Practical application of the patient data-based quality control method: the potassium example.

Introduction: Internal quality control (IQC) is a core pillar of laboratory quality control strategies. Internal quality control commercial materials lack the same characteristics as patient samples and IQC contributes to the costs of laboratory testing. Patient data-based quality control (PDB-QC) may be a valuable supplement to IQC; the smaller the biological variation, the stronger the ability to detect errors. Using the potassium concentration in serum as an example study compared error detection effectiveness between PDB-QC and IQC. Materials and methods: Serum potassium concentrations were measured by using an indirect ion-selective electrode method. For the training database, 23,772 patient-generated data and 366 IQC data from April 2022 to September 2022 were used; 15,351 patient-generated data and 246 IQC data from October 2022 to January 2023 were used as the testing database. For both PDB-QC and IQC, average values and standard deviations were calculated, and z-score charts were plotted for comparison purposes. Results: Five systematic and three random errors were detected using IQC. Nine systematic errors but no random errors were detected in PDB-QC. The PDB-QC showed systematic error warnings earlier than the IQC. Conclusions: The daily average value of patient-generated data was superior to IQC in terms of the efficiency and timeliness of detecting systematic errors but inferior to IQC in detecting random errors.

Engineering pH responsive carboxyethyl chitosan and oxidized pectin -based hydrogels with self-healing, biodegradable and antibacterial properties for wound healing.

As an important organ of the human body, effective protection of the skin during trauma is crucial. An ideal wound dressing should have adhesion, adsorption of wound secretions, and good antibacterial properties. Two kinds of natural polysaccharide-based hydrogels, carboxyethyl chitosan/oxidized pectin hydrogel (CEC/OP) and carboxyethyl chitosan/oxidized pectin/polyethyleneimine hydrogel (CEC/OP/PEI), were reported by using carboxyethyl chitosan as the matrix, and oxidized pectin and branched polyethyleneimine as the crosslinking agents. Both hydrogels could be formed in a short time and exhibited the pH responsively due to the presence of imine bond. Compared with carboxyethyl chitosan/oxidized pectin hydrogel, polyethyleneimine containing hydrogel can form gel quickly, a more compact and stable three-dimensional space network structure was formed, which exhibited better swelling performance, the swelling ration, rheology property, self-repair ability, and antibacterial performance. When the mass fractions of carboxyethyl chitosan and oxidized pectin solutions are 4 wt% and 9 wt%, respectively, the hydrogel exhibited an antibacterial efficiency of >96 % against both Staphylococcus aureus and Escherichia coli. After adding 0.75 wt% polyethyleneimine, the antibacterial efficiency of hydrogel could reach up to >98 %. More importantly, the polyethyleneimine containing hydrogel has a significant effect in the treatment of bacterially infected wounds.

MAT as a promising therapeutic strategy against triple-negative breast cancer via inhibiting PI3K/AKT pathway.

Triple-negative breast cancer (TNBC), a highly aggressive and heterogeneous subtype of breast cancer, lacks effective treatment options. Sophora flavescens Aiton, a Chinese medicinal plant, is often used in traditional Chinese medicine to treat cancer. Matrine (MAT) is an alkaloid extracted from Sophora flavescens. It has good anticancer effects, and thus can be explored as a new therapeutic agent in TNBC research. We performed bioinformatics analysis to analyze the differentially expressed genes between normal breast tissues and TNBC tissues, and comprehensive network pharmacology analyses. The activity and invasion ability of TNBC cells treated with MAT were analyzed. Apoptosis and cell cycle progression were determined using cytometry. We used Monodansylcadaverine (MDC) staining to determine the condition of autophagosomes. Finally, the expression levels of the key target proteins of the PI3K/AKT pathway were determined using western blotting. The proliferation and invasion ability of MDA-MB-231 and MDA-MB-468 can be effectively inhibited by MAT. The results of flow cytometry indicated that MAT arrested the TNBC cell cycle and induced apoptosis. In addition, we confirmed that MAT inhibited the expression of BCL-2 while up-regulating the expression of cleaved caspase-3. Moreover, enhanced intensity of MDC staining and high LC3-II expression were observed, which confirmed that MAT induced autophagy in TNBC cells. Western blotting showed that MAT inhibited the PI3K/AKT pathway and downregulated the expressions of PI3K, AKT, p-AKT, and PGK1. This study provides feasible methods, which include bioinformatics analysis and in vitro experiments, for the identification of compounds with anti-TNBC properties. MAT inhibited the PI3K/AKT signaling pathway, arrested cell cycle, as well as promoted cell apoptosis and autophagy. These experiments provide evidence for the anti-TNBC effect of MAT and identified potential targets against TNBC.

