ObjectiveTo investigate the effect of icariin （ICA） on the phenotype of dendritic cells （DCs） in heart tissue of the Dahl salt-sensitive myocardial remodeling model of rats and its regulation on the vitamin D system. MethodsMale Dahl salt-resistant rats were divided into a normal group， and male Dahl salt-sensitive rats were divided into a model group， low-， medium-， and high-dose ICA groups （30， 60， 120 mg·kg^-1·d^-1）， and Vitamin D group （3×10^-5 mg·kg^-1·d^-1）. In addition to the normal group， the other groups were given an 8% high salt diet to establish a myocardial remodeling model and received intragastric administration after successful modelling once a day for six weeks. The dynamic changes in tail artery blood pressure were monitored， and detection of cardiac ultrasound function in rats was performed. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the morphological changes in rat heart tissue. The phenotype of DCs and T helper cell 17 （Th17）/regulatory T cell （Treg） ratio were detected by flow cytometry. The mRNA and protein expression of vitamin D receptor （VDR）， 1α-hydroxylase （CYP27B1）， 24-hydroxylase （CYP24A1）， forkhead frame protein 3 （FoxP3）， solitaire receptor γt （RORγt）， myocardial type Ⅰ collagen （ColⅠ）， and type collagen （ColⅢ） in heart tissue was detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultsCompared with the normal group， the model group showed disordered arrangement and rupture of myocardial cells， nuclear condensation， significant edema of myocardial tissue， significant proliferation of collagen fibers in a network distribution， and a significant increase in tail artery blood pressure， left ventricular end diastolic diameter （LVEDD）， and left ventricular end systolic diameter （LVESD） （P<0.05）. The phenotype of cardiac DCs was CD40， CD80， and CD86， and the levels of major histocompatibility complex Ⅱ （MHC-Ⅱ）， Th17 cells， and Th17/Treg were significantly increased （P<0.05）. The mRNA and protein expression of CYP24A1 and RORγt in the heart， as well as the mRNA expression of ColⅠ and ColⅢ， were significantly increased （P<0.05）. The left ventricular ejection fraction （LVEF）， interventricular septal thickness （IVSD）， and left ventricular posterior wall thickness （LVPWD） were significantly decreased （P<0.05）. The phenotype of cardiac DCs such as CD11， CD11b， and Treg cells， were significantly reduced （P<0.05）， while the mRNA and protein expression of cardiac VDR， CYP27B1， and FoxP3 were significantly decreased （P<0.05）. Compared with the model group， the low-， medium-， and high-dose ICA groups and vitamin D group significantly reduced myocardial cell rupture and nuclear consolidation in rats. The high-dose ICA group and vitamin D group showed a small amount of myocardial cell rupture and nuclear consolidation， improving myocardial fiber arrangement to varying degrees and significantly reducing myocardial fiber rupture and proliferation. The tail artery blood pressure， LVEDD， and LVESD were significantly decreased in the low-， medium-， and high-dose ICA groups and vitamin D group （P<0.05）， and the phenotype of cardiac DCs including CD40， CD80， CD86， MHC-Ⅱ， Th17 cells， and Th17/Treg were significantly decreased （P<0.05）. The mRNA and protein expression of CYP24A1 and RORγt， and the mRNA expression of ColⅠ and ColⅢ in the heart were significantly decreased in the medium- and high-dose ICA groups and vitamin D group （P<0.05）. The LVEF， IVSD， and LVPWD of myocardial remodeling model rats in the low-， medium-， and high-dose ICA groups and vitamin D group were significantly increased （P<0.05）. The phenotypes of cardiac DCs including CD11， CD11b， and Treg cells were significantly increased in the medium- and high-dose ICA groups and the Vitamin D group （P<0.05）. The mRNA and protein expressions of VDR， CYP27B1， and FoxP3 in the heart were significantly increased in the medium- and high-dose ICA groups and vitamin D group （P<0.05）. ConclusionICA can regulate tail artery blood pressure， cardiac structural and functional damage， and myocardial tissue fibrosis and inhibit phenotype and functional maturation of DCs in heart tissue in the myocardial remodeling model of Dahl salt-sensitive rats. It can also affect the gene and protein expression of VDR， CYP24A1， and CYP27B1， achieving its intervention in Th17/Treg balance in the immune process of myocardial remodeling possibly by regulating vitamin D/VDR in heart tissue.

