BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Mice ; Animals ; Spiral Ganglion/physiology* ; Cochlea/physiology* ; Neurons

Objective: To analyze the epidemiology and spatial-temporal distribution characteristics of hand, foot and mouth disease (HFMD) in Shanxi province. Methods: The data of HFMD in Shanxi province from 2009 to 2020 were collected from notifiable disease management information system of Chinese information system for disease control and prevention and analyzed by descriptive epidemiology, Joinpoint regression, spatial autocorrelation analysis and spatio- temporal scanning analysis. Results: A total of 293 477 HFMD cases were reported in Shanxi province from 2009 to 2020, with an average annual incidence of 67.64/100 000 (293 477/433 867 454), severe disease rate of 5.36/100 000 (2 326/433 867 454), severe disease ratio of 0.79%(2 326/293 477), mortality of 0.015/100 000 (66/433 867 454), and fatality rate of 22.49/100 000 (66/293 477). The reported incidence rate, severe disease rate, mortality rate and fatality rate of HFMD showed decreasing trends. The main high-risk groups were scattered children and kindergarten children aged 0-5. The incidence of HFMD had obvious seasonal variation, with two peaks every year: the main peak was during June-July, the secondary peak was during September-October and the peak period is from April to November. A total of 13 942 laboratory cases were confirmed, with a diagnosis rate of 4.75% (13 942/293 477), including 4 438 (35.11%, 4 438/293 477) Enterovirus A71 (EV-A71) positive cases, 4 609 (33.06%, 4 609/293 477) Coxsackievirus A16 (CV-A16) positive cases, and 4 895 (31.83%, 4 895/293 477) other enterovirus positive cases. There was a spatial positive correlation (Moran's I ranged from 0.12 to 0.58, all P<0.05) and the spatial clustering was obvious. High-risk regions were mainly distributed in Taiyuan in central Shanxi province, Linfen and Yuncheng in southern Shanxi province, and Changzhi in southeastern Shanxi province. Spatial-temporal scanning analysis revealed 1 the most likely cluster and 8 secondary likely clusters, of which the most likely cluster (RR=2.65, LLR=22 387.42, P<0.001) located in Taiyuan and Jinzhong city, Shanxi province, including 12 counties (districts), and accumulated from April 1, 2009 to November 30, 2018. Conclusions: There was obvious spatial-temporal clustering of HFMD in Shanxi province, and the epidemic situation was in decline. The key areas were the districts in urban areas and the counties adjacent to it. Meanwhile, the monitoring and classification of other enterovirus types of HFMD should be strengthened.
Child ; Humans ; Hand, Foot and Mouth Disease/epidemiology* ; Spatial Analysis ; Enterovirus Infections ; Spatio-Temporal Analysis ; Cluster Analysis

OBJECTIVE: To study the risk factors and treatment for neutropenia of late newborns (NLN). METHODS: Related clinical data were collected from the preterm infants and critically ill neonates who were admitted to the neonatal intensive care unit from July 2019 to January 2020. A total of 46 newborns with a blood absolute neutrophil count (ANC) of < 1.5×10 RESULTS: Among the 46 neonates in the NLN group, 29 had a gestational age of < 32 weeks, 14 had a gestational age of 32-37 weeks, and 3 had a gestational age of > 37 weeks. There was no significant difference between the two groups in the incidence rates of gestational hypertension, premature rupture of membranes > 18 hours and intrauterine distress, 5-minute Apgar score, the duration of positive pressure ventilation, the incidence rate of early-onset sepsis, and the type of initially used antibiotics ( CONCLUSIONS The risk of NLN increases with the presence of late-onset sepsis and the increase in the duration of antibiotic use. NLN is generally a benign process. G-CSF appears to be safe and effective for NLN with severe disease conditions or severe reduction in ANC.
Granulocyte Colony-Stimulating Factor ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Leukocyte Count ; Neutropenia ; Risk Factors ; Sepsis

Animals ; Cell Proliferation ; Male ; Mice ; Mice, Inbred C57BL ; Spermatogonia ; Stem Cells ; Testis