Protocol for the derivation and external validation of a 30-day postoperative pulmonary complications (PPCs) risk prediction model for elderly patients undergoing thoracic surgery: a cohort study in southern China.

INTRODUCTION: Postoperative pulmonary complications (PPCs) occur after up to 60% of non-cardiac thoracic surgery (NCTS), especially for multimorbid elderly patients. Nevertheless, current risk prediction models for PPCs have major limitations regarding derivation and validation, and do not account for the specific risks of NCTS patients. Well-founded and externally validated models specific to elderly NCTS patients are warranted to inform consent and treatment decisions. METHODS AND ANALYSIS: We will develop, internally and externally validate a multivariable risk model to predict 30-day PPCs in elderly NCTS patients. Our cohort will be generated in three study sites in southern China with a target population of approximately 1400 between October 2021 and December 2023. Candidate predictors have been selected based on published data, clinical expertise and epidemiological knowledge. Our model will be derived using the combination of multivariable logistic regression and bootstrapping technique to lessen predictors. The final model will be internally validated using bootstrapping validation technique and externally validated using data from different study sites. A parsimonious risk score will then be developed on the basis of beta estimates derived from the logistic model. Model performance will be evaluated using area under the receiver operating characteristic curve, max-rescaled Brier score and calibration slope. In exploratory analysis, we will also assess the net benefit of Probability of PPCs Associated with THoracic surgery in elderly patients score in the complete cohort using decision curve analysis. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Institutional Review Board of the Affiliated Cancer Hospital and Institute of Guangzhou Medical University, the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine and the University of Hongkong-Shenzhen Hospital, respectively. The final risk prediction model will be published in an appropriate journal and further disseminated as an online calculator or nomogram for clinical application. Approved and anonymised data will be shared. TRIAL REGISTRATION NUMBER: ChiCTR2100051170.

Anti-apoptotic effect of HeidihuangWan in renal tubular epithelial cells via PI3K/Akt/mTOR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Heidihuang Wan (HDHW) is a classic Chinese herbal formula, which was first recorded in the "Suwen Bingji Qiyi Baoming Collection" written by Liu Wansu during the Jin Dynasty (1115-1234 AD). It is commonly used clinically for the treatment of kidney diseases and its curative effect is stable. Previous animal experiments have confirmed that HDHW can effectively improve renal fibrosis. However, the underlying pharmacological mechanism remains unclear. AIMS OF THIS STUDY: Renal tubular epithelial cell (RTEC) apoptosis is one of the main pathological features of renal fibrosis. This study aimed to observe the effect and underlying mechanism of HDHW on the apoptosis of RTECs to further explore the pathological mechanism of HDHW against renal fibrosis. MATERIALS AND METHODS: We examined the HDHW composition in rat serum. In vitro, we first screened out the optimal intervention concentration of HDHW on RTECs using the MTT assay. Hypoxia/reoxygenation was then used to induce apoptosis of RTECs (H/R-RTECs), which were divided into H/R-RTEC, astragaloside IV (positive control), HDHW, and RTECs groups. After 48 h of drug intervention, apoptosis of RTECs was detected using flow cytometry and protein expression was detected by western blotting. The 5/6 nephrectomy rat model was constructed and divided into the normal control, 5/6 nephrectomy, HDHW, and astragaloside IV groups. After 8 weeks of treatment, TUNEL staining was used to detect cell apoptosis, and western blotting was used to detect protein expression. RESULTS: HDHW downregulated the expression of pro-apoptotic proteins Bax and Caspase3, up-regulated the expression of anti-apoptotic protein Bcl-2, activated the PI3K/Akt/mTOR signaling pathway, and reversed the early apoptosis of RTECs, thereby resisting the apoptosis of RTECs. CONCLUSION: HDHW inhibits apoptosis of RTECs by modulating the PI3K/Akt/mTOR signaling pathway. This study provides experimental evidence for the anti-fibrotic effect of HDHW on the kidneys and partially elucidates its pharmacological mechanism of action.

Gut microbiota profiling revealed the regulating effects of salidroside on iron metabolism in diabetic mice.

