BPO-promoted [4 + 2] cyclization of enaminones and o-phenylenediamines to 2-acyl quinoxalines via a cascade transamination and C-H amination.

Rapid assembly of quinoxalines in a single step from readily available precursors has been recognized as an ideal platform in terms of efficiency and operation. Herein, we report a BPO-promoted metal-free approach to 2-acyl quinoxalines from enaminones and o-phenylenediamines via cascade transamination and C-H amination. This methodology demonstrates excellent compatibility with various substrates, including o-hydroxy enaminones, drug derivatives and natural products under mild reaction conditions.

Metals/bisulfite system involved generation of 24-sulfonic-25-ene ginsenoside Rg1, a potential quality control marker for sulfur-fumigated ginseng.

Ginseng is a most popular health-promoting food with ginsenosides as its main bioactive ingredients. Illegal sulfur-fumigation causes ginsenosides convert to toxic sulfur-containing derivatives, and reduced the efficacy/safety of ginseng. 24-sulfo-25-ene ginsenoside Rg1 (25-ene SRg1), one of the sulfur-containing derivatives, is a potential quality control marker of fumigated ginseng, but with low accessibility owing to its unknown generation mechanism. In this study, metals/bisulfite system involved generation mechanism was investigated and verified. The generation of 25-ene SRg1 in sulfur-fumigated ginseng is that SO2, formed during sulfur-fumigation, reacted with water and ionized into HSO3-. On the one hand, under the metals/bisulfite system, HSO3- generates HSO5- and free radicals which converted ginsenoside Rg1 to 24,25-epoxide Rg1; on the other hand, as a nucleophilic group, HSO3- reacted with 24,25-epoxide Rg1 and further dehydrated to 25-ene SRg1. This study provided a technical support for the promotion of 25-ene SRg1 as the characteristic quality control marker of sulfur-fumigated ginseng.

Danggui Sini decoction alleviates oxaliplatin-induced peripheral neuropathy by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

BACKGROUND: Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated. METHODS: The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation. RESULTS: DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, L-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota. CONCLUSION: DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

Rationality of the ethanol precipitation process in modern preparation production of Zishui-Qinggan decoction evaluated by integrating UPLC-QTOF-MS/MS-based chemical profiling/serum pharmacochemistry and network pharmacology.

INTRODUCTION: Zishui-Qinggan decoction (ZQD) is a classical traditional Chinese medicine formula (TCMF) for alleviating menopausal symptoms (MPS) induced by endocrine therapy in breast cancer patients. In the production of TCMF modern preparations, ethanol precipitation (EP) is a commonly but not fully verified refining process. OBJECTIVES: Chemical profiling/serum pharmacochemistry and network pharmacology approaches were integrated for exploring the rationality of the EP process in the production of ZQD modern preparations. MATERIAL AND METHODS: Ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS) was applied to identify the chemical profiles and absorbed components of ZQD. Network pharmacology was used to identify targets and pathways related to MPS-relieving efficacy. RESULTS: The chemicals of ZQDs without/with EP process (referred to as ZQD-W and ZQD-W-P, respectively) were qualitatively similar with 89 and 87 components identified, respectively, but their relative contents were different; 51 components were detectable in the serum of rats orally administered with ZQD-W, whereas only 19 were detected in that administered with ZQD-W-P. Key targets, such as AKT1, and pathways, such as the PI3K-Akt signalling pathway, affected by ZQD-W and ZQD-W-P were similar, while the neuroactive ligand-receptor interaction pathway among others and the MAPK signalling pathway among others were specific pathways affected by ZQD-W and ZQD-W-P, respectively. The specifically absorbed components of ZQD-W could combine its specific key targets. CONCLUSION: The EP process quantitatively altered the chemical profiles of ZQD, subsequently affected the absorbed components of ZQD, and then affected the key targets and pathways of ZQD for relieving MPS. The EP process might result in variation of the MPS-relieving efficacy of ZQD, which deserves further in vivo verification.

Active polypeptide MDANP protect against necrotizing enterocolitis (NEC) by regulating the PERK-eIF2ɑ-QRICH1 axis.

