1.Biomarkers in the diagnosis and treatment of postural tachycardia syndrome in children
Chinese Journal of Applied Clinical Pediatrics 2016;(1):10-12
Postural tachycardia syndrome (POTS)is one common type of orthostatic intolerance (OI)in chil-dren.POTS is characterized by OI symptoms and excessively increased heart rate from supine to upright position.Main treatments for POTS are physical training,automatic function exercise and medications including α-receptor agonists,β-receptor blockers and oral rehydration salts.This review aimed to summarize the biomarkers in the diagnosis and treatment of POTS.
2.Clinical study advance of orthostatic hypertension in children
Chinese Journal of Applied Clinical Pediatrics 2016;31(13):1037-1040
Orthostatic hypertension (OHT)in children was first proposed by Chinese scholars in 2012.The diagnostic criterion was revised in 2015.OHT in children was not rare in clinical practice.Children and adolescents are susceptible to OHT when they suddenly change posture or standing for a long time.The mechanisms of OHT were not clear.Dizziness,headache,nausea and vomiting were the main manifestations of OHT.Severe symptom in childhood OHT includes syncope.The prognosis of OHT was good,but the abnormal blood pressure will last to adults.Further study in OHT will help to predict the risk of cardiovascular and cerebrovascular diseases and help to evaluate target or-gan injury.The treatment of OHT has been explored,and non -medical treatment is the main option.Study in medical treatment for OHT has not been conducted.Now,the diagnostic criteria in children,epidemiologic status,clinical fea-tures and treatment of OHT were focused to deepen the understanding of OHT in children and improve the clinical standard of the disease.
3.Electro-acupuncture decreases hydrogen sulfide concentration in brain cortex of baby rats with hypoxic-ischemic brain damage
Ying LIU ; Liping ZOU ; Hongfang JIN
Chinese Pediatric Emergency Medicine 2011;18(2):142-145
Objective To establish hypoxic-ischemic brain damaged (HIBD) rat model,investigate whether H2S and cystathionine-β-synthase (CBS), the key enzyme for its generation, may be a mediator of electro-acupuncture(EA) stimulation treatment for HIBD. Methods Thirty-two healthy Sprague-Dawley neonatal rats were divided into four groups randomly: sham control group ( n = 8 ); sham + EA group ( n =8); HIBD control group ( n = 8); and HIBD + EA group ( n = 8 ). HIBD rat models were established on their 7-day-old. From the next day ,rats of sham + EA group and HIBD + EA group were electric stimulated 30 min daily for 14 d,BAIHUI and DAZHUI as the acupoints. Control ones were just fixed at the same time,without acupuncture. The rats were sacrificed on the 22 nd day, one day after the treatment course. Cortical H2S concentration was measured by sensitive sulphur electrode assay. The CBS protein expression was measured by western blot analysis and immunohistochemistry for localization. Results The concentration of cortical H2S in HIBD control group was (26. 83 ± 4. 31 ) nmol/mg protein, which was significantly higher than that of sham control group[(22. 78 ± 1.54) nmol/mg protein]( P < 0. 01 ). The H2 S levels in HIBD + EA group and sham + EA group were ( 18.08 ± 2.71 ) nmol/mg protein and ( 18.91 ± 2. 78 ) nmol/mg protein, respectively. Compared with corresponding control group, they were much lower( P < 0. 01 ). The expression of CBS protein in rats with EA stimulation decreased in cortex compared to corresponding control group( P <0. 05 ).Conclusion EA can down-resulate H2S/CBS pathway. This may be one of the mechanisms of how EA contributes to the recovery of brain damage.
