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

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

The study aims to elucidate the existence forms(original constituents and metabolites) of Notoginseng Radix et Rhizoma in rats and reveal its metabolic pathways. After Notoginseng Radix et Rhizoma was administered orally once a day for seven consecutive days to rats, all urine and feces samples were collected for seven days, while the blood samples were obtained 6 h after the last administration. Using the ultra high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technique, this study identified 6, 73, and 156 existence forms of Notoginseng Radix et Rhizoma in the rat plasma, urine, and feces samples, respectively. Among them, 101 compounds were identified as new existence forms, and 13 original constituents were identified by comparing with reference compounds. The metabolic reactions of constituents from Notoginseng Radix et Rhizoma were mainly deglycosylation, dehydration, hydroxylation, hydrogenation, dehydrogenation, acetylation, and amino acid conjugation. Furthermore, the possible in vivo metabolic pathways of protopanaxatriol(PPT) in rats were proposed. Through comprehensive analysis of the liquid chromatography-mass spectrometry(LC-MS) data, isomeric compounds were discriminated, and the planar chemical structures of 32 metabolites were clearly identified. According to the literature, 48 original constituents possess antitumor and cardiovascular protective bioactivities. Additionally, 32 metabolites were predicted to have similar bioactivities by SuperPred. This research lays the foundation for further exploring the in vivo effective forms of Notoginseng Radix et Rhizoma.
Animals ; Rats ; Drugs, Chinese Herbal/pharmacokinetics* ; Rhizome/metabolism* ; Male ; Rats, Sprague-Dawley ; Chromatography, High Pressure Liquid ; Panax notoginseng/chemistry* ; Tandem Mass Spectrometry ; Feces/chemistry*

This study aims to explore the effects and mechanisms of 4'-O-methylbavachalcone(MeBavaC), an active compound from Psoraleae Fructus, in regulating white matter neuroinflammation to improve vascular cognitive impairment. Male Sprague-Dawley(SD) rats were randomly divided into four groups: sham group, model group, high-dose MeBavaC group(14 mg·kg~(-1)), and low-dose MeBavaC group(7 mg·kg~(-1)). The rat model of chronic cerebral hypoperfusion(CCH) was established using bilateral common carotid artery occlusion. The Morris water maze test was performed to evaluate the learning and memory abilities of the rats. Luxol fast blue staining, Nissl staining, immunofluorescence, immunohistochemistry, and transmission electron microscopy were utilized to observe the morphology and ultrastructure of the white matter myelin sheaths, axon integrity, the morphology and number of hippocampal neurons, and the loss and activation of glial cells in the white matter. Transcriptome analysis was performed to explore the potential mechanisms of white matter injury induced by CCH. Western blot and quantitative real-time polymerase chain reaction(qRT-PCR) assays were conducted to measure the expression levels of NOD-like receptor protein 3(NLRP3), absent in melanoma 2(AIM2), gasdermin D(GSDMD), cysteinyl aspartate-specific proteinase-1(caspase-1), interleukin-18(IL-18), interleukin-1β(IL-1β), erythropoietin(EPO), nuclear factor erythroid 2-related factor 2(Nrf2), and heme oxygenase-1(HO-1) in the white matter of rats. The results showed that compared with the model group, MeBavaC significantly improved the learning and memory abilities of rats with CCH, improved the damage of white matter myelin sheath, maintained axonal integrity, reduced the loss of hippocampal neurons and oligodendrocytes in the white matter, inhibited the activation of microglia and the proliferation of astrocytes in the white matter, and suppressed the NLRP3/AIM2/caspase-1/GSDMD pathway. The expression levels of inflammatory cytokines IL-1β and IL-18 were significantly reduced, while EPO expression and the expression of Nrf2/HO-1 antioxidant pathway were notably elevated. In conclusion, MeBavaC can alleviate cognitive impairment in rats with CCH and suppress neuroinflammation in cerebral white matter. The mechanism of action may involve activation of EPO activity, promotion of endogenous antioxidant pathways, and inhibition of neuroinflammation in the white matter. This study suggests that MeBavaC exhibits antioxidant and anti-neuroinflammatory effects, showing potential application in improving cognitive dysfunction.
Animals ; Male ; Rats, Sprague-Dawley ; NF-E2-Related Factor 2/immunology* ; Rats ; Chalcones/administration & dosage* ; Cognitive Dysfunction/metabolism* ; Signal Transduction/drug effects* ; Neuroinflammatory Diseases/drug therapy* ; Heme Oxygenase-1/metabolism* ; Humans ; Heme Oxygenase (Decyclizing)/genetics*

