Application and clinical economic evaluation of three intervention methods in high-dose methotrexate chemotherapy-induced oral mucositis in acute lymphoblastic leukemia / 中国感染控制杂志

Objective To explore the clinical efficacy and cost-effectiveness of honey,low-temperature oxygen ato-mization and conventional mouthwash on chemotherapy-induced oral mucositis(CIOM)in patients with acute lym-phoblastic leukemia(ALL).Methods 129 ALL patients who were hospitalized in the hematology department of a tertiary first-class hospital in Yinchuan City of Ningxia from February to May 2023 and met the inclusion and exclu-sion criteria were selected,they were randomly divided into honey group,low-temperature oxygen atomization group,and conventional mouthwash group,with 43 cases in each group.During chemotherapy period,the honey group applied honey to oral mucosa surface,the low-temperature oxygen atomization group inhaled granulocyte stimulating factors through low-temperature oxygen atomization,the conventional mouthwash group gargled with prescribed mouthwash.Results There were 7(16.28％),9(20.93％),and 20(46.51％)patients with CIOM in honey group,low-temperature oxygen atomization group,and conventional mouthwash group,respectively.The in-cidence and severity of CIOM among three groups of patients were statistically different(H=11.598,P=0.003).Honey and low-temperature oxygen atomization were superior to conventional mouthwash in the prevention and treatment efficacy on CIOM in ALL patients(both P＜0.05),but the efficacy was no statistically different between honey and low-temperature oxygen atomization(P＞0.05).The cost of honey group was lower than low-tempera-ture oxygen atomization group and conventional mouthwash group(both P＜0.05),although the low-temperature oxygen atomization group has certain therapeutic effect,its cost was much higher than that of the honey group and the conventional mouthwash group(both P＜0.05).Conclusion Honey has a better prevention and treatment effect on CIOM in ALL patients,and can also reduce the hospitalization cost of patients.

Functional and morphological evaluation of the meibomian glands and ocular surface assessment at high altitude

Purpose: To compare the function and morphology of the meibomian glands and the ocular surface of individuals from highland and lowland. Methods: This was a randomized controlled trial. The study was performed with 104 individuals (51 individuals from the highland and 53 individuals from the lowland). Detailed eye examinations comprising tear meniscus height, lipid layer grading, non?invasive Keratograph tear breakup time (NIKBUT), and scoring of the meibomian glands from the upper and lower eyelids of the individuals were performed by Keratograph 5M (OCULUS, Wetzlar, Germany). Symptoms related to dry eye disease were assessed using the Ocular Surface Disease Index (OSDI). Results: In the highland group, tear meniscus height was lower (P = 0.024), lipid layer grade, as well as all the meiboscores were higher (P < 0.05) than that in the lowland group. The OSDI (P = 0.018) and the percentage of dry eye disease were also higher as compared to that of the lowland group (P = 0.032). The first NIKBUT and average NIKBUT did not differ significantly between groups. The frequency of plugged meibomian gland orifices was greater in the lowland group compared to the highland group (P = 0.036). Conclusion: It was observed that dry eye disease was more common in the highland group. The morphological changes of meibomian gland dropout were significant in highlanders as demonstrated objectively with Keratograph 5M. Our study may raise a concern for environmental influences on ocular surface changes

Effect of pirfenidone on paraquat-induced pulmonary fibrosis in rats / 中华劳动卫生职业病杂志

