Objectives:To investigate the clinical and cardiopulmonary functional characteristics of cardiopulmonary-phenotype idiopathic pulmonary arterial hypertension(IPAH)patients in comparison with classical IPAH patients and pulmonary hypertension patients associated with chronic lung disease(CLD-PH).Methods:In this retrospective study,data were collected from 30 patients with classical IPAH,20 cardiopulmonary phenotype IPAH patients,and 20 patients with CLD-PH,who were hospitalized in the Department of Respiratory and Critical Care Medicine at Beijing Chaoyang Hospital from November 2017 to February 2025.Pulmonary hypertension was diagnosed via right heart catheterization and all patients underwent pulmonary function tests,chest computed tomography(CT),echocardiography,and patients were followed up to 5 years.Results:Compared to classical IPAH patients,both cardiopulmonary phenotype IPAH patients and CLD-PH patients exhibited later onset age,higher proportions of World Health Organization(WHO)functional class Ⅲ-Ⅳ,males,and smokers(all P<0.05).The cardiopulmonary-phenotype IPAH patients also had higher rates of coronary artery disease and diabetes compared to classical IPAH patients(all P<0.05).Physiologically,the cardiopulmonary-phenotype IPAH patients showed reduced diffusing capacity for carbon monoxide(DLCO)and partial pressure of oxygen(PaO2),along with higher rates of emphysema and pulmonary fibrosis compared to classical IPAH(all P<0.05).In contrast,CLD-PH patients had lower mean pulmonary arterial pressure(mPAP),pulmonary vascular resistance(PVR),and pulmonary artery wedge pressure(PAWP),as well as reduced forced expiratory volume in the first second(FEV1%predicted),FEV1/forced vital capacity(FVC)ratio,and DLCO.However,CLD-PH patients demonstrated higher tricuspid annular plane systolic excursion(TAPSE),peak systolic velocity of the tricuspid annulus(S`),and partial pressure of carbon dioxide(PaCO2),along with increased rates of emphysema and pulmonary fibrosis(all P<0.05).Compared with LCD-PH,cardiopulmonary-phenotype IPAH patients had higher mPAP,PVR,FEV1%predicted,FEV1/FVC ratio,PAWP,and systolic pulmonary artery pressure,but lower DLCO,cardiac output,TAPSE,S′,and PaCO2(all P<0.05).No statistical difference was observed in PaO2 between these two groups.All cardiopulmonary-phenotype IPAH patients and classical IPAH patients received targeted medications,55%of CLD-PH patients did not receive targeted therapy,45%received monotherapy only(compared with cardiopulmonary-phenotype IPAH patients and classical IPAH groups,P<0.05).The 1,2,and 5-year survival rates were 79.2%,62.2%,and 46.7%,respectively in patients with cardiopulmonary-phenotype IPAH,100%,94.4%,and 94.4%,respectively in classic IPAH patients,and 92.9%,77.4%and 77.4%,respectively in patients with CLD-PH.Survival rates for cardiopulmonary-phenotype IPAH patients were significantly lower than those of classical IPAH and CLD-PH patients(log-rank P=0.008).Conclusions:IPAH cardiopulmonary phenotype patients are older,predominantly male,and often have a smoking history(median 30 pack-years).They exhibit severe hypoxemia,markedly reduced DLCOc,preserved spirometry,and severe pulmonary hypertension and lower survival rate.

