1.Mechanisms of hypertension inducing erectile dysfunction via the cGMP/PKG signaling pathway:An investigation using transcriptomics and network pharmacology
Jun-Long FENG ; Hai-Song LI ; Song SUN ; Bin WANG ; Hua-Nan ZHANG ; Zi-Xiang GAO ; Peng-Ming MAO ; Long-Ji SUN ; Nian-Wen HUANG ; Ji-Sheng WANG
National Journal of Andrology 2024;30(9):771-781
Objective:To explore the mechanism of hypertension inducing erectile dysfunction(ED)using transcriptomics and network pharmacology.Methods:We randomly divided 12 male rats with spontaneous hypertension(SHT)into an L-arginine(LA)group(n=6)and an SHT model control(MC)group(n=6),took another 6 Wistar Kyoto male rats as normal controls(NC),and treated the animals in the LA group by intraperitoneal injection of LA at 400 mg/kg and those in the latter two groups with physio-logical saline,once a day,all for 7 days.Then we observed the blood pressure and penile erection of the rats,and determined the ex-pressions of the cGMP/PKG signaling pathway-related proteins and mRNAs in different groups using ELISA,Western blot and RT-qPCR.Results:Transcriptomics combined with network pharmacology showed that the cGMP/PKG signaling pathway played a key role in hypertension-induced ED.In vivo animal experiments revealed a significantly lower frequency of penile erections in the MC than in the NC group(1.33±0.52 vs 2.67±0.51,P<0.05).The protein expressions of eNOS,PKG and sGC were markedly de-creased in the model controls compared with those the normal controls(P<0.05),but remarkably upregulated in the LA group com-pared with those in the MC group(P<0.05).Conclusion:Hypertension decreases the expressions of eNOS,NO,sGC,cGMP and PKG proteins and the level of testosterone by inhibiting the cGMP/PKG signaling pathway,which consequently suppresses the relaxa-tion of the penile vascular smooth muscle and reduces erectile function.
2.Determination ideas and influencing factors of essential performance for GB 9706 series of standards
Bo LIU ; Ya-Nan LI ; Long-Fei ZHANG ; Fei-Xiang HOU ; Yu-Chen MAO ; Peng-Yue GAO
Chinese Medical Equipment Journal 2024;45(11):72-76
The risks related to the essential performance were analyzed with considerations on the concept of the essential performance in GB 9706.1-2020 Medical electrical equipment-Part 1:General requirements for basic safety and essential performance,and the determination process for the essential performance of medical electrical equipment was summarized.The essential performance of the example equipment was clarified with the semi-quantitative risk analysis,and the influences of the arrangement of the electromagnetic compatibility test on the determination of the essential performance were explored with the conducted immunity test and conventional test.References were provided for standard users to understand and determine the essential performance effectively.[Chinese Medical Equipment Journal,2024,45(11):72-76]
3.Comparative Study on Effect of Yiqi Liangxue Shengji Formula (益气凉血生肌方) and Atorvastatin Tablets on Vascular Injury and Differences in Serum Metabolites in Abdominal Aortic Balloon Injury Model Rats
Tianshi MAO ; Long XIE ; Qun GAO ; Yi PAN ; Wenhao JIA ; Qian LIN
Journal of Traditional Chinese Medicine 2024;65(11):1180-1188
ObjectiveTo compare the effects and differences of Yiqi Liangxue Shengji Formula (益气凉血生肌方) and atorvastatin on the repair of vascular injury in rats from the perspective of metabolomics. MethodsTwenty-four male SD rats were randomly divided into sham-surgery, model, traditional Chinese medicine (TCM), and ator-vastatin groups, with 6 rats in each group. The rat model was established by balloon-induced abdominal aorta injury. Gavage was started on the day after surgery in all groups of rats. The sham and model groups were given with deio-nized water, TCM group received Yiqi Liangxue Shengji Formula 6 g/(kg·d), and the atorvastatin group treated with atorvastatin suspension 2 mg/(kg·d) for 4 weeks. HE staining was used to observe the pathological morphology of the injured segment of the abdominal aorta; ELISA detection was used to test serum nitric oxide (NO) and C-reactive protein (CRP) levels; UPLC MS/MS technology was used for widely targeted metabolomics detection in serum, and multivariate statistical analysis was used to screen metabolic markers and pathways of two drugs; finally, compare serum levels of key metabolic markers of the above two medications in rats of each group. ResultsCompared with the sham-surgery group, the neointima significantly thickened, the level of NO decreased significantly and the level of CRP increased in serum of the model group (P<0.01); compared with the model group, the degree of arterial intimal hyperplasia in TCM group and atorvastatin group reduced, with an increase in NO levels and a decrease in CRP levels (P< 0.05 or P<0.01). The results of serum