Objective: To construct paraquat (PQ) poisoning rat model and to explore the effect of pirfenidone (PFD) on PQ-induced pulmonary fibrosis. Methods: In April 2017, male 6-8 week-old Wistar rats were selected, and PQ was administered intraperitoneally at one time. PFD was administered by gavage 2 hours after poisoning. The daily gavage doses were 100, 200 and 300 mg/kg, and the rats were divided into physiological saline group, PQ group, PQ+PFD 100 group, PQ+PFD 200 group, PQ+PFD 300 group, with 10 rats in each group at each observation time point. The pathological changes of lung tissue at different time points (the 1st, 3rd, 7th, 14th, 28th, 42nd and 56th days) after poisoning and the effect of PFD intervention with different dose on PQ-induced pulmonary fibrosis were observed. Pathological evaluation of lung tissue was performed by Ashcroft scale method. The PQ+PFD 200 group was selected to further explore the pathological changes of lung tissue, the contents of hydroxyproline and malondialdehyde in lung tissue were determined.And the tumor necrosis factor (TNF) -α, interleukin (IL) -6, transforming growth factor (TGF) -β1, fibroblast growth factor (FGF) -B, platelet-derived growth factor (PDGF) -AB, insulin-like growth factor (IGF) -1 and PQ concentrations in serum and lung tissue were determined. Results: On the 1st to 7th day after PQ exposure, rats developed lung inflammation, which was aggravated on the 7th to 14th day, and pulmonary fibrosis appeared on the 14th to 56th day. Compared with PQ group, the Ashcroft scores of lung fibrosis in PQ+PFD 200 group and PQ+PDF 300 group decreased significantly in 7th and 28th day (P<0.05), while the Ashcroft score of lung fibrosis in PQ+PFD 100 group had no significant difference (P>0.05). After PQ exposure, the content of hydroxyproline in lung tissue increased gradually and reached the peak value on the 28th day. Compared with the PQ group, the contents of hydroxyproline in the PQ+PFD 200 group decreased at the 7th, 14th and 28th day, and the contents of malondialdehyde decreased at the 3rd and 7th day, the differences were statistically significant (P<0.05). The levels of TNF-α, IL-6 in rat serum and lung tissue reached the peak value on the 7th day after PQ exposure, and the levels of TGF-β1, FGF-B and IGF-1 in rat serum and lung tissue reached the peak value on the 14th day after PQ exposure, and the level of PDGF-AB in rat serum and lung tissue reached the peak value on the 28th day after PQ exposure. Compared with PQ group, the level of serum IL-6 in PQ+PFD 200 group decreased significantly on the 7th day, and serum TGF-β1, FGF-B, PDGF-AB and IGF-1 on the 14th and 28th day were decreased significantly (P<0.05). The levels of TNF-α, IL-6 in lung tissue of rats in PQ+PFD 200 group on the 7th day decreased significantly, and the levels of TGF-β1, FGF-B and IGF-1 in lung tissue of rats on the 14th day were significantly decreased, and the level of PDGF-AB in lung tissue of rats on the 28th day were significantly decreased (P<0.05) . Conclusion: PFD partially alleviates the PQ-induced lung inflammation and fibrosis by inhibiting oxidative stress, reducing the levels of pro-inflammatory and pro-fibrotic cytokines in serum and lung tissue, but does not affect the concentrations of PQ in serum and lung tissue.

Correlation between children and adolescents behavioral habits and the occurrence of myopia in Qamdo / 中国学校卫生

Objective@#To investigate the current status of myopia in children and adolescents in Qamdo, Tibet, and analyze related influencing factors, so as to provide a basis for the prevention and control of adolescents in plateau areas.@*Methods@#A cross sectional study was conducted among 959 children and adolescents randomly selected from one district and two counties in Qamdo (from the fourth grade of elementary school to the second grade of high school) for visual acuity and refraction tests and filled out a vision related behavior questionnaire to analyze the incidence of myopia among adolescents in the region and its associated factors.@*Results@#The myopia rate of adolescents in grades 4-11 was 54.43%, the rate of undercorrection of refractive errors was 85.25%, and the percentage of students wearing eyeglasses was 34.67%,fully vision correction rate was 42.54%. The myopia rate of students in grades 4-6 was 35.14%, 64.71% in grades 7-9, and 73.48% in grades 10-11. The myopia rate increased with grades( χ 2= 101.18 , P <0.01). The myopia rate (70.40%) of urban students (grades 4-9) was higher than that of county level(41.45%), and the myopia rate of students with myopia from either parent (68.24%) was higher than that of students without myopia (51.91%) , the myopia rate of girls (59.96%) was higher than that of boys (48.36%)( χ 2=53.19，13.46，12.98， P <0.01). Use electronic products for more than 2.5 hours per day, electronic devices usage after bedtime, the light low indoor brightness when studying on a sunny day, and only use one of the table lamps or roof lights when studying at night, preference for fried food, poor sleep quality, in the morning the students who still feel tired are at higher risk of myopia( χ 2=10.35, 10.91, 6.87, 4.25, 4.97, 5.71, 12.11, P < 0.05). Multivariate regression analysis showed that the occurrence of myopia was related to region, grade, gender, parental myopia, time spent on electronic products every day in the past 5 months, and sleep quality( P <0.05).@*Conclusion@#The high rate of myopia in children and adolescents in Qamdo may be related to the quality of sleep, the length of time electronic products are used, the eye environment, and the frequency of eating fried foods. Outdoor activities do not show significant differences.

