AIM: To investigate the effects of nitric oxide (NO) inhalation on nitric oxide synthase (NOS) and endothelin-1 (ET-l) of patients with hypoxic pulmonary hypertension. METHODS: Examined 13 pulmonic blood samples to determine the concentration of NOS in leukocyte and ET - 1 in plasma before NO inhalation, 30 minutes after inhalation, 2 and 12 hours after stopping of inhalation respectiviy. RESULTS: The values taken before inhalation was NOS (0.70 ? 0.21 )mol/min?mg-l, ET-1 (78.89 ? 46.59) Pmol/L; 30 minutes after inhalation (0.74?0.14)mol/min.mg-l, ET - 1 (88 .27 ? 45 .41 )pmol/L; 2 hours after stopping of inhalation NOS (0.64 ? 0.22)mol/min.mg-1, ET - 1 (80.76?42.66)pmol/L; and 12 hours after stopping of inhalation NOS (0. 63? 0. 17)mol/min.mg-1, ET-1(61.07?29.44)pmol/L. NO significant difference was found in the values of NOS and ET- 1 before and after inhalation, P＞ 0. 05. CONCLUSION: The effects of NO inhalation on NOS and ET-l in patients with hypoxic pulmonary hypertension are not significant according to the above investigation.

Objective To assess the clinical short-term to mid-term efficacy of transcatheter closure of coronary artery fistula by using patent ductus arteriosus occluder in pediatric patients. Methods During the period from Jan. 2008 to May 2013 at authors’ hospital, transcatheter closure of coronary artery fistula using patent ductus arteriosus occluder was performed in 8 pediatric patients. The clinical data, including follow-up information, were retrospectively analyzed. Results A total of 8 pediatric patients with a mean age of (4.1 ± 3.8) years were enrolled in this study. The fistula originated from the right coronary artery in five cases and from the left coronary artery in three cases. The blood flow shunted to the right atrium (n=4) or to the right ventricle (n = 4). Obstruction of the fistula was successfully accomplished in all patients. All patients were followed up for (2.2 ± 1.2) years. No procedure-related complications or cardiac ischemia occurred. Conclusion For the treatment of coronary artery fistula in pediatric patients, the use of domestic patent ductus arteriosus occluder is safe and effective with satisfactory short-term to mid-term clinical efficacy.

Objective To analyze a rare genotype with β-thalassemia intermadia.Methods Phenotypic analysis was performed using routine hematological tests to measure red blood cell parameters and high performance liquid chromatography (HPLC)was used to measure hemoglobin fractions.The β-globin gene mutations were conducted using reverse-dot-blot and DNA sequencing of the breakpoint region were characterized with gap-PCR.Results The proband had a trait of thalassemia intermedia with reduced hemoglobin (86 g/L).The proband's father had a trait of microcytic hypochromic with reduced mean corpuscular volume(MCV),mean corpuscular hemoglobin (MCH) (63.7 fl and 20.4 pg,respectively) and an elevated level of HbA2.He had the phenotype of heterozygosity for β-thalassemia.The preband's mother,grandmother and sister had a trait of heterezygote for hereditary persistence of fetal hemoglobin (HPFH) with elevated level of HbF,which were 28.3%,21.1% and 33.7%,respectively.After molecular characterization of the family members,the proband was identified as a patient with β-thalassemia intermedia caused by co-existence of β-thalassemia(β41-42) and HPFH-6.The father was heterozygoas for β-thaiassemia (β41-42/βN) and the mother,grandmother and sister were all heterozygons for HPFH-6.Condusions A rare β-thalassemia intermedia case resulting from compound heterezygote of β41-42 with HPFH-6 is found.This study may provide clinical experiences for antenatal diagnosis.