The effect of MDANP effects on ER stress signalling not well known or elucidated. Endoplasmic reticulum (ER) stress plays a critical role in necrotizing enterocolitis (NEC) pathogenesis through the PERK-eIF2ɑ-QRICH1 axis. The present study aimed to explore the protective effects of MDANP in NEC development. Firstly, a function screening was designed to identify the candidate peptides in human milk, and then the identified peptides were validated in NEC patients. In vivo, NEC was induced in mice pups and divided into four groups: (1) control group, (2) NEC group, (3) MDANP + NEC group, and (4) NS + NEC group. In vitro, lentivirus-mediated QRICH1 silencing, was used to transfect NCM460 cell lines, then stimulated with LPS. After LPS stimulation, cells were treated with chemically synthesized MDANP, and the essential proteins in the QRICH1 signalling pathway in cells were tested and compared. After the small-scale screening, a peptide (SKSKKFRRPDIQYPDATDED) named MDANP was determined as the principal peptide. Its protective effect against NEC through inhibiting the expression of ERS key proteins and impeding the intestinal cells' apoptosis was observed in the animal models. Furthermore, the inhibitive effect of MDANP on apoptosis of intestinal epithelial cells through modulating the PERK-eIF2ɑ-QRICH1 ERS pathway was also confirmed in vitro. Taken together, our data suggest that MDANP effectively ameliorates apoptosis in NEC through attenuating PERK-eIF2ɑ-QRICH1.

A Traceless Heterocyclic Amine Mediator in Regioselectivity-Switchable Formal [1 + 2 + 2] Cycloaddition Reaction to 1,3,4- and 1,4,5-Trisubstituted Pyrazoles.

Switchable multicomponent reactions have been attractive tools for the construction of compound libraries with skeleton diversity and complexity by slightly changing the reaction conditions. Described herein is a regioselectivity-switchable formal [1 + 2 + 2] cycloaddition reaction from difluoroalkyl compounds, enaminones, and RNHNH2, ultimately using 1-methylindazol-3-amine as a traceless mediator to switch the inherent regioselectivity of 1,3,4-trisubstituted pyrazole formation to 1,4,5-trisubstituted pyrazoles. Remarkable features of this work include mild conditions, simple operation, and broad scopes.

Comparison and Investigation of Exosomes from Human Amniotic Fluid Stem Cells and Human Breast Milk in Alleviating Neonatal Necrotizing Enterocolitis.

In view of the devastating impact of neonatal necrotizing enterocolitis (NEC) on newborns, the research on its intervention is particularly important. Although exosomes from human amniotic fluid stem cells (AFSC) and human breast milk (HBM) can protect against NEC, their mechanisms remain unclear. Here, we intend to compare the intervention effects of two types of exosomes on NEC mouse model and reveal their respective regulatory mechanisms. In general, both AFSC-derived exosomes (AFSC-exos) and HBM-derived exosomes (HBM- exos) can alleviate NEC- associated intestinal injury, significantly reduce NEC score, and reduce systemic and ileal inflammation and NEC related brain injury during experimental NEC. However, the mode and mechanism of action of the two sources of exosomes were not identical. In vivo, the number of ileal crypts was more significantly restored after HBM-exos intervention than AFSC-exos, and in vitro, HBM-exos preferentially inhibited the inflammatory response of intestinal epithelial cells (IECs), whereas AFSC-exos preferentially regulated the migration of IECs. Mechanistically, GO and KEGG analyses revealed the different therapeutic mechanisms of AFSC-exos and HBM-exos in NEC. Taken together, our results illustrate that AFSC-exos and HBM-exos reduce the severity of experimental NEC and intestinal damage through different mechanisms, supporting the potential of cell-free or breast milk free exosome therapy for NEC.

Erratum: [Corrigendum] Stormorken syndrome caused by STIM1 mutation: A case report and literature review.

[This corrects the article DOI: 10.3892/mi.2022.54.].

Influence of Heme Oxygenase-1 on Rats with Diabetic Retinopathy Through ERK1/2 Signaling Pathway.

