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

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of～260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.

Objective:To compare the efficacy of amide proton transfer-weighted (APTw) imaging with time-dependent diffusion MRI (td-dMRI) in the diagnosis of malignant breast lesions.Methods:This study was a cross-sectional study. The clinical, pathological and imaging data of patients with breast lesions admitted to the First Affiliated Hospital of Zhengzhou University from March to August 2023 were prospectively analyzed. All patients firstly underwent T 2WI, diffusion-weighted imaging, followed by dynamic contrast-enhanced MRI (DCE-MRI), and finally APTw imaging and td-dMRI were performed for breast lesions using DCE-MRI as reference. Reconstructed images from APTw imaging measured lesions with a frequency shift of 3.5 ppm asymmetric magnetic susceptibility MTR asym(+3.5 ppm). The apparent diffusion coefficient (ADC) values at different oscillating frequency gradients (ADC PGSE, ADC 17 Hz, ADC 33 Hz values) were measured using reconstructed td-dMRI images. Independent sample t-test was used to compare APTw imaging, td-dMRI parameter differences between benign and malignant breast tumors, breast malignant tumors with different molecular types [estrogen receptor (ER) negative and positive, progesterone receptor (PR) negative and positive, human epidermal growth factor receptor (HER-2) negative and positive, proliferation index (Ki-67) low and high expression] and different histological grades (grade Ⅱ and Ⅲ). Receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the efficacy of APTw imaging and td-dMRI parameters in differentiating benign and malignant breast tumors, molecular classification and histological grading of malignant breast lesions. Results:There were 171 lesions in 171 patients, including 103 malignant lesions and 68 benign lesions. Histological grades were grade Ⅱ in 51 cases and grade Ⅲ in 38 cases of 89 cases of invasive carcinoma. Totally 98 cases of malignant lesions were included in molecular typing analysis, 36 cases were ER negative and 62 cases were ER positive. PR was negative in 51 cases and positive in 47 cases. There were 33 negative HER-2 patients, 65 positive HER-2 patients. There were 50 cases of low Ki-67 expression and 48 cases of high Ki-67 expression. The MTR asym(+3.5 ppm) value of malignant breast lesions was higher than that of benign lesions ( t=5.76, P<0.001), and the ADC PGSE, ADC 17 Hz and ADC 33 Hz values were lower than those of benign breast lesions ( t was 4.84, 4.62, 4.01, respectively, all P<0.001). MTR asym(+3.5 ppm) had the highest AUC value (0.83) and the highest specificity (90.38%), and ADC PGSE had the highest sensitivity (85.86%). There were no significant differences in MTR asym(+3.5 ppm), ADC PGSE, ADC 17 Hz and ADC 33 Hz between grade Ⅱ and grade Ⅲ histological grades of malignant breast lesions (all P>0.05). The ADC PGSE value of ER negative was higher than that of ER positive ( t=2.34, P=0.018), and the AUC for distinguishing ER positive from negative was 0.64. The ADC PGSE and ADC 17 Hz values of PR negative were higher than those of PR positive ( t=2.87, 2.81, P=0.004, 0.006, respectively), and their AUCs for identifying PR positive versus negative breast malignant lesions were 0.68 and 0.67, respectively. The ADC 33 Hz value of negative HER-2 was lower than that of positive HER-2 ( t=3.00, P=0.003), and the AUC for distinguishing positive and negative HER-2 was 0.67. There were no significant differences in other parameters among different subtypes of breast malignant lesions (all P>0.05). Conclusion:Compared with td-dMRI, APTw imaging is more effective in differentiating benign and malignant lesions of breast tumors, and ADC values at different gradient oscillation frequencies obtained by td-dMRI show better diagnostic efficacy in differentiating different molecular types of breast malignant lesions.

This article mainly elaborated the acupuncture and moxibustion treatment scheme of"eighteen needles for reproduction"based on Professor You Zhaoling's reproductive axis theory of"heart-kidney-Chong Ren-uterus".The"eighteen needles for reproduction"aims to regulate the disordered reproductive axis in gynecological reproductive diseases.It selects the acupoints on the main viscera and meridians of the reproductive axis as the main acupoints,and the acupoints regulating the qi and blood of the related viscera as the matching acupoints.Through specific manipulation,it can regulate the qi and blood,dredge the meridians,and treat the viscera,so as to nourish the essence and help pregnancy,and provide ideas and reference for the treatment of gynecological reproductive diseases with acupuncture and moxibustion.

Particle size and surface properties are crucial for lymphatic drainage (LN), dendritic cell (DC) uptake, DC maturation, and antigen cross-presentation induced by nanovaccine injection, which lead to an effective cell-mediated immune response. However, the manner in which the particle size and surface properties of vaccine carriers such as mesoporous silica nanoparticles (MSNs) affect this immune response is unknown. We prepared 50, 100, and 200 nm of MSNs that adsorbed ovalbumin antigen (OVA) while modifying β-glucan to enhance immunogenicity. The results revealed that these MSNs with different particle sizes were just as efficient in vitro, and MSNs with β-glucan modification demonstrated higher efficacy. However, the in vivo results indicated that MSNs with smaller particle sizes have stronger lymphatic targeting efficiency and a greater ability to promote the maturation of DCs. The results also indicate that β-glucan-modified MSN, with a particle size of ∼100 nm, has a great potential as a vaccine delivery vehicle and immune adjuvant and offers a novel approach for the delivery of multiple therapeutic agents that target other lymph-mediated diseases.

Purpose The aim of this study is to explore the application value of ALK(1A4)in ALK fused non-small cell lung cancer(NSCLC).Methods A total of 1 035 NSCLC specimens were collected.The expression of ALK(1A4)and ALK(D5F3)antibodies was detected by immunohistochemical(IHC)staining,and their consistency was analyzed.FISH and next-generation sequencing(NGS)were used to detect ALK positive,and the sensitivity and specificity of ALK in the two groups were evaluated.Results ALK fused NSCLC patients accounted for about 5.4％(56/1 035).The positive rate of ALK(1A4)was 7.2％(75/1 035),and that of ALK(D5F3)was 5.7％(59/1 035).The consistency between them was high,with a Kappa value of 0.874.The consistency of ALK(1A4)and ALK(D5 F3)antibodies with FISH was high,with Kappa values of 0.845 and 0.954,respectively.The consisten-cy of ALK(1A4)and ALK(D5F3)with NGS was also high,with Kappa values of 0.836 and 0.988,respectively.According to the FISH results,the sensitivities of ALK(1A4)and ALK(D5F3)antibodies were 100％and 98.2％,and the specifici-ties were 98.1％and 99.6％,respectively.Conclusion ALK(1A4)antibody has high sensitivity and slightly low specificity,and can be used for clinical screening of ALK fused NSCLC.

Objective:To investigate the current situation and influencing factors of humanistic care needs of family members of pregnant women in maternal intensive care unit, and to explore the relationship between humanistic care needs of family members of pregnant women in maternal intensive care unit, relocation stress level and perceived social support ability, so as to provide a basis for clinical nursing staff to implement targeted humanistic care for family members of pregnant women in maternal intensive care unit.Methods:From July to December 2022, 267 family members of pregnant women who were observed in the Maternal Intensive Care Unit of Maternity Hospital Affiliated to Nanjing Medical University/Nanjing Maternal and Child Health Hospital were selected as the research objects by the convenient sampling method. The general information questionnaire, Humanistic Care Needs Scale for Family Members of Pregnant Women in the Obstetric Intensive Care Unit, Family Relocation Stress Scale for Intensive Care Unit Patients and Perceived Social Support Scale were used to carry out a cross sectional investigation.Results:The scores of humanistic care needs, relocation stress scale and perceived social support scale were (175.32 ± 16.04), (35.12 ± 8.11), (57.30 ± 15.43) points, respectively. The length of maternal intensive care unit stay ( B=1.301, P<0.05), the family′s role changed for the first time ( B=2.328, P<0.05), the delivery mode doesn′t match the family′s expectations ( B=-2.407, P<0.05), maternal admission to maternal intensive care unit due to childbirth complications ( B=3.228, P<0.05), relocation stress level of intensive care unit patients′ family members ( B=0.891, P<0.05), and family members′ perceived social support ability ( B=0.461, P<0.05) were the influencing factors of humanistic care needs of maternal family members in maternal intensive care unit factors, which explained 83.2% of the total variation. Conclusions:The humanistic care needs of family members of pregnant women in maternal intensive care unit are at a high level. Medical staff should pay more attention to the family members of pregnant women who stay in maternal intensive care unit for a long time, undergo role change for the first time, have unexpected delivery mode and stay in maternal intensive care unit due to childbirth complications, so as to provide them with more comprehensive humanistic care and establish multiple support system, in order to improve the level of humanistic care for the family members of maternal intensive care unit.

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

Objective:To report the sampling study design and radiography protocol of a large-sample investigation on skeletal maturation of 3 to 18-year-old children in China.Methods:Multi-stage stratified random sampling was employed in this study. Two provinces, municipalities, or autonomous regions were randomly selected from each of the seven regions of China, including Northeast China, Northwest China, North China, Central China, East China, Southwest China, and South China. Then one rural and one urban investigation site were randomly selected from each province, municipality, or autonomous region. In total 28 sites were included. Among those sites, four residential districts were randomly selected from each urban site, and four townships from each rural site. For each residential district or township, 1-4 kindergartens, primary schools, and middle schools were chosen. Random cluster sampling was used to extract 3-<6-year-old children in kindergartens, and 6-18-year-old children in primary schools and middle schools. The investigation on skeletal maturation was sampled proportionate to the sampling of the whole study. The estimated simple size was 780 for each site, and 21 840 for all 28 sites in total. There were six groups of 3-<6-year-old children classified at 0.5-year intervals, and 12 groups of 6-18-year-old children classified at 1-year intervals. Posteroanterior position radiography of the left hand and wrist was achieved for all subjects.Results:The study was performed from August 26, 2019 to October 16, 2021. In total, 20 444 children received posteroanterior position radiography of the left hand and wrist, including 10 196 males and 10 248 females, 9 711 urban and 10 733 rural, respectively. The 3-<6-year-old group included 1 611 (male 819, female 792) subjects, and the 6 to 18-year-old group included 18 833 (male 9 377, female 9 456) subjects.Conclusion:This nationwide investigation on skeletal maturation of 3 to 18-year-old children in seven regions of China was successfully preformed. The results of this study can provide an important reference for establishing the current evaluation criteria of bone age in Chinese children and adolescents.