OBJECTIVE: Critical effective constituents were identified from Bufei Yishen formula (BYF), a traditional herbal compound and combined as effective-constituent compatibility (ECC) of BYF I, which may have potential bioactive equivalence to BYF. METHODS: The active constituents of BYF were identified using four cellular models and categorised into Groups 1 (Bufeiqi), 2 (Bushen), 3 (Huatan) and 4 (Huoxue) according to Chinese medicinal theory. An orthogonal design and a combination method were used to determine the optimal ratios of effective constituents in each group and the ratios of "Groups 1 to 4" according to their pharmacological activity. We also comprehensively assessed bioactive equivalence between the BYF and the ECC of BYF I in a rat model of chronic obstructive pulmonary disease (COPD). RESULTS: We identified 12 active constituents in BYF. The numbers of constituents in Groups 1 to 4 were 3, 2, 5 and 2, respectively. We identified the optimal ratios of effective constituents within each group. In Group 1, total ginsenosides:Astragalus polysaccharide:astragaloside IV ratio was 9:5:2. In Group 2, icariin:schisandrin B ratio was 100:12.5. In Group 3, nobiletin:hesperidin:peimine:peiminine:kaempferol ratio was 4:30:6.25:0:0. In Group 4, paeoniflorin:paeonol ratio was 4:1. An orthogonal design was then used to establish the optimal ratios of Group 1, Group 2, Group 3 and Group 4 in ECC of BYF I. The ratio for total ginsenosides:Astragalus polysaccharide:astragaloside IV:icariin:schisandrin B:nobiletin:hesperidin:peimine:paeoniflorin:paeonol was determined to be 22.5:12.5:5:100:12.5:4:30:6.25:25:6.25. A comprehensive evaluation confirmed that ECC of BYF I presented with bioactive equivalence to the original BYF. CONCLUSION Based on the ECC of traditional Chinese medicine formula method, the effective constituents of BYF were identified and combined in a fixed ratio as ECC of BYF I that was as effective as BYF itself in treating rats with COPD.

Objective:To investigate the topological alterations in brain functional networks following comprehensive treatment including brain-computer interface (BCI) training in subacute stroke subjects. Methods:From January, 2018 to June, 2019, 14 subacute stroke patients with moderate to severe upper limbs paralysis accepted routine physical therapy, occupational therapy and BCI training based on motor imagery, for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE), Action Research Arm Test (ARAT) and Wolf Motor Function Test (WMFT) before and after treatment, while the functional connectivity (FC) was investigated with resting state functional magnetic resonance imaging. Results:The scores of FMA-UE, ARAT and WMFT increased after treatment (|t| > 5.298, Z = -3.297, P < 0.01). The FC also increased across the whole brain, including temporal, parietal, occipital lobes and subcortical regions. The FC between left piriform cortex of parietal lobule (BA5L) and right medial surface of temporal lobe (BA48R), as well as those between left precentral gyrus (BA4L) and right anterior transverse temporal gyrus (BA41R) (r > 0.416, P < 0.05). Conclusion:Comprehensive rehabilitation including BCI training may promote recovery of motor function and activities of FC in brain in subacute stroke patients.

OBJECTIVE: To analyze the clinical outcomes of engraftment, graft-versus-host disease (GVHD) and survival in the patients with AML1-ETO positive acute myeloid leukemia (AML) treated with unrelated umbilical cord blood transplantation (UCBT). METHODS: Forty-Five patients with high-risk refractory AML1-ETO positive AML were treated with a single UCBT in a single center from July 2010 to April 2018. All the patients underwent a myeloablative preconditioning regimen，and cyclosporine A (CSA) combined with mycophenolate mofetil (MMF) was used to prevent GVHD. RESULTS: The median value of total nucleated cells (TNC) in cord blood was 5.21 (1.96-12.68)×10/kg recipient body weight, and that of CD34+ cells was 5.61 (0.56-15.4)×10/kg recipient weight. The implantation rate of neutrophil at 42 d and that of platelet at 120 d were 95.6% and 86.7%, respectively. The median time of absolute neutrophil count (ANC)＞0.5×10/L and platelet 20×10/L were 16 (12-18) d and 37 (17-140) d after transplantation, respectively. The cumulative incidence of Ⅰ -Ⅳ grade acute GVHD (aGVHD) at 100 d after transplantation was 48.9% (95% CI 33.5%-62.6%), Ⅱ-Ⅳ grade aGVHD occurred in 12 cases (33.3%) (95% CI 20%-47.2%) , and Ⅲ-Ⅳ grade a GVHD in 8 cases (20%) (95% CI 9.8% -32.8%). In 5 cases of 40 patients survived over 100 days, the chronic GVHD (cGVHD) occurred after transplantation, among which 4 were localized, and 1 was extensive. 3 patients relapsed, and the 2-year cumulative relapse rate was 9.5% (95% CI 2.4%-22.8%). The median follow-up time was 23.5 (0.9-89.67) months, 10 patients died, 2-year disease-free survival rate (DFS) was 72.7%, and overall survival rate (OS) was 75.5%. Multivariate analysis showed that Ⅲ-Ⅳ. acute GVHD (aGVHD) affected overall survival. CONCLUSION UCBT is an effective rescue treatment for patients with high-risk refractory AML1-ETO positive AML.
Cord Blood Stem Cell Transplantation ; Core Binding Factor Alpha 2 Subunit ; Graft vs Host Disease ; Humans ; Leukemia, Myeloid, Acute ; Mycophenolic Acid ; Oncogene Proteins, Fusion ; Peripheral Blood Stem Cell Transplantation ; RUNX1 Translocation Partner 1 Protein ; Transplantation Conditioning