Objectives:To investigate the clinical and cardiopulmonary functional characteristics of cardiopulmonary-phenotype idiopathic pulmonary arterial hypertension(IPAH)patients in comparison with classical IPAH patients and pulmonary hypertension patients associated with chronic lung disease(CLD-PH).Methods:In this retrospective study,data were collected from 30 patients with classical IPAH,20 cardiopulmonary phenotype IPAH patients,and 20 patients with CLD-PH,who were hospitalized in the Department of Respiratory and Critical Care Medicine at Beijing Chaoyang Hospital from November 2017 to February 2025.Pulmonary hypertension was diagnosed via right heart catheterization and all patients underwent pulmonary function tests,chest computed tomography(CT),echocardiography,and patients were followed up to 5 years.Results:Compared to classical IPAH patients,both cardiopulmonary phenotype IPAH patients and CLD-PH patients exhibited later onset age,higher proportions of World Health Organization(WHO)functional class Ⅲ-Ⅳ,males,and smokers(all P<0.05).The cardiopulmonary-phenotype IPAH patients also had higher rates of coronary artery disease and diabetes compared to classical IPAH patients(all P<0.05).Physiologically,the cardiopulmonary-phenotype IPAH patients showed reduced diffusing capacity for carbon monoxide(DLCO)and partial pressure of oxygen(PaO2),along with higher rates of emphysema and pulmonary fibrosis compared to classical IPAH(all P<0.05).In contrast,CLD-PH patients had lower mean pulmonary arterial pressure(mPAP),pulmonary vascular resistance(PVR),and pulmonary artery wedge pressure(PAWP),as well as reduced forced expiratory volume in the first second(FEV1%predicted),FEV1/forced vital capacity(FVC)ratio,and DLCO.However,CLD-PH patients demonstrated higher tricuspid annular plane systolic excursion(TAPSE),peak systolic velocity of the tricuspid annulus(S`),and partial pressure of carbon dioxide(PaCO2),along with increased rates of emphysema and pulmonary fibrosis(all P<0.05).Compared with LCD-PH,cardiopulmonary-phenotype IPAH patients had higher mPAP,PVR,FEV1%predicted,FEV1/FVC ratio,PAWP,and systolic pulmonary artery pressure,but lower DLCO,cardiac output,TAPSE,S′,and PaCO2(all P<0.05).No statistical difference was observed in PaO2 between these two groups.All cardiopulmonary-phenotype IPAH patients and classical IPAH patients received targeted medications,55%of CLD-PH patients did not receive targeted therapy,45%received monotherapy only(compared with cardiopulmonary-phenotype IPAH patients and classical IPAH groups,P<0.05).The 1,2,and 5-year survival rates were 79.2%,62.2%,and 46.7%,respectively in patients with cardiopulmonary-phenotype IPAH,100%,94.4%,and 94.4%,respectively in classic IPAH patients,and 92.9%,77.4%and 77.4%,respectively in patients with CLD-PH.Survival rates for cardiopulmonary-phenotype IPAH patients were significantly lower than those of classical IPAH and CLD-PH patients(log-rank P=0.008).Conclusions:IPAH cardiopulmonary phenotype patients are older,predominantly male,and often have a smoking history(median 30 pack-years).They exhibit severe hypoxemia,markedly reduced DLCOc,preserved spirometry,and severe pulmonary hypertension and lower survival rate.

Objective:To explore the effect and mechanism of c-Myc on regulating the expression of immune-related ligands in Y subtype small-cell lung cancer (SCLC) characterized by high expression of immune-related molecules.Methods:The Y subtype SCLC cell line H196 was randomly divided into the control group, c-Myc inhibitor 10058-F4 group, histone deacetylase 1 (HDAC1) inhibitor pyroxamide group, and 10058-F4 plus pyroxamide group. The co-culture system with NK-92MI cells was used to determine the effect of H196 cells on the function of natural killer (NK) cells. Western Blotting and co-immunoprecipitation assays were used to detect the effect of c-Myc on class Ⅰ HDAC, and flow cytometry was used to detect the regulatory effect of c-Mycon CD47, programmed cell death ligand 1 (PD-L1), and CD155, which are highly expressed immune checkpoints in Y subtype SCLC, and major histocompatibility complex classⅠ-related chains A and (MICA/B), which is a poorly expressed immune-activating ligand in SCLC, and the role of HDAC. Chromatin immunoprecipitation (ChIP) assay and real-time quantitative polymerase chain reaction (RT-qPCR) were used to determine the regulatory mechanism of c-Myc-HDAC1 on MICA/B expression.Results:Inhibition of c-Myc decreased the mortality of H196 cells in the co-culture system and down-regulated the expression of MICA/B. Compared with the NK+H196 group [(42.54±2.47)%], the proportion of cells killed by NK-92MI cells in the NK+H196+10058-F4 group was lower [(28.48±3.38)%, P＜0.001]. The mean fluorescence intensity (MFI) of MICA/B on the cells in the 10058-F4 group (36.40±0.82) was lower than that in the control group (91.23±8.60, P＜0.001). And c-Myc could bind to HDAC1, whose protein level was up-regulated by 10058-F4 while the mRNA level was not. Compared with the cells in the control group (90.10±4.91), the MFI of MICA/B on the cells in the pyroxamide group was significantly increased (145.70±5.86, P＜0.001), and the MFI of MICA/B on the cells in the 10058-F4+pyroxamide group (54.60±2.88) was significantly increased compared with the cells in the 10058-F4 group (35.97±1.60, P＜0.001). The percentage of MICA promoter gene fragments in the c-Myc antibody precipitation group (0.125±0.037) was significantly higher than that in the IgG group (0.000 8±0.000 3, P=0.004). MICB had a similar trend, suggesting that the c-Myc-HDAC1 complex could bind to the promoter region of MICA/B. The MFI of CD47 on the cells in the 10058-F4 group (60.07±0.21) was significantly lower than cells in the control group (70.27±1.37, P＜0.001), but the MFIs of PD-L1 (13.50±0.61) and CD155 (829.70±41.19) were significantly higher than those on the cells in the control group (9.23±0.94, P＜0.01; 496.00±4.36, P＜0.001, respectively). Conclusions:c-Myc may promote the expression of MICA/B and CD47 in Y subtype SCLC cells by binding and inhibiting HDAC1, while it may also be involved in inhibiting the expression of PD-L1 and CD155 in SCLC cells.