The study aimed to investigate the influence of heme oxygenase-1 (HO-1) on rats with diabetic retinopathy (DR) through the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway. 40 rats were selected and divided into Control group (n=10), diabetes mellitus (DM) group (n=10), cobalt protoporphyrin (CoPP) group (n=10) and zinc protoporphyrin (ZnPP) group (n=10) according to weight. Streptozotocin (STZ) was intraperitoneally injected to establish the DM model in DM, CoPP and ZnPP groups, and CoPP and ZnPP solution was intraperitoneally injected in CoPP and ZnPP groups, respectively. Blood was drawn to determine fasting blood glucose. The changes in the protein and messenger ribonucleic acid (mRNA) levels were evaluated via Western blotting and polymerase chain reaction (qRT-PCR), respectively. Enzyme-linked immunosorbent assay (ELISA) was performed to measure antioxidant capacity and the levels of total reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase (GPx). The weight of rats was notably higher in the CoPP group and lower inZnPP group than in the DM group (p<0.05). After induction of DM, compared with those in the DM group, the protein expression levels of Nrf2 and pERK were considerably elevated in the CoPP group (p<0.05) but declined remarkably in the ZnPP group (p<0.05). The levels of total ROS and MDA were notably elevated (p<0.05) in DM and ZnPP groups, with a lowered level of GPx and distinctly elevated levels of MDA and total ROS (p<0.05). Moreover, the mRNA expression level of HO-1 in the retinas of rats was remarkably raised in the DM group and CoPP group (p<0.05), but it declined markedly in the ZnPP group (p<0.05). The red fluorescent aggregation of Nrf2 and pERK proteins was overtly less in the ZnPP group than that in the DM group (p<0.05). HO-1 can affect the level of oxidative stress and intervene in retinopathy in DM rats through the Nrf2/ERK pathway.

Vitamin D Ameliorates Apoptosis and Inflammation by Targeting the Mitochondrial and MEK1/2-ERK1/2 Pathways in Hyperoxia-Induced Bronchopulmonary Dysplasia.

Purpose: Bronchopulmonary dysplasia (BPD) is a common and severe complication in preterm infants. Vitamin D (VitD) has been reported to protect against BPD; however, its role in the mitochondria-mediated and MEK1/2-ERK1/2 pathways has not yet been reported. Methods: We first performed in vivo studies using neonatal C57BL/6 mice in which we induced BPD by exposing them to a hyperoxic environment (85% O2). The mice were divided into room air (RA; 21% O2), RA+VitD, BPD, and BPD+VitD groups. Hematoxylin and eosin and Masson's trichrome staining were used to evaluate lung injury. Inflammation and apoptosis were measured using ELISA, RT-qPCR, and TUNEL assays. We then analyzed BEAS-2B cells divided into the same groups along with an additional BPD+VitD+inhibitor group. Mitochondrial apoptosis was evaluated by transmission electron microscopy, mitochondrial membrane potential, and Western blotting. We then used VDR-shRNA to silence the Vitamin D Receptor (VDR) in the BEAS-2B cells. The inflammation, apoptotic rate, and the phosphorylated forms of MEK1/2 and ERK1/2 in cells were detected by RT-qPCR, flow cytometry, and Western blotting. Results: The mean linear intercept, septal thickness, and abnormal fibrosis increased, while radial alveolar count decreased in BPD lungs compared to RA lungs. VitD administration was able to ameliorate the phenotype in BPD lungs. IL-6, IFN-γ, and TNF-α expression and the apoptotic rate decreased in the BPD+VitD lung group. VitD pretreatment restored abnormal mitochondrial morphology, reduced mitochondrial membrane loss, and reduced the expression of cleaved caspase-3, Bax, and Bcl-2 in BEAS-2B cells. VitD administration also reduced IL-6, IFN-γ, and TNF-α mRNA, as well as pMEK1/2 and pERK1/2 expression and apoptosis rate in cells exposed to hyperoxia. Conclusion: We concluded that VitD treatment ameliorated apoptosis and inflammation by targeting the mitochondrial pathway and via the MEK1/2-ERK1/2 signaling pathway in BPD, thus supporting its potential therapeutic use in this condition.

[UPLC-Q-TOF-MS analysis of chemical constituents of classical prescription Yiguanjian standard decoction].

An UPLC-Q-TOF-MS method was employed to characterize and classify the chemical components of the standard decoction of Yiguanjian, a classical famous recipe. Chromatographic separation was performed on an Acquity HSS T3(2.1 mm ×100 mm, 1.8 µm) column with a mobile phase of 0.1% formic acid water-0.1% formic acid acetonitrile using gradient elution. The flow rate was 0.4 mL·min~(-1) and the column temperature was 40 ℃. Mass spectrometry was performed on electrospray ionization source(ESI) with positive and negative ion scanning modes. The potential compounds were identified by comparing the reference compounds, analyzing the mass spectrometry data and matching the published articles on Masslynx 4.1 software and SciFinder database. Finally, a total of 113 compounds, including 11 amino acids, 19 terpenoids, 13 phthalides, 11 steroidal saponins, 10 coumarins, 9 alkaloids, 7 flavonoids, 8 phenylethanoid glycosides, 8 organic acids and 17 other categories were identified. The established method systematically and accurately characterized the chemical components in Yiguanjian, which could provide experimental evidences for the subsequent studies on the pharmacodynamical material basis and quality control of Yiguanjian.