ObjectiveTo investigate the effect of icariin （ICA）-mediated vitamin D system on peripheral blood dendritic cells （DCs） and helper T cells 17 （Th17）/regulatory T cells （Treg） balance in myocardial remodeling model of Dahl salt-sensitive rats. MethodFifty SPF Dahl salt-sensitive rats were divided into model group， vitamin D group （3×10^-5 mg·kg^-1·d^-1）， and high-， medium-， and low-dose ICA groups （120， 60， 30 mg·kg^-1·d^-1）， and 10 Dahl salt-resistant rats were used as normal group. The myocardial remodeling model was established by feeding rats with a high-salt diet containing 8% NaCl. After six weeks of modeling， the normal group and the model group were given an equal volume of ultrapure water by gavage， and other groups were continuously administrated for six weeks. Cardiac echocardiography， hematoxylin-eosin （HE） staining， and Masson staining were used to observe the pathological changes in cardiac structure and fibrosis. The levels of serum 25（OH）D₃， B-type N-terminal pro-brain natriuretic peptide （NT-ProBNP）， interleukin （IL）-17， transforming growth factor （TGF）-β₁， IL-12， and IL-10 were detected by enzyme-linked immunosorbent assay （ELISA）. The phenotype of peripheral blood DCs and the ratio of Th17/Treg cells of rats were detected by flow cytometry. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the mRNA and protein expressions of vitamin D receptor （VDR），1α-hydroxylase （CYP27B1）， and 24-hydroxylase （CYP24A1） in peripheral blood DCs of rats. ResultCompared with the control group， the rats in the model group had pathological changes such as disordered arrangement of myocardial cells and cytoplasmic hypertrophy and swelling. Myocardial collagen fibers proliferated significantly， and the arrangement of myocardial fibers was disordered. The levels of serum 25（OH）D₃ and IL-10 were significantly decreased， and the levels of serum IL-17， TGF-β₁， IL-6， IL-12， and NT-ProBNP were significantly increased （P<0.05）. The costimulatory molecules CD40， CD80， CD86， and MHC-Ⅱ were highly expressed in the peripheral blood DCs， and the expression of CD11 and CD11b was lower （P<0.05）. The proportion of Th17 cells in the peripheral blood was significantly increased， and the proportion of Treg cells was decreased. The ratio of Th17/Treg was increased （P<0.05）. The mRNA and protein expressions of CYP24A1 in peripheral blood DCs increased， and the mRNA and protein expressions of CYP27B1 and VDR decreased （P<0.05）. Compared with the model group， the arrangement of myocardial fibers in each drug administration group was relatively regular， and the swelling of myocardial cells was significantly reduced. The pathological morphology of myocardial tissue was improved to varying degrees. The pathological changes in myocardial tissue were improved and alleviated to varying degrees. The drug could reduce the serum levels of NT-ProBNP， IL-17， TGF-β₁， IL-6， and IL-12 and increase the level of serum 25（OH）D₃ and IL-10 （P<0.05）. The expression of costimulatory molecules CD40， CD80， CD86， and MHC-Ⅱ in the peripheral blood DCs of rats was decreased， and the expression of CD11 and CD11b molecules was increased （P<0.05）. The drug could reduce the proportion of Th17 cells in peripheral blood and the ratio of Th17/Treg cells and increase the proportion of Treg cells （P<0.05）. It could decrease the mRNA and protein expressions of CYP24A1 in peripheral blood DCs of rats and elevate the mRNA and protein expression of VDR and CYP27B1 （P<0.05）. ConclusionICA can regulate the phenotype of peripheral blood DCs and the ratio of Th17/Treg cells by regulating the vitamin D system and play a role in improving myocardial remodeling from the perspective of immune balance.