Background: Diabetes is a common metabolic disease that is associated with gut microbiota dysbiosis and iron metabolism. Salidroside (SAL) is the main ingredient of the traditional Chinese herb Rhodiola, previous studies have shown that SAL could reshape the gut microbiota and limit iron accumulation. Therefore, it is possible that SAL can act as an alternative therapy for diabetes, and its underlying mechanism is worth exploring. Methods: SAL was used to treat diabetic db/db mice. Serum glucose and iron levels and the histopathology of myocardial fibres were evaluated. The gut microbiota composition was determined by 16S rRNA Illumina sequencing technology. Results: Treatment with SAL significantly reduced blood glucose and ameliorated diabetic cardiomyopathy in diabetic db/db mice, which was accompanied by inhibited ferroptosis and iron accumulation. Furthermore, the 16S rRNA sequencing results showed that SAL induced a change in the gut microbiota composition. Overall, SAL could increase the proportion of probiotic bacteria and decrease Lactobacillus to improve gut microbiota. Specifically, SAL increased the ratio of Bacteroidetes to Firmicutes in diabetic mice. The most significant biomarker was the genus Lactobacillus between the MD group and the SAL group. In addition, COG and KEGG analyses suggested that SAL mainly participated in nutrient metabolism, among them iron metabolism was associated with the abundance of Lactobacillus. Conclusions: SAL could reduce the glucose level and protect against diabetic cardiomyopathy in diabetic mice, which might be mediated by the change in the gut microbiota and the regulation of iron metabolism. The findings suggested that SAL was a promising complementary option for diabetes therapy.

Response of aerobic granular sludge under polyethylene microplastics stress: Physicochemical properties, decontamination performance, and microbial community.

Microplastics are widely detected in sewage and sludge in wastewater treatment plants and can thereby influence biological processes. In this study, the overall impacts of polyethylene microplastics (PE MPs) and their toxicity mechanisms on aerobic granular sludge (AGS) were investigated. Particle structure, settling properties, particle size distribution, and extracellular polymeric substance characteristics of AGS were significantly affected by PE MPs with concentrations of 20 and 200 n/L. Increased relative contents of reactive oxygen species (ROS) (146.34% and 191.43%) and lactate dehydrogenase (LDH) (185.71% and 316.67%) under PE MPs (20 and 200 n/L) exposure resulted in disruption of cellular structure. The activities of enzymes related to denitrification and phosphorus removal were greatly decreased, while ammonia monooxygenase (AMO) was stable, supporting the high efficiency removal of ammonia nitrogen. High-throughput sequencing demonstrated that the relative abundance of nitrifying and denitrifying bacteria (Nitrospira, Thermomonas, Flavobacterium), and PAOs (Comamonas and Rhodocyclus) were significantly reduced from 4.47%, 3.57%, 2.02%, 9.38%, and 5.45%-2.95%, 2.88%, 1.77%, 8.01%, and 4.86% as the concentration of PE MPs increased from 0 to 200 n/L, respectively. Those findings were consistent with the deterioration in decontamination capability.

Modified Xiaochaihu Decoction Combined with Mirtazapine in the Treatment of Persistent Depression: A Pilot Randomized Controlled Trial.

Background: Western drugs effectively manage persistent depressive disorder (PDD) but are associated with side effects. Objective: To observe the efficacy and safety of modified Xiaochaihu Decoction combined with mirtazapine in treating PDD. Methods: Patients with PDD were enrolled at the Naval General Hospital (06/2018-02/2019) and randomized to modified Xiaochaihu Decoction and modified Xiaochaihu Decoction with mirtazapine. The self-rating depression scale (SDS) and traditional Chinese medicine (TCM) scale were assessed at baseline and after 12 weeks. The overall clinical efficacy (primary outcome) and adverse reactions were observed. Results: Sixty-four participants completed the trial in the combined and control groups (30 and 28), respectively. In controls, the total effective rate was 78.6%, compared with 96.7% in the combined group (P=0.035). The scores of the SDS and TCM syndrome scale in the two groups were lower after treatment (P < 0.001) but without difference between groups (P=0.077). The combined group showed higher improvement rates regarding insomnia (96.4% vs. 44.0%, P < 0.001), bitter taste (90.5% vs. 52.6%, P=0.007), languid (72.0% vs. 31.8%, P=0.006), and belching/anorexia (100% vs. 52.6%, P < 0.001). The combined group showed a higher frequency of adverse events (73.3% vs. 3.6%) (P < 0.001). Conclusion: Modified Xiaochaihu Decoction combined with mirtazapine effectively treats PDD, and its curative effect is better than that of TCM alone. Trial Registration. This trial was registered with https://www.chictr.org.cn/index.aspx/ChiCTR2100048188.

