ and injection volume was 5 μL.The deprotonated ions of analytes were ionized by positive ion,electron spray ionization and multiple reaction monitoring mode.The specificity,standard curve and lower limit of quantification,precision and recovery,matrix effect,stability and dilution effect of the method were investigated.Results Excellent linear relationship with correlation coefficient of r2 ≥ 0.997 7 was obtained.The linear of esazolam,alprazolam,oxazepam,clonazepam,lorazepam,triazolam,midazolam,diazepam and zolpidem were 18-1 800,4.5-450,25-2 500,3.5-350,25-2 500,1.5-150,5.5-550,35-3 500,4-400 ng·mL-1,respectively.The lower limit of quantification were 18,4.5,25,3.5,25,1.5,5.5,35,4 ng·mL-1.The method was accurate and precise with acceptable intra-day and inter-day precisions(relative standard deviations were less than 20％for a lower limit of quantification and less than 15％for other quality control samples)and an accuracy of 86.21％-112.38％.The extraction recovery rate were 93.07％-110.50％.The matrix factors normalized by internal standard were 86.61％-108.41％,relative standard deviations were less than 15％.Plasma samples remained stable under various storage conditions.The precision and accuracy of plasma samples were acceptable after dilution.Conclusion The method is simple,rapid,sensitive and specific,and it can be used for simultaneous detection of the 9 sedative-hypnotics in human plasma.

A 31P-quantitative nuclear magnetic resonance(qNMR)method was established for simultaneous determination of sodium α-glycerophosphate,sodium β-glycerophosphate and phosphoric acid in concentrated divitamins and sodium phosphate syrup.The qNMR experimental conditions were optimized,including hexamethylphosphoramide as internal standard,20%deuterium oxide solution as solvent,zgig pulse sequence,delay time of 30 s,and scan number of 64.The 31P-NMR peaks atδ29.80 of hexamethylphosphoramide,δ0.69 of sodiumα-glycerophosphate,δ0.17 of sodiumβ-glycerophosphate andδ0.03 of phosphoric acid were chosen as the quantitative peaks(pH of the test solution was around 4.8).Method validation was performed in terms of precision(Relative standard deviation less than 0.6%),linearity(Correlative coefficient greater than 0.999),limit of detection(23.58 μg/mL for sodium glycerophosphate and 11.61 μg/mL for phosphoric acid)and limit of quantitation(78.60 μg/mL for sodium glycerophosphate and 38.70 μg/mL for phosphoric acid).The recoveries were 99.8%?103.2%,and relative standard deviations were 0.41%?1.98%.The results showed that the reliability of 31P-qNMR method were suitable for its intended use.Seven batches of concentrated divitamins and sodium phosphate syrups were tested by the established method,of which the total phosphorus content was consistent with that of colorimetry method,but the content of sodium glycerophosphate(Sum ofαtype andβtype)was relatively low,about 82%of the labeled amount.The content of phosphoric acid was high.This method simplified sample pretreatment and had high specificity,and was more suitable for determination and quality control of concentrated divitamins and sodium phosphate syrup.

Objective:To investigate the effects of emodin on lipopolysaccharide(LPS)induced pyroptosis of human dental pulp fibro-blasts(HDPFs)by regulating the high mobility group protein B1(HMGB1)/Toll-like receptor 4(TLR4)signaling pathway.Methods:HDPFs were in vitro cultured and grouped into control(normal culture),LPS with low,medium and high dose emodin groups,pcDNA(transfected with pcDNA3.1)and pcDNA-HMGB1 groups(transfected with pcDNA3.1 HMMGB1).qRT-PCR was applied to detect the expression level of HMGB1 mRNA in cells,MTT assay,plate cloning assay and flow cytometry were applied to detect cell prolifera-tion and pyrotosis,respectively.ELISA was applied to detect levels of IL-18,IL-1β and TNF-α in cell supernatant.Western blot was applied to detect the expression of pyroptosis protein Nod-like receptor protein 3(NLRP3),cleaved caspase-1,GSDMD,HMGB1 and TLR4 proteins in the cells.Results:Compared with the control group,the HMGB1 mRNA level,pyrotosis rate,IL-18,IL-1β,TNF-α levels,NLRP3,cleaved Caspase-1,GSDMD,HMGB1,TLR4 protein levels in the LPS group obviously increased,the A490 value and colony formation obviously decreased(P＜0.05).Compared with the LPS group,the above indicators in the low,medium,and high dose emodin groups decreased,the A490 value and colony formation increased,the high-dose emodin group showed more obvious changes(P＜0.05);overexpression of HMGB1 attenuated the inhibitory effects of emodin on LPS-induced pyroptosis and inflammation of HDPFs,and promoted cell proliferation(P＜0.05).Conclusion:Emodin inhibit the activation of NLRP3 inflammasome by inhibiting the HMGB1/TLR4 pathway,thereby reduces LPS induced pyroptosis of HDPFs.