Evaluation of school lunch recipes based on digital platform / 中国学校卫生

Objective@#To understand levels of various foods and nutrients in school lunch based on digital platform and to provide reference for food preparation and serving.@*Methods@#A total of 13 018 school lunch recipes in Binhai New Area of 96 schools in Tianjin from November 2020 to April 2021 were collected by using digital management platform for food safety and nutritional health.Food types including cereals and tubers, vegetables, fruits, livestock and poultry meat, fish and shrimp, eggs, milk and dairy products, legumes and their products/nuts and others energy, and nutrients including protein, fat, carbohydrate, calcium, iron, zinc, selenium, vitamin A, vitamin B 1, vitamin B 2, vitamin C and dietary fiber were evaluated.@*Results@#The qualified rate of all kinds of food for students lunch from high to low were 96.8% (116.4 g) of livestock and poultry meat, 92.3% (179.5 g) of cereal and potato, 65.0% (170.6 g) of vegetables, 47.7% (21.4 g) of soybeans and their products/nuts, 33.4% (18.0 g) of eggs, 14.4% (8.5 g) of fish and shrimp, 14.1% (19.6 g) of fruits, 0.3% (35.4 g) of milk and dairy products. There were significant differences in the qualified rate of various food intake among different grades( P <0.05). The qualified rate of students lunch energy was 76.9%(932.6 kcal). The qualified rates of various nutrients from high to low were iron 96.9%(9.7 mg), zinc 96.8%(5.9 mg), protein 96.4%(43.8 g), carbohydrate 87.6%(130.8 g) and selenium 82.9%(23.5 μg), vitamin C 78.5%(48.8 mg), vitamin B 1 75.9%(0.5 mg), fat 74.3%(28.5 g), vitamin A 74.1%(327.1 μ g) vitamin B 2 49.9%(0.5 mg), dietary fiber 19.5%(5.9 g) and calcium 13.4%(246.1 mg). There were significant differences in the qualified rates of energy and nutrients among different grades( P <0.05).@*Conclusion@#The digital platform basically meets school lunch requirments on food types and nutrients, but still with problems regarding insufficient fish and shrimp, fruits, milk and dairy products, vitamin B 2, dietary fiber and calcium. It is suggested to optimize school lunch recipes or increase corresponding nutrients content in other meals.

Purification and component identification of total proanthocyanidins in Choerospondias axillaris pericarp / 中国中药杂志

The present study determined the quantitative markers of total proanthocyanidins in the purification of the industrial waste Choerospondias axillaris pericarp based on the comparison results of high-performance liquid chromatography(HPLC) and mass spectrometry(MS) and optimized the purification process with two stable procyanidins as markers. The adsorption and desorption of five different macroporous adsorption resins, the static adsorption kinetics curve of NKA-Ⅱ resin, the maximum sample load, and the gradient elution were investigated. The UPLC-Q-TOF-MS/MS was employed for qualitative analysis of the newly-prepared total proanthocyanidins of C. axillaris pericarp. As revealed by the results, NKA-Ⅱ resin displayed strong adsorption and desorption toward total proanthocyanidins. The sample solution(50 mg·mL~(-1)) was prepared from 70% ethanol crude extract of C. axillaris pericarp dissolved in water and 7-fold BV of the sample solution was loaded, followed by static adsorption for 12 h. After 8-fold BV of distilled water and 6-fold BV of 10% ethanol were employed to remove impurities, the solution was eluted with 8-fold BV of 50% ethanol, concentrated, and dried under reduced pressure, and purified total proanthocyanidin powder was therefore obtained. Measured by vanillin-hydrochloric acid method, the purity and transfer rate of total proanthocyanidins were 47.67% and 59.92%, respectively, indicating the feasibi-lity of the optimized process. UPLC-Q-TOF-MS/MS qualitative analysis identified 16 procyanidins in C. axillaris total proanthocyanidins. The optimized purification process is simple in operation and accurate in component identification, and it can be applied to the process investigation of a class of components that are difficult to be separated and purified. It can also provide technical support and research ideas for the comprehensive utilization of industrial waste.

Prevalence trends and related factors of hypertension patients complicating with dyslipidemia in community of Guandong province between 2013 and 2018 / 中华心血管病杂志