The Protective Effect of Evodiamine in Osteoarthritis: An In Vitro and In Vivo Study in Mice Model.

Osteoarthritis (OA) is a chronic disease with high economic burden characterized by cartilage degradation and joint inflammation. Evodiamine (EV), which can be extracted from Evodia rutaecarpa (Rutaceae), is a traditional Chinese medicine to treat inflammation, cardiovascular disorders, infection, and obesity. Studies have shown that EV can suppress the activation of immune cells and restrain the secretion of pro-inflammatory cytokines. However, it is still not well known about its role in the treatment of OA. In this study, we utilized interleukin-1ß (IL-1ß)-stimulated mouse chondrocytes in vitro and the destabilization of the medial meniscus (DMM) model in vivo to demonstrate the anti-inflammatory properties of EV in OA. The results suggested that EV decreased the generation of NO, IL-6, TNF-α, and PGE2. Meanwhile, the increased expression of iNOS, COX-2, and MMP-13 and the degradation of aggrecan and Col-II were significantly alleviated by EV in IL-1ß-activated mouse chondrocytes. Moreover, EV can inhibit the considerable IL-1ß-stimulated phosphorylation of the NF-κB signaling pathway and nuclear translocation of p65, compared with the control group. Furthermore, EV alleviated cartilage degeneration and reversed the increased Osteoarthritis Research Society International (OARSI) scores in the OA model in vivo. Our study demonstrates that EV can suppress inflammation in vitro and cartilage degeneration in vivo in OA, which implies that EV may be a potential candidate for the treatment of OA.

A Candidate Drug Screen Strategy: The Discovery of Oroxylin A in Scutellariae Radix Against Sepsis via the Correlation Analysis Between Plant Metabolomics and Pharmacodynamics.

Sepsis is an acute systemic infectious disease with high mortality, which urgently needs more effective treatment. Scutellariae radix (SR), a commonly used traditional Chinese medicine (TCM) for clearing heat and detoxification, contains rich natural products possessing anti-inflammatory activity. In previous studies, it was found that the anti-inflammatory activities of SR extracts from different ecological conditions varied wildly. Based on this, in the present study, a screening strategy of antisepsis active components from SR based on correlation analysis between plant metabolomics and pharmacodynamics was established, and the mechanism was explored. First of all, a mass spectrum database of SR (above 240 components) was established to lay the foundation for the identification of plant metabolomics by liquid chromatography tandem mass spectrometry (LC-MS/MS). Through the correlation analysis between plant metabolomics and anti-inflammatory activity of SR from different ecology regions, 10 potential components with high correlation coefficients were preliminarily screened out. After the evaluation of anti-inflammatory activity and toxicity at the cellular level, the pharmacodynamic evaluation in vivo found that oroxylin A had the potentiality of antisepsis both in LPS- and CLP-induced endotoxemia mice. Network pharmacology and Western blot (WB) results indicated that oroxylin A significantly inhibited the toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway, which was further confirmed by secreted embryonic alkaline phosphatase (SEAP) assay. Moreover, the molecular docking analysis indicated that oroxylin A might competitively inhibit LPS binding to myeloid differentiation 2 (MD-2) to block the activation of TLR4. The study provided a feasible research strategy for the screening and discovery of antisepsis candidate drugs from TCM.

Liraglutide Attenuates Restenosis After Vascular Injury in Rabbits With Diabetes Via the TGF-ß/Smad3 Signaling Pathway.