OBJECTIVE: To investigate the therapeutic effect of Xiangshao Granules (XSG) on post-stroke depression (PSD) and explore the underlying mechanisms. METHODS: Forty-three C57BL/6J mice were divided into 3 groups: sham (n=15), PSD+vehicle (n=14), and PSD+XSG (n=14) groups according to a random number table. The PSD models were constructed using chronic unpredictable mild stress (CUMS) after middle cerebral artery occlusion (MCAO). The sham group only experienced the same surgical operation, but without MACO and CUMS stimulation. The XSG group received XSG (60 mg/kg per day) by gavage for 4 weeks. The mice in the sham and vehicle groups were given the same volume of 0.9% saline at the same time. The body weight and behavior tests including open field test, sucrose preference test, tail suspension test, and elevated plus-maze test, were used to validate the PSD mouse model. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining were used to evaluate the anti-inflammatory effects of XSG. The potential molecular mechanisms were explored and verified through network pharmacology analysis, Nissl staining, Western blot, ELISA, and RT-qPCR, respectively. RESULTS: The body weight and behavior tests showed that MCAO combined with CUMS successfully established the PSD models. XSG alleviated neuronal damage, reduced the expressions of pro-apoptotic proteins Caspase-3 and B-cell lymphoma-2 (BCL-2)-associated X (BAX), and increased the expression of anti-apoptotic protein BCL-2 in PSD mice (P<0.05 or P<0.01). XSG inhibited microglial activation and the expressions of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin (IL)-1 β, and IL-6 via the toll-like receptor 4/nuclear factor kappa-B signaling pathway in PSD mice (P<0.05 or P<0.01). Furthermore, XSG decreased the expression of indoleamine 2,3-dioxygenase1 (IDO1) and increased the concentration of 5-hydroxytryptamine in PSD mice (P<0.05 or P<0.01). CONCLUSION XSG could reverse the anxiety/depressionlike behaviors and reduce the neuronal injury in the hippocampus and prefrontal cortex of PSD mice, which may be a potential therapeutic agent for PSD.
Animals ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism* ; Depression/etiology* ; Drugs, Chinese Herbal/therapeutic use* ; Hippocampus/metabolism* ; Male ; Mice, Inbred C57BL ; Prefrontal Cortex/pathology* ; Microglia/metabolism* ; Stroke/drug therapy* ; Disease Models, Animal ; Mice ; Behavior, Animal/drug effects*

OBJECTIVE: To explore the efficacy and safety of Juan Bi Pill (JBP) in treatment of active rheumatoid arthritis (RA). METHODS: From February 2017 to May 2018, 115 participants from 4 centers were randomly divided into JBP group (57 cases) and placebo group (58 cases) in a 1:1 ratio using a random number table method. Participants received a dose of JBP (4 g, twice a day, orally) combined with methotrexate (MTX, 10 mg per week) or placebo (4 g, twice a day, orally) combined with MTX for 12 weeks. Participants were required with follow-up visits at 24 and 48 weeks, attending 7 assessment visits. Participants were undergo disease activity assessment 7 times (at baseline and 2, 4, 8, 12, 24, 48 weeks) and safety assessments 6 times (at baseline and 4, 8, 12, 24, 48 weeks). The primary endpoint was 28-joint Disease Activity Score (DAS28-ESR and DAS28-CRP). The secondary endpoints included American College of Rheumatology (ACR) criteria for 20% and 50% improvement (ACR20/50), Health Assessment Questionnaire Disability Index (HAQ-DI), clinical disease activity index (CDAI), visual analog scale (VAS), Short Form-36 (SF-36) score, Medial Outcomes Study (MOS) sleep scale score, serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender joint count, swollen joint count, and morning stiffness. The adverse reactions were observed during the treatment. RESULTS: After 12 weeks of treatment, DAS28-ESR and DAS28-CRP scores in both groups were lower than before treatment (both P<0.01), while the remission rate of DAS28-ESR and DAS28-CRP and low disease activity of JBP group were higher than those in the placebo group (both P<0.01). JBP demonstrated better efficacy on ACR20 and ACR50 compliance rate at 12 and 48 weeks comparing to placebo (all P<0.05). The CDAI and HAQ-DI score, pain VAS and global VAS change of RA patients and physicians, the serum ESR and CRP levels, and the number of tenderness and swelling joints were lower than before treatment at 4, 8, 12, 24, 48 weeks in both groups (P<0.05 or P<0.01), while the reduction of above indices in the JBP group was more obvious than those in the placebo group at 12 weeks (ESR and CRP, both P<0.05) or at 12 and 48 weeks (all P<0.01). There was no difference in adverse reactions between the 2 groups during treatment (P=0.75). CONCLUSION JBP combined with MTX could effectively reduce disease activity in patients with RA in active stage, reduce the symptoms of arthritis, and improve the quality of life, while ensuring safety, reliability, and fewer adverse effects. (Trial Registration: ClinicalTrials.gov, No. NCT02885597).
Humans ; Arthritis, Rheumatoid/drug therapy* ; Methotrexate/adverse effects* ; Female ; Double-Blind Method ; Male ; Middle Aged ; Treatment Outcome ; Drugs, Chinese Herbal/adverse effects* ; Drug Therapy, Combination ; Adult ; Antirheumatic Agents/adverse effects* ; Aged