Objective: To analyze the prevalence trends and related factors of hypertension patients complicating with dyslipidemia in community. Methods: This was a cross-sectional survey, patients with hypertension were selected from the different communities of Guangdong province in 2013 and 2018 respectively. General clinical characteristics, including demographic information, past history, family history, and medication history, were collected. Dyslipidemia was defined as follows: at least 1 item elevation of total cholesterol (TC)≥5.2 mmol/L, triglyceride (TG) ≥1.7 mmol/L, low-density lipoprotein cholesterol (LDL-C)≥3.4 mmol/L, or reduced high-density lipoprotein cholesterol (HDL-C)<1.0 mmol/L. The incidence of dyslipidemia was standardized based on the 2010 China Census data, and further subgroup analysis was performed according to age (<50, 50-60, ≥60 years old) and sex (male, female). Multivariate logistic regression was used to analyze the related factors of dyslipidemia. Results: In 2013 and 2018, 7 866 (4 148 (52.7%) females, with the age of (62.4±13.6) years) and 11 611 (6 692 (57.6%) females, with the age of (58.2±9.3)years) patients with hypertension were enrolled for data analysis, respectively. In 2013, the total prevalence rate of dyslipidemia in patients with hypertension in the community of Guangdong province was 56.3%, among which the prevalence rates of hypercholesterolemia, hypertriglyceridemia, high LDL-Cemia, and low HDL-Cemia were 17.1. %, 21.3%, 2.3% and 24.4%, respectively. The total prevalence of dyslipidemia in patients with hypertension in the community of Guangdong in 2018 was 47.3%, prevalence of hypercholesterolemia, hypertriglyceridemia, high LDL-Cemia and low HDL-Cemia was 14.1%, 20.3%, 12.0% and 19.4%, respectively. Subgroup analysis showed that the total prevalence of dyslipidemia in male patients with hypertension in the community of Guangdong in 2013 and 2018 was 59.0% and 50.7%, respectively, among which hypercholesterolemia was 13.8% and 8.0%, and hypertriglyceridemia was 22.3%, 20.9%, high LDL-Cemia was 1.7%, 8.1%, low HDL-Cemia was 32.9%, 30.3%, respectively. In 2013 and 2018, the total prevalence of dyslipidemia in female patients with hypertension in the community of Guangdong province was 53.9% and 44.8%, among which prevalence of hypercholesterolemia was 20.5% and 18.5%, hypertriglyceridemia was 20.4% and 19.8%, and high LDL-Cemia was 2.7% and 14.9%, and hypo-HDL-Cemia was 16.8% and 11.3%, respectively. Age subgroup analysis showed that the prevalence of dyslipidemia among hypertensive patients aged<50, 50-60, and ≥60 years in Guangdong community in 2013 were 60.1%, 60.6%, and 53.7%, respectively; and 46.2%, 49.3% and 46.5% in 2018, respectively. Multivariate logistic regression analysis showed that women (OR=0.860,95%CI 0.761-0.973,P=0.017), obese (OR=2.295,95%CI 2.007-2.624,P<0.001), diabetes (OR=1.314,95%CI 1.090-1.583,P=0.004), stroke (OR=1.894,95%CI 1.227-2.924,P=0.004) and the level of fasting blood glucose (OR=1.105,95%CI 1.066-1.146,P<0.001) were independently related with the occurrence of dyslipidemia. Conclusions: The prevalence of dyslipidemia in patients with hypertension in the communities of Guangdong province is relatively high, and the prevalence differs in sex and age. Between 2013 and 2018, the total prevalence of dyslipidemia, hyper-TCemia, and hypo-HDL-Cemia in hypertensive patients shows a downward trend. The prevalence of hyper-TGemia remains unchanged, but the prevalence of high LDL-C shows an upward trend. Several factors are related to the prevalence of dislipidemia in hypertension patients in Guandong community.

Effect of Bimin Decoction on Aquaporin 5 in Nasal Mucosa of Allergic Rhinitis Rats with Lung and Spleen Qi Deficiency Syndrome Via NF-κB Signaling Pathway / 中国实验方剂学杂志