Background: Lower limb ischemia due to arterial stenosis is a major complication in patients with diabetes mellitus (DM). Liraglutide is a long-acting analogue of a glucagon-like peptide 1 (GLP-1) receptor agonist used for lowering blood glucose in patients with DM, and is believed to possess cardiovascular protective effects. The aim of this study was to investigate whether liraglutide has a protective effect on blood vessels and alleviates vascular intimal hyperplasia in streptozotocin (STZ)-induced rabbits with DM and its molecular mechanism. Methods: Rabbits with DM were induced by STZ, and a lower limb ischemia model was established. The animals were divided into a control group, DM-injury group and liraglutide treatment group. Pathological staining was used to observe the intimal growth, analyze the oxidation levels of malondialdehyde (MDA), superoxide dismutase (SOD) and plasma glutathione peroxidase (GSH-Px), and analyze the changes in expression of marker proteins and signaling pathway proteins by Western blotting. A hyperglycemia (HG)-injured vascular smooth muscle cells (VSMCs) model was established to analyze reactive oxygen species (ROS) levels, Cell-Counting Kit-8 (CCK-8) was used to analyze cell proliferation, scratch assay and Transwell Migration Assay to analyze cell migration, flow cytometry to analyze apoptosis and Western blotting was used to analyze changes in the expression of marker and signaling pathway proteins. Results: The results of pathological staining showed that intimal hyperplasia was severe after diabetes-induced lower limb ischemia in rabbits at 4 weeks, and liraglutide treatment reduced symptoms. Liraglutide treatment significantly decreased MDA content, increased SOD, GSH-Px content, and augmented total antioxidant capacity levels in tissues. The results of Western blotting analysis showed that E-cadherin, mitochondrial membrane potential 9 (MMP-9), proliferating cell nuclear antigen (PCNA), and type I collagen protein expression levels were significantly decreased after liraglutide treatment compared with the DM injury group. The results indicated that liraglutide inhibited epithelial-mesenchymal transition (EMT) progression, vascular cell proliferation and migration and collagen production. Liraglutide inhibits transforming growth factor beta 1 (TGF-ß1)/Smad3 signaling pathway protein expression. In vitro assays have shown that liraglutide reduces cellular ROS levels, inhibits cell proliferation and migration and promotes apoptosis. Liraglutide down-regulated the expression of E-cadherin, MMP-9, PCNA, type I collagen protein as well as the TGF-ß1/Smad3 signaling pathway, but this effect could be reversed by tumor necrosis factor alpha (TNF-α). Conclusion: Liraglutide can significantly improve tissue antioxidant capacity, reduce vascular cell proliferation and migration via the TGF-ß1/Smad3 signaling pathway, inhibit the EMT and collagen production processes, and alleviate hyperglycemia(HG)-induced lower limb ischemia and intimal hyperplasia.

Unveiling Dynamic Changes of Chemical Constituents in Raw and Processed Fuzi With Different Steaming Time Points Using Desorption Electrospray Ionization Mass Spectrometry Imaging Combined With Metabolomics.

Fuzi is a famous toxic traditional herbal medicine, which has long been used for the treatment of various diseases in China and many other Asian countries because of its extraordinary pharmacological activities and high toxicity. Different processing methods to attenuate the toxicity of Fuzi are important for its safe clinical use. In this study, desorption electrospray ionization mass spectrometry imaging (DESI-MSI) with a metabolomics-combined multivariate statistical analysis approach was applied to investigate a series of Aconitum alkaloids and explore potential metabolic markers to understand the differences between raw and processed Fuzi with different steaming time points. Moreover, the selected metabolic markers were visualized by DESI-MSI, and six index alkaloids' contents were determined through HPLC. The results indicated visible differences among raw and processed Fuzi with different steaming times, and 4.0 h is the proper time for toxicity attenuation and efficacy reservation. A total of 42 metabolic markers were identified to discriminate raw Fuzi and those steamed for 4.0 and 8.0 h, which were clearly visualized in DESI-MSI. The transformation from diester-diterpenoid alkaloids to monoester-diterpenoid alkaloids and then to non-esterified diterpene alkaloids through hydrolysis is the major toxicity attenuation process during steaming. DESI-MSI combined with metabolomics provides an efficient method to visualize the changeable rules and screen the metabolic markers of Aconitum alkaloids during steaming. The wide application of this technique could help identify markers and reveal the possible chemical transition mechanism in the "Paozhi" processes of Fuzi. It also provides an efficient and easy way to quality control and ensures the safety of Fuzi and other toxic traditional Chinese medicine.

SOX2 modulated astrocytic process plasticity is involved in arsenic-induced metabolic disorders.