BACKGROUND:Calcium metaphosphate has excel ent biocompatibility, degradability, and cel affinity. Human bone marrow mesenchymal stem cel s can grow and proliferate in the pores of the porous calcium metaphosphate, but less is known about calcium metaphosphate nanoparticles.
OBJECTIVE:To prepare calcium metaphosphate nanoparticles, and to analyze the effect of calcium metaphosphate nanoparticles at different concentrations on apoptosis of human bone marrow mesenchymal stem cel s by flow cytometry.
METHODS:The calcium metaphosphate nanoparticles were prepared by wet bal mil ing. Scanning electron microscopy and transmission electron microscopy were used to observe the morphology of the calcium metaphosphate nanoparticles, and the crystal structure of nanoparticles was analyzed by X-ray diffraction. Calcium metaphosphate nanoparticles were mixed in the CYAGON Oricel TM basal medium, and the concentrations of calcium metaphosphate nanoparticles in the medium were 10, 1, 0.1 mg/L. Human bone marrow mesenchymal stem cel s were cultured for 7 days in the above-mentioned media, and apoptosis of human bone marrow mesenchymal stem cel s was analyzed by flow cytometry.
RESULTS AND CONCLUSION:Calcium metaphosphate nanoparticles were successful y prepared by wet bal mil ing, irregular in shape, and the mean diameter was 10-30 nm. X-ray diffraction results showed the crystal structure of nonaparticles was mainlyβ-Ca(PO3)2. The cel ratio of G0/G1 phase and G2/M phase in 10 mg/L group was obviously higher than that in 1, 0.1 mg/L groups (P<0.01). The cel apoptosis rates during the early, middle, late stages in 10 mg/L group were obviously higher than those in 1, 0.1 mg/L groups (P<0.01), and the total cel apoptosis was also significantly increased in 10 mg/L group (P<0.01). These findings indicate that human bone marrow mesenchymal stem cel s proliferation can be inhibited by calcium metaphosphate nanoparticles, and apoptosis rate is increased significantly when the concentration of calcium metaphosphate nanoparticles increases from 1 mg/L to 10 mg/L.

AIM: To screen and identify the differentially expressed genes in lymphocytes of patients with unstable angina in order to find the molecular mechanism of unstable angina. METHODS: Suppression subtractive hybridizations (SSH) and dot blot hybridizations were performed to screen the relatively differentially expressed genes in lymphocyte RNA between the patients with unstable angina pectoris and stable angina pectoris. The obtained expressed sequence tags (ESTs) were used as probes to perform Reverse Northern blot with forward and reverse suppression products. And the positive ESTs were performed RNA slot hybridization with unstable and stable angina group. The obtained ESTs were sequenced and analyzed using BLAST (nr) at NCBI. RESULTS: Three up-regulated ESTs in the unstable angina group, and one down-regulated EST in the stable angina group were obtained. All of them are sequences of known genes. CONCLUSION: All these ESTs may be associated with the unstablization of plaque of coronary artery in patients with unstable angina.