Objective:To explore the effect and mechanism of c-Myc on regulating the expression of immune-related ligands in Y subtype small-cell lung cancer (SCLC) characterized by high expression of immune-related molecules.Methods:The Y subtype SCLC cell line H196 was randomly divided into the control group, c-Myc inhibitor 10058-F4 group, histone deacetylase 1 (HDAC1) inhibitor pyroxamide group, and 10058-F4 plus pyroxamide group. The co-culture system with NK-92MI cells was used to determine the effect of H196 cells on the function of natural killer (NK) cells. Western Blotting and co-immunoprecipitation assays were used to detect the effect of c-Myc on class Ⅰ HDAC, and flow cytometry was used to detect the regulatory effect of c-Mycon CD47, programmed cell death ligand 1 (PD-L1), and CD155, which are highly expressed immune checkpoints in Y subtype SCLC, and major histocompatibility complex classⅠ-related chains A and (MICA/B), which is a poorly expressed immune-activating ligand in SCLC, and the role of HDAC. Chromatin immunoprecipitation (ChIP) assay and real-time quantitative polymerase chain reaction (RT-qPCR) were used to determine the regulatory mechanism of c-Myc-HDAC1 on MICA/B expression.Results:Inhibition of c-Myc decreased the mortality of H196 cells in the co-culture system and down-regulated the expression of MICA/B. Compared with the NK+H196 group [(42.54±2.47)%], the proportion of cells killed by NK-92MI cells in the NK+H196+10058-F4 group was lower [(28.48±3.38)%, P＜0.001]. The mean fluorescence intensity (MFI) of MICA/B on the cells in the 10058-F4 group (36.40±0.82) was lower than that in the control group (91.23±8.60, P＜0.001). And c-Myc could bind to HDAC1, whose protein level was up-regulated by 10058-F4 while the mRNA level was not. Compared with the cells in the control group (90.10±4.91), the MFI of MICA/B on the cells in the pyroxamide group was significantly increased (145.70±5.86, P＜0.001), and the MFI of MICA/B on the cells in the 10058-F4+pyroxamide group (54.60±2.88) was significantly increased compared with the cells in the 10058-F4 group (35.97±1.60, P＜0.001). The percentage of MICA promoter gene fragments in the c-Myc antibody precipitation group (0.125±0.037) was significantly higher than that in the IgG group (0.000 8±0.000 3, P=0.004). MICB had a similar trend, suggesting that the c-Myc-HDAC1 complex could bind to the promoter region of MICA/B. The MFI of CD47 on the cells in the 10058-F4 group (60.07±0.21) was significantly lower than cells in the control group (70.27±1.37, P＜0.001), but the MFIs of PD-L1 (13.50±0.61) and CD155 (829.70±41.19) were significantly higher than those on the cells in the control group (9.23±0.94, P＜0.01; 496.00±4.36, P＜0.001, respectively). Conclusions:c-Myc may promote the expression of MICA/B and CD47 in Y subtype SCLC cells by binding and inhibiting HDAC1, while it may also be involved in inhibiting the expression of PD-L1 and CD155 in SCLC cells.