Stormorken syndrome caused by STIM1 mutation: A case report and literature review.

The aim of the present case study was to identify the genetic cause of a patient with a clinical presentation of tubular aggregate myopathy (TAM)/Stormorken syndrome (STRMK) and review the published clinical data of patients with TAM/STRMK. A child with thrombocytopenia and hyperCKemia at the Children's Hospital of Soochow University were recruited in the study. Peripheral blood samples of the infant and her parents were collected, and then whole-exome sequencing was performed. Detection of the stromal interaction molecule 1 (STIM1) level of the child was performed using western blot analysis. In addition, a literature review was performed based on a thorough retrieval of published literature from the PubMed database, as well as domestic databases. In the present study, the c.326A>G mutation in a STIM1 allele (p.H109R) was identified only in the child, as opposed to the unaffected parents. The level of STIM1 was not decreased in the child. Among the mutation sites identified in previous studies, there were 46 cases across 30 families of STIM1 EF-hand mutations, 21 cases across 14 families of STIM1 CC1 mutations and 20 cases across 8 families of calcium release-activated calcium channel protein 1 mutations, in which 7 parents had the same mutation site as the patient described herein. On the whole, it is demonstrated that TAM/STRMK is an extremely rare disease with autosomal dominant inheritance. Patients often have multisystemic signs. Gene detection at an early stage is helpful for diagnosis. Long-term exercise training may also have a certain curative effect.

Using a WeChat mini-program-based lactation consultant intervention to increase the consumption of mother's own milk by preterm infants in the neonatal intensive care unit: a study protocol for a cluster randomized controlled trial.

BACKGROUND: The benefits of mother's own milk (MOM) for preterm infants have been widely recognized. Many studies have shown that the rate of breastfeeding of premature infants remains very low. Although many studies use measures to promote breastfeeding, few high-quality cluster randomized controlled studies have evaluated the effectiveness of these measures. WeChat is an instant messaging software for smart terminals, and WeChat mini-programs have been widely used to promote health and self-management in China. Based on this background, we designed a randomized controlled study based on WeChat mini-programs to promote MOM feeding of premature infants in the neonatal intensive care unit (NICU). METHODS/DESIGN: This study will evaluate the effectiveness of WeChat mini-programs to increase the consumption of MOM feeding in twelve NICUs in Jiangsu Province, namely, six "intervention" NICUs and six "control" NICUs. The study process is as follows: (1) design and preparation, (2) NICU recruitment and training, (3) interpretation and analysis of baseline data, (4) quality control implementation process, and (5) data analysis feedback and publication of study reports. The primary outcome is the proportion of MOM feeding of premature infants during NICU hospitalization. The secondary outcomes are as follows: (1) time to initiation of MOM feeding (hours) and proportion of first-time MOM feeding (%), (2) duration of parenteral nutrition (days), (3) time to total gastrointestinal feeding (days), (4) hospitalization time and hospitalization cost, and (5) incidence of complications (necrotizing enterocolitis, bronchopulmonary dysplasia, feeding intolerance, late-onset sepsis, retinopathy of prematurity). DISCUSSION: This study is the first cluster randomized controlled trial on the intervention of using a WeChat mini-program-based lactation consultant for premature infants in the NICU in China. We hope this study can improve the consumption of MOM by NICU premature infants during hospitalization through the intervention of WeChat mini-programs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04383379. Registered on May 5, 2020.

Dysfunction of the Klotho-miR-30s/TRPC6 axis confers podocyte injury.