Objective:To investigate the application value of magnetic resonance imaging (MRI) intravoxel incoherent motion (IVIM)-diffusion-weighted imaging (DWI) metrics and texture analysis in the differential diagnosis and staging of nasopharyngeal carcinoma.Methods:The clinical data of 125 nasopharyngeal carcinoma patients (the research group) in Tangshan People's Hospital from October 2019 to October 2021 and 76 patients with nasopharyngeal hyperplasia during the same period (the control group) were retrospectively analyzed. All patients underwent MRI T2WI and IVIM-DWI sequence scanning, and then the plain T2WI images, DWI, and IVIM-DWI quantitative parameter pseudo-color maps including pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) were obtained. The texture analysis metrics like apparent diffusion coefficient (ADC), D, D* and f were recorded. IVIM-DWI and texture analysis metrics were compared among patients in both groups and patients in different clinical stages; and the receiver operating characteristic (ROC) curve was plotted to evaluate the efficacy of IVIM sequence parameters and texture analysis metrics in the differential diagnosis and staging of nasopharyngeal carcinoma.Results:Compared with the control group, a marked reduction in D value [(0.80±0.13)×10 -3 mm 2/s vs. (1.19±0.27)×10 -3 mm 2/s], f value [(11.3±2.2)% vs. (15.6±3.3)%], mean ADC value [(0.92±0.17)×10 -3 mm 2/s vs. (1.16±0.19)×10 -3 mm 2/s] and variance (2 189±862 vs. 3 563±925) (all P < 0.05); a notable increase in skewness (0.50±0.17 vs. 0.31±0.12), kurtosis (0.56±0.13 vs. -0.21±0.06) and entropy (10.5±2.3 vs. 7.1±2.1) (all P < 0.05). The area under the curve (AUC) of IVIM sequence parameters and texture analysis metrics in the differential diagnosis of nasopharyngeal carcinoma was 0.763 and 0.803, respectively; the AUC, sensitivity and specificity of the combination of IVIM sequence parameters and texture analysis metrics for the differential diagnosis of nasopharyngeal carcinoma was 0.868, 89.6% and 86.8%, respectively. Compared with patients in stage Ⅰ-Ⅱ nasopharyngeal carcinoma, patients in stage Ⅲ-Ⅳ reported the lower D value [(0.75±0.13)×10 -3 mm 2/s vs. (0.89±0.16)×10 -3 mm 2/s], f value [(10.8±2.8)% vs. (12.1±3.0)%] (all P < 0.05), and the lower mean ADC value [(0.90±0.14)×10 -3 mm 2/s vs. (0.96±0.16)×10 -3 mm 2/s], and variance (2 063±831 vs. 2 431±846) (all P < 0.05), skewness (0.56±0.15 vs. 0.39±0.16), kurtosis (0.62±0.15 vs. 0.44±0.13) and entropy (11.0±2.1 vs. 9.1±2.4) (all P < 0.05). The AUC of IVIM sequence parameters and texture analysis metrics in differentiating nasopharyngeal carcinoma with different stages was 0.863 and 0.796, respectively; the AUC, sensitivity and specificity of the combination of IVIM sequence parameters and texture analysis metrics in differentiating nasopharyngeal carcinoma with different stages was 0.894, 85.4% and 90.7%, respectively. Conclusions:MRI texture analysis and IVIM quantitative analysis are of high value in the differential diagnosis and staging of nasopharyngeal carcinoma; and the texture analysis achieves higher sensitivity and specificity in the differential diagnosis and staging of nasopharyngeal carcinoma compared with IVIM quantitative analysis; the combined application of both has the highest overall efficacy.

OBJECTIVE To systematically review the background of bioequivalence assessment of nasal sprays and nasal aerosols and the guiding considerations for the bioequivalence assessment of these complex drug-device combination products by regulatory authorities in the United States, the European Union(EU) and China. METHODS This article provided detailed explanations on the innovative weight of evidence assessment approach adopted by the US Food and Drug Administration(FDA), and the statistical rationale, methods and considerations for the bioequivalence assessment of nasal sprays and nasal aerosols. Using the calculation methods described in the draft guidance for budesonide inhalation suspension and the draft guidance for fluticasone nasal spray propionate issued by FDA, the statistical parameters of two-sided and one-sided population bioequivalence calculation were realized through R language programming, and pseudo-code for the population bioequivalence (PBE) calculation programs was provided. This article also presented a comprehensive review of published guidelines and summaries review principles of the EU and China for nasal sprays and nasal aerosols equivalence assessment. RESULTS & CONCLUSION Nasal sprays/nasal aerosols is the focus of innovative and generic drug development in recent years. This paper provided valuable considerations references for the research and development, quality control and bioequivalence evaluation of generic preparations of nasal sprays/nasal aerosols.

Patients exhibit good tolerance to messenger ribonucleic acid (mRNA) vaccines, and the choice of encoded molecules is flexible and diverse. These vaccines can be engineered to express full-length antigens containing multiple epitopes without major histocompatibility complex (MHC) restriction, are relatively easy to control and can be rapidly mass produced. In 2021, the U.S. Food and Drug Administration (FDA) approved the first mRNA-based coronavirus disease 2019 (COVID-19) vaccine produced by Pfizer and BioNTech, which has generated enthusiasm for mRNA vaccine research and development. Based on the above characteristics and the development of mRNA vaccines, mRNA cancer vaccines have become a research hotspot and have undergone rapid development, especially in the last five years. This review analyzes the advances in mRNA cancer vaccines from various perspectives, including the selection and expression of antigens/targets, the application of vectors and adjuvants, different administration routes, and preclinical evaluation, to reflect the trends and challenges associated with these vaccines.