Objective::To observe the effect of Bimin decoction(BMD) on nuclear factor-kappa B(NF-κB) signaling pathway and aquaporin 5(AQP5) expression in allergic rhinitis (AR) rats with lung and spleen Qi deficiency syndrome(LSQDS), in order to study the mechanism in treating AR. Method::Fifty-six SD rats were randomly divided into seven groups: control group, AR group, LSQDS AR group, BMD low dose two weeks group and four weeks group, BMD high dose two weeks group and four weeks group. The control group did not intervened, the AR group established the AR disease model with ovalbumin (OVA) as the allergen, the other five groups established the LSDQS model with smoke and senna gavage, and also established the AR disease model with OVA sensitization at the same time as the AR group. After the model was established successfully, four BMD intervention groups were separately given low dose BMD (11.3 g·kg-1) for 2 weeks and 4 weeks, and high dose BMD (22.6 g·kg-1) for 2 weeks and 4 weeks. To observe the general situation of the rats, hematoxylin eosin (HE) staining was used to observe the pathological changes of the nasal mucosa, immunohistochemistry and Western blot were used to detect the expression levels of NF-κB and AQP5, real-time fluorescent quantitative polymerase chain reaction technique (Real-time PCR)was used to detect mRNA levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6). Result::The typical AR symptoms were found in AR rats, the AR symptoms and lung and spleen Qi deficiency symptoms were found in AR rats with LSQDS at the same time, and the AR symptoms and lung and spleen Qi deficiency symptoms were significantly improved after the intervention of BMD. Compared with the control group, the typical histopathological changes of nasal mucosa were found in AR group and LSQDS AR group, with a higher behavioral score (P<0.05), and the expression of NF-κB and AQP5 protein increased (P<0.05), the expression of IL-1β, TNF-α, IL-6 and AQP5 mRNA increased (P<0.05). Compared with AR group, the pathological changes of nasal mucosa in LSQDS AR group were more serious, and the expression of NF-κB protein in nucleus increased (P<0.05), the expression of TNF-α and AQP5 mRNA increased (P<0.05). Compared with LSQDS AR group, the pathological changes of nasal mucosa in the groups which interfered by BMD were improved, and the expression of NF-κB and AQP5 protein decreased (P<0.05), the expression of IL-1β, TNF-α, IL-6 and AQP5 mRNA decreased (P<0.05). Compared with BMD low-dose two-week group, the expression of NF-κB protein in nucleus decreased (P<0.05) in BMD high dose four week group. Conclusion::Compared with AR group, the AR condition of the rats with LSQDS is more serious under the same allergen stimulation, BMD can treat AR and reduce the over secretion of glands, which may be related to inhibit the expression of AQP5 by inhibiting the NF-κB signaling pathway.

Different effects of long-term and short-term repeated restraints on the hematopoietic stem cells in mice / 生理学报

Humans with chronic psychological stress are prone to develop multiple disorders of body function including impairment of immune system. Chronic psychological stress has been reported to have negative effects on body immune system. However, the underlying mechanisms have not been clearly demonstrated. All immune cells are derived from hematopoietic stem cells (HSC) in the bone marrow, including myeloid cells which comprise the innate immunity as a pivotal component. In this study, to explore the effects of chronic psychological stress on HSC and myeloid cells, different repeated restraint sessions were applied, including long-term mild restraint in which mice were individually subjected to a 2 h restraint session twice daily (morning and afternoon/between 9:00 and 17:00) for 4 weeks, and short-term vigorous restraint in which mice were individually subjected to a 16 h restraint session (from 17:00 to 9:00 next day) for 5 days. At the end of restraint, mice were sacrificed and the total cell numbers in the bone marrow and peripheral blood were measured by cell counting. The proportions and absolute numbers of HSC (LinCD117Sca1CD150CD48) and myeloid cells (CD11bLy6C) were detected by fluorescence activated cell sorting (FACS) analysis. Proliferation of HSC was measured by BrdU incorporation assay. The results indicated that the absolute number of HSC was increased upon long-term mild restraint, but was decreased upon short-term vigorous restraint with impaired proliferation. Both long-term mild restraint and short-term vigorous restraint led to the accumulation of CD11bLy6C cells in the bone marrow as well as in the peripheral blood, as indicated by the absolute cell numbers. Taken together, long-term chronic stress led to increased ratio and absolute number of HSC in mice, while short-term stress had opposite effects, which suggests that stress-induced accumulation of CD11bLy6C myeloid cells might not result from increased number of HSC.

Comparative of functional components, antioxidant and α-glucosidase inhibition activities between Choerospondias axillaris fruit peel vinegar and apple vinegar / 中国中药杂志

Based on the idea of plant metabolomics, ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was used to compare the chemical composition between 6 batches of fruit vinegar brewed from Choerospondias axillaris fruit peel and 6 batches of apple vinegar purchased from 3 companies. Antioxidant and α-glucosidase inhibition activities were also tested in vitro. A total of 43 compounds were identified by reference substance, liquid chromatography-mass spectrometry(LC-MS/MS) fragmentation information or literature data. A total of 40 compounds were identified in the C. axillaris fruit peel vinegar. A total of 16 compounds were identified in apple vinegar. There were 13 common ingredients including organic acids and esters such as citric acid, 2-isopropyl malic acid, and triethyl citrate. The results of partial leastsquares-discriminant analysis(PLS-DA) indicated that they had 33 significantly different compounds such as proanthocyanidin oligomer, quercetin-3-O-rhamnoside and heptadecanoic acid. The proanthocyanidins and flavonoid glycosides in C. axillaris peel vinegar were more abundant than apple vinegar, so it had better health function than ordinary fruit vinegar. The results showed that C. axillaris fruit peel vinegar had stronger antioxidant and α-glucosidase inhibition activities in vitro. The vinegar brewed from waste C. axillaris fruit peel had more chemical ingredients than the apple vinegar. C. axillaris fruit peel vinegar had better biological activity and health function, so it had good development prospect. This study provided the scientific evidence for exploiting the C. axillaris fruit peel into high value-added products. It also provided ideas for the comprehensive development and utilization of similar Chinese medicine waste.

