BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

OBJECTIVES: To explore the bioactive components in Jiawei Xiaoyao Pills (JWXYP) and their mechanisms for alleviating depression-like behaviors. METHODS: The active compounds, key targets, and pathways of JWXYP were identified using TCMSP and TCMIP databases. Thirty-six SD rats were randomized equally into 6 groups including a control group and 5 chronic unpredictable mild stress (CUMS)-induced depression groups. After modeling, the 5 model groups were treated with daily gavage of normal saline, 1.8 mg/kg fluoxetine hydrochloride (positive control drug), or JWXYP at 1.44, 2.88, and 4.32 g/kg. The depression-like behaviors of the rats were evaluated using behavioral tests, and pathological changes in the liver and hippocampus were examined with HE staining. The biochemical indicators in the serum and brain tissues were detected using ELISA. Serum metabolomics analysis was performed to identify the differential metabolites using OPLS-DA, and gut microbiota changes were analyzed using 16S rDNA sequencing. RESULTS: Network pharmacology revealed that menthone and paeonol in JWXYP were capable of penetrating the blood-brain barrier to regulate inflammatory pathways and protect the nervous system. In the rat models subjected to CUMS, treatment with JWXYP significantly improved body weight loss, sucrose preference and open field activities, reduced liver inflammation, alleviated structural changes in the hippocampal neurons, decreased serum levels of TNF‑α, IL-1β, IL-6 and LBP, and increased 5-HT and VIP concentrations in the serum and brain tissue, and these effects were the most pronounced in the high-dose group. Metabolomics analysis showed changes in such metabolites as indole-3-acetamide and acetyl-L-carnitine in JWXYP-treated rats, involving the pathways for bile acid biosynthesis and amino acid metabolism. 16S rDNA analysis demonstrated increased gut microbiota diversity and increased abundance of Lactobacillus species in JWXYP-treated rats. CONCLUSIONS JWXYP alleviates depression-like symptoms in rats by regulating the neurotransmitters, inhibiting inflammation and oxidation, and modulating gut microbiota.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Neurotransmitter Agents/metabolism* ; Rats ; Inflammation ; Male ; Hippocampus ; Behavior, Animal/drug effects*

During the hyperacute phase of intracerebral hemorrhage (ICH), the mass effect and blood components mechanically lead to brain damage and neurotoxicity. Our findings revealed that the mass effect and transferrin precipitate neuronal oxidative stress and iron uptake, culminating in ferroptosis in neurons. M6A (N6-methyladenosine) modification, the most prevalent mRNA modification, plays a critical role in various cell death pathways. The Fto (fat mass and obesity-associated protein) demethylase has been implicated in numerous signaling pathways of neurological diseases by modulating m6A mRNA levels. Regulation of Fto protein levels in neurons effectively mitigated mass effect-induced neuronal ferroptosis. Applying nanopore direct RNA sequencing, we identified voltage-dependent anion channel 3 (Vdac3) as a potential target associated with ferroptosis. Fto influenced neuronal ferroptosis by regulating the m6A methylation of Vdac3 mRNA. These findings elucidate the intricate interplay between Fto, Vdac3, m6A methylation, and ferroptosis in neurons during the hyperacute phase post-ICH and suggest novel therapeutic strategies for ICH.
Ferroptosis/physiology* ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics* ; Animals ; Neurons/metabolism* ; Transferrin/pharmacology* ; Mice ; Methylation ; Mice, Inbred C57BL ; Adenosine/metabolism* ; RNA, Messenger/metabolism* ; Male ; Oxidative Stress/physiology*

Objective To explore the bioactive components in Jiawei Xiaoyao Pills(JWXYP)and their mechanisms for alleviating depression-like behaviors.Methods The active compounds,key targets,and pathways of JWXYP were identified using TCMSP and TCMIP databases.Thirty-six SD rats were randomized equally into 6 groups including a control group and 5 chronic unpredictable mild stress(CUMS)-induced depression groups.After modeling,the 5 model groups were treated with daily gavage of normal saline,1.8 mg/kg fluoxetine hydrochloride(positive control drug),or JWXYP at 1.44,2.88,and 4.32 g/kg.The depression-like behaviors of the rats were evaluated using behavioral tests,and pathological changes in the liver and hippocampus were examined with HE staining.The biochemical indicators in the serum and brain tissues were detected using ELISA.Serum metabolomics analysis was performed to identify the differential metabolites using OPLS-DA,and gut microbiota changes were analyzed using 16S rDNA sequencing.Results Network pharmacology revealed that menthone and paeonol in JWXYP were capable of penetrating the blood-brain barrier to regulate inflammatory pathways and protect the nervous system.In the rat models subjected to CUMS,treatment with JWXYP significantly improved body weight loss,sucrose preference and open field activities,reduced liver inflammation,alleviated structural changes in the hippocampal neurons,decreased serum levels of TNF-α,IL-1β,IL-6 and LBP,and increased 5-HT and VIP concentrations in the serum and brain tissue,and these effects were the most pronounced in the high-dose group.Metabolomics analysis showed changes in such metabolites as indole-3-acetamide and acetyl-L-carnitine in JWXYP-treated rats,involving the pathways for bile acid biosynthesis and amino acid metabolism.16S rDNA analysis demonstrated increased gut microbiota diversity and increased abundance of Lactobacillus species in JWXYP-treated rats.Conclusion JWXYP alleviates depression-like symptoms in rats by regulating the neurotransmitters,inhibiting inflammation and oxidation,and modulating gut microbiota.

Forsythia suspensa is a traditional Chinese medicine and a commonly used landscaping plant. Its dried fruit is used in medicine for its functions of clearing heat, removing toxins, reducing swelling, dissipating masses, and dispersing wind and heat. It possesses extremely high medicinal and economic value. However, the genetic differentiation and diversity of its wild populations remain unclear. In this study, chloroplast genome sequences were obtained from 15 wild individuals of F. suspensa using high-throughput sequencing technology. The sequence characteristics and intraspecific variations were analyzed. The results were as follows:(1) The full length of the F. suspensa chloroplast genome ranged from 156 184 to 156 479 bp, comprising a large single-copy region, a small single-copy region, and two inverted repeat regions. The chloroplast genome encoded a total of 132 genes, including 87 protein-coding genes, 37 tRNA genes, and 8 rRNA genes.(2) A total of 166-174 SSR loci, 792 SNV loci, and 63 InDel loci were identified in the F. suspensa chloroplast genome, indicating considerable genetic variation among individuals.(3) Population structure analysis revealed that F. suspensa could be divided into five or six groups. Both the population structure analysis and phylogenetic reconstruction results indicated significant genetic variation within the wild populations of F. suspensa, with no obvious correlation between intraspecific genetic differentiation and geographical distribution. This study provides new insights into the genetic diversity and differentiation within F. suspensa species and offers additional references for the conservation of species diversity and the utilization of germplasm resources in wild F. suspensa.
Genome, Chloroplast ; Forsythia/classification* ; Phylogeny ; Genetic Variation ; Chloroplasts/genetics* ; Microsatellite Repeats

Background::The increasing incidence of inflammatory bowel disease (IBD) presents significant medical and societal challenges. A well-designed IBD database is crucial for both epidemiological studies and clinical management. However, inconsistencies between regional databases hinder cross-institutional and international research, especially between Eastern and Western societies.Methods::We developed a new IBD database, the 301 IBD database, integrating the IBD clinical characteristics from the Penn IBD database (USA) and the latest IBD guidelines and consensus and clinical practices of the Chinese PLA General Hospital (PLAGH). We applied this database to analyze clinical data of IBD inpatients at PLAGH from 2008 to 2023.Results::The 301 IBD database contains 490 items in 6 sections including demographic characteristics, personal history, clinical phenotype, disease activity, laboratory tests and examinations, and treatment. Features of the 301 IBD database include inpatient focus, biochemical indicators and opportunistic infection focus, and more about ulcerative colitis (UC)-associated complications. Single-center analysis revealed an increasing hospitalization trend, from 2.35% in 2008 to 3.94% in 2023. We found that the clinical characteristics of our UC inpatients are predominantly male (62.5%), extensive lesions (55.1%), low usage of biologics (4.1%), and a high incidence of UC-CRC (3.0%). The clinical characteristics of CD inpatients included male predominance (68.39%), early onset age (35.43 ± 14.75-year-old), and high rate of surgery (25.81%).Conclusion::The 301 IBD database, integrating Eastern and Western clinical data, provides a valuable tool for IBD clinical research. Future international, multicenter collaborations are expected to further enhance its utility.