Objective To explore the transitive regularity of holistic constituents from the crude slices of the medicinal raw materials (MCS) to the formula granules (FG), fufang decoction (FD), and finally, the concentrated pills (CP) of Liuwei Dihuang Fufang (六味地黄复方, LWDHF). Methods Samples for MCS, FG, FD, and CP of LWDHF were obtained, and a fingerprint database was established using high-performance liquid chromatography (HPLC), by separating the samples in an XB-C18 column and analyzing the transitive regularity of components using the total quantum statistical moment (TQSM), including total quantum zero moment (AUCT), total quantum first moment (MRTT), total quantum second moment (VRTT), and its similarity approach. The AUCT, MRTT, and VRTT were calculated based on the representative HPLC chromatograms of FG, FD, and CP of LWDHF. Results AUCT of FG, FD, and CP of LWDHF was 71 804, 46 553, and 144 646 µV·s, respectively; MRTT was 14.43, 14.54, and 18.85 min, respectively; and VRTT was 106.98, 112.84, and 269.12 min2, respectively. Comparing the similarity of FG/FD, FG/CP and FD/CP of LWDHF, the TQSM similarity values were 98.66%, 76.62%, and 75.37%, respectively, whereas the traditional similarity evaluation values were 98.68%, 85.43%, and 85.60%, respectively. Conclusion The results perform little distinction in the total composition between FG and FD, whereas some distinction existed between FD and CP. Experimental evidence, therefore indicates that FG could be used as the alternative of MCS in clinical applications.

Objective To assess the diet quality of pregnant women during the second trimester using the dietary inflammatory index ( DII) and to explore the correlation between the DII in second trimester of preg-nancy and preterm delivery.Methods A total of 253 women with singleton pregnancy in 16-20 gestational weeks who had received routine prenatal care between August 2014 and April 2015 at the First Affiliated Hospi-tal of Anhui Medical University were enrolled with cluster random sampling.The included women were asked to recall daily dietary intake in the 3 days prior to the survey.All dietary data were analyzed for energy and nutri-ents intake with a nutritional analysis software, followed by calculation of DII according to previous reports. Based on quartiles of the DII scores, the participants were divided into three groups, namely the anti-inflam-matory group (DII<-5.10), intermediate group (DII -5.10--2.55), and the pro-inflammatory group (DII>-2.55).The participants were followed up until delivery and the pregnancy outcomes were recorded. The relationship between the DII in second trimester of pregnancy and preterm delivery were analyzed. Results DII scores of the 253 pregnant women during the second trimester of pregnancy ranged from -7.913 to 3.872.The risks of preterm birth in the anti-inflammatory diet group, the intermediate group, and the pro-inflammatory diet group were 0, 1.6%, and 6.3%, respectively, with statistically significant differences among the groups (P=0.034).The higher DII scores (pro-inflammatory) were associated with higher inci-dence of preterm birth ( P<0.05 ) .Conclusion DII may be used to assess diet quality of pregnant women during the second trimester and to predict the risk of preterm birth.

Objective To investigate the value of combined 3D-constructive interference in steady state(3D-CISS) with phase-contrast MR(PC-MR) in diagnosis of hydrocephalus children.Methods We collected retrospectively 28 children with hydrocephalus who caused by obstructive membranes.They all underwent MR imaging examination with a 1.5 T consisting of 3D-CISS, conventional sequences and PC-MR.With the result of surgery and CT cisternography as gold standard,we analysised different sequence in the diagnosis of membranous obstruction.The results of obstructive were analysed by x2 test between 3D-CISS combined with PC-MR and conventional sequences.Results The study included 28 children, of whom 16 showed obstructive membranes in CSF pathways of ventricle and 12 displayed obstructive membranes in CSF pathways of cistern.Conventional sequences diagnosed obstructive membranes of 15 children, and obstructive membranes of 11 children were consistent with gold standard, and 4 cases were false positive.The 3D-CISS diagnosed obstructive membranes of 40, and 12 cases were false positive.There were significant difference between 3D-CISS combined with PC-MR and conventional sequence about obstructive membranes diagnosis of CSF pathways(x2=24.410, P=0.001).Conclusions Making use of jointing 3D-CISS sequence and PC-MR sequence successively, and we can diagnose the position of obstructive membrane for hydrocephalus, which can be helpful to select a perfect surgical approach.

Objective To explore the protective effect of folic acid supplementation in different ways on lipopolysaccharide-induced external malformations and skeletal malformations in mice.Methods The pregnant mice were divided into six groups randomly,including saline control group,FA control group,LPS group,LPS+FAig group,LPS+FAip group,and LPS+FAdw group.All dams were medicated on gestational day 8～12,and then sacrificed on gestational day 18,for each litter,the number of live fetuses,dead fetuses,resorption fetuses and external malformations of live fetuses were all counted.All fetuses were subsequently evaluated the skeletal malformations.Results A low dose of LPS injection during the second trimester resulted in external and skeletal malformations.Exencephaly and encephalomeningocele were two of the most common external malformations,skeletal malformations consisted mainly of the incompletion of supraoccipital ossification,sternal malformation and rib malformation.FA supplementation by three ways all attenuated the external and skeletal malformations.And the best protective effect was by oral administration.The incidence of external,sternal and rib malformation was all decreased.Conclusions Three ways can prevent the mice during the second trimester from the external and skeletal malformations caused by LPS injection,and the best protective effect was by intragastric administration.

BACKGROUND:At present, the development of reprogramming technology provides a wide prospect for stem cellresearch. Through the ectopic co-expression of reprogramming factors, the somatic cells can be reprogrammed to a pluripotent state, termed as induced pluripotent stem cells, which can avoid the ethical controversy faced in the research and application of embryonic stem cells. Also, we can generate patient-specific and disease-specific induced pluripotent stem cells, which significantly decrease immuno-rejection. However, reprogramming technology faces some chal enges, such as low efficiency and safety.
OBJECTIVE:Based on the characteristics of induced pluripotent stem cells and the principles of reprogramming, to detail the progress in reprogramming technology from five aspects, including cellresources, carriers, transcription factors, microRNA and signal transduction pathway. 
METHODS:A computer-based online retrieval was performed to search papers published form January 1990 to April 2013 in VIP periodical ful-text database, Wanfang periodical ful-text database, CNKI periodical ful-text database, PubMed database and Springer database with key words of“reprogramming, induced pluripotent stem cell, signal transduction pathway, epigenetics, microRNA, transcription factor, vector, somatic cell, smal molecule compound, safety”both in Chinese and English. After excluding objective-independent papers, 67 papers were included for further analysis.
RESULTS AND CONCLUSION:By exploring different cellresources, different carriers, various combination of transcription factors, microRNAs or inhibition of the signal transduction pathways, the reprogramming efficiency and safety have been improved greatly. However, currently, induced pluripotent stem cells stil could not meet the requirement of clinical application. To achieve the clinical application of induced pluripotent stem cells, it is urgent to explore the mechanism of reprogramming, and to optimize the programming strategy.

Aim To investigate the effect of N-acetylcysteine (NAC) pretreatment/posttreatment on lipopolysaccharide (LPS)-induced intra-uterine fetal death (IUFD) and intra-uterine growth retardation (IUGR) in mice.Methods In the first experiment,all pregnant mice except controls received an intraperitoneal (75 ?g?kg-1) injection of LPS on gd 15~17.In LPS+NAC groups,the pregnant mice were treated with NAC before and/or after LPS. The saline-and NAC-treated pregnant mice served as controls. The dams were sacrificed on gd 18. In the second experiment,all pregnant mice except controls received an intraperitoneal (75 ?g?kg-1) injection of LPS on gd 15. In LPS+NAC groups,the pregnant mice were treated with NAC before and/or after LPS. The saline-and NAC-treated pregnant mice served as controls. The dams were sacrificed at 1.5 h or 6 h after LPS.Results pretreatment with NAC significantly alleviated LPS-induced fetal mortality and reversed LPS-induced growth development retardation.Correspondingly,pretreatment with NAC significantly attenuated LPS-induced elevation in TNF-? concentration in maternal serum and amniotic fluid and lipid peroxidation in maternal and fetal livers. By contrast to pretreatment,posttreatment with NAC had no effect on LPS-induced TNF-? production and lipid peroxidation,and did not protect against LPS-induced IUFD and IUGR and in fact aggravated LPS-induced preterm labor.Conclusion Pretreatment with NAC attenuates LPS-induced IUFD and IUGR,whereas posttreatment with NAC aggravates LPS-induced preterm labor.