Correlation of serum urate and gout with calcific aortic stenosis / 中华老年医学杂志

Objective To investigate the correlation of serum urate and gout with calcific aortic stenosis.Methods Patients aged over 60 years admitted into our hospital from July 2009 to January 2019 were retrospectively analyzed.A total of 230 patients were diagnosed as calcific aortic stenosis according to clinical history and transthoracic echocardiography(TTE),and enrolled in the aortic stenosis group.During the same period,460 age-matched patients without aortic stenosis confirmed by TTE were randomly recruited in the 1 ∶ 2 case-control study.The correlations of calcific aortic stenosis with serum urate and gout were analyzed.According to the differential pressure across the valve leaflets assessed by TTE,patients with calcific aortic stenosis were divided into 3 subgroups:the mild stenosis subgroup(n=42),the moderate stenosis subgroup(n=79)and the severe stenosis subgroup(n =109).Relationships of serum urate and gout with different degrees of calcific aortic stenosis were analyzed.Risk factors for the degree of calcific aortic stenosis were analyzed by Logistic regression analysis.Results Serum urate level was higher in aortic stenosis group than in control group [(401.8±139.7) μmol/L vs.(320.7± 106.2) μmol/L,P＜0.05].And the proportion of patients with gout was higher in aortic stenosis group than in control group[11.3％ (26 cases) vs.5.0％ (23 cases),P＜ 0.05].Multivariate Logistic regression analysis indicated that serum urate (OR =3.47,95 ％CI:2.24～ 5.38,P ＜ 0.01) was an independent risk factor for calcific aortic stenosis,while gout (OR=1.41,95％CI:0.74～2.71,P =0.30)was not.There was no correlation of serum urate and gout with the severity of calcific aortic stenosis among the three subgroups(P＞0.05).Conclusions Serum urate level is significantly increased in patients with calcified aortic stenosis.Serum urate is an independent risk factor for calcified aortic stenosis,but has no relationship with stenosis degree.The correlation between gout and calcified aortic stenosis still needs to be further explored.

Effects of NEDD8 covalent modification inhibitor MLN4924 on proliferation and apoptosis of human ovarian cancer cell line SKOV3 / 中国免疫学杂志

Objective:To explore the effects of neural precursor cell-expressed developmentally down regulated 8(NEDD8) covalent modification on ovarian cancer cell proliferation and apoptosis,and the possible underlying mechanisms.Methods:Use different concentrations of MLN4924 (0,0.125,0.25,0.5 mol/L) and human ovarian cancer cell line SKOV3,the expression levels of PAR3, HER2,Neddylated-cullins,P-IκBα were detected by Western blot and the secretion of IL-6 was measured by ELISA after 4 h treatment.The cell proliferation was determined by CCK-8 staining and the cell cycle and apoptosis were analyzed by flow cytometry after 72 h treatment.Results:MLN4924 inhibits the proliferation of SKOV3 cells in a dose-dependent manner,which is associated with reduced IL-6 secretion.Western blot revealed that MLN4924 dose-dependently inhibits the neddylation of cullins(reduced neddylated-cullins) and induced the accumulation of P-IκBα,whereas the expression levels of PARs and HER2 remained largely unchanged.At the same time MLN4924 dose-dependently induced cell cycle prove at S phase and the formation of a large number of tetraploids.Furthermore,apoptosis increased with the dose of MLN4924.Conclusion:NEDD8 covalent modification specific inhibitor MLN4924 can significantly inhibit the proliferation of SKOV3 cells and induce cell cycle arrest and apoptosis.The above inhibitory effects may partially result from impaired P-IκBα degradation and IL-6 secretion.

Genetic and epigenetic predispositions underlying cardiovascular outcomes among patients treated with clopidogrel and aspirin / 中国药理学与毒理学杂志