Objective:To evaluate the clinical efficacy and safety of sulodexide soft capsules in treating proteinuria after renal transplantation, as well as its impact on graft function.Methods:The clinical data from 80 recipients who developed proteinuria after renal transplantation and were treated with sulodexide soft capsules during regular follow-up at the outpatient department of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from March 1, 2019, to March 1, 2023, were retrospectively analyzed. Proteinuria levels, graft function, safety-related indicators (coagulation function), and adverse events were compared before treatment and at 1, 2, 3, 6, and 12 months after treatment. Based on efficacy, recipients were divided into a satisfactory efficacy group (67 cases) and a general efficacy group (13 cases). Univariate and multivariate logistic regression analyses were conducted to stratify baseline data and explore factors influencing efficacy.Results:Among the 80 recipients, 63 (78.75%) had mild proteinuria and 17 (21.25%) had moderate proteinuria. The overall treatment response rate was 91.25% (73/80). Drug-related adverse events occurred in 12 patients (15.0%). Median urinary protein excretion at 1, 2, 3, 6, and 12 months post-treatment was 0.35 (0.20, 0.55) g/24 h, 0.30 (0.17, 0.44) g/24 h, 0.23 (0.15, 0.39) g/24 h, 0.21 (0.13, 0.32) g/24 h, and 0.15 (0.10, 0.23) g/24 h, respectively, all significantly lower than the pre-treatment level of 0.52 (0.43, 0.90) g/24 h (all P<0.001). The median urinary albumin-to-creatinine ratios at the corresponding time points were 99.15 (45.33, 201.13) μg/mg, 77.20 (43.30, 176.20) μg/mg, 57.50 (31.35, 173.75) μg/mg, 53.55 (25.90, 142.00) μg/mg, and 39.05 (20.53, 103.60) μg/mg, also significantly reduced compared to the pre-treatment value of 152.05 (71.90, 271.23) μg/mg ( P=0.012, P=0.003, P<0.001, P<0.001, P<0.001, respectively). At 12 months post-treatment, the serum creatinine level (132.86±36.86 μmol/L) showed a statistically significant improvement compared to the pre-treatment level (146.60±48.42 μmol/L) ( P=0.045). Univariate analysis indicated that satisfactory efficacy was associated with the time of proteinuria onset post-transplantation, the interval between proteinuria onset and treatment initiation, and recipient age ( HR= 1.001, 95% CI: 1.001-1.020, P=0.043; HR = 1.034, 95% CI: 1.009-1.058, P=0.006; HR=1.058, 95% CI: 1.003-1.116, P=0.040). Stratified univariate analysis revealed that proteinuria onset within 2 years post-transplantation, treatment initiation within 2 years of proteinuria onset, and age younger than 45 years were significantly associated with satisfactory efficacy ( HR=5.524, 95% CI: 1.510-20.207, P=0.010; HR= 7.800, 95% CI: 2.104-28.920, P=0.002; HR=5.972, 95% CI: 1.497-23.822, P=0.011). Multivariate analysis identified the interval between proteinuria onset and treatment initiation as an independent factor influencing satisfactory efficacy ( HR=1.025, 95% CI: 1.010-1.093, P=0.015). Conclusions:Sulodexide effectively reduces proteinuria after renal transplantation, particularly in mild-to-moderate or early-onset cases, while maintaining stable allograft function without significant adverse effects