Research status of pathogenesis of anxiety or depression after percutaneous coronary intervention and Traditional Chinese Medicine intervention.

ETHNIC PHARMACOLOGICAL RELEVANCE: Anxiety or depression after percutaneous coronary intervention (PCI) is a common clinical disease. Currently, conventional pharmacotherapy primarily involves the administration of anxiolytic or antidepressant medications in conjunction with anticoagulants, antiplatelet agents, and other cardiovascular drugs. However, challenges such as drug dependence, adverse reactions and related concerns persist in the treatment of this disease. Numerous pertinent studies have demonstrated that Traditional Chinese Medicine (TCM) exhibits significant therapeutic efficacy and distinctive advantages in managing post-PCI anxiety or depression. AIM OF THIS REVIEW: This review attempted to summarize the characteristics of TCM for treating anxiety or depression after PCI, including single Chinese herbs, Chinese medicine monomers, compound TCM prescriptions, TCM patented drugs, and other TCM-related treatment methods, focusing on the analysis of the relevant mechanism of TCM treatment of this disease. METHODS: By searching the literature on treating anxiety or depression after PCI with TCM in PubMed, Web of Science, CNKI, and other relevant databases, this review focuses on the latest research progress of TCM treatment of this disease. RESULTS: In the treatment of anxiety or depression after PCI, TCM exerts significant pharmacological effects such as anti-inflammatory, antioxidant, anti-anxiety or anti-depression, cardiovascular and cerebrovascular protection, and neuroprotection, mainly by regulating the levels of related inflammatory factors, oxidative stress markers, neurotransmitter levels, and related signaling pathways. TCM has a good clinical effect in treating anxiety or depression after PCI with individualized treatment. CONCLUSIONS: TCM has terrific potential and good prospects in the treatment of anxiety or depression after PCI. The main direction of future exploration is the study of the mechanism related to Chinese medicine monomers and the large sample clinical study related to compound TCM prescriptions.

Down-regulation of MKP-1 in hippocampus protects against stress-induced depression-like behaviors and neuroinflammation.

Chronic stress is the primary environmental risk factor for major depressive disorder (MDD), and there is compelling evidence that neuroinflammation is the major pathomechanism linking chronic stress to MDD. Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) is a negative regulator of MAPK signaling pathways involved in cellular stress responses, survival, and neuroinflammation. We examined the possible contributions of MKP-1 to stress-induced MDD by comparing depression-like behaviors (anhedonia, motor retardation, behavioral despair), neuroinflammatory marker expression, and MAPK signaling pathways among rats exposed to chronic unpredictable mild stress (CUMS), overexpressing MKP-1 in the hippocampus, and CUMS-exposed rats underexpressing MKP-1 in the hippocampus. Rats exposed to CUMS exhibited MKP-1 overexpression, greater numbers of activated microglia, and enhanced expressions of neuroinflammatory markers (interleukin [IL]-6, [IL]-1ß, tumor necrosis factor [TNF]-ɑ, and decreased phosphorylation levels of ERK and p38 in the hippocampus as well as anhedonia in the sucrose preference test, motor retardation in the open field, and greater immobility (despair) in the forced swimming tests. These signs of neuroinflammation and depression-like behaviors and phosphorylation levels of ERK and p38 were also observed in rats overexpressing MKP-1 without CUMS exposure, while CUMS-induced neuroinflammation, microglial activation, phosphorylation levels of ERK and p38, and depression-like behaviors were significantly reversed by MKP-1 knockdown. Moreover, MKP-1 knockdown promoted the activation of the MAPK isoform ERK, implying that the antidepressant-like effects of MKP-1 knockdown may be mediated by the ERK pathway disinhibition. These findings suggested that hippocampal MKP-1 is an essential regulator of stress-induced neuroinflammation and a promising target for antidepressant development.

Pancreatic Paragonimiasis in Children: A Case Report.

ABSTRACT: A few pediatric cases of abdominal paragonimiasis have been described. Here we describe a case of pulmonary and abdominal paragonimiasis with involvement of the pancreas in a 9-year-old boy. The aim of this study was to analyze the clinical and radiological features of pancreatic paragonimiasis in children and raise the awareness of this disease.

A Wearable Fluorescence Imaging Device for Intraoperative Identification of Human Brain Tumors.