Metabolic disorders induced by arsenic exposure have attracted great public concern. However, it remains unclear whether hypothalamus-based central regulation mechanisms are involved in this process. Here, we exposed mice to 100 µg/L arsenic in drinking water and established a chronic arsenic exposure model. Our study revealed that chronic arsenic exposure caused metabolic disorders in mice including impaired glucose metabolism and decreased energy expenditure. Arsenic exposure also impaired glucose sensing and the activation of proopiomelanocortin (POMC) neurons in the hypothalamus. In particular, arsenic exposure damaged the plasticity of hypothalamic astrocytic process. Further research revealed that arsenic exposure inhibited the expression of sex-determining region Y-Box 2 (SOX2), which decreased the expression level of insulin receptors (INSRs) and the phosphorylation of AKT. The conditional deletion of astrocytic SOX2 exacerbated arsenic-induced effects on metabolic disorders, the impairment of hypothalamic astrocytic processes, and the inhibition of INSR/AKT signaling. Furthermore, the arsenic-induced impairment of astrocytic processes and inhibitory effects on INSR/AKT signaling were reversed by SOX2 overexpression in primary hypothalamic astrocytes. Together, we demonstrated here that chronic arsenic exposure caused metabolic disorders by impairing SOX2-modulated hypothalamic astrocytic process plasticity in mice. Our study provides evidence of novel central regulatory mechanisms underlying arsenic-induced metabolic disorders and emphasizes the crucial role of SOX2 in regulating the process plasticity of adult astrocytes.

Clinical and psychobehavioral features of outpatients with somatic symptom disorder in otorhinolaryngology clinics.

OBJECTIVE: In the Otorhinolaryngology Department, patients exhibiting somatic symptoms without a medical cause are frequently neglected and left untreated. The aim of this study was to characterize the psychosomatic features of outpatients with somatic symptom disorder (SSD) to better identify patients needing treatment. METHODS: This cross-sectional study enrolled 883 consecutive patients with medically unexplained symptoms. A semistructured clinical interview was employed to confirm the diagnosis of SSD. Data, including sociodemographic and clinical measures, were collected. The Patient Health Questionnaire-15 (PHQ-15) and Somatic Symptom Scale-China (SSS-CN) were used to assess the severity of somatic symptoms; the Patient Health Questionnaire-9 (PHQ-9) was used to assess depression; the General Anxiety Disorder-7 (GAD-7) was used to assess anxiety; and the 12-item Short-form Health Survey (SF-12) was used to assess quality of life (QoL). RESULTS: Based on the DSM-5 criteria, 641 patients were placed in the SSD group, and 212 were placed in the normal group. Compared with the normal group, the SSD group had significantly more doctor visits, longer symptom durations, higher GAD-7 and PHQ-9 scores, and lower physical composite scores (PCSs) and mental composite scores (MCSs). Spearman's correlation analysis and multiple linear regression analyses showed that the SSS-CN score, PHQ-15 score and the patient's subjective feeling that his or her daily life was affected by the disorder were significant risk factors for low PCSs; the SSS-CN, PHQ-15, PHQ-9, and GAD-7 scores were independent risk factors for low MCSs. CONCLUSION: Our findings demonstrated that SSD patients are not rare in otorhinolaryngology clinics in China and that their QoL is significantly affected by SSD. Otolaryngologists should thoroughly evaluate these patients from the perspective of psychosomatic medicine.

Molecular classification and clinical diagnosis of acute-on-chronic liver failure patients by serum metabolomics.

Prevalence of acute-on-chronic liver failure (ACLF) patients is growing worldwide, associating with multi-organ failure and high short-term mortality rates. ACLF can be of varying entity manifestation, whereas it remains poorly defined. Traditional Chinese medicine (TCM) stratifies ACLF into two types, damp hot (DH) and cold damp (CD), by seasoned TCM practitioners, for specific treatment with different TCMs. The biggest challenge for the outcome of TCM therapy is the accuracy of diagnosis. However, it is difficult to guarantee it due to lack of the molecule classification of ACLF. Herein, we recruited 58 subjects including 34 ACLF patients (18 DH and 16 CD) and 24 healthy controls, and analyzed serum metabolic profiles using untargeted ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) metabolomics approach. A total of 10 serum metabolites were found as potential biomarkers for diagnosis of ACLF. Among them, taurochenodesoxycholic acid (N3), glycyldeoxycholic acid (N5) and 12-HETE-GABA (N7), varied between two types of ACLF and can be merged as a combination marker to differentiate CD from DH patients with area under the receiver operating curve (AUC) of 0.928 (95 % CI 0.8-1). CD patients possessed comparatively higher bile acid metabolism and lower arachidonic acid metabolism compared with DH patients. The results provide not only serum molecules for early accurate diagnosis of ACLF patients, but also potential clinical biomarkers for classification of CD and DH types. The findings clarify that molecular markers will be objective criteria for diagnosis of clinical types in TCM practice.

Effectiveness and safety of Chinese herbal medicines for hepatitis B virus-related acute-on-chronic liver failure: study protocol for a multicenter randomized controlled trial.