metabolomics showed that TCM group obtained 49 metabolic markers and 6 metabolic pathways, while atorvastatin group obtained 41 metabolic markers and 4 metabolic pathways. The two medications jointly regulated 38 metabolites. Glycerophospholipid metabolism and arginine-related metabolism were common metabolic pathways for both medications. Lysophosphatidylcholine (16∶1/0∶0) [LPC (16∶1/ 0∶0)], phosphatidylcholine (15∶0/15∶0) [PC (15∶0/15∶0)] were the key metabolites of glycerophospholipid metabolic pathway; ornithine, spermidine were the key metabolites of arginine-related metabolic pathway. The tricarboxylic acid cycle and glutathione metabolism were the unique metabolic pathways of Yiqi Liangxue Shengji Formula. Compared with the sham-surgery group, LPC (16∶1/0∶0), ornithine, and spermidine levels elevated and PC (15∶0/15∶0) levels decreased in the model group (P<0.05 or P<0.01). Compared with the model group, LPC (16∶1/0∶0), ornithine, and spermidine levels decreased, and PC (15∶0/15∶0) levels increased in both TCM group and atorvastatin group (P<0.05 or P<0.01). The degree of LPC reduction (16∶1/0∶0) was more significant in atorvastatin group compared with that in the TCM group (P<0.01). ConclusionsBoth sham-surgery and atorvastatin could regulate lipid metabolism and arginine-related metabolism, exert the characteristics of lipid-lowering, anti-inflammatory, improve arginine/NO bioavailability, and improve endothelial dysfunction. Atorvastatin showed more advantages in lipid-lowering and anti-inflammatory, while Yiqi Liangxue Shengji Formula has unique characteristics in regulating energy metabolism and improving oxidative stress.
4.Ursolic acid improved demyelination and interstitial fluid drainage disorders in schizophrenia mice
Ren LONG ; Xin MAO ; Tianzi GAO ; Qian XIE ; Hanbo TAN ; Ziyin LI ; Hongbin HAN ; Lan YUAN
Journal of Peking University(Health Sciences) 2024;56(3):487-494
Objective:To unveil the pathological changes associated with demyelination in schizophre-nia(SZ)and its consequential impact on interstitial fluid(ISF)drainage,and to investigate the thera-peutic efficacy of ursolic acid(UA)in treating demyelination and the ensuing abnormalities in ISF drainage in SZ.Methods:Female C57BL/6J mice,aged 6-8 weeks and weighing(20±2)g,were randomly divided into three groups:control,SZ model,and UA treatment.The control group received intraperitoneal injection(ip)of physiological saline and intragastric administration(ig)of 1%carboxy-methylcellulose sodium(CMC-Na).The SZ model group was subjected to ip injection of 2 mg/kg dizo-cilpine maleate(MK-801)and ig administration of 1%CMC-Na.The UA treatment group underwent ig administration of 25 mg/kg UA and ip injection of 2 mg/kg MK-801.The treatment group received UA pretreatment via ig administration for one week,followed by a two-week drug intervention for all the three groups.Behavioral assessments,including the open field test and prepulse inhibition experiment,were conducted post-modeling.Subsequently,changes in the ISF partition drainage were investigated through fluorescent tracer injection into specific brain regions.Immunofluorescence analysis was employed to examine alterations in aquaporin 4(AQP4)polarity distribution in the brain and changes in protein expres-sion.Myelin reflex imaging using Laser Scanning Confocal Microscopy(LSCM)was utilized to study modifications in myelin within the mouse brain.Quantitative data underwent one-way ANOVA,followed by TukeyHSD for post hoc pairwise comparisons between the groups.Results:The open field test re-vealed a significantly longer total distance[(7 949.39±1 140.55)cm vs.(2 831.01±1 212.72)cm,P<0.001]and increased central area duration[(88.43±22.06)s vs.(56.85±18.58)s,P=0.011]for the SZ model group compared with the controls.The UA treatment group exhibited signifi-cantly reduced total distance[(2 415.80±646.95)cm vs.(7 949.39±1 140.55)cm,P<0.001]and increased central area duration[(54.78±11.66)s vs.(88.43±22.06)s,P=0.007]compared with the model group.Prepulse inhibition test results demonstrated a markedly lower inhibition rate of the star-tle reflex in the model group relative to the controls(P<0.001 for both),with the treatment group dis-playing significant improvement(P<0.001 for both).Myelin sheath analysis indicated significant demy-elination in the model group,while UA treatment reversed this effect.Fluorescence tracing exhibited a significantly larger tracer diffusion area towards the rostral cortex and reflux area towards the caudal thala-mus in the model group relative to the controls[(13.93±3.35)mm2 vs.(2.79±0.94)mm2,P<0.001 for diffusion area;(2.48±0.38)mm2 vs.(0.05±0.12)mm2,P<0.001 for reflux area],with sig-nificant impairment of drainage in brain regions.The treatment group demonstrated significantly reduced tracer diffusion and reflux areas[(7.93±2.48)mm2 vs.