Klotho deficiency was observed in virtually all kinds of kidney disease and is thought to play a critical role in podocyte injury. However, the underline mechanisms involved in podocyte injury remain unknown. miRNAs have diverse regulatory roles, and miR-30 family members were essential for podocyte homeostasis. Our study revealed that Klotho and miR-30s were downregulated in PAN-treated podocytes. The ectopic expression of Klotho ameliorates PAN induced podocyte apoptosis through upregulating miR-30a and downregulating Ppp3ca, Ppp3cb, Ppp3r1, and Nfact3 expression, which are the known targets of miR-30s. We also found that Klotho regulates TRPC6 via miR-30a to activate calcium/calcineurin signaling. Further, glucocorticoid (Dexamethasone, DEX) was found to sustain Klotho and miR-30a levels during PAN treatment in vitro. Eventually, in rats, PAN treatment substantially downregulated Klotho and miR-30a levels, lead to podocyte injury and increased proteinuria. The transfer of exogenous Klotho to podocytes of PAN-treated rats could increase miR-30a expression, reduce TRPC6 expression, and also ameliorated podocyte injury and proteinuria. In conclusion, Klotho, acting on miR-30s, which directly regulates its target genes, contributes to podocyte apoptosis induced by PAN. It is a novel mechanism underlying PAN-induced podocyte injury.

Multivalent Ion-Mediated Attraction between Like-Charged Colloidal Particles: Nonmonotonic Dependence on the Particle Charge.

Ion-mediated effective interactions are important for the structure and stability of charged particles such as colloids and nucleic acids. It has been known that the intrinsic electrostatic repulsion between like-charged particles can be modulated into effective attraction by multivalent ions. In this work, we examined the dependence of multivalent ion-mediated attraction between like-charged colloidal particles on the particle charge in a wide range by extensive Monte Carlo simulations. Our calculations show that for both divalent and trivalent salts, the effective attraction between like-charged colloidal particles becomes stronger with the increase of the particle charge, whereas it gradually becomes weakened when the particle charge exceeds a "critical" value. Correspondingly, as the particle charge is increased, the driving force for such effective attraction transits from an attractive electrostatic force to an attractive depletion force, and the attraction weakening by high particle charges is attributed to the transition of electrostatic force from attraction to repulsion. Our analyses suggest that the attractive depletion force and the repulsive electrostatic force at high particle charges result from the Coulomb depletion which suppresses the counterion condensation in the limited region between two like-charged colloidal particles. Moreover, our extensive calculations indicate that the "critical" particle charge decreases apparently for larger ions and smaller colloidal particles due to stronger Coulomb depletion and decreases slightly at higher salt concentrations due to the slightly enhanced Coulomb depletion in the intervening space between colloidal particles. Encouragingly, we derived an analytical formula for the "critical" particle charge based on the Lindemann melting law.

Neonatal Severe Hyperbilirubinemia Online Registry in Jiangsu Province: protocol for a multicentre, prospective, open, observational cohort study.

INTRODUCTION: Severe hyperbilirubinaemia in newborns can be easily complicated by acute bilirubin encephalopathy or even kernicterus, which could lead to neurological sequelae or death. However, there is no systematic study of the management of severe hyperbilirubinaemia in China. The Neonatal Severe Hyperbilirubinemia Online Registry study aims to investigate the management of jaundice before admission, risk factors and outcomes of severe hyperbilirubinaemia in a real-world setting in China. METHODS AND ANALYSIS: This is a prospective, multicentre, open, observational cohort study. From May 2020 to April 2023, more than 2000 patients with neonatal severe hyperbilirubinaemia from 13 tertiary hospitals in Jiangsu Province will join the study. Demographic data and treatment information will be collected from their clinical data. Management measures for jaundice before admission will be collected by the WeChat applet (called 'Follow-up of jaundice') after being provided by the patient's guardian using a mobile phone. Follow-up data will include cranial MRI examination results, brainstem auditory-evoked potential or automatic auditory brainstem response, physical examination results and Griffiths Development Scales-Chinese at the corrected ages of 3-6 months and 1 and 2 years. Results and conclusions will be recorded using 'Follow-up of jaundice.' In-hospital outcomes, including severity of hyperbilirubinaemia (severe, extreme, hazardous), acute bilirubin encephalopathy (mild, moderate, severe) and survival status (death or survival), will be collected at discharge. Follow-up outcomes will include loss to follow-up, survival status and kernicterus (yes or no) at 2 years. The research will enhance our comprehensive knowledge of jaundice management before admission, risk factors and outcomes of severe hyperbilirubinaemia in China, which will ultimately help to reduce the incidence of neonatal severe hyperbilirubinaemia. ETHICS AND DISSEMINATION: Our protocol has been approved by the Medical Ethics Committee of Nanjing Maternity and Child Health Care Hospital. We will present our findings at national conferences and peer-reviewed paediatrics journals. TRIAL REGISTRATION NUMBER: NCT04251286.