Coronary artery disease (CAD)is a major cause of death and disability worldwide, and consumes a considerable amount of medical resources every year.Clopidogrel is a first-line antiplate-let therapy for CHD, butit is associated with substantial variability in PK and pharmacodynamics re-sponse. To date, gene variants explain only a smallproportion of the variability.The study aimed to identify new genetic loci-modifying antiplatelet response to clopidogrel in Chinese patients with CAD by a systematic analysis combining antiplatelet effects and PK, and further to investigate the PON1 gene promoter DNA methylation and genetic variations possibly influencing clinical outcomes in pa-tients undergoing PCI. We identified novel variants in two transporter genes (SLC14A2rs12456693, ATP-binding cassette [ABC]A1 rs2487032) and in N6AMT1 (rs2254638) associated with P2Y12 reac-tion unit (PRU) and plasma active metabolite (H4) concentration. These new variants dramatically im-proved the predictability of PRU variability to 37.7％. The associations between these loci and PK pa-rameters of clopidogrel and H4 were observed in additional patients, and its function on the activation of clopidogrel was validated in liver S9 fractions (P<0.05). Rs2254638 was further identified to exert a marginal risk effect formajor adverse cardiac events in an independent cohort.Multivariate logistic regression analysis indicated that PON1methylation level at CpG site-161 (OR=0.95; 95％ CI=0.92–0.98;P<0.01)and the use of angiotensin converting enzyme inhibitors(OR=0.48;95％ CI=0.26–0.89;P<0.01) were associated with decreased risk of bleeding events. In conclusion, new genetic variants were systematically identified as risk factors for the reduced efficacy of clopidogrel treatment.The ab-normal expression of DNA methylation-regulating key genes in the pharmacokinetic and pharmacody-namics pathways of clopidogrel and aspirin may modify clinical outcomes in dual antiplatelet-treated pa-tients undergoing PCI.

Association between Contrast Media Volume and 1-Year Clinical Outcomes in Patients Undergoing Coronary Angiography / 中华医学杂志(英文版)

<p><b>Background</b>The excess volume of contrast media (CM) is a marker of a more severe coronary culprit lesion and longer intervention duration in patients undergoing cardiac procedures. However, it is unclear whether the contrast volume is directly correlated with worse clinical outcomes. The aim of this study was to investigate the association between contrast dose and the incidence of 1-year major adverse cardiac and cerebrovascular events (MACCE) and all-cause bleeding events in patients undergoing cardiac catheterization and coronary angiography (CAG).</p><p><b>Methods</b>We prospectively enrolled 10,961 consecutive patients diagnosed with coronary heart disease expecting CAG from 2012 to 2013. The study population was pursued with a follow-up duration of 1 year. The predictive value of contrast volume, divided into quartiles, for the risk of MACCE and all-cause bleeding events was assessed using logistic regression analysis.</p><p><b>Results</b>The cumulative incidence of 1-year MACCE was 8.65%, which was directly associated with increasing contrast volume. In particular, MACCE was observed in 7.16%, 7.89%, 9.31%, and 11.73% of cases in the contrast volume quartile Q1 (≤100 ml), Q2 (101-140 ml), Q3 (141-200 ml), and Q4 (>200 ml), respectively (P < 0.001). Moreover, the incidence of 1-year all-cause bleeding events was noted in 4.70%, 5.93%, 7.28%, and 8.21% of patients in Q1, Q2, Q3, and Q4, respectively (P < 0.001). The survival analysis showed that the 1-year MACCE rate was higher in patients using greater CM volume during the CAG. CM volume used >140 ml was associated with the occurrence of 1-year MACCE, and the incidence was dramatically elevated in patients exceeding a contrast volume of 200 ml (P = 0.007).</p><p><b>Conclusion</b>Our data suggested that higher contrast volume was significantly correlated with an increased risk of MACCE and all-cause bleeding events in patients undergoing cardiac catheterization.</p><p><b>Trial Registration</b>ClinicalTrials.gov, NCT01735305; https://clinicaltrials.gov/ct2/show/NCT01735305?id=NCT017353057rank=1.</p>

Influence of the Right Ventricular Lead Location on Ventricular Arrhythmias in Cardiac Resynchronization Therapy / 中华医学杂志(英文版)

<p><b>Background</b>The influence of different right ventricular lead locations on ventricular arrhythmias (VTA) in patients with a cardiac resynchronization therapy (CRT) is not clear. This study aimed to evaluate the influence on VTA in patients with a CRT when right ventricular lead was positioned at the right ventricular middle septum (RVMS) and the right ventricular apical (RVA).</p><p><b>Methods</b>A total of 352 patients implanted with a CRT-defibrillator (CRT-D) between May 2012 and July 2016 in the Department of Cardiology of Anhui Provincial Hospital were included. Two-year clinical and pacemaker follow-up data were collected to evaluate the influence of the right ventricular lead location on VTA. Patients were divided into the RVMS group (n = 155) and the RVA group (n = 197) based on the right ventricular lead position. The VTA were compared between these two groups using a Kaplan-Meier curve and Cox multivariate analysis.</p><p><b>Results</b>When the left ventricular lead location was not considered, RVMS and RVA locations did not affect VTA. However, the subgroup analysis results showed that when the left ventricular lead was positioned at the anterolateral cardiac vein (ALCV), the RVMS group had an increased risk of ventricular arrhythmias and appropriate defibrillation (hazard ratio [HR] = 3.29, P = 0.01 and HR = 4.33, P < 0.01, respectively); when the left ventricular lead was at the posterolateral cardiac vein (PLCV), these risks in the RVMS group decreased (HR = 0.45, P = 0.02 and HR = 0.33, P < 0.01, respectively), and when the left ventricular lead was at the lateral cardiac vein, there was no difference between the two groups. In regard to inappropriate defibrillation, there was no significant difference among all these groups.</p><p><b>Conclusions</b>When the left ventricular lead was positioned at ALCV or PLCV, the right ventricular lead location was associated with VTA and appropriate defibrillation after CRT. Greater distances between leads not only improved cardiac function but also may reduce the risk of VTA.</p>

Screening Serum Differential Proteins for Childhood Asthma at Different Control Levels by Isobaric Tags for Relative and Absolute Quantification-based Proteomic Technology / 中国医学科学院学报

Objective To screen serum differential proteins for childhood asthma at different control levels,which provided the basis for the prevention and treatment of childhood asthma. Methods Isobaric tags for relative and absolute quantification,two-dimensional liquid chromatography,nanoelectrospray ionization,and high-resolution tandem mass spectrometry using the hybrid quadrupole time-of-flight platform was used to screen the differential proteins in serum samples from pediatric patients with controlled,partly controlled,or uncontrolled childhood asthma. Differential proteins were validated using enzyme-linked immunosorbent assay (ELISA). Results A total of 260 expressed proteins were identified. Among them 57 differentially expressed proteins were found among the different control levels of childhood asthma (fold<0.8 or fold>1.2). The differentially expressed proteins were involved mainly in 21 biological processes and 8 molecular functions and were located in 17 cellular components. ELISA showed that the serum vitronectin level was significantly higher in controlled group [(573.92±412.43) μg/ml] than in uncontrolled group[(382.27±238.64)]μg/ml (P=0.0399). Conclusion We identified 57 differential proteins for childhood asthma at different control levels,which may be used as potential biological targets for the control of childhood asthma.

Impact of Cardiac Resynchronization Therapy on Ventricular Remodeling in Patients With III°Atrio-ventricular Block Combining Systolic Dysfunction / 中国循环杂志

Objective: To observe the impact of cardiac resynchronization therapy (CRT) on ventricular remodeling in patients with III°atrio-ventricular block (AVB) combining systolic dysfunction. Methods: A total of 49 III °AVB patients received CRT in our hospital from 2009-01 to 2014-10 were studied. Echocardiography was conducted at pre-operation and 6, 12 months post-operation to measure left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD) and mitral regurgitation (MR) grade in order to observe the changes of cardiac structure and function in relevant patients. Results: Compared with pre-operative condition, at 6 months post-operation, LVEF was increased (4.92±5.24)%and at 12 months post-operation, it was further increased (5.02±6.52)%, both P Conclusion:CRT may reverse ventricular remodeling and improve cardiac function in patients with III°AVB combining systolic dysfunction.

Finite element analysis of the biomechanical characteristics of ankylosing kyphosis osteotomy using the vertebral column decancellation and the vertebral column resection / 中国组织工程研究

BACKGROUND: Patients with severe ankylosing kyphosis are often treated with orthopedic osteotomy, but with high surgical risk, treatment schemes are individualized, and the biological morphology and mechanical properties of the deformed spine are complex. Meanwhile, the finite element model is more adaptable for biomechanical analysis of the spinal deformity. However, its application in the treatment of ankylosing kyphosis in China was little reported.OBJECTIVE: To establish an ankylosing kyphosis finite element model so as to investigate the relationship between different osteotomy methods and the deformation and stress distribution of the spine.METHODS: A three-dimensional finite element model of ankylosing kyphosis was established, and then imported into ANASYS software, to simulate vertebral column decancellation and vertebral column resection at T12 and L1 levels,respectively. The vertebrae and screw were loaded with the same load, and deformation and stress nephograms were obtained.RESULTS AND CONCLUSION: (1) The deformation of the osteotomy at T12 level was significantly larger than that at L1 level. (2) The stress distribution of the decancellation osteotomy concentrated on the pedicle screw and titanium bar; the stress concentration of vertebral column resection was the intervertebral cage. (3) Individualized surgical treatment of ankylosing kyphosis may influence the selection of the osteotomy segment and osteotomy operation. The osteotomy segment may affect the stability of the spine, and stress distribution of internal fixation is likely related to the method of internal fixation. (4) This conclusion may provide theoretical reference for the biomechanical study of analysing ankylosing kyphosis.