Malignant glioma (MG) is the most common type of primary malignant brain tumors. Surgical resection of MG remains the cornerstone of therapy and the extent of resection correlates with patient survival. A limiting factor for resection, however, is the difficulty in differentiating the tumor from normal tissue during surgery. Fluorescence imaging is an emerging technique for real-time intraoperative visualization of MGs and their boundaries. However, most clinical grade neurosurgical operative microscopes with fluorescence imaging ability are hampered by low adoption rates due to high cost, limited portability, limited operation flexibility, and lack of skilled professionals with technical knowledge. To overcome the limitations, we innovatively integrated miniaturized light sources, flippable filters, and a recording camera to the surgical eye loupes to generate a wearable fluorescence eye loupe (FLoupe) device for intraoperative imaging of fluorescent MGs. Two FLoupe prototypes were constructed for imaging of Fluorescein and 5-aminolevulinic acid (5-ALA), respectively. The wearable FLoupe devices were tested on tumor-simulating phantoms and patients with MGs. Comparable results were observed against the standard neurosurgical operative microscope (PENTERO® 900) with fluorescence kits. The affordable and wearable FLoupe devices enable visualization of both color and fluorescence images with the same quality as the large and expensive stationary operative microscopes. The wearable FLoupe device allows for a greater range of movement, less obstruction, and faster/easier operation. Thus, it reduces surgery time and is more easily adapted to the surgical environment than unwieldy neurosurgical operative microscopes. Clinical and Translational Impact Statement-The affordable and wearable fluorescence imaging device developed in this study enables neurosurgeons to observe brain tumors with the same clarity and greater flexibility compared to bulky and costly operative microscopes.

Decoding diffuse light scattering dynamics in layered tissues: path length versus fluctuation time scale.

Dynamic multiple light scattering (DMLS) has found numerous applications, including soft matter physics and biomedical optics. Yet biological tissues may have complex internal geometries, presenting a challenge for noninvasive measurements. Deciphering laminar dynamics is crucial to accurately interpret tissue or organ physiology. Seminal DMLS work noted that one can probe deeper layers indirectly by analyzing light fluctuations on shorter time scales. Recent technologies have enabled probing deeper layers directly by analyzing fluctuations at longer path lengths. The following question arises: are the indirect and direct approaches synergistic or redundant? Here, by adding an optical switch to path-length-filtered interferometric diffusing wave spectroscopy, we experimentally address this question in the context of a forearm occlusion study. We find that both approaches afford better distinction of light scattering dynamics in layered tissues than either approach alone. This motivates further development of methods that integrate both decorrelation time scale and light path length to probe layered tissues.

Role of Brain-Derived Neurotrophic Factor in Anxiety or Depression After Percutaneous Coronary Intervention.

Anxiety or depression after percutaneous coronary intervention (PCI) is one of the key clinical problems in cardiology that need to be solved urgently. Brain-derived neurotrophic factor (BDNF) may be a potential biomarker for the pathogenesis and treatment of anxiety or depression after PCI. This article reviews the correlation between BDNF and cardiovascular system and nervous system from the aspects of synthesis, release and action site of BDNF, and focuses on the latest research progress of the mechanism of BDNF in anxiety or depression after PCI. It includes the specific mechanisms by which BDNF regulates the levels of inflammatory factors, reduces oxidative stress damage, and mediates multiple signaling pathways. In addition, this review summarizes the therapeutic potential of BDNF as a potential biomarker for anxiety or depression after PCI.

MicroRNA-specific therapeutic targets and biomarkers of apoptosis following myocardial ischemia-reperfusion injury.

MicroRNAs are single-stranded non-coding RNAs that participate in post-transcriptional regulation of gene expression, it is involved in the regulation of apoptosis after myocardial ischemia-reperfusion injury. For example, the alteration of mitochondrial structure is facilitated by MicroRNA-1 through the regulation of apoptosis-related proteins, such as Bax and Bcl-2, thereby mitigating cardiomyocyte apoptosis. MicroRNA-21 not only modulates the expression of NF-κB to suppress inflammatory signals but also activates the PI3K/AKT pathway to mitigate ischemia-reperfusion injury. Overexpression of MicroRNA-133 attenuates reactive oxygen species (ROS) production and suppressed the oxidative stress response, thereby mitigating cellular apoptosis. MicroRNA-139 modulates the extrinsic death signal of Fas, while MicroRNA-145 regulates endoplasmic reticulum calcium overload, both of which exert regulatory effects on cardiomyocyte apoptosis. Therefore, the article categorizes the molecular mechanisms based on the three classical pathways and multiple signaling pathways of apoptosis. It summarizes the targets and pathways of MicroRNA therapy for ischemia-reperfusion injury and analyzes future research directions.

[Correlation between preoperative platelet parameters and clinicopathological features of differentiated thyroid cancer].

Objective:To investigate the correlation between preoperative platelet parameters and the clinicopathological features of differentiated thyroid cancer. Methods:We retrospectively analyzed the medical records of patients with thyroid tumors admitted to Zhongda Hospital affiliated to Southeast University and healthy adults with normal physical examination results in our hospital from January 2019 to December 2020, and collected their general information and preoperative blood routine data. Patients with undifferentiated thyroid cancer, diabetes, coronary heart disease, hematological diseases, kidney diseases, autoimmune diseases, genetic diseases, infectious diseases, other systemic tumors, hepatitis or cirrhosis, or those taking anticoagulants were excluded. The exclusion criteria for healthy adults were the absence of the above diseases and normal physical examination results. Differences in platelet parameters among the three groups were compared, and the correlation between clinicopathological characteristics of thyroid cancer, accompanying cervical lymph node metastasis, and platelet parameters of patients was analyzed. A multivariate logistic regression model was used to analyze the risk factors of thyroid cancer with cervical lymph node metastasis. Results:A total of 117 cases of differentiated thyroid cancer were collected, including 33 males and 84 females, with an average age of （41.64±12.25） years; 46 patients had benign thyroid tumors, including 15 males and 31 females, with an average age of （41.35±12.52） years; 50 healthy adults with normal physical examination results in our hospital during the same period were also included, including 18 males and 32 females, with an average age of（42.02±9.62） years, without underlying diseases. The platelet count of the differentiated thyroid cancer group was higher than that of the benign thyroid tumor group（t=-2.219, P=0.028） and the normal control group（t=2.069, P=0.04）, while the platelet distribution width of the differentiated thyroid cancer group was lower than that of the benign thyroid tumor group（t=2.238, P=0.027） and the normal control group（t=-2.618, P=0.002）. These differences were statistically significant. Preoperative age ≤45 years（χ²=4.225, P=0.04）, tumor diameter>1 cm（χ²=4.415, P=0.036）, PLT（t=-4.018, P<0.01） increase, and PDW（t=4.568, P<0.01） decrease were significantly correlated with cervical lymph node metastasis of thyroid cancer and had statistical significance. Univariate analysis showed that age ≤45 years（OR=0.447, 95%CI 0.206-0.970, P=0.042）, tumor diameter>1 cm（OR=2.3, 95%CI 1.050-5.039, P=0.037）, PLT（OR=1.012, 95%CI 1.005-1.019, P=0.001）, and PDW（OR=0.693, 95%CI 0.518-0.827, P<0.01） were risk factors for cervical lymph node metastasis of thyroid cancer. The results of multifactorial logistic regression analysis showed that PLT（OR=1.008, 95%CI 1.001-1.016, P=0.026） and PDW（OR=0.692, 95%CI 0.564-0.848, P<0.01） were independent risk factors for thyroid cancer with cervical lymph node metastasis. Conclusion:PLT and PDW may be useful predictive factors for the differentiation of thyroid cancer malignancy and central lymph node metastasis.

Interferometric diffusing wave spectroscopy imaging with an electronically variable time-of-flight filter.

Diffuse optics (DO) is a light-based technique used to study the human brain, but it suffers from low brain specificity. Interferometric diffuse optics (iDO) promises to improve the quantitative accuracy and depth specificity of DO, and particularly, coherent light fluctuations (CLFs) arising from blood flow. iDO techniques have alternatively achieved either time-of-flight (TOF) discrimination or highly parallel detection, but not both at once. Here, we break this barrier with a single iDO instrument. Specifically, we show that rapid tuning of a temporally coherent laser during the sensor integration time increases the effective linewidth seen by a highly parallel interferometer. Using this concept to create a continuously variable and user-specified TOF filter, we demonstrate a solution to the canonical problem of DO, measuring optical properties. Then, with a deep TOF filter, we reduce scalp sensitivity of CLFs by 2.7 times at 1 cm source-collector separation. With this unique combination of desirable features, i.e., TOF-discrimination, spatial localization, and highly parallel CLF detection, we perform multiparametric imaging of light intensities and CLFs via the human forehead.

Paliperidone Palmitate versus Risperidone Long-Acting Injectable in Patients with Schizophrenia: A Meta-Analysis of Efficacy and Safety.