4.Relationship between expression of PGP9 .5 and clinicopathological fea-tures of cervical carcinoma, and in vitro study of underlying mechanism
Rong JIN ; Hongfang LI ; Lidong ZHANG
Chinese Journal of Pathophysiology 2016;32(7):1235-1240
AIM: To detect the protein expression of protein gene product (PGP9.5) in cervical carcinoma samples, and to explore its relationship with clinicopathological features and prognosis of cervical carcinoma patients.The potential value of PGP9.5-siRNA in the treatment of cervical cancer was preliminarily investigated in vitro.METHODS:The clinical data of cervical cancer patients ( n=180 ) who received surgical treatment in Department of Gynecology of Tianjin Fifth Central Hospital and Tianjin Central Hospital of Gynecology and Obstetrics from January 2008 to June 2015 were retrospectively analyzed.Immunohistochemical staining for PGP9.5 in all pathological specimens from cervical cancer biopsy was performed.The patients were divided into high expression of PGP9.5 group and low expression of PGP9.5 group.The relationship between PGP9.5 expression and clinicopathological parameters, such as age, HPV infection, path-ological grade, tumor diameter, lymph node metastasis, depth of invasion and clinical stage, were analyzed.The overall survival was analyzed by Kaplan-Meier method and the log-rank test.The PGP9.5-siRNA, NC-siRNA, PGP9.5 eukaryotic expression plasmid and empty vector were transfected into the SiHa cells, and the effects of PGP9.5 expression on the abili-
ties of colony formation and cell invasion were determined by Western blot, colony formation assay and Transwell experi-ment.RESULTS:The relationships between the expression level of PGP9.5 and patients’ pathological characteristics in-cluding grade, tumor size, lymph node metastasis, depth of invasion, vascular involvement and clinical stage were statisti-cally significant ( P<0.05) .The overall survival rates of 3 and 5 years in PGP9.5 high expression group were significantly lower than those in PGP9.5 low expression group ( P<0.05 ) .Compared with control group, the protein expression of PGP9.5, the number of colony formation and the number of invasive cells in si-PGP9.5 group were significantly decreased. The protein expression of PGP9.5, the number of colony formation and the number of invasive cells in PGP9.5 group were significantly increased.CONCLUSION:Over-expression of PGP9.5 protein indicates poor prognosis of cervical cancer, which may be a good predictor for the prognosis of cervical cancer patients.Inhibition of PGP9.5 expression may be an ef-fective way of gene therapy for cervical cancer.
5.Effect of hydrogen sulfide on vasorelaxation and content of guanosine 3', 5'-cyclic phosphate in vascular tissue of rats
Qiuyu YAO ; Hongfang JIN ; Junbao DU
Chinese Journal of Applied Clinical Pediatrics 2015;30(10):776-778
Obgective To observe the effect of hydrogen sulfide (H2S) on vasorelaxation and expression of guanosine 3',5'-cyclic phosphate (cGMP) and activity of cyclic nucleotide phosphodiesterase (PDE) in vascular tissue.Methods H2S donor was provided by sodium bisulfide sodium hydrosulfide.The isolated perfused rat thoracic aorta rings were used to test the relaxation responses to H2S,which recorded by Power Lab system,and the enzyme linked immuno assay was used to detect intracellular cGMP.The activity of PDE was evaluated by using cyclic nucleotide PDE assay kit.Results (1) H2S relaxed the thoracic aorta rings,and the half maximal effective concentration (EC50) for the H2 S relaxation curve,represented by the corresponding concentration of H2 S that achieved 50% of the maximum relaxation effect,was (1.79 ± 0.31) × 10-5 mol/L.(2)The cGMP content in vascular tissue increased from (22.29 ± 1.59) pmol/L to(41.45 ± 7.49) pmol/L and (31.35 ± 2.56) pmol/L after incubation with 50 μmol/L and 300 μmol/L H2 S,respectively (t =-3.09,t =-2.88;all P < 0.05,n =7-8).(3) cGMP could be lysed into 5'-guanylicacid(5'-GMP) by PDE,which was an important pathway for cGMP degradation.This study showed that PDE activity was decreased in vascular tissue,the 5'-GMP decreased from (0.52 ±0.06) mol/L to (0.25 ±0.06) mol/Land (0.27 ±0.07) mol/L after incubation with 50 μmol/L and 300 μ mol/L H2S,respectively (t =3.21,t =2.58;all P < 0.05,n =7-8).Conclusion The vasorelaxant effects of H2 S might be related to the inhibited activity of PDE and elevated content of cGMP.
6.The clinical diagnosis and treatment of vasovagal syncope in children
Junbao DU ; Jinyan YANG ; Hongfang JIN
Journal of Clinical Pediatrics 2013;(7):601-604
Vasovagal syncope (VVS) was a neurally-mediated functional disease, a transient disturbance of consciousness triggered by transient cerebral ischemia due to peripheral vasodilation resulting from a variety of incentives, accompanied by the loss of muscle tone and even fainting. Children with VVS are characterized by recurrent syncopal attacks induced by prolonged standing, postural changes and muggy environment, etc. Currently treatments of VVS include non-pharmacological therapy and pharmacological therapy.