Gastrodia elata is a kind of precious traditional Chinese medicine. In artificial cultivation, it has not got rid of its dependence on forest resources. In order to maintain the balance of the ecological system and reduce the waste of resources as much as possible, based on the information from field investigation at many places, this paper introduced the new ecological circulation planting patterns of G. elata, such as "forest-G. elata" supporting planting, G. elata-edible mushroom rotation, forest-G. elata-edible mushroom three-dimensional planting, fungus material classification planting technology, and so on. In this paper, we expounded the ecological problems solved by several planting patterns in G. elata production and analyzed their shortcomings. Finally, based on the exis-ting models, a complete ecological planting system of G. elata was summarized. This planting system emphasizes: ① The follow-up forests should be started before the planting of G. elata. And the economic forests were used to cultivation of G. elata. ② The classified utilization of fungus-growing materials. The leaves were used to cultivate germination bacteria of G. elata, the small branches were used to cultivate protocorm and juvenile tuber, the large branches were used to cultivate immature tuber, and the tree trunk was used to cultivate mature tuber. ③ Recycle utilization G. elata fungus material. The old fungus materials were used to produce strains or cultivate edible fungus. This design project not only solves the problems of the source of G. elata fungus material, the efficient utilization of fungus material and land resources, but also enriches the industrial structure. Using limited time and land resources to obtain greater economic benefits. It has certain guiding significance for poverty alleviation and ecological improvement.
Agaricales ; Bacteria ; Gastrodia ; Medicine, Chinese Traditional ; Plant Tubers

Gastrodia elata is a kind of precious traditional Chinese medicine. In the process of cultivation of G. elata, due to the influence of continuous cropping obstacles and other factors, the fungus materials and land that have been planted with G. elata are often abandoned, resulting in a great waste of resources. Based on the planting characteristics of G. elata and Phallus impudicus and the previous research experience in ecological agriculture, this paper analyzed the ecological adaptability characteristics of G. elata and P. impudicus, and summarized the key techniques of the G. elata-P. impudicus sequential planting pattern. Keeping track of the planting area, fungus-growing materials consumption and market sales of G. elata-P. impudicus sequential planting pattern, the ecological benefits of G. elata-P. impudicus sequential planting pattern from the aspects of utilization rate of fungus-growing materials were analyzed, the value of land resources per unit area, ecological environmental protection, labor cost and economic benefits were consi-dered. The technical principle of G. elata-P. impudicus sequential planting pattern was expounded according to their ecological habit, the season of harvest and planting, the difference of composition of fungus-growing materials, and the microbial ecology. The sequential planting pattern of G. elata-P. impudicus not only realized the double production of medicinal materials and edible fungi, reduced the waste of old fungus-growing materials, but also transformed the energy from nutrition-supplied fungi to edible and medicinal fungi, which guaranteed the ecological recycling and utilization of G. elata in the process of cultivation.
Agaricales/growth & development* ; Agriculture/methods* ; Gastrodia/growth & development* ; Medicine, Chinese Traditional ; Plants, Medicinal/growth & development*