Purpose: The aim of this study was to assess the efficacy and safety of paliperidone palmitate (PP) treatment compared with risperidone long-acting injectable (LAI) treatments for patients with schizophrenia. Patients and Methods: Data mining was conducted in April 2022 across PubMed, Web of Science, Embase, the Cochrane Library, ClinicalTrials.gov, and PsycINFO. All published randomized controlled trials (RCTs) that assessed the effect of PP treatment for patients with schizophrenia when compared with the risperidone-LAIAs group were included. Relevant data were extracted and synthesized narratively. Results were expressed as standardized mean differences (SMDs) or risk ratios (RRs), with 95% confidence intervals (CIs). Results: Four RCTs with 2451 patients met all the inclusion and exclusion criteria. Efficacy analyses showed no significant statistical differences in Positive and Negative Syndrome Scale (PANSS) total score changes at the endpoint (SMD = 0.10, P = 0.19), or in response rates (RR = 0.93; P = 0.40). Regarding the safety outcomes, PP treatment showed significantly increased risks of discontinuation rates for any reason (35.7% vs 30.4%; RR = 1.19; 95% CI, 1.03 to 1.39; P = 0.02) and nonsignificantly increased risks of total treatment emergent adverse events (TEAEs) (66.6% vs.64.8%; RR = 1.01; 95% CI, 0.94 to 1.09; P = 0.78) compared with the risperidone-LAIAs-treated group. Furthermore, PP may significantly increase total discontinuation rates compared with risperidone-LAIAs. Conclusion: Our meta-analysis did not find a more beneficial effect of PP compared to risperidone-LAIAs treatments for schizophrenia. Clinicians should interpret and translate our data with caution, as the meta-analysis was based on a limited number of randomized controlled trials and patients.

Semi-Supervised Classification of PolSAR Images Based on Co-Training of CNN and SVM with Limited Labeled Samples.

Recently, convolutional neural networks (CNNs) have shown significant advantages in the tasks of image classification; however, these usually require a large number of labeled samples for training. In practice, it is difficult and costly to obtain sufficient labeled samples of polarimetric synthetic aperture radar (PolSAR) images. To address this problem, we propose a novel semi-supervised classification method for PolSAR images in this paper, using the co-training of CNN and a support vector machine (SVM). In our co-training method, an eight-layer CNN with residual network (ResNet) architecture is designed as the primary classifier, and an SVM is used as the auxiliary classifier. In particular, the SVM is used to enhance the performance of our algorithm in the case of limited labeled samples. In our method, more and more pseudo-labeled samples are iteratively yielded for training through a two-stage co-training of CNN and SVM, which gradually improves the performance of the two classifiers. The trained CNN is employed as the final classifier due to its strong classification capability with enough samples. We carried out experiments on two C-band airborne PolSAR images acquired by the AIRSAR systems and an L-band spaceborne PolSAR image acquired by the GaoFen-3 system. The experimental results demonstrate that the proposed method can effectively integrate the complementary advantages of SVM and CNN, providing overall classification accuracy of more than 97%, 96% and 93% with limited labeled samples (10 samples per class) for the above three images, respectively, which is superior to the state-of-the-art semi-supervised methods for PolSAR image classification.

Fungal names: a comprehensive nomenclatural repository and knowledge base for fungal taxonomy.

Fungal taxonomy is a complex and rapidly changing subject, which makes proper naming of fungi challenging for taxonomists. A registration platform with a standardized and information-integrated database is a powerful tool for efficient research on fungal taxonomy. Fungal Names (FN, https://nmdc.cn/fungalnames/; launched in 2011) is one of the three official fungal nomenclatural repositories authorized by the International Nomenclature Committee for Fungi (NCF). Currently, FN includes >567 000 taxon names from >10 000 related journals and books published since 1596 and covers >147 000 collection records of type specimens/illustrations from >5000 preserving agencies. FN is also a knowledge base that integrates nomenclature information with specimens, culture collections and herbaria/fungaria, publications and taxonomists, and represents a summary of the history and recent advances in fungal taxonomy. Published fungal names are categorized based on well-accepted nomenclature rules and can be readily searched with different keywords and strategies. In combination with a standardized name checking tool and a sequence alignment-based identification package, FN makes the registration and typification of nomenclatural novelties of fungi convenient and accurate.

Interferometric diffuse optics: recent advances and future outlook.

The field of diffuse optics has provided a rich set of neurophotonic tools to measure the human brain noninvasively. Interferometric detection is a recent, exciting methodological development in this field. The approach is especially promising for the measurement of diffuse fluctuation signals related to blood flow. Benefitting from inexpensive sensor arrays, the interferometric approach has already dramatically improved throughput, enabling the measurement of brain blood flow faster and deeper. The interferometric approach can also achieve time-of-flight resolution, improving the accuracy of acquired signals. We provide a historical perspective and summary of recent work in the nascent area of interferometric diffuse optics. We predict that the convergence of interferometric technology with existing economies of scale will propel many advances in the years to come.

Efficacy and Safety of Low-Dose Brexpiprazole for Acute Schizophrenia: Meta-Analysis of Randomized Placebo-Controlled Trials.

Purpose: The purpose of this meta-analysis was to compare the efficacy and safety profile of low-dose brexpiprazole (<2 mg/d) compared to placebo and standard-dose brexpiprazole (2-4 mg/d). Patients and Methods: We identified relevant studies pertaining to the specific purpose of our meta-analysis by searching PubMed, Web of Science, Embase, Cochrane library, and PsycINFO using the search terms "schizophrenia" or "schizophrenic" AND "brexpiprazole" or "REXULTI". We systematically reviewed all randomized controlled trials (RCTs) comparing low-dose brexpiprazole with placebo. Primary efficacy outcomes were the PANSS total score change and response rate. Primary safety outcomes were total treatment discontinuation rate, and total serious adverse events (SAEs). Risk ratios (RR) and standardized mean differences (SMDs) were pooled implementing a random effect model. Results: Four RCTs (2178 patients) were included for effect assessment of low-dose brexpiprazole treatment on the patients with acute schizophrenia. Low-dose brexpiprazole was not superior to placebo (SMD = -0.11, 95% CI = -0.23, 0.02, P = 0.10, I2 = 0%), and significantly inferior to standard-dose brexpiprazole (SMD = 0.15, 95% CI = 0.03, 0.26, P = 0.01, I2 = 0%) for PANSS total score change. Low-dose brexpiprazole did not result in significant difference for response rate when compared to placebo and standard-dose brexpiprazole (RR = 1.16, 95% CI = 0.95, 1.41, P = 0.14, I2 = 25%; RR = 0.92, 95% CI = 0.76, 1.12, P = 0.40, I2 = 38%, respectively). For ratio of total discontinuation, low-dose brexpiprazole did not exhibit significant difference when compared to placebo (RR = 0.95, 95% CI = 0.81, 1.11, P = 0.53, I2 = 0%) and standard-dose brexpiprazole group (RR = 1.11, 95% CI = 0.95, 1.29, P = 0.19, I2 = 0%). Total SAEs in low-dose brexpiprazole group did not differ significantly from placebo and standard-dose brexpiprazole group (RR = 0.96, 95% CI = 0.52, 1.80, P = 0.90, I2 = 0%; RR = 1.29, 95% CI = 0.65, 2.57, P = 0.47, I2 = 26%, respectively). Conclusion: The results indicated that low-dose brexpiprazole may be not superior for improving the efficacy and safety for acute schizophrenia compared to placebo and standard-dose brexpiprazole, and may cause additional risk of increasing body weight. Therefore, using low-dose brexpiprazole in acute schizophrenia patients may be not recommended.

Application Effect of Bladder Function Training Combined with Kangaiping Pills on Permanent Bladder Stoma after Radical Prostatectomy.

Objective: To investigate the application effect of bladder function training combined with Kangaiping pills on permanent bladder stoma after radical prostatectomy (RP). Methods: The clinical data of 80 patients with a permanent bladder stoma after RP in our hospital from December 2018 to December 2019 were retrospectively analyzed, and they were equally split into the experimental group (EG) and control group (CG) according to the odd and even hospitalization numbers. EG received bladder function training combined with Kangaiping pills while CG received routine nursing for permanent bladder stomas to compare the urodynamic indexes and quality of life (QOL) scores after intervention between the two groups. Results: Compared with CG, EG after intervention achieved an obviously higher number of patients with bladder function grade I (∗), higher urodynamic indexes (P < 0.001), a higher SF-36 score (P < 0.001), a lower LUTS score (P < 0.001), and a lower total incidence of postoperative adverse reactions (P < 0.05). Conclusion: Bladder function training combined with Kangaiping pills is a reliable method to improve the bladder function of patients with a permanent bladder stoma after RP. This intervention method greatly enhances the QOL of patients and reduces the risk of postoperative adverse reactions, which is recommended for clinical application.

Scanning interferometric near-infrared spectroscopy.

In diffuse optics, quantitative assessment of the human brain is confounded by the skull and scalp. To better understand these superficial tissues, we advance interferometric near-infrared spectroscopy (iNIRS) to form images of the human superficial forehead blood flow index (BFI). We present a null source-collector (S-C) polarization splitting approach that enables galvanometer scanning and eliminates unwanted backscattered light. Images show an order-of-magnitude heterogeneity in superficial dynamics, implying an order-of-magnitude heterogeneity in brain specificity, depending on forehead location. Along the time-of-flight dimension, autocorrelation decay rates support a three-layer model with increasing BFI from the skull to the scalp to the brain. By accurately characterizing superficial tissues, this approach can help improve specificity for the human brain.

Extraction of tissue optical property and blood flow from speckle contrast diffuse correlation tomography (scDCT) measurements.

Measurement of blood flow in tissue provides vital information for the diagnosis and therapeutic monitoring of various vascular diseases. A noncontact, camera-based, near-infrared speckle contrast diffuse correlation tomography (scDCT) technique has been recently developed for 3D imaging of blood flow index (αDB) distributions in deep tissues up to a centimeter. A limitation with the continuous-wave scDCT measurement of blood flow is the assumption of constant and homogenous tissue absorption coefficient (µ a ). The present study took the advantage of rapid, high-density, noncontact scDCT measurements of both light intensities and diffuse speckle contrast at multiple source-detector distances and developed two-step fitting algorithms for extracting both µ a and αDB. The new algorithms were tested in tissue-simulating phantoms with known optical properties and human forearms. Measurement results were compared against established near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) techniques. The accuracies of our new fitting algorithms with scDCT measurements in phantoms (up to 16% errors) and forearms (up to 23% errors) are comparable to relevant study results (up to 25% errors). Knowledge of µ a not only improved the accuracy in calculating αDB but also provided the potential for quantifying tissue blood oxygenation via spectral measurements. A multiple-wavelength scDCT system with new algorithms is currently developing to fit multi-wavelength and multi-distance data for 3D imaging of both blood flow and oxygenation distributions in deep tissues.

Multi-exposure interferometric diffusing wave spectroscopy.

We present multi-exposure interferometric diffusing wave spectroscopy (MiDWS), which measures brain blood flow index (BFI) continuously and non-invasively. MiDWS employs interferometry to detect low light levels, probing the optical field autocorrelation indirectly by varying the sensor exposure time. Here MiDWS is compared with conventional interferometric diffusing wave spectroscopy and speckle contrast optical spectroscopy in phantoms. Notably, the MiDWS approach enables the use of low frame rate, two-dimensional complementary metal-oxide semiconductor cameras in a short exposure time regime, where detector noise greatly exceeds the sample photon count. Finally, we show that MiDWS can monitor the BFI simultaneously at two source-collector separations (1 and 3 cm) on the adult human head on a single camera, enabling the use of superficial signal regression techniques to improve brain specificity.

Detection of an anti-angina therapeutic module in the effective population treated by a multi-target drug Danhong injection: a randomized trial.

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

Using conflict negativity to index psychological tension between impartiality and status-upholding principles.

People often endorse the moral principle that all human lives are equally valuable. At the same time, people often privilege high-status individuals over low-status individuals. These two inclinations come into conflict in a scenario involving the potential killing of a high-status person to save the lives of multiple low-status people. In the present study, participants viewed a series of sacrificial dilemmas in which the social status of the victims and beneficiaries was varied. We measured participants' choice (sacrifice vs. don't sacrifice), response time, and electroencephalographic activity, with an emphasis on conflict negativity (CN). Overall, we found no effects of victim/beneficiaries status on choice and response time. However, participants displayed a more pronounced CN effect when contemplating a high-status victim/low-status beneficiaries tradeoff than a low-status-victim/high-status beneficiaries tradeoff. Further analyses revealed that this effect was primarily driven by participants who endorsed deontological principles (e.g., "Some rules must never be broken, no matter the consequences"). In contrast, those who endorsed utilitarian principles displayed equivalent levels of conflict negativity, regardless of the social status of victims and beneficiaries. These findings shed light on the role of conflict in the phenomenology of moral decision making.