Objective To investigate the distribution of traditional Chinese medicine(TCM)syndromes in the patients with acute cerebral infarction,and to analyze the correlation of TCM syndromes with collateral circulation,cerebral blood perfusion and prognosis.Methods A total of 300 patients with acute cerebral infarction were selected.All patients underwent head-neck CT angiography(CTA)and CT perfusion imaging(CTP),and then were followed up for 30 days.The prognosis was evaluated by modified Rankin Scale(MRS)score.In addition,the dynamic evolution of TCM syndromes was observed to explore the correlation of TCM syndromes with collateral circulation,cerebral blood flow perfusion in the lesion area and prognosis.Logistic regression analysis was used to explore the influences of TCM syndromes,blood flow perfusion and collateral circulation establishment on stroke outcomes.Results(1)Highest incidences of syndrome elements of phlegm,blood stasis and wind were presented in ACI patients.The syndrome element of qi deficiency was predominated in the patients with anterior/posterior communicating artery opening and extracranial-to-intracranial collateral circulation establishment.On the first day of onset,the incidence of qi deficiency syndrome element in the good collateral circulation group was lower than that in the poor collateral circulation group(P＜0.05).On the 30th day after onset,the incidences of qi deficiency syndrome element and phlegm syndrome element in the good collateral circulation group were significantly lower than those in the poor collateral circulation group(P＜0.01).The results of correlation analysis showed that the score of qi deficiency was negatively correlated with regional cerebral blood volume(rCBV)of region of interest(r=-0.472,P＜0.05),and the score of yin deficiency was positively correlated with rCBV(r=-0.557,P＜0.01)on the first day of onset.The incidence of qi deficiency in the lesion area was relatively high in the patients of decreased rCBV(rCBV＜1.0 score)group(P＜0.01),while the incidence of yin deficiency in the lesion area was relatively high in the patients of elevated rCBV(rCBV＞1.0 score)group(P＜0.05).(2)The distribution of syndrome elements on the first day of onset showed that the incidence of qi deficiency syndrome element in the poor prognosis group was significantly higher than that in the good prognosis group(P＜0.01);on the 30th day after onset,the incidences of qi deficiency syndrome element and phlegm syndrome element in the good prognosis group was significantly lower than those in the poor prognosis group(P＜0.05 or P＜0.01).The incidence of phlegm syndrome element in the good prognosis group was significantly reduced on the 30th day after onset compared with that on the first day of onset(χ2=7.409,P＜0.01),while there was no significant difference shown in the poor prognosis group(P＞0.05).(3)Logistic regression analysis showed that syndrome elements(qi deficiency,phlegm),collateral circulation grading,and rCBV in the lesion area were the independent risk factors for stroke outcomes.Conclusion The acute cerebral infarction patients with poor collateral circulation,decreased blood perfusion and poor prognosis are predominated by qi deficiency syndrome element.Moreover,phlegm syndrome element is presented in the patients with poor prognosis throughout the course of disease.It is indicated that qi deficiency syndrome element and phlegm syndrome element play an important role in the pathogenesis and progression of acute cerebral infarction.

Cells are the fundamental structural and functional units of biological organisms,with inherent differences in composition and interactions with exogenous substances,known as cellular heterogeneity.Single cell inductively coupled plasma-mass spectrometry(SC-ICP-MS)allows for the high-throughput introduction of individual cells,enabling the highly sensitive detection and quantification of elements within a single cell,thus effectively providing information on cellular heterogeneity.This review outlined the SC-ICP-MS sample preparation process for different types of cells(single-cell systems,aggregation-prone and adherent cell systems,animal tissues,and plant tissues),including steps such as separation,washing,and fixation,as well as the advantages and existing issues of the current sample introduction systems and quantification methods.The recent applications of SC-ICP-MS in detecting endogenous substances(endogenous elements and proteins),exogenous substances(heavy metals,metal-based drugs and nanoparticles),and the simultaneous detection of both endogenous and exogenous substances were summarized.Finally,the perspectives on the future development of SC-ICP-MS in analytical methods and application fields were presented,including the optimization of single-cell sample preparation,transport efficiency,evaluation standards of ionization efficiency,and the establishment of multiparametric cell analysis platforms.