Danggui Sini decoction protects against oxaliplatin-induced peripheral neuropathy in rats.

The effects of Danggui Sini decoction on peripheral neuropathy in oxaliplatin-induced peripheral is established. The results indicated that Danggui Sini decoction treatment significantly reduced the current amplitude of dorsal root ganglia cells undergoing agonists stimuli compared to the model-dorsal root ganglia group (P < 0.05). Danggui Sini decoction treatment significantly inhibited the inflammatory response of dorsal root ganglia cells compared to the model-dorsal root ganglia group (P < 0.05). Danggui Sini decoction treatment significantly enhanced the amounts of Nissl bodies in dorsal root ganglia cells compared to the Model-dorsal root ganglia group (P < 0.05). Danggui Sini decoction treatment improved ultra-microstructures of dorsal root ganglia cells. In conclusion, Danggui Sini decoction protected against neurotoxicity of oxaliplatin-induced peripheral neuropathy in rats by suppressing inflammatory lesions, improving ultra-microstructures, and enhancing amounts of Nissl bodies.

Exploring the Possible Mechanism and Drug Targets of Huang-Qi-Gui-Zhi-Wu-Wu Decoction for the Treatment of Chemotherapy-Induced Peripheral Neuropathy on Network Pharmacology.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of anticancer treatment, which may influence its successful completion. The Huang-Qi-Gui-Zhi-Wu-Wu decoction (HQGZWWD) has been widely used to treat CIPN in China although the pharmacological mechanisms involved have not been clarified. Using the network pharmacology approach, this study investigated the potential pathogenesis of CIPN and the therapeutic mechanisms exerted by the HQGZWWD herbal formula in CIPN. The targets of HQGZWWD were identified using traditional Chinese medicine (TCM) databases (TCMSP and ETCM) and prediction platforms (PharmMapper and TargetNet), and the genes of CIPN were collected by DisGeNET, GeneCards, and literature search. The common target interaction network between herbal formula and diseases was constructed by using Cytoscape. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to reveal the mechanism and efficacy of HQGZWWD in the treatment of CIPN. A total of 153 CIPN-related genes were screened, and a protein-protein interaction (PPI) network with 96 nodes and 424 edges was constructed. Sixty-three active components were retrieved from HQGZWWD, with a herb-composite compound-target network including 748 nodes and 5448 edges. Forty-one targets belong to the above two networks. The analysis of network results and literature review shows that the main pathological processes of CIPN may be the inflammatory response and nerve injury, and HQGZWWD plays a therapeutic role in CIPN by regulating inflammatory response and repairing nerve injury, thus verifying the reliable efficacy of this herbal formula. In addition, we found two new potential therapeutic targets (CDK7 and GSTM2) warranting further investigation. This study fully illustrates that TCM has the characteristics of a multicompound, multitarget, and multipathway treatment, which is of great significance to study the curative effect of herbal formulations.

[UPLC-Q-TOF-MS analysis on chemical constituents of classical prescription Huangqi Guizhi Wuwu Tang standard decoction].

UPLC-Q-TOF-MS technology was used to analyze the chemical constituents from classical prescription Huangqi Guizhi Wuwu Tang standard decoction. Acquity HSS T3 column(2.1 mm × 100 mm, 1.8 µm) was used as the chromatographic column, with 0.1% formic acid solution-0.1% formic acid acetonitrile as the mobile phase for gradient elution. The volume flow rate was 0.4 mL·min~(-1) and the column temperature was 40 ℃. Mass spectrometry data of Huangqi Guizhi Wuwu Tang standard decoction were collected in positive and negative ion modes. The chemical constituents from classical prescription Huangqi Guizhi Wuwu Tang standard decoction were analyzed and identified by Masslynx 4.1 software combined with SciFinder database, comparison with reference mate-rials, mass spectrometry data analysis and reference to relevant literature. A total of 110 compounds were analyzed and identified, including 33 flavonoids, 14 monoterpene glycosides, 8 triterpenoids, 8 gingerols, 17 phenylpropanoids, 12 organic acids, 7 amino acids and 11 other compounds. The results of this study provide an experimental basis for the further research on the substance basis and quality control of Huangqi Guizhi Wuwu Tang standard decoction.

Supervoxel based method for multi-atlas segmentation of brain MR images.

Multi-atlