Harnessing TME depicted by histological images to improve cancer prognosis through a deep learning system.

Spatial transcriptomics (ST) provides insights into the tumor microenvironment (TME), which is closely associated with cancer prognosis, but ST has limited clinical availability. In this study, we provide a powerful deep learning system to augment TME information based on histological images for patients without ST data, thereby empowering precise cancer prognosis. The system provides two connections to bridge existing gaps. The first is the integrated graph and image deep learning (IGI-DL) model, which predicts ST expression based on histological images with a 0.171 increase in mean correlation across three cancer types compared with five existing methods. The second connection is the cancer prognosis prediction model, based on TME depicted by spatial gene expression. Our survival model, using graphs with predicted ST features, achieves superior accuracy with a concordance index of 0.747 and 0.725 for The Cancer Genome Atlas breast cancer and colorectal cancer cohorts, outperforming other survival models. For the external Molecular and Cellular Oncology colorectal cancer cohort, our survival model maintains a stable advantage.

Prediction of Human Pharmacokinetics of E0703, a Novel Radioprotective Agent, Using Physiologically Based Pharmacokinetic Modeling and an Interspecies Extrapolation Approach.

E0703, a new steroidal compound optimized from estradiol, significantly increased cell proliferation and the survival rate of KM mice and beagles after ionizing radiation. In this study, we characterize its preclinical pharmacokinetics (PK) and predict its human PK using a physiologically based pharmacokinetic (PBPK) model. The preclinical PK of E0703 was studied in mice and Rhesus monkeys. Asian human clearance (CL) values for E0703 were predicted from various allometric methods. The human PK profiles of E0703 (30 mg) were predicted by the PBPK model in Gastro Plus software 9.8 (SimulationsPlus, Lancaster, CA, USA). Furthermore, tissue distribution and the human PK profiles of different administration dosages and forms were predicted. The 0.002 L/h of CL and 0.005 L of Vss in mice were calculated and optimized from observed PK data. The plasma exposure of E0703 was availably predicted by the CL using the simple allometry (SA) method. The plasma concentration-time profiles of other dosages (20 and 40 mg) and two oral administrations (30 mg) were well-fitted to the observed values. In addition, the PK profile of target organs for E0703 exhibited a higher peak concentration (Cmax) and AUC than plasma. The developed E0703-PBPK model, which is precisely applicable to multiple species, benefits from further clinical development to predict PK in humans.

Positive benefit-risk ratio of Psoraleae Fructus: Comprehensive safety assessment and osteogenic effects in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoraleae Fructus (PF), the dried fruit of Psoralea corylifolia L., is a commonly used traditional medicine that has contributed to the treatment of orthopedic diseases for thousands of years in China. However, recent PF-related liver injury reports have drawn widespread attention regarding its potential hepatotoxicity risks. AIM OF THE STUDY: This study was aimed to evaluate the long-term efficacy and chronic toxicity of PF using a 26-week administration experiment on rats in order to simulate the clinical usage situation. MATERIALS AND METHODS: The PF aqueous extract was consecutively administrated to rats daily at dosages of 0.7, 2.0, and 5.6 g/kg (equivalent to 1-8 times the clinical doses for humans) for as long as 26 weeks. Samples were collected after 13, 26, and 32 weeks (withdrawal for 6 weeks) since the first administration. The chronic toxicity of PF was evaluated by conventional toxicological methods, and the efficacy of PF was evaluated by osteogenic effects in the natural growth process. RESULTS: In our experiments, only the H group (5.6 g/kg) for 26-week PF treatment demonstrated liver or kidney injury, which the injuries were reversible after 6 weeks of withdrawal. Notably, the PF treatment beyond 13 weeks showed significant benefits for bone growth and development in rats, with a higher benefit-risk ratio in female rats. CONCLUSIONS: PF displayed a promising benefit-risk ratio in the treatment and prevention of osteoporosis, a disease that lacks effective medicine so far. This is the first study to elucidate the benefit-risk balance associated with clinical dosage and long-term use of PF, thereby providing valuable insights for rational clinical use and risk control of PF.

Acute sarcoidosis Löfgren Syndrome treated by Chinese medicinal formula based on Syndrome Differentiation: a case - based review / Tratamiento de síndrome de Löfgren de sarcoidosis con fórmula medicinal china basada en diferenciación de síndrome: una revisión basada en casos

Löfgren syndrome (LS) is a unique acute manifestation of sarcoidosis and characterized by erythema nodosum, bilateral hilar lymphadenectasis, and/or bilateral ankle arthritis or periarthritis. A 37 - year - old female patient with LS presented with fever accompanied by multiple joint swelling and pain, nodular skin erythema, and bilateral hilar lymphadenectasis. The patient had received treatment involving non - steroidal anti - inflammatory drugs and glucocorticoids in other hospitals, but the effects were poor, and the conditions reemerged. The LS duration has lasted for more than 3 months. Following traditional Chinese medicine (TCM) treatment, syndrome differentiation as well as giving patients oral Chinese medicine decoction, the symptoms of the patient were rapidly relieved within one week and did not recur during a six - month follow - up period. This case is the first clinical report of acute sarcoidosis LS treated using T CM and reflects the significant advantages of this form of therapy in emergency treatment

El síndrome de Löfgren (LS) es una manifest ación única y aguda de sarcoidosis, caracterizada por eritrema nodoso, linfadenectasis hilar bilateral, y/o a r tritis de tobillo bilateral o periartritis. Una paciente de 37 años de sexo femenino con LS se presentó con fiebre, acompañada de inflamación y do lor múltiple de articulaciones, eritrema nodular cutáneo, y linfadenectasis hilar bilateral. La paciente recibió un tratamiento que consistió en antiinflamatorios no esteroidales y glucocorticoides en otros hospitales, pero los efectos fueron leves y las c ondiciones reemergieron. El LS ha durado más de tres meses. Siguiendo el tratamiento de medicina tradicional china (MTC), la diferenciación de síndrome, así como darles a los pacientes una decocción de medicina china por vía oral, los síntomas de la pacien te rápidamente fueron aliviados en el curso de una semana y no recidivaron durante los seis meses de un seguimiento. El caso es el primer reporte clínico de tratamiento de sarcoidosis aguda asociada a LS usando TCM y refleja las significativas ventajas de esta forma de terapia en el tratamiento de emergencia.

Lower and upper bounds for numbers of linear regions of graph convolutional networks.

Graph neural networks (GNNs) have become a popular choice for analyzing graph data in the last few years, and characterizing their expressiveness has become an active area of research. One popular measure of expressiveness is the number of linear regions in neural networks with piecewise linear activations. In this paper, we present estimates for the number of linear regions in classic graph convolutional networks (GCNs) with one layer and multiple-layer scenarios and ReLU activation function. We derive an optimal upper bound for the maximum number of linear regions for one-layer GCNs and upper and lower bounds for multi-layer GCNs. Our simulated results suggest that the true maximum number of linear regions is likely closer to our estimated lower bound. These findings indicate that multi-layer GCNs have exponentially greater expressivity than one-layer GCNs per parameter, implying that deeper GCNs are more expressive than their shallow counterparts.

The effectiveness of the puncture channel plugging for reduction of complications after CT-guided percutaneous transthoracic needle biopsy.

The effect of plugging the puncture channel with a mixture of hemocoagulase injection on the complications of CT-guided percutaneous transthoracic need biopsy (PTNB) was discussed. The medical records of PTNB were retrospectively studied from June 2017 to May 2022. In the study, the puncture channel of 626 patients were blocked, while remain 681 patients' were not. The Mantel Haenszel method performed layered analysis and evaluated the correlation of adjusted confounding factors. The Odds Ratio and its 95% confidence interval were calculated using the Woof method. The incidence of high-level pulmonary hemorrhage was significantly reduced in patients with lesions ≤ 2 cm and different needle lengths. Patients with different pleural-needle tip angle and perineedle emphysema were blocked, and the incidence of pneumothorax and thoracic implants was significantly reduced. Through puncture channel plugging, the incidence of pulmonary hemorrhage, pneumothorax and thoracic catheterization of PTNB under CT guidance was reduced.

SESNet: sequence-structure feature-integrated deep learning method for data-efficient protein engineering.

Deep learning has been widely used for protein engineering. However, it is limited by the lack of sufficient experimental data to train an accurate model for predicting the functional fitness of high-order mutants. Here, we develop SESNet, a supervised deep-learning model to predict the fitness for protein mutants by leveraging both sequence and structure information, and exploiting attention mechanism. Our model integrates local evolutionary context from homologous sequences, the global evolutionary context encoding rich semantic from the universal protein sequence space and the structure information accounting for the microenvironment around each residue in a protein. We show that SESNet outperforms state-of-the-art models for predicting the sequence-function relationship on 26 deep mutational scanning datasets. More importantly, we propose a data augmentation strategy by leveraging the data from unsupervised models to pre-train our model. After that, our model can achieve strikingly high accuracy in prediction of the fitness of protein mutants, especially for the higher order variants (> 4 mutation sites), when finetuned by using only a small number of experimental mutation data (< 50). The strategy proposed is of great practical value as the required experimental effort, i.e., producing a few tens of experimental mutation data on a given protein, is generally affordable by an ordinary biochemical group and can be applied on almost any protein.

Cell graph neural networks enable the precise prediction of patient survival in gastric cancer.

Gastric cancer is one of the deadliest cancers worldwide. An accurate prognosis is essential for effective clinical assessment and treatment. Spatial patterns in the tumor microenvironment (TME) are conceptually indicative of the staging and progression of gastric cancer patients. Using spatial patterns of the TME by integrating and transforming the multiplexed immunohistochemistry (mIHC) images as Cell-Graphs, we propose a graph neural network-based approach, termed Cell-Graph Signature or CGSignature, powered by artificial intelligence, for the digital staging of TME and precise prediction of patient survival in gastric cancer. In this study, patient survival prediction is formulated as either a binary (short-term and long-term) or ternary (short-term, medium-term, and long-term) classification task. Extensive benchmarking experiments demonstrate that the CGSignature achieves outstanding model performance, with Area Under the Receiver Operating Characteristic curve of 0.960 ± 0.01, and 0.771 ± 0.024 to 0.904 ± 0.012 for the binary- and ternary-classification, respectively. Moreover, Kaplan-Meier survival analysis indicates that the "digital grade" cancer staging produced by CGSignature provides a remarkable capability in discriminating both binary and ternary classes with statistical significance (P value < 0.0001), significantly outperforming the AJCC 8th edition Tumor Node Metastasis staging system. Using Cell-Graphs extracted from mIHC images, CGSignature improves the assessment of the link between the TME spatial patterns and patient prognosis. Our study suggests the feasibility and benefits of such an artificial intelligence-powered digital staging system in diagnostic pathology and precision oncology.

[Protective effect of ophiopogonin D against isoproterenol-induced cardiomyocyte injury and targets].

This study aims to unveil the effect of ophiopogonin D(OPD) on isoproterenol(ISO)-induced apoptosis of rat cardiomyocytes and the possible targets, which is expected to provide clues for further research on the myocardial protection of ophiopogonins. Cell count kit-8(CCK-8) assay was used to detect viability of cells treated with OPD and ISO, Western blot to examine the effect of OPD and ISO on the expression of endoplasmic reticulum stress-related Bip, Bax, Perk, ATF4, caspase-12, and CHOP, flow cytometry to determine cell apoptosis rate, and Hoechst 33258 and Tunel staining to observe cell apoptosis and morphological changes. In addition, the probe for calcium ion-specific detection was employed to investigate calcium ion release from the endoplasmic reticulum, and OPD-bond epoxy-activated agarose solid-phase microspheres were prepared and used as affinity matrix to capture OPD-binding target proteins in H9 c2 cell lysate. For the target proteins of OPD identified by high-resolution mass spectrometry, the related signal pathways were enriched and the potential targets of OPD against cardiomyocyte injury were discussed. The experimental result showed that 10 µmol·L~(-1) ISO can significantly induce the expression of endoplasmic reticulum stress-related proteins and promote cell apoptosis. Different concentration of OPD can prevent the damage of myocardial cells caused by ISO. According to mass spectrometry results, 19 proteins, including Fam129 a and Pdia6, were involved in multiple signaling pathways such as the unfolded protein reaction bound by the ERN1 sensor, tricarboxylic acid cycle, and Nrf2 signal transduction pathway. The above results indicate that OPD protects cardiomyocytes by regulating multiple signaling pathways of target proteins and affecting cell cycle progression.

Responsive Hydrogels Based on Triggered Click Reactions for Liver Cancer.

Globally, liver cancer, which is one of the major cancers worldwide, has attracted the growing attention of technological researchers for its high mortality and limited treatment options. Hydrogels are soft 3D network materials containing a large number of hydrophilic monomers. By adding moieties such as nitrobenzyl groups to the network structure of a cross-linked nanocomposite hydrogel, the click reaction improves drug-release efficiency in vivo, which improves the survival rate and prolongs the survival time of liver cancer patients. The application of a nanocomposite hydrogel drug delivery system can not only enrich the drug concentration at the tumor site for a long time but also effectively prevents the distant metastasis of residual tumor cells. At present, a large number of researches have been working toward the construction of responsive nanocomposite hydrogel drug delivery systems, but there are few comprehensive articles to systematically summarize these discoveries. Here, this systematic review summarizes the synthesis methods and related applications of nanocomposite responsive hydrogels with actions to external or internal physiological stimuli. With different physical or chemical stimuli, the structural unit rearrangement and the controlled release of drugs can be used for responsive drug delivery in different states.

Embedding graphs on Grassmann manifold.

Learning efficient graph representation is the key to favorably addressing downstream tasks on graphs, such as node or graph property prediction. Given the non-Euclidean structural property of graphs, preserving the original graph data's similarity relationship in the embedded space needs specific tools and a similarity metric. This paper develops a new graph representation learning scheme, namely Egg, which embeds approximated second-order graph characteristics into a Grassmann manifold. The proposed strategy leverages graph convolutions to learn hidden representations of the corresponding subspace of the graph, which is then mapped to a Grassmann point of a low dimensional manifold through truncated singular value decomposition (SVD). The established graph embedding approximates denoised correlationship of node attributes, as implemented in the form of a symmetric matrix space for Euclidean calculation. The effectiveness of Egg is demonstrated using both clustering and classification tasks at the node level and graph level. It outperforms baseline models on various benchmarks.

Comparison of CT findings and histopathological characteristics of pulmonary cryptococcosis in immunocompetent and immunocompromised patients.

Pulmonary cryptococcosis (PC) is a common fungal infectious disease, and infection can occur in patients with any immune function. To better understand PC, we compared the CT findings and histopathological results in immunocompetent and immunocompromised patients. The clinical data of 68 patients with PC were collected retrospectively and divided into the immunocompetent group and immunocompromised group. The clinical characteristics, CT manifestations and histopathological characteristics of the two groups of patients were compared. Forty-two patients (61.8%) were immunocompetent, and 26 patients (38.2%) were immunocompromised. Compared with immunocompromised patients, 57.14% (24/42) of immunocompetent patients were asymptomatic (p = 0.002). Compared with immunocompetent patients, cough (14/26, 53.9%) and fever (13/26, 50.0%) were the main symptoms in immunocompromised patients (p = 0.044, p = 0.007). Nodular lesions (97.6%, 41/42) were the most common CT type in immunocompetent patients, and the CT characteristic was a single lesion (25/42, 59.5%); the main histopathological type was nodular fibrogranuloma (30/42, 71.4%), and the main histopathological characteristic was inflammatory granuloma (31/42, 73.81%) formed by macrophage phagocytosis of Cryptococcus. Consolidation (15/26, 57.7%) was more common in the CT type of immunocompromised patients. Multiple lesions (24/26, 92.31%), air bronchial signs (19/26, 73.081%) and cavities (9/26, 34.62%) were the main CT characteristics. The mucinous colloid type (19/26, 73.1%) was its main histopathological type, which was mainly characterized by a small amount of surrounding inflammatory cell infiltration (17/26, 65.4%). There were significant differences in the classification and characteristics of CT and pathology between the two groups (p < 0.05). Through the CT manifestations and histopathological characteristics of PC under different immune function states, it was found that immune function has a significant impact on the CT manifestations and histopathological characteristics of patients with PC.

Efficacy of Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) on myocardial infarction by enhancing autophagy in rat.

OBJECTIVE: To elucidate the protective effects of Renshen (Radix Ginseng) and Fuzi (Radix Aconiti Lateralis Preparata) on myocardial infarction (MI) through regulating myocardial autophagy. METHODS: Thirty-one male Sprague-Dawley rats were randomized into five groups (n = 6 or 7 for each). After treatment for 3 weeks, electrocardiogram ( ECG ) and cardiac function were recorded. Hematoxylin and eosin (HE) staining was used to detect pathological changes in the heart. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum B-type brain natriuretic peptide (BNP), cardiac troponin T (cTnT), tumor necrosis factor-α (TNF-α), and serum inflammatory cytokines. Metabolomic analysis was used to identify differential biomarkers of MI in rats. Immunohistochemistry and western blotting were used to detect BNP, cTnT, TNF-α, LC3B, Beclin-1, p62, and adenosine monophosphate activated protein kinase (AMPK) expression in cardiac tissue. RESULTS: Fuzi (Radix Aconiti Lateralis Preparata) alone or Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) markedly ameliorated cardiac dysfunction and abnormal ECGs, demonstrated by decreases in the heart weight/body weight ratio, BNP, and cTnT. Pro-inflammation cytokine interleukin (IL)-1α significantly decreased and anti-inflammatory cytokine IL-10 significantly increased in Renshen (Radix Ginseng) single or Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) groups compared with the control group. HE results suggested that co-treatment produced a greater reduction in cardiomyocyte cross-sectional area than Renshen (Radix Ginseng) or Fuzi (Radix Aconiti Lateralis Preparata) alone. Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) reversed these changes to different degrees in MI rats. Furthermore, Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) down-regulated LC3B, Beclin-1, and AMPK expression in cardiac tissue and upregulated p62 expression. CONCLUSIONS: Renshen (Radix Ginseng) plus Fuzi (Radix Aconiti Lateralis Preparata) may have a greater effect on heart injury induced by MI in rats than Fuzi (Radix Aconiti Lateralis Preparata) treatment alone, and the underlying mechanism may be associated with the regulation of myocardial autophagy and anti-inflammation effects. These results provide fresh insight into the mechanism of co-treatment with Renshen (Radix Ginseng) and Fuzi (Radix Aconiti Lateralis Preparata) for MI.

[Research progress in pharmacology and toxicology of evodiamine].

Evodiamine, a bioactive indole alkaloid from Evodia rutaecarpa, E. rutaecarpa var. officinalis, or E. rutaecarpa var. bodinieri, has been extensively investigated due to its pharmacological activities in recent years. At present, evodiamine is proved to significantly suppress the proliferation of a variety of cancer cells and mediate cell processes such as cell cycle arrest and cell migration. In addition, evodiamine displays significant pharmacological activities against cardiovascular diseases(hyperlipidemia, etc.), and tinea manus and pedis. Recently, evodiamine has been found to have potential toxic effects, such as hepatotoxicity, nephrotoxicity, and cardiotoxicity. However, the pharmacological and toxicological mechanism of evodiamine is not clear, and its toxicity in vitro and in vivo has been rarely reported. Therefore, this study reviewed the pharmacological and toxicological articles of evodiamine in recent years, aiming at providing new ideas and references for future research.

Clinical Evaluation of 532-nm Green Laser on Dentin Hypersensitivity: A Randomized Double-Blind Clinical Trial.

Objective: The aim of this study was to evaluate the therapies of low-level green laser and chemical desensitizer in the treatment of dentin hypersensitivity (DH). Methods: Forty-eight patients with 96 sensitive teeth were invited to participate in this clinical trial and were randomly divided into three groups. One group was treated with low-level green laser, the second group was treated with desensitizer [sodium fluoride (NaF)], and the third group acted as the placebo group and was treated with distilled water and placebo laser. The wavelength of green laser was 532 nm and the irradiance was 15 J/cm2 per treatment site. Hypersensitivity was assessed by visual analogue scale (VAS) according to cold test and probing at baseline. Immediately, 2 weeks, and 3 months after the application of green laser, NaF, and placebo, the participants' sensitivity level was accessed by new VAS analysis. Results: Forty-five patients with 90 teeth (n = 15 patients/group; 30 teeth/group) were followed up for 2 weeks and 3 months after treatment. There were significant differences in VAS scores between the placebo group and intervention group (green laser group and NaF group; analysis of variance, p < 0.05) at all three time points. The mean pain scores in DH reduced significantly immediately after treatment in the green laser group and NaF group when stimulated by cold and probing, whereas no significant difference was observed with these two therapies after 2 weeks (p > 0.05). After 3 months, mean VAS scores of the NaF group were higher than those of the green laser group (p < 0.01). Conclusions: Therefore, the green laser displayed similar effectiveness as NaF in treatment of DH and could be a promising new therapy to reduce DH.

A rare occurrence of a hereditary Birt-Hogg-Dubé syndrome: A case report.

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal dominant disease caused by germline mutations in the folliculin (FLCN) protein gene, which usually manifests as cutaneous fibrofolliculoma, pulmonary cysts, renal cell carcinoma, and spontaneous pneumothorax. CASE SUMMARY: A 26-year-old woman with no history of smoking was admitted to the Respiratory Department of our hospital due to intermittent wheezing that lasted for 8 mo. She had experienced recurrent spontaneous pneumothorax more than four times during the past 8 mo. After admission, the patient again suffered from left pneumothorax without a clear reason. Lung computed tomography (CT) showed multiple low-density cystic changes in both lungs. Physical examination on admission revealed multiple white dome-shaped papules in the neck, the nape, and behind the ear. In addition, the patient had a family history of spontaneous pneumothorax. Her mother had suffered from pneumothorax four times (at age 36, 37, 42, and 50 years). Her second maternal aunt had suffered from a right pneumothorax at the age of 40. The multidisciplinary diagnosis of BHD, which included the Respiratory Department, Radiology Department, Pathology Department, and Dermatological Department, was BHD and was later confirmed by family genetic testing. The same variation (FLCN gene) was found in the patient's mother and aunt. CONCLUSION: This case highlights the importance of multidisciplinary diagnosis and a treatment platform for the diagnosis of BHD.

[Effects of ophiopogonin D on fatty acid metabolic enzymes in cardiomyocytes].

To explore the effect of ophiopogonin D on main fatty acid metabolic enzymes in human cardiomyocyte AC-16,so as to provide reference for cardiovascular protection mechanism and safe clinical application of Ophiopogon japonicus.CCK-8 (cell counting kit-8) was used to detect the effect of different concentrations of ophiopogonin D on the viability of cardiomyocytes.Meanwhile,the effect of different concentrations of ophiopogonin D on the morphology and quantity of cardiomyocytes was observed under microscope.The effect of ophiopogonin D on the mRNA expression of CYP2J2,CYP4F3,CYP4A11,CYP4A22 and CYP4F2 in cardiomyocytes was detected by RT-PCR.Western blot was used to detect the protein expression of CYP4F3 in different concentrations of ophiopogonin D.Compared with the control group,low-concentration ophiopogonin D had no effect on the viability of cardiomyocytes.However,ophiopogonin D with a concentration of higher than 20µmol·L~(-1)could promote the viability.Under the microscope,ophiopogonin D with a concentration of below 100µmol·L~(-1)had no significant effect on the morphology and number of cardiomyocytes.RT-PCR results showed that compared with the control group,5µmol·L~(-1)ophiopogonin D could slightly up-regulate mRNA expressions of CYP2J2 and CYP4F3,while high-concentration ophiopogonin D (10 and 20µmol·L~(-1)) could significantly induce mRNA expressions of CYP2J2and CYP4F3 in a dose-dependent manner (P<0.05).The same concentration of ophiopogonin D had a little effect on the mRNA expressions of CYP4A11,CYP4A22 and CYP4F2.Western blot results showed that 20µmol·L~(-1)ophiopogonin D could significantly induce the protein expression of CYP4F3 in a dose-dependent manner (P<0.05).Based on the above results,ophiopogonin D (less than100µmol·L~(-1)) has no effect on the viability of AC-16 cardiomyocytes.Ophiopogonin D (less than 100µmol·L~(-1)) can selectively induce the expressions of CYP2J2 and CYP4F3,regulate the metabolic pathway of fatty acid signaling molecules,and thus protecting the cardiovascular system.

[Expert consensus on Antiviral Oral Liquid in treatment of influenza in clinical practice].

Antiviral Oral Liquid is modified on the basis of Baihu Decoction in Treatise on Febrility Diseases by ZHANG Zhongjing and Qingwen Baidu Yin in Qing Dynasty, with effects in clearing toxic heat, repelling dampness and cooling blood. It is widely used in clinical treatment of common colds, influenza and upper respiratory tract infection, mumps, viral conjunctivitis and hand-foot-mouth disease, with a good clinical efficacy and safety. Based on a questionnaire survey of clinicians and a systematic review of study literatures on Antiviral Oral Liquid, the international clinical practice guidelines development method was adopted to analyze the optimal available evidences and expert experiences in the "evidence-based, consensus-based and experience-based" principles. The consensus was jointly reached by more than 30 multidisciplinary experts nationwide, including clinical experts of traditional Chinese and Western medicine in the field of respiratory diseases and infectious diseases, and methodological experts. In the study, literatures were retrieved based on clinical problems in the clinical survey as well as PICO clinical problems. The GRADE system was used for the classification and evaluation of evidence, and fully combined with clinical expert experience, so as to reach expert consensus by the nominal grouping method. This expert consensus recommended or suggested indications, usage and dosage, course of treatment, intervention time for treatment, and the safety and precautions of Antiviral Oral Liquid for treatment of influenza, and can provide reference for the rational use of this drug in clinical practice.

Emodin-Induced Oxidative Inhibition of Mitochondrial Function Assists BiP/IRE1α/CHOP Signaling-Mediated ER-Related Apoptosis.

Cassiae Semen is a widely used herbal medicine and a popular edible variety in many dietary or health beverage. Emerging evidence disclosed that improper administration of Cassiae Semen could induce obvious liver injury, which is possibly attributed to emodin, one of the bioactive anthraquinone compounds in Cassiae Semen, which caused hepatotoxicity, but the underlying mechanisms are not completely understood. Hence, the present study firstly explored the possible role of oxidative stress-mediated mitochondrial dysfunction and ER stress in emodin-cause apoptosis of L02 cells, aiming to elaborate possible toxic mechanisms involved in emodin-induced hepatotoxicity. Our results showed that emodin-induced ROS activated ER stress and the UPR via the BiP/IRE1α/CHOP signaling pathway, followed by ER Ca2+ release and cytoplasmic Ca2+ overloading. At the same time, emodin-caused redox imbalance increased mtROS while decreased MMP and mitochondrial function, resulting in the leaks of mitochondrial-related proapoptotic factors. Interestingly, blocking Ca2+ release from ER by 2-APB could inhibit emodin-induced apoptosis of L02, but the restored mitochondrial function did not reduce the apoptosis rates of emodin-treated cells. Besides, tunicamycin (TM) and doxorubicin (DOX) were used to activate ER stress and mitochondrial injury at a dosage where obvious apoptosis was not observed, respectively. We found that cotreatment with TM and DOX significantly induced apoptosis of L02 cells. Thus, all the results indicated that emodin-induced excessive ROS generation and redox imbalance promoted apoptosis, which was mainly associated with BiP/IRE1α/CHOP signaling-mediated ER stress and would be enhanced by oxidative stress-mediated mitochondrial dysfunction. Altogether, this finding has implicated that redox imbalance-mediated ER stress could be an alternative target for the treatment of Cassiae Semen or other medicine-food homologous varieties containing emodin-induced liver injury.