7.Regulatory effect and significance of hydrogen sulfide on low-density lipoprotein receptor
Yuan WANG ; Hongfang JIN ; Junbao DU
Chinese Journal of Applied Clinical Pediatrics 2016;31(13):1017-1020
Objective To observe the regulatory effect and significance of hydrogen sulfide (H2 S)on low -density lipoprotein receptor (LDLR).Methods Mouse primary hepatocytes were divided into control group,low -den-sity lipoprotein (LDL)group and LDL +sodium hydrosulfide (NaHS,the donor of H2 S)group.The cells in LDL group were treated with LDL (50 mg/L)and the cells in LDL +NaHS group were pretreated with NaHS (100 μmol/L)for 0.5 hours and then treated with LDL (50 mg/L).Real -time PCR and Western blot were used to detect the expres-sions of LDLR mRNA and protein,respectively.Mouse primary hepatocytes were divided into control group,1,1′-dioctadecyl -3,3,3′,3′-tetramethyl -indocarbocyanine perchlorate low -density lipoprotein (DiI -LDL)group and DiI -LDL +NaHS group.The cells in DiI -LDL group were incubated with DiI -LDL (10 mg/L)for 3 hours.The cells in DiI -LDL +NaHS group were pretreated with NaHS (100 μmol/L)for 1 hour before DiI -LDL (10 mg/L) was added.Confocal method was used to measure the uptake of DiI -LDL by mouse primary hepatocytes,and fluores-cent quantitative method was performed to detect the content of DiI -LDL in the supernatant of mouse primary hepato-cytes.Results The levels of LDLR mRNA and protein in the mouse primary hepatocytes were significantly downregu-lated compared with those in the control group (t =5.733,P <0.01;t =2.527,P <0.05);after NaHS was adminis-tered,LDLR mRNA and protein level in the mouse primary hepatocytes were significantly upregulated (t =-7.639, P <0.01;t =2.388,P <0.05).In the mouse primary hepatocytes,compared with that in the control group,the uptake of DiI -LDL by cells in DiI -LDL group was increased;the uptake of DiI -LDL by mouse primary hepatocytes in DiI -LDL +NaHS group was significantly increased in comparison with that in the DiI -LDL group.Compared with that in the control group,the DiI -LDL content of culture supernatant in the DiI -LDL group was significantly increased (t =-39.156,P <0.01);after treatment with H2 S donor,the content of DiI -LDL in the culture supernatant was sig-nificantly decreased in comparison with that in the mouse primary hepatocytes without H2 S donor treatment (t =17.202,P <0.01).Conclusion H2 S upregulated the expression of LDLR protein in the mouse primary hepatocytes.
8.Change of endogenous hydrogen sulfide pathway in the monocrotaline-induced pulmonary hypertensive rats
Shasha FENG ; Wen YU ; Shuxu DU ; Junbao DU ; Hongfang JIN
Chinese Journal of Applied Clinical Pediatrics 2016;31(19):1489-1492
Objective To investigate the production of hydrogen sulfide (H2S) in rats with monocrotaline (MCT)-induced pulmonary hypertension(PAH).Methods Fourteen male Wistar rats were randomly divided into 2 groups (7 cases for each group):control group and MCT group.Rats in the MCT group were intraperitoneally injected with MCT (60 mg/kg) on day 1 while rats in the control group received only the same volume of 9 g/L saline.And then the conventional breeding was given for 21 days.Mean pulmonary artery pressure (mPAP) was evaluated via right cardiac catheterization procedure.The ratio of right ventricular mass (RV) and left ventricular plus septal mass (LV + SP) [RV/(LV + SP)] was calculated.The morphological change of pulmonary artery was observed by applying hematoxylin-eosin (HE) staining on the lung tissue paraffin section by measuring relative media thickness (RMT) and relative media area (RMA) of pulmonary aetery.H2S contents in serum and lung tissue rat were detected by using free radicals detector.The expression of cystathionine-γ-lyase (CSE),a key enzyme catalyzing endogenous H2S generaion,in lung tissue was detected by using Western blot method.CSE mRNA level in lung was detected by adopting the real-time polymerase chain reaction (RT-PCR) method.Results Compared with control group,mPAP of rats in MCT group was increased significantly [(49.31 ±3.67) mmHg vs (14.31 ±2.07) mmHg(1 mm Hg =0.133 kPa),P < 0.01] and the ratio of RV/(LV + SP) was increased (0.43 ± 0.03 vs 0.21 ± 0.03,P < 0.01),while RMT and RMA of pulmonary artery were enlarged [(43.46 ± 1.94) μm vs (13.16 ± 1.48) μm,P < 0.01;(3 321.10 ± 318.20) μm2 vs (963.40 ± 127.26) μm2,P <0.01].The evaluation of microstructure of pulmonary artery showed that the vessel wall of pulmonary artery in control rats was thin and no inflammatory cell was observed around artery.However,the vessel wall of pulmonary artery in rats of MCT group was thickened and there was evident infiltration of inflammatory cells in perivascular area.Compared with control group,H2S contents in serum and lung tissue of rats in MCT group were markedly decreased [(9.28 ± 0.94) μmol/L vs (14.20 ± 1.21) μmol/L,P < 0.01;(0.43 ± 0.08) μmol/g protein vs (0.87 ±0.17) μmol/g protein,P <0.01],while CSE protein and mRNA expression in lung tissue of rats in MCT group were downregulated (0.14 ± 0.02 vs 0.28 ± 0.09,P < 0.01;0.84 ± 0.06 vs 1.12 ± 0.04,P < 0.01).Condusion Endogenous H2S pathway is significantly downregulated in rats with monocrotaline-induced pulmonary hypertension.