(13.93±3.35)mm2,P<0.001 for diffusion area;(0.50±0.30)mm2 vs.(2.48±0.38)mm2,P<0.001 for reflux area].Immunofluorescence staining revealed disrupted AQP4 polarity distribution and reduced AQP4 protein expression in the model group compared with the controls[(3 663.88±733.77)μm2 vs.(13 354.92±4 054.05)μm2,P<0.001].The treatment group exhibited restored AQP4 polarity distribution and elevated AQP4 protein expression[(11 104.68±3 200.04)μm2 vs.(3 663.88±733.77)μm2,P<0.001].Conclusion:UA intervention ameliorates behavioral performance in SZ mice,Thus alleviating hyperactivity and anxiety symptoms and restoring sensorimotor gating function.The underlying mechanism may involve the improve-ment of demyelination and ISF drainage dysregulation in SZ mice.
5.Effect of Interval Between Neoadjuvant Chemotherapy and Surgery on Oncological Outcomes in Poor Responders With Locally Advanced Breast Cancer
Man LONG ; Chunxia LI ; Keyu MAO ; Zhenhui LI ; Zhen LI ; Guili DONG ; Xia ZHENG ; Songliang GAO ; Zhuolin LI ; Guangjun YANG ; Yu XIE
Journal of Breast Cancer 2024;27(4):270-280
Purpose:
The interval between neoadjuvant chemotherapy (NAC) and surgery for locally advanced breast cancer (LABC) remains controversial. At the same time, the prognostic effect of delayed surgery in patients with poor responses is currently unclear.
Methods:
Data was collected from patients who had poor responses to NAC and underwent modified radical surgery from January 2013 to December 2018. The interval from completion of NAC to surgery was divided into two groups: a longer (greater than four weeks) or shorter (four weeks or less) interval. The associations of these interval groups with overall survival (OS) and recurrence-free survival (RFS) were evaluated by multivariable Cox models adjusting for the existing prognostic factors. Propensity score matching (PSM) was used to minimize election bias.
Results:
A total of 1,229 patients (mean age, 47.2 ± 8.9 years; median follow-up duration, 32.67 [6.57–52.63] months) were included. The 5-year OS rates were 73.2% and 60.8% in the shorter (n = 171) and longer interval group (n = 1,058), respectively, while the 3-year RFS rates were 80.8% and 71.7%, respectively. In multivariate Cox analysis, the longer interval was associated with an increased risk of mortality (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.01–2.02; p = 0.046) and recurrence (HR, 1.50; 95% CI, 1.12–1.99; p = 0.006).There was an interaction between the molecular subtype and the surgery interval for OS (pinteraction = 0.014) and RFS (pinteraction = 0.027). After PSM, no significant difference in OS (p = 0.180) and RFS (p = 0.069) was observed between the two groups.
Conclusion
Among LABC patients with a poor response, those with a longer interval between NAC and surgery had worse OS and RFS. The results indicate that these patients should receive modified radical surgery timely, which may in turn improve their prognosis.
6.Identification and expression analysis of apple PDHB-1 gene family.
Jinghua YANG ; Ju GAO ; Wenfang LI ; Ji LIU ; Jiaxing HUO ; Zhenshuo REN ; Long LI ; Baihong CHEN ; Juan MAO ; Zonghuan MA
Chinese Journal of Biotechnology 2023;39(12):4965-4981
Pyruvate dehydrogenase E1 component subunit beta-1 (PDHB-1) is a gene encoding the β-subunit of pyruvate dehydrogenase complex, which plays an important role in fruit acid accumulation. The aim of this study was to investigate the evolution characteristics of apple PDHB-1 family and its expression in apples with different acid contents. Bioinformatics analysis was performed using databases including NCBI, Pfam and software including ClustalX, MEGA, and TBtools. By combining titratable acid content determination and quantitative real-time PCR (qRT-PCR), the expression of this family genes in the peel and pulp of apple 'Asda' and 'Chengji No.1' with different acid content were obtained, respectively. The family members were mainly located in chloroplast, cytoplasm and mitochondria. α-helix and random coil were the main factors for the formation of secondary structure in this family. Tissue-specific expression profiles showed that the expression of most members were higher in fruit than in other tissues. qRT-PCR results showed that the expression profile of most members was consistent with the profile of titratable acid contents. In the peel, the expression levels of 14 members in 'Asda' apples with high acid content were significantly higher than that in 'Chengji No.1' apples with low acid content, where the expression difference of MdPDHB1-15 was the most significant. In the pulp, the expression levels of 17 members in 'Asda' apples were significantly higher than that in 'Chengji No.1' apples, where MdPDHB1-01 was the most highly expressed. It was predicted that PDHB-1 gene family in apple plays an important role in the regulation of fruit acidity.