OBJECTIVE: To conduct a multicenter randomized controlled trial of the efficacy of standardized Chinese herbal medicines (CHMs) against acute- on-chronic liver failure (ACLF) and provide reproducible and high-level evidence for clinical practice. METHODS: This is a prospective, multicenter, centrally randomized controlled trial. Patients diagnosed with hepatitis B virus-related ACLF (n = 510) will be allocated to the standard medical therapy or CHM group at a 1∶1 ratio. Two CHMs will be used on the basis of the traditional Chinese medicine syndrome: Liangxue Jiedu granules for excess syndromes and Yiqi Jiedu granules for deficiency syndromes. The primary outcome is transplant-free survival at week 12. The secondary outcomes are (a) transplant-free survival at week 24, (b) liver function as assessed using the model for end-stage liver disease score at week 12, (c) liver function as assessed using the Child-Pugh score at week 12, and (d) the incidence of complications at week 12. DISCUSSION: The effectiveness and safety of CHM formulations will be assessed following treatment for ACLF.

The cardiac protection of Baoyuan decoction via gut-heart axis metabolic pathway.

BACKGROUND: Gut-heart axis has emerged as a novel concept to provide new insights into the complex mechanisms of heart failure (HF) and offer new therapeutic targets. Cardiac hypertrophy (CH) is one of the etiological agents contributing to the development of HF. Baoyuan Decoction (BYD), a traditional Chinese medicine (TCM) formula, exhibits unambiguous effects on treating CH and preventing HF. Previously, we have reported that BYD-targeted endogenous metabolites are potentially linked to gut microbiota metabolism, but the contribution of gut microbiota and metabolic interaction to the cardioprotective efficacy of BYD remains to be elucidated. PURPOSE: To investigate whether the gut microbiota plays a key role in anti-CH effects of BYD. STUDY DESIGN: A comprehensive strategy via incorporating pharmacodynamics, microbiomics, metabolomics, and microflora suppression model was adopted to investigate the links between the microbiota-host metabolic interaction and BYD efficacy in CH rats. METHOD: Firstly, the efficacy evaluation of BYD in treating chronic isoproterenol (ISO)-induced CH rats was performed by using multiple pharmacodynamic approaches. Then, the fecal metabolomics and 16S rRNA sequencing techniques were used to obtain the microbial and metabolic features of BYD against CH. After that, the potential gut-heart axis-based mechanism of BYD against CH was predicted by bioinformatic network analysis and validated by multiple molecular biology approaches. Finally, the antibiotics (AB)-induced gut microbiota suppression was employed to investigate whether the anti-CH effects of BYD is associated with the gut microflora. RESULTS: The fecal microbial communities and metabolic compositions were significantly altered in ISO-induced CH rats, while BYD effectively ameliorated the CH-associated gut microbiota dysbiosis, especially of Firmicutes and Bacteroidetes, and time-dependently alleviated the disturbance of fecal metabolome and reversed the changes of key CH and gut microbiota-related metabolites, such as short/medium chain fatty acids, primary/secondary bile acids, and amino acids. The mechanism study showed that the anti-CH effect of BYD was related to inhibition of the derivatives of arginine and tryptophan and their downstream pro-hypertrophic, pro-inflammatory, and pro-oxidant signaling pathways. The following microflora suppression test showed that BYD-mediated myocardial protection was decreased either in pharmacodynamics or in metabolic modulation. CONCLUSION: This study demonstrates that the protection of BYD against CH is partially gut microbiota dependent, and the regulatory effects of gut metabolism-related tryptophan and arginine derivatives is an important cardioprotection mechanism of BYD.

[Professor YANG Jun's clinical characteristics in the treatment of chronic diarrhea with acupuncture and herbal medicine based on qi activity theory in Huangdi Neijing].

Professor YANG Jun believes that chronic diarrhea is located in the "intestine" and its pathogenesis focuses on the dysfunction of the spleen and the stomach which results in the impairment of qi activity. In the treatment, the comprehensive therapy is adopted, including acupuncture, moxibustion, herbal medicine, cupping method, etc. Regarding acupuncture therapy, Tianshu (ST 25) is selected specially for regulating the spleen and stomach function, Xiabai (LU4) for dispersing the lung qi to stop diarrhea, as well as Yintang (GV 29), Shuigou (GV 26), Chengjiang (CV 24), Qihai (CV 6), Guanyuan (CV 4) and Zhongwan (CV 12) for promoting the circulation of the conception vessel and the governor vessel. Regarding moxibustion therapy, moxibustion is exerted at the abdominal region to regulate qi and blood circulation and unblocking the meridians. Moreover, the retained cupping method is used at Shenque (CV 8) to consolidate the primary qi and the modified sijunzi tang, the herbal decoction is supplemented to tonify the acquired foundation for assisting the congenital one. All of these therapies co-work on promoting and regulating qi activity so as to stop diarrhea.

