OBJECTIVE: To evaluate the association between erectile dysfunction (ED) and myocardial infarction (MI) using two sample Mendelian randomization. METHODS: A Mendelian randomization study was conducted using comprehensive data on ED and MI from extensive genome-wide association data. Using inverse variance weighted analysis for causal relationships, and correct for confounding factors using multivariate Mendelian randomization, the potential mediating effects were evaluated as well. Based on Genecard data, the genes related to ED and MI were identified. Molecular docking was used to reveal spontaneously bound drug molecules. RESULTS: Our study found that exposure to ED was a risk factor for MI (OR: 1.001 0, 95% CI: 1.000 2－1.001 8, P=0.017 7), which also held true in the validation dataset (OR: 1.028 5, 95% CI: 1.005 0－1.052 6, P=0.017 2). No statistically significant heterogeneity or horizontal pleiotropy was found. The results of reverse Mendelian randomization analysis showed any reverse causal relationship between ED and MI. In multivariate Mendelian randomization analysis, after excluding confounding factors (excluding triglycerides and high-density lipoprotein), the P-value remained less than 0.05, and the OR ranged from 1.000 1 to 1.000 7, indicating that ED was still a risk factor for MI. In the mediation analysis, it was found that the current mediation ratio of smoking to MI was 13.06%. In summary-data-based mendelian randomization analysis, it was found that the gene PTPN11 was a common target gene for MI and ED (OR=0.990, P<0.001). Subsequent molecular docking with sildenafil, clopidogrel, and dapoxetine could spontaneously bind to the PTPN11 gene receptor. CONCLUSION There is a causal relationship between ED and MI, with smoking as a potential mediating factor, and the gene PTPN11 being a co-target gene.
Humans ; Male ; Mendelian Randomization Analysis ; Myocardial Infarction/genetics* ; Erectile Dysfunction/complications* ; Risk Factors ; Genome-Wide Association Study ; Molecular Docking Simulation ; Polymorphism, Single Nucleotide

Acute kidney injury (AKI) is a critical clinical condition characterized by rapid renal function decline, with high morbidity, mortality, and healthcare costs. Traditional Chinese medicine (TCM) has shown potential effects on mitigating oxidative stress and programmed cell death in AKI models. Scutellaria barbata D. Don (SB) and Scleromitrion diffusum (Willd.) R. J. Wang (SD), a classic TCM herbal pair exhibited anti-inflammatory and antioxidant activities. Using advanced chromatographic separation technology, we enriched the effective fractions of water extracts from SB-SD, obtaining self-assembled herbal nanoparticles (SB and SD nanoparticles, SSNPs) rich in flavonoids and terpenoids. These SSNPs demonstrated robust antioxidant properties in vitro and mitigated AKI progression in vivo by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Oral administration of SSNPs in mice resulted in absorption into the bloodstream, formation of a protein corona, reduced macrophage phagocytosis, and enhanced bioavailability and renal targeting. Furthermore, we investigated the self-assembly principle of SSNPs using representative flavonoids and terpenoids. Kinetic studies and in situ transmission electron microscopy (in situ TEM) revealed that these compounds self-assemble via supramolecular forces like hydrogen bonding and π-π interactions, forming stable nanostructures. This study elucidates the renoprotective effects and mechanisms of SB and SD, and provides a novel approach for the development of TCM-based nanomedicines, highlighting the potential of nano-TCM in AKI treatment.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

ObjectiveTo investigate the effects of Aconiti Coreani Radix and Typhonii Rhizoma on the urinary metabolites of gerbils with stroke by non-targeted metabolomics technique， and then to clarify the mechanism of the two， as well as their similarities and differences. MethodTwenty-four gerbils were randomly divided into control group（CG）， model group（MG）， Aconiti Coreani Radix group（RA） and Typhonii Rhizoma group（RT）. Except for the CG， ischemic stroke model was constructed using right unilateral ligation of gerbil carotid artery in the remaining groups. Except for the CG and MG， rats in the other groups received whole powder suspension（0.586 mg·g^-1） was administered for 14 days. The neurological deficit in each group was scored by Longa scoring on days 0， 3， 7 and 14. After the end of administration， the serum， brain tissue and urine of gerbils in each group were collected， and the rate of cerebral infarction was detected by 2，3，5-triphenyltetrazolium chloride（TTC）， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， malondialdehyde（MDA）， superoxide dismutase（SOD）， glutathione（GSH）， and nitric oxide（NO） in serum and brain tissue were determined by enzyme-linked immunosorbent assay（ELISA）. The urine metabolomics of gerbils in each group was studied by ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Orbitrap-MS）， and the data were processed by multivariate statistical analysis， and differential metabolites were screened based on value of variable importance in the projection（VIP） of the first principal component>1 and t-test P<0.05. Metabolic pathway analysis of the screened differential metabolites was performed using Kyoto Encyclopedia of Genes and Genomes（KEGG） database and Metaboanalyst 5.0. ResultCompared with the CG， the neurological deficit score was significantly increased in the MG（P<0.05）， compared with the MG， the neurological deficit scores in the RA and RT were significantly reduced after 7 d and 14 d（P<0.05）. Compared with the CG， the rate of cerebral infarction was significantly increased in the MG（P<0.05）， compared with the MG， the rates of cerebral infarction in the RA and RT were significantly reduced（P<0.05）. Compared with the CG， the levels of IL-6， TNF-α， and MDA in the serum and brain tissue of gerbils from the MG were significantly increased（P<0.05）， and the levels of SOD， GSH and NO were significantly reduced（P<0.05）. Compared with the MG， Aconiti Coreani Radix and Typhonii Rhizoma could down-regulate the levels of IL-6， TNF-α and MDA， and up-regulated the levels of SOD， GSH and NO. A total of 112 endogenous differential metabolites were screened by urine metabolomics， of which 16 and 26 metabolites were called back by Aconiti Coreani Radix and Typhonii Rhizoma， and could be used as potential biomarkers for both treatments in stroke gerbils， respectively. The results of the pathway analysis showed that both Aconiti Coreani Radix and Typhonii Rhizoma had regulatory effects on arginine and proline metabolism， pyrimidine metabolism， and aminoacyl-tRNA biosynthesis. In addition， Aconiti Coreani Radix could also regulate riboflavin metabolism， Typhonii Rhizoma could also regulate purine metabolism， glycine， serine and threonine metabolism， arachidonic acid metabolism， biosynthesis of pantothenate and coenzyme A， and β-alanine metabolism. ConclusionBoth Aconiti Coreani Radix and Typhonii Rhizoma have better therapeutic effects on stroke， with Aconiti Coreani Radix having stronger effects. From the metabolomics results， the main metabolic pathways regulated by Aconiti Coreani Radix involve amino acid metabolism， oxidative stress and so on， while Typhonii Rhizoma mainly involve amino acid metabolism， lipid metabolism， energy metabolism， etc.

Critically ill patients are at high risk for hospital acquired infections, which can significantly increase the mortality rate and treatment costs for these patients. Therefore, in the process of treating the primary disease, strict prevention and control of new hospital infections is an essential component of the treatment for critically ill patients. The treatment of critically ill patients involves multiple steps and requires a concerted effort from various aspects such as theory, management, education, standards, and supervision to achieve effective prevention and control of hospital infections. However, there is currently a lack of unified understanding and standards for hospital infection prevention and control. To address this, in March 2024, a group of experts in critical care medicine, infectious diseases, and hospital infection from China discussed the current situation and issues of hospital infection control in the intensive care unit together. Based on a review of the latest evidence-based medical evidence from both domestic and international sources, 2024 Expert Consensus on Hospital Acquired Infection Control Principles in the Department of Critical Care Medicine was formed, aiming to provide a basis for the development of hospital infection prevention and control strategies in the field of critical care medicine.

OBJECTIVE: Despite the combination of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang (SB-SD) being a recognized Chinese medicinal herbal pair that is commonly used in the treatment of ovarian cancer, there is a poor understanding of their pharmacological mechanisms. This study examines the antitumor properties and potential mechanisms of SB-SD on human ovarian cancer A2780 cells through a multi-omics approach, establishing a pharmacological basis for clinical utilization. METHODS: A range of mass ratios and reagents were used in the hot reflux extraction of SB-SD. The inhibitory effect of the SB-SD extracts on A2780 cell proliferation was assessed using the cell-counting kit 8 assay. A zebrafish tumor implantation model was used to evaluate the effects of SB-SD extracts on tumor growth and metastasis in vivo. Transcriptomics and proteomics were used to investigate alterations in biological pathways in A2780 cells after treatment with different concentrations of SB-SD extract. Cell cycle, cell apoptosis, intracellular free iron concentration, intracellular reactive oxygen species (ROS) concentration, malondialdehyde (MDA), and mitochondrial membrane potential were measured. Real-time quantitative reverse transcription polymerase chain reaction and Western blotting were utilized to investigate the effects of heme catabolism and ferritinophagy on ferroptosis induced by SB-SD extract in A2780 cells. RESULTS: The 70% ethanol extract of SB-SD (a mass ratio of 4:1) inhibited A2780 cell proliferation significantly with a half maximal inhibitory concentration of 660 μg/mL in a concentration- and time-dependent manner. Moreover, it effectively suppressed tumor growth and metastasis in a zebrafish tumor implantation model. SB-SD extract induced the accumulation of free iron, ROS, MDA, and mitochondrial damage in A2780 cells. The mechanisms might involve the upregulated expression of ferritinophagy-related genes microtubule-associated protein 1 light chain 3, autophagy-related gene 5, and nuclear receptor coactivator 4. CONCLUSION SB-SD extract effectively inhibited the development of ovarian cancer both in vitro and in vivo. Its mechanism of action involved inducing ferroptosis by facilitating heme catabolism and ferritinophagy. This herbal pair holds promise as a potential therapeutic option for ovarian cancer treatment and may be utilized in combination with routine treatment to improve the treatment outcomes of ovarian cancer patients. Please cite this article as: Wang Z, Liu M, Li GX, Zhang L, Ding KY, Li SQ, Gao BQ, Chen P, Choe HC, Xia LY, Yang YT, Liu Y, Sui X, Ma JN, Zhang L. A herbal pair of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang induced ferroptosis in ovarian cancer A2780 cells via inducing heme catabolism and ferritinophagy. J Integr Med. 2024; 22(6): 666-683.
Ferroptosis/drug effects* ; Female ; Humans ; Animals ; Scutellaria/chemistry* ; Ovarian Neoplasms/genetics* ; Zebrafish ; Cell Line, Tumor ; Ferritins/genetics* ; Plant Extracts/pharmacology* ; Heme/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Cell Proliferation/drug effects* ; Reactive Oxygen Species/metabolism* ; Antineoplastic Agents, Phytogenic/pharmacology* ; Autophagy/drug effects* ; Apoptosis/drug effects*

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN).AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

AIM:To evaluate the efficacy of intravitreal dexamethasone implant(DEX-I)in the treatment of different types of macular edema secondary to retinal vein occlusion(RVO).METHODS:A retrospective observational case study was conducted. A total of 46 patients(46 eyes)who were diagnosed with RVO-macular edema(ME)and received DEX-I of 0.7 mg as the initial treatment in Dalian No.3 People's Hospital from July 2019 to June 2020 were collected. According to the morphological characteristics of optical coherence tomography(OCT), they were divided into diffuse retinal thickening type(DRT type, 13 patients, 13 eyes), cystoid macular edema type(CME type, 22 patients, 22 eyes )and serous retinal detachment type(SRD type, 11 patients, 11 eyes ). The best corrected visual acuity(BCVA)and central retinal thickness(CRT)of patients with three types of macular edema were observed and compared before treatment and 1, 2 and 3mo after treatment.RESULTS:Compared with before treatment, BCVA of patients with DRT, CME and SRD were significantly improved at 1, 2 and 3mo after treatment, and CRT was significantly decreased(all P<0.017). At 3mo after treatment, BCVA(0.21±0.12, 0.22±0.10LogMAR)of DRT and SRD patients was significantly better than that of CME(0.45±0.14LogMAR, both P<0.017), and CRT(254.08±49.07, 248.92±44.19μm)was significantly lower than that of CME(314.70±92.66 μm, both P<0.017).CONCLUSIONS: DEX-I is effective in the treatment of various OCT types of macular edema secondary to RVO, and the treatment response of CME type is worse than that of DRT and SRD types.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

BACKGROUND: Limited data are available on the comparison of clinical outcomes of complete vs. incomplete percutaneous coronary intervention (PCI) for patients with chronic total occlusion (CTO) and multi-vessel disease (MVD). The study aimed to compare their clinical outcomes. METHODS: A total of 558 patients with CTO and MVD were divided into the optimal medical treatment (OMT) group ( n = 86), incomplete PCI group ( n = 327), and complete PCI group ( n = 145). Propensity score matching (PSM) was performed between the complete and incomplete PCI groups as sensitivity analysis. The primary outcome was defined as the occurrence of major adverse cardiovascular events (MACEs), and unstable angina was defined as the secondary outcome. RESULTS: At a median follow-up of 21 months, there were statistical differences among the OMT, incomplete PCI, and complete PCI groups in the rates of MACEs (43.0% [37/86] vs. 30.6% [100/327] vs. 20.0% [29/145], respectively, P = 0.016) and unstable angina (24.4% [21/86] vs. 19.3% [63/327] vs. 10.3% [15/145], respectively, P = 0.010). Complete PCI was associated with lower MACE compared with OMT (adjusted hazard ratio [HR] = 2.00; 95% confidence interval [CI] = 1.23-3.27; P = 0.005) or incomplete PCI (adjusted HR = 1.58; 95% CI = 1.04-2.39; P = 0.031). Sensitivity analysis of PSM showed similar results to the above on the rates of MACEs between complete PCI and incomplete PCI groups (20.5% [25/122] vs. 32.6% [62/190], respectively; adjusted HR = 0.55; 95% CI = 0.32-0.96; P = 0.035) and unstable angina (10.7% [13/122] vs. 20.5% [39/190], respectively; adjusted HR = 0.48; 95% CI = 0.24-0.99; P = 0.046). CONCLUSIONS For treatment of CTO and MVD, complete PCI reduced the long-term risk of MACEs and unstable angina, as compared with incomplete PCI and OMT. Complete PCI in both CTO and non-CTO lesions can potentially improve the prognosis of patients with CTO and MVD.
Humans ; Treatment Outcome ; Percutaneous Coronary Intervention/methods* ; Coronary Occlusion/surgery* ; Prognosis ; Angina, Unstable/surgery* ; Chronic Disease ; Risk Factors