Malus/metabolism*
;
Fruit/genetics*
;
Protein Structure, Secondary
7.Trend of drowning mortality among children and adolescent in Chongqing, 2012-2021
DING Xianbin, JIAO Yan, YANG Xianxian, CEHN Ting, GAO Yang, MAO Deqiang, LONG Feng, DING Rui
Chinese Journal of School Health 2022;43(9):1388-1390
Objective:
To analyze the trend change of the drowning mortality among children and adolescents in Chongqing, 2012-2021, and to provide suggestion for drowning prevention and control.
Methods:
Drowning death cases (ICD-10:W65.0-W74.9) among children and adolescents in Chongqing from 2012 to 2021 were derived from Chongqing death registration system. The difference of the drowning mortality between male and female, urban and rural area were compared by Chi square test. The trend change of the drowning mortality between 2012 and 2021 was analyzed by annual percent change( APC ).
Results:
The mortality and ASMR of drowning among children and adolescents decreased from 9.57/10 5, 9.42/10 5 in 2012 to 2.80/10 5, 2.83/10 5 in 2021 significantly( t=10.93, 10.52, P <0.01). And its APC were -13.15% and 13.06% respectively. The drowning mortality in male was higher than that in female( P <0.05). The drowning mortality in rural area was higher than that in urban area( P <0.05). The mortality of drowning among children aged between 0 and 4 years old, 5 and 9 years old, 10 and 14 years old decreased by 15.30 %,17.80% and 11.40%( APC =-15.30%, -17.80%, -11.40%, t=11.11, 9.22, 5.62, P <0.05). The proportion of drowning in natural water field among children and adolescents accounted for about 80%.
Conclusion
The mortality of drowning among children and adolescents in Chongqing decreases rapidly. Vulnerable population of drowning includes boys, rural children and adolescents, and children age of 0-14 years old. Comprehensive prevention for drowning should be carried out continuously.
8.Research progress of Angelicae Sinensis Radix and predictive analysis on its quality markers.
Cheng-Long LYU ; Hui-Hui LI ; Yong-Jie SHI ; Yu-Jie MAO ; Qing-He GAO ; Hui-Juan YAN ; Lai-Bin ZHANG ; Jie-Li LYU
China Journal of Chinese Materia Medica 2022;47(19):5140-5157
Angelicae Sinensis Radix, as a medicinal and edible Chinese medicinal herb, is widely used in clinical practice. It is mainly cultivated in Minxian, Tanchang, Zhangxian and Weiyuan counties of Gansu province. In recent years, with the comprehensive and in-depth study of Angelicae Sinensis Radix in China and abroad, its chemical composition, pharmacological effects and application and development have attracted much attention. In this study, the chemical composition, traditional efficacy, and modern pharmacological effects of Angelicae Sinensis Radix were summarized. On this basis, combined with the core concept of quality markers(Q-markers), the Q-markers of Angelicae Sinensis Radix were discussed from the aspects of mass transfer and traceability and chemical composition specificity, availability, and measurability, which provided scientific basis for the quality evaluation of Angelicae Sinensis Radix.
Angelica sinensis/chemistry*
;
Drugs, Chinese Herbal/pharmacology*
;
Plant Roots/chemistry*
;
China
9.Clinical follow-up analysis of multidisciplinary treatment of children with spinal muscular atrophy.