ObjectiveBy comparing the difference of volatile components of the decoction pieces before and after being processed by braising method of Jianchangbang and steaming method included in the 2020 edition of Chinese Pharmacopoeia， the influence of processing methods on the flavor formation of Polygoni Multiflori Radix （PMR） was compared. MethodHeadspace-gas chromatography-mass spectrometry （HS-GC-MS） was used to detect the volatile components of 30 batches of PMR samples from 3 origins with 3 processing methods. The GC was performed under programmed temperature （starting temperature of 40 ℃， rising to 150 ℃ at 5 ℃·min^-1， and then rising to 195 ℃ at 10 ℃·min^-1） with high purity helium as carrier gas and the split ratio of 10∶1. Mass spectrometry conditions were electron impact ion source （EI） and the detection range of m/z 50-650， the peak area normalization method was used to calculate the relative mass fraction of each component. The chromaticity values of different processed products were measured by a precision colorimeter， the relationship between chromaticity values and relative contents of volatile components was investigated by OriginPro 2021， principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） were performed on the sample data by SIMCA14.1. The differential components of different processed products of PMR were screened according to the principle of variable importance in the projection （VIP） value>1.5， and the material basis of different odor formation of PMR and its processed products was explored. ResultA total of 59 volatile components were identified， among which 34 were raw products， 33 were braised products， and 27 were steamed products. PCA and OPLS-DA results showed that there were significant differences between the three， but there was no significant difference between samples from different origins of the same processing method. Color parameters of a^*， b^*， E^*ab had no significant correlation with contents of volatile components， while L^* was negatively correlated with contents of 2-methyl-2-butenal， 2-methyltetrahydrofuran-3-one and 2，3-dihydro-3，5-dihydroxy-6-methyl-4（H）-pyran-4-one （P<0.05）. The contents of pungent odor components such as caproic acid， nonanoic acid and synthetic camphor decreased after processing， while the contents of sweet flavor components such as 2-methyl-2-butenal， furfural and 5-hydroxymethylfurfural increased after processing， and the contents of furfural， 5-methyl-2-furanmethanol， 5-hydroxymethylfurfural and other aroma components in the braised products were significantly higher than that in the steamed products. ConclusionHS-GC-MS can quickly identify the volatile substance basis that causes the different odors of PMR and its processed products. The effect of processing methods on the odor is greater than that of origin. There is a significant correlation between the color parameter of L^* and contents of volatile components， the "raw" taste of PMR may be related to volatile components such as caproic acid， pelargonic acid and synthetic camphor， the "flavor" after processing may be related to the increase of the contents of 2-methyl-2-butenal， furfural， 5-hydroxymethylfurfural， methyl maltol and furfuryl alcohol.

Metastasis and resistance are main causes to affect the outcome of the current anticancer therapies. Heat shock protein 90 (Hsp90) as an ATP-dependent molecular chaperone takes important role in the tumor metastasis and resistance. Targeting Hsp90 and downregulating its expression show promising in inhibiting tumor metastasis and resistance. In this study, a redox-responsive dual-drug nanocarrier was constructed for the effective delivery of a commonly used chemotherapeutic drug PTX, and a COA-modified 4-arm PEG polymer (4PSC) was synthesized. COA, an active component in oleanolic acid that exerts strong antitumor activity by downregulating Hsp90 expression, was used as a structural and functional element to endow 4PSC with redox responsiveness and Hsp90 inhibitory activity. Our results showed that 4PSC/PTX nanomicelles efficiently delivered PTX and COA to tumor locations without inducing systemic toxicity. By blocking the Hsp90 signaling pathway, 4PSC significantly enhanced the antitumor effect of PTX, inhibiting tumor proliferation and invasiveness as well as chemotherapy-induced resistance in vitro. Remarkable results were further confirmed in vivo with two preclinical tumor models. These findings demonstrate that the COA-modified 4PSC drug delivery nanosystem provides a potential platform for enhancing the efficacy of chemotherapies.

Metastasis is crucial for the mortality of non-small cell lung carcinoma (NSCLC) patients. The epithelial-mesenchymal transition (EMT) plays a critical role in regulating tumor metastasis. Glioma-associated oncogene 1 (Gli1) is aberrantly active in a series of tumor tissues. However, the molecular regulatory relationships between Gli1 and NSCLC metastasis have not yet been identified. Herein, we reported Gli1 promoted NSCLC metastasis. High Gli1 expression was associated with poor survival of NSCLC patients. Ectopic expression of Gli1 in low metastatic A549 and NCI-H460 cells enhanced their migration, invasion abilities and facilitated EMT process, whereas knock-down of Gli1 in high metastatic NCI-H1299 and NCI-H1703 cells showed an opposite effect. Notably, Gli1 overexpression accelerated the lung and liver metastasis of NSCLC in the intravenously injected metastasis model. Further research showed that Gli1 positively regulated Snail expression by binding to its promoter and enhancing its protein stability, thereby facilitating the migration, invasion and EMT of NSCLC. In addition, administration of GANT-61, a Gli1 inhibitor, obviously suppressed the metastasis of NSCLC. Collectively, our study reveals that Gli1 is a critical regulator for NSCLC metastasis and suggests that targeting Gli1 is a prospective therapy strategy for metastatic NSCLC.