Aim To investigate the molecular mecha-nism of mTORC1/2 inhibitor PP242, which inhibiting cholangiocyte cell preliferation and cystic diliatation via inducing apoptosis and autophagy in the polycystic kid-ney ( PCK ) rats. Methods The expression of p-mTOR and p-Akt in the bile duct epithelial cells was examined by immunohistochemistry. The inhibiting effect of rapamycin and PP242 on cell proliferation ac-tivity on bile duct epithelial cells, the effect of gene si-lence on LC3, Beclin-1 and the effect of the authoph-agy-specific inhibitor 3-methyladenine (3-MA) on cell proliferation were respectively analyzed by WST-1 as-say. The expression of PI3K/Akt signaling pathway re-lated proteins, autophagy-related proteins LC3, Bec-lin-1 and clevead caspase-3, which were treated by PP242 were determined by Western blot. The effect of PP242 on apoptosis was detected by Annexin V/PI double staining and ELISA. The expression of LC3 in cytoplasm was detected by immunofluorescence. The a-bility of rat bile duct epithelial cells spheroid formation was detected by 3D cell culture method, and the cells were treated by single applied with rapamycin and ap- plied rapamycin combined with Rictor gene silencing respectively. Results The protein levels of p-Akt and p-mTOR markedly increased in the bile duct epitheli-um of PCK rats. PP242 inhibited the proliferation of bile duct epithelial cells more effectively than rapamy-cin and showed a dose-and time-dependent manner ( P<0.05 ) . PP242 significantly reduced the levels of PI3K/Akt signaling pathway-related proteins in PCK rat cholangiocytes. PP242 induced apoptosis and auto-phagy, up-regulated the levels of cleaved caspase-3, Beclin-1 and increased the ratio of LC3-II/LC3-I. The combination of Rictor gene silencing and rapamycin was more effective than rapamycin alone in inhibiting cholangiocytes in PCK rats. The inhibitory effect of PP242 on the cell viability was significantly weakened by treatment with 3-MA and knockdown of LC3 and Beclin-1 ( P <0.05 ) . Conclusions PP242 inhibits the proliferation of PCK rat cholangiocytes through PI3K/Akt/mTOR signaling pathway, and the mecha-nism is closely related with autophagy and apoptosis.

AIM:To explore the effects of mammalian target of rapamycin (mTOR) double inhibitor AZD8055 on autophagy and apoptosis of human cholangiocarcinoma cell line HuCCT1. METHODS:The effect of AZD8055 on the viability of HuCCT1 cells was detected by MTT assay. Autophagosome was detected by acridine orange (AO) staining. Af-ter treated with AZD8055, the expression levels of apoptosis-related proteins Bcl-2, Bax and cleaved caspase-3 and auto-phagy marker proteins beclin 1, LC3 and p62 were determined by Western blot. Apoptotic rate was analyzed by flow cyto-metry with Annexin V-FITC/PI double staining. RESULTS:AZD8055 significantly inhibited the viability of HuCCT1 cells (P<0.05). AO staining showed that AZD8055 significantly increased orange granules in the cytoplasm. After treated with AZD8055, compared with the control group, the protein level of beclin 1 and the ratio of LC3-Ⅱ/LC3-Ⅰ were enhanced, while p62 was attenuated (P<0.05). The protein expression level of pro-apoptotic regulator Bax was down-regulated and anti-apoptotic regulator Bcl-2 was increased. The protein level of cleaved caspase-3 was reduced (P<0.05). The results of flow cytometry showed that AZD8055 inhibited cell apoptosis. CONCLUSION:AZD8055 inhibits the viability of cholangiocarcinoma cells, and the mechanism is closely related with autophagy induced by AZD8055.