Objective: To investigate the prognostic impact of alterations of epidermal growth factor receptor(EGFR) and MGMT in glioblastoma. Methods: The retrospective study included 161 supratentorial glioblastomas diagnosed in the Department of Pathology, Xuanwu Hospital, Capital Medical University from 2009 to 2015. EGFR and EGFRvⅢ protein expression was detected by immunohistochemistry; EGFR amplification was detected by fluorescence in situ hybridization; MGMT promoter methylation was detected by pyrosequencing. The change of molecular genetics EGFR and MGMT and outcome were assessed statistically. Results: There were 161 patients, including 85 (52.8%) males and 76 (47.2%) females. The mean age was 53 years, and the median overall survival was 13 months. The integrated classification of glioblastoma included 16 IDH-mutant, 134 wild type, and 11 NOS. The rate of overexpression of EGFR protein was 32.9%(53/161), and that of EGFR amplification was 37.5%(18/48). There was high concordance between immunohistochemistry and FISH(85.4%, Kappa=0.475, P<0.01) and between the level of EGFR protein and EGFR amplification (P<0.01). Twelve cases showed EGFRvⅢ expression, and all also showed EGFR protein overexpression; 149 cases were EGFRv Ⅲ wild type, and EGFR protein overexpression was seen in 27.5%(41/149) of cases. There was no correlation between EGFR and EGFRv Ⅲ expression. Of all cases, 70.2%(106/151) showed MGMT promoter methylation by pyrosequencing. The changes of molecular genetics of EGFR and MGMT were not related. EGFR amplification and protein overexpression had no significant relationship with prognosis. Patients with EGFRv Ⅲ-mutant had shorter survival time than the EGFRv Ⅲ-wild type(P=0.014); patients with MGMT promoter methylation had better prognosis than without (PFS:P=0.002,OS:P=0.006),and MGMT promoter methylation was an independent predictor for overall survival (HR=0.269, 95%CI 0.124-0.583, P=0.001). Conclusions EGFR protein expression by immunohistochemistry correlates with the status of EGFR amplification. Patients with EGFRv Ⅲ-mutant tumors have poorer prognosis than that with EGFRv Ⅲ-wild type tumors. MGMT promoter methylation is closely associated with prognosis and an independent predictor for overall survival.

Objective To investigate the the treatment of class Ⅲ malocclusion by orthognathic surgery combined with postoperative orthodontics.Methods Nine patients with skeletal class Ⅲ malocclusion were treated by surgery-first approach without pre-surgical orthodontic from January 2012 to August 2014.The studied sample consisted of 7 women and 2 men (aged 15-28 years old, mean age 19.7 years), who had obvious mandibular protrusion.2 to 3 days after surgery, intermaxillary traction was used to made the maxilla and mandible together by board;we replaced a rubber band every 2 to 3 days and lasted for four weeks.We would dismantle board and performed conventional orthodontic treatment after patient's facial swelling subsided, and the positional relationship between the jaw stabilized.Results The face type of 9 patients were greatly improved after orthodontic treatment for 6.5 to 19.5 months.Patients and their family members felt satisfied, and their occlusal function returned to normal.At 3 to 32 months follow-up, the postoperative appearance and occlusion were becoming good without obvious signs of recurrence.Conclusions The surgery-first approach is an effective method to treat skeletal class Ⅲ malocclusion.

OBJECTIVETo explore the predictive value of high-sensitivity C reactive protein (hsCRP) in middle-aged population during the peripheral arteriosclerosis.

METHODSRandom sampling method was used in the study. In 2006-2007 Kailuan Group health examination of 101,510 employees, using stratified random sampling method to select 5,852 as observational cohort included, in the final with a standard queue 5,440 in December 2009. This study selected to participate in the 2012-2013 health examination cohort as the research object, in accordance with the inclusion criteria ultimately selected survey 3,978, select the epidemiological investigation, physical examination, laboratory testing data analysis. Of the 3 978 subjects, 2,282 were male and 1,696 were female, and the baseline age was (53.80±11.14) years. According to the baseline hsCRP quartile level was divided into four groups for comparison of baseline data, using multiple linear regression analysis between hsCRP and brachial-ankle pulse wave velocity (baPWV). Area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the prediction of hsCRP levels in peripheral arteriosclerosis.

RESULTSWith increase of hsCRP levels, the survey of baseline levels of baPWV showed increasing trend, (1,445.49±300.55), (1,494.46±307.94), (1,547.67±320.34), (1,621.32±342.53) cm/s, respectively. Multiple linear regression results showed that age, by logarithmic transformation of hsCRP (lghsCRP) level, systolic blood pressure and fasting blood glucose for each additional unit, baPWV levels were increased 266.47, 58.00, 5.02, 39.79 cm/s (P<0.001), and BMI for each additional unit, baPWV level decreased 9.52 cm/s (P=0.030). The prediction of hsCRP in peripheral artery showed that lghsCRP level of AUC to 0.59 (95% CI: 0.57-0.61), lower than the age and systolic blood pressure predicted value AUC (95% CI) of 0.69 (0.67-0.71), 0.75 (0.73-0.77), respectively.

CONCLUSIONThe hsCRP level could not predict the peripheral arteriosclerosis alone, and the combined age and systolic blood pressure level could have better predictive value.

Ankle ; Ankle Brachial Index ; Biomarkers ; Blood Flow Velocity ; Blood Pressure ; C-Reactive Protein ; Female ; Humans ; Male ; Middle Aged ; Peripheral Arterial Disease ; Pulsatile Flow