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 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.

Animals ; Macaca mulatta ; Optic Disk ; Glaucoma ; Craniocerebral Trauma ; Intraocular Pressure ; Low Tension Glaucoma

Objective This study aims to establish a non-puerperal mastitis (NPM) rat model by simulating hyperprolactinemia and immune-inflammatory states, and to evaluate its local inflammatory characteristics in the mammary gland, thereby laying the foundation for research on the diagnosis and treatment of this clinically challenging disease. Methods Twelve SPF-grade Wistar female rats were evenly divided into a control group and a model group. During the experiment, the control group received no experimental treatment or medication. The model group received daily subcutaneous injections of 100 mg/kg metoclopramide hydrochloride for 7 consecutive days. Serum prolactin (PRL) levels were measured using ELISA on the 10th, 20th, and 30th days after the first injection. After 7 days of injections, 200 μL of lactating SD rat milk was mixed with 200 μL of complete Freund's adjuvant to prepare an oil-in-water emulsion, which was administered by multiple subcutaneous injections into the back of the Wistar rats for the initial immunization. Seven days after the initial immunization, the emulsion was injected subcutaneously into the third, fourth, and fifth mammary glands for the final immunization. After the final immunization, the rats were observed for 28 days for changes in mammary gland appearance, and the size of mammary nodules was calculated. On the 3rd, 7th, 14th, and 28th days, hematoxylin-eosin (HE) staining was used to analyze mammary tissue morphology. Immunohistochemistry was employed to detect CD138 expression levels. ELISA was used to measure the levels of interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, and inducible nitric oxide synthase (iNOS) in mammary tissue to comprehensively assess the model. Results Rats in the model group exhibited mammary skin ulceration and foul odor at the ulcer sites. Palpation and ultrasound revealed the formation of mammary nodules. HE staining showed that on the 3rd day after the final immunization, normal ductal and lobular structures in the mammary glands disappeared, with significant infiltration of plasma cells. On the 7th day, ductal dilation, epithelial necrosis and detachment, and pronounced periductal plasma cell and lymphocyte (predominantly T-lymphocytes) infiltration were observed. On the 14th day, there was a proliferation of fibrofatty tissue, small blood vessels, and granulation tissue, with scattered plasma cells in the interstitium. By the 28th day, inflammatory cell infiltration and fibrous tissue proliferation were reduced, with granuloma formation. Serum PRL levels in the model group were significantly increased on the 10th day (P<0.05) and the 20th day (P<0.001). IL-6 and TNF-α levels in mammary tissue were higher in the model group compared to the control group on the 3rd, 7th, 14th, and 28th days (P<0.05). IL-1β levels were higher on the 3rd, 7th, and 14th days compared with the control group (P<0.01) but lower than the control group on the 28th day (P>0.05). iNOS levels were significantly higher on the 7th day after the final immunization (P<0.001). Conclusion A successful NPM model was established in rats, which exhibited typical pathological features such as local mammary masses, abscesses, ulcers, ductal dilation and plasma cell infiltration. This model can serve as a foundation for further research into the diagnosis and treatment of this clinically challenging disease.

Objective To observe the efficacy and safety of repetitive transcranial magnetic stimulation(rTMS)on refractory tinnitus and the differences of resting-state functional magnetic resonance imaging(rs-fMRI)imaging between before and after treatment,and to explore the possible central mechanism of rTMS regulation of tinnitus.Methods Thirty-seven patients with refractory tinnitus admitted in Affiliated Hospital of North Sichuan Medical College from September 2022 to February 2023 were selected and were divided into experimental group(n=20)and control group(n=1 7).The experimental group was given true rTMS treatment,and the control group was given sham stimulation with the same parameters.Tinnitus handicap inventory(THI)score,tinnitus loudness visual analogue scale(VAS)score and rs-fMRI scan were performed before and after treatment.Regional homogeneity(ReHo)was calculated after scanning,and the different brain regions were selected as the area of interest(ROI)and the whole brain functional connection(FC)was performed.Results There were no significant differences in age,gender,education level,tinnitus side,course of disease,hearing level,self-rating depression scale,self-rating anxiety scale the experimental group and control group.There were no significant differences in THI and VAS scores between the two groups before treatment;the THI and VAS scores in the experimental group decreased after 2 weeks of rTMS treatment(P＜0.001),while there was no significant difference in the two scores in the control group before and after treatment.Only 3 patients in the experimental group experienced left facial muscle tremor or transient mild scalp pain during treatment,without other serious side effects.The ReHo of the left cerebellar area 9 increased in the experimental group after rTMS(P＜0.005);the ReHo values in the right inferior temporal gyrus,left posterior central gyrus and left anterior central gyrus increased in the control group after intervention(P＜0.005).The FCs between the right inferior temporal gyrus and the left orbital inferior frontal gyrus,the left anterior cingulate gyrus increased in the experimental group(P＜0.005),and FC between the right inferior temporal gyrus and the left superior marginal gyrus decreased(P＜0.005).The FCs between the right cuneus and the left fusiform gyrus,right superior occipital gyrus decreased in the experimental group after rTMS(P＜0.005).The FC between the right cuneus and the left fusiform gyrus increased in the control group after intervention(P＜0.005),while other FCs remained unchanged.Conclusions rTMS has a certain therapeutic effect on refractory tinnitus with higher safety;regulation of auditory brain network and related non-auditory brain network may be one of the central mechanisms of rTMS treating refractory tinnitus.

Objective To establish reference intervals for serum soluble transferrin receptor(sTfR)and sTfR/log ser-um ferritin index(sTfR/lgSF)in apparently healthy adults in the Wuhan area,so as to provide reference for clinical diagno-sis and treatment of iron deficiency and iron-deficiency anemia.Methods A total of 273 individuals from the Wuhan Aisa General Hospital,including health examination participants and blood donors,were selected to measure sTfR,other iron metabolism indicators and high sensitivity C-reactive protein(hsCRP).The sTfR/lgSF values were calculated and reference intervals for sTfR and sTfR/lgSF were established using the percentile method(P2.5 to P97.5).Spearman correlation anal-ysis was used to evaluate the relationships between sTfR,sTfR/lgSF,and other iron metabolism indicators,as well as hsCRP.Results The sTfR levels(M,mg/L)between males and females(1.01 vs 1.07)were not statistically significant(P＞0.05),but the sTfR/lgSF levels if males were significantly lower than those in females(0.45 vs 0.62)(P＜0.05).There was no significant difference in sTfR(M,mg/L)and sTfR/lgSF(M)among different age groups,with values of 1.07 vs 1.02 vs 1.00 and 0.52 vs 0.53 vs 0.51,respectively(P＞0.05).The reference interval for STfR was(0.72-1.68)mg/L,the sTfR/lgSF reference interval was(0.31-0.88)for males,and(0.37-1.19)for females.Correlation analysis showed no correlation between sTfR,sTfR/lgSF and hsCRP(r=0.043,P＞0.05;r=-0.064,P＞0.05),while serum ferritin(SF),serum iron(SI),transferrin saturation(TSAT)were correlated with hsCRP(r=0.128,P＜0.05;r=-0.195,P＜0.01;r=-0.173,P＜0.01).There was no correlation between sTfR and SF(r=-0.115,P＞0.05),while sTfR/lgSF was significantly correlated with and SF(r=-0.685,P＜0.01).Conclusion Preliminary reference intervals for serum sTfR and sTfR/lgSF in apparently healthy adults in the Wuhan has been established.sTfR and sTfR/lgSF are not affected by inflammatory factors and are significant for identifying iron deficiency in anemia patients with elevated serum ferritin caused by inflammation.