Yu XIA ; Yi Jie FENG ; Mei YAO ; Jia Ning JIN ; Jia WEI ; Yi Qin CUI ; Ling Shuang WANG ; Ting Ting CHEN ; Xiao Yang CHEN ; Hai Bing LI ; Jing Fang XU ; Qi LONG ; Yuan JIANG ; Jin Ling LIU ; Jin Gan LOU ; Feng GAO ; Shan Shan MAO
Chinese Journal of Pediatrics 2022;60(11):1134-1139
Objective: To analyze the follow-up and clinical effect of multidisciplinary treatment on the children with spinal muscular atrophy (SMA). Methods: The clinical data including nutritional status, respiratory function, bone health and motor function of 45 children with SMA who received multidisciplinary management 1-year follow-up in the Children's Hospital, Zhejiang University School of Medicine from July 2019 to October 2021 were retrospectively collected. Comparisons before and after management were performed using paired-samples t-test or Wilcoxon rank-sum test, etc. Results: The age of 45 patients (25 boys and 20 girls) was 50.4 (33.6, 84.0) months at the enrollment, with 6 cases of type 1, 22 cases of type 2, and 17 cases of type 3 respectively. After the multidisciplinary management, the cases of SMA patients with malnutrition decreased from 22 to 12 (P=0.030), the level of vitamin D were significantly increased ((45±17) vs. (48±14) nmol/L, t=-4.13, P<0.001). There was no significant difference in the forced vital capacity %pred, the forced expiratory volume at 1 second %pred, and the peak expiratory flow %pred ((76±19)% and (76±21)%, (81±18)% and (79±18)%, (81±21)% and (78±17)%; t=-0.24, 1.36, 1.21; all P>0.05). The Cobbs angle of scoliosis also improved significantly (8.0°(0°, 13.0°) vs. 10.0°(0°, 18.5°), Z=-3.01, P=0.003). The Hammersmith functional motor scale expanded scores of children with SMA type 2 and type 3 both showed significant elevation (11.0 (8.0, 18.0) vs. 11.0 (5.0, 18.5) scores, 44.0 (36.5, 53.0) vs. 44.0 (34.0, 51.5) scores, Z=2.44, 3.11, P=0.015, 0.002). Conclusion: Multidisciplinary management is beneficial for delaying the progression of the multi-system impairments of SMA patients, such as malnutrition, restrictive ventilation dysfunction and scoliosis.
Child
;
Male
;
Female
;
Humans
;
Child, Preschool
;
Scoliosis
;
Retrospective Studies
;
Follow-Up Studies
;
Muscular Atrophy, Spinal
;
Malnutrition
10.Clinical follow-up analysis of nusinersen in the disease-modifying treatment of pediatric spinal muscular atrophy
Shanshan MAO ; Yijie FENG ; Lu XU ; Mei YAO ; Yu XIA ; Jianing JIN ; Lingshuang WANG ; Tingting CHEN ; Xiaoyang CHEN ; Yi ZHANG ; Huan ZHANG ; Yuan JIANG ; Haibing LI ; Qi LONG ; Feng GAO
Chinese Journal of Pediatrics 2022;60(7):688-693
Objective:To explore the clinical efficacy of disease-modifying drug nusinersen on children with spinal muscular atrophy.Methods:The baseline and longitudinal clinical data of 15 children who were treated with nusinersen in the Children′s Hospital, Zhejiang University School of Medicine from October 2019 to October 2021 were retrospectively collected. The general data (gender, age, genotype, and clinical classification, etc.), motor function, nutritional status, scoliosis and respiratory function were analyzed. Wilcoxon rank-sum test was used for comparing multi-system conditions before and after treatment.Results:The age of 15 cases (7 males, 8 females) was 6.8 (2.8, 8.3) years, with 2 cases of type 1, 6 cases of type 2, and 7 cases of type 3 respectively, and the course of disease was 55.0 (21.0, 69.0) months. After 9.0 (9.0, 24.0) months of treatment, the motor function scale evaluations of the Hammersmith neurological examination section 2 (13.0 (7.0, 23.0) vs. 18.0 (10.0, 25.0) scores, Z=-2.67, P=0.018) of 15 children, the Hammersmith functional motor scale expanded (38.0 (18.5, 45.5) vs. 42.0 (23.0, 51.0) scores, Z=-2.38, P=0.018), and the revised upper limb module (27.0 (19.5, 32.0) vs. 33.0 (22.5, 35.5) scores, Z=-2.52, P=0.012) of children with type 2 and 3 had significantly improved. Thirteen patients achieved clinically significant motor function improvement, and 2 of them had kept stable scale scores. Subjective reports also indicated that the muscle strength and daily exercise ability of these children improved after treatment, and no serious adverse reactions were reported. Supplemented by the multi-disciplinary team management, the levels of some indicators such as Cobbs angle of scoliosis and forced vital capacity all had significantly improved (all P<0.05). Conclusions:Nusinersen can improve the motor function of patients with 5q spinal muscular atrophy, which is also proved safe to be used in children. The drug treatment supplemented by the multi-disciplinary team management is helpful to improve the multi-system function of the children with spinal muscular atrophy.


Result Analysis
Print
Save
E-mail