9.Effects of sulfur dioxide on vasoactive peptides in aorta of atherosclerotic rats
Yaqian HUANG ; Wei LI ; Junbao DU ; Hongfang JIN
Chinese Journal of Applied Clinical Pediatrics 2015;30(17):1341-1343
Objective To observe the effect of sulfur dioxide (SO2) on vasoactive peptides in aorta of atherosclerotic(AS) rats.Methods Twenty-eight male SD rats were randomly divided into control group (8 cases),AS group (10 cases) ,AS + SO2 group (10 cases).The rats in AS group and AS + SO2 group were given 700 000 U/kg Vitamin D3 and fed a high-cholesterol diet for 8 weeks to induce AS.Meanwhile, the rats in AS + SO2 group were intraperitoneally injected SO2 donor Na2SO3/NaHSO3 (0.54 mmol/kg,0.18 mmol/kg) every day.And the rats in control group and AS group were given the same dose of saline.After 8 weeks, the changes in atherosclerosis plaque size in the aortic root were observed by way of oil red O staining.Angiotensin Ⅱ (Ang Ⅱ) and endothelin-1 (ET-1) in the aortic homogenate were detected by using radioactive immunoassay.Results Compared with the control group, the atherosclerosis plaque size was markedly increased in AS group, while SO2 treatment significantly decreased the atherosclerosis plaque size in AS rats.Meanwhile,the content of Ang Ⅱ and ET-1 in the aortic homogenate from AS group were increased compared to those in the control group [(11.52 ±4.15) ng/g vs (5.46 ± 1.21) ng/g, (11.91 ± 4.93) ng/g vs (3.81 ± 1.21) ng/g,all P <0.01] ,while SO2 donor treatment markedly decreased the content of Ang Ⅱ and ET-1 in AS rats [(6.25 ± 2.85) ng/g, (8.35 ± 2.45) ng/g] (all P < 0.01).Conclusions SO2 can play an important role in the regulation of vasoactive peptide Ang Ⅱ and ET-1 in AS rat aorta.This effect may be one of the mechanisms by which SO2 antagonize AS.
10.Intermedin inhibits pulmonary collagen synthesis in rats with pulmonary hypertension induced by high pulmonary blood flow
Lulu PANG ; Jianguang QI ; Yang GAO ; Hongfang JIN ; Junbao DU
Chinese Journal of Pathophysiology 2014;(12):2185-2189
[ ABSTRACT] AIM:To explore the regulatory effect of intermedin ( IMD) on pulmonary collagen synthesis and ac-cumulation in rats with pulmonary hypertension induced by high pulmonary blood flow.METHODS: Healthy male SD rats (n=20) were randomly divided into control group (n=7), shunt group (n=7) and shunt with IMD group (n=6).The shunting of abdominal aorta and inferior vena cava was produced in rats of shunt group and shunt with IMD group.After 8 weeks, IMD was administered into the rats of shunt with IMD group subcutaneously by mini-osmotic pump for 2 weeks.Mean pulmonary artery pressure (mPAP), relative medial thickness (RMT) of pulmonary arteries, contents of hydroxyproline, collagen type I and III, bone morphogenetic protein-2 (BMP-2), and the mRNA expression of procollagen I and III in lung tissues were measured and compared.RESULTS:Compared with control group, mPAP and RMT of medium and small pul-monary arteries in the rats of shunt group were significantly increased.Meanwhile, the lung hydroxyproline, collagens I and III and BMP-2 contents, and the mRNA expression of lung procollagen I and III were all significantly increased compared with control group.However, IMD significantly decreased mPAP, alleviated the changes of pulmonary vascular micro-struc-ture, decreased the collagen accumulation and pulmonary tissue homogenate BMP-2 contents, and inhibited the mRNA ex-pression of procollagen I and III in the lung tissue of shunting rats.CONCLUSION:IMD plays a protective role in the de-velopment of pulmonary hypertension and pulmonary vascular structural remodeling induced by high blood flow by inhibiting pulmonary collagen synthesis and accumulation, possibly in association with the BMP-2 pathway.