The Modulatory Properties of Astragalus membranaceus Treatment on Triple-Negative Breast Cancer: An Integrated Pharmacological Method.

Background: Studies have shown that the natural products of Astragalus membranaceus (AM) can effectively interfere with a variety of cancers, but their mechanism of action on breast cancer remains unclear. Triple-negative breast cancer (TNBC) is associated with a severely poor prognosis due to its invasive phenotype and lack of biomarker-driven-targeted therapies. In this study, the potential mechanism of the target composition acting on TNBC was explored by integrated pharmacological models and in vitro experiments. Materials and Methods: Based on the Gene Expression Omnibus (GEO) database and the relational database of Traditional Chinese Medicines (TCMs), the drug and target components were initially screened to construct a common network module, and multiattribute analysis was then used to characterize the network and obtain key drug-target information. Furthermore, network topology analysis was used to characterize the betweenness and closeness of key hubs in the network. Molecular docking was used to evaluate the affinity between compounds and targets and obtain accurate combination models. Finally, in vitro experiments verified the key component targets. The cell counting kit-8 (CCK-8) assay, invasion assay, and flow cytometric analysis were used to assess cell viability, invasiveness, and apoptosis, respectively, after Astragalus polysaccharides (APS) intervention. We also performed western blot analysis of key proteins to probe the mechanisms of correlated signaling pathways. Results: We constructed "compound-target" (339 nodes and 695 edges) and "compound-disease" (414 nodes and 6458 edges) networks using interaction data. Topology analysis and molecular docking were used as secondary screens to identify key hubs of the network. Finally, the key component APS and biomarkers PIK3CG, AKT, and BCL2 were identified. The in vitro experimental results confirmed that APS can effectively inhibit TNBC cell activity, reduce invasion, promote apoptosis, and then counteract TNBC symptoms in a dose-dependent manner, most likely by inhibiting the PIK3CG/AKT/BCL2 pathway. Conclusion: This study provides a rational approach to discovering compounds with a polypharmacology-based therapeutic value. Our data established that APS intervenes with TNBC cell invasion, proliferation, and apoptosis via the PIK3CG/AKT/BCL2 pathway and could thus offer a promising therapeutic strategy for TNBC.

Assembly and Annotation of a Draft Genome of the Medicinal Plant Polygonum cuspidatum.

Polygonum cuspidatum (Japanese knotweed, also known as Huzhang in Chinese), a plant that produces bioactive components such as stilbenes and quinones, has long been recognized as important in traditional Chinese herbal medicine. To better understand the biological features of this plant and to gain genetic insight into the biosynthesis of its natural products, we assembled a draft genome of P. cuspidatum using Illumina sequencing technology. The draft genome is ca. 2.56 Gb long, with 71.54% of the genome annotated as transposable elements. Integrated gene prediction suggested that the P. cuspidatum genome encodes 55,075 functional genes, including 6,776 gene families that are conserved in the five eudicot species examined and 2,386 that are unique to P. cuspidatum. Among the functional genes identified, 4,753 are predicted to encode transcription factors. We traced the gene duplication history of P. cuspidatum and determined that it has undergone two whole-genome duplication events about 65 and 6.6 million years ago. Roots are considered the primary medicinal tissue, and transcriptome analysis identified 2,173 genes that were expressed at higher levels in roots compared to aboveground tissues. Detailed phylogenetic analysis demonstrated expansion of the gene family encoding stilbene synthase and chalcone synthase enzymes in the phenylpropanoid metabolic pathway, which is associated with the biosynthesis of resveratrol, a pharmacologically important stilbene. Analysis of the draft genome identified 7 abscisic acid and water deficit stress-induced protein-coding genes and 14 cysteine-rich transmembrane module genes predicted to be involved in stress responses. The draft de novo genome assembly produced in this study represents a valuable resource for the molecular characterization of medicinal compounds in P. cuspidatum, the improvement of this important medicinal plant, and the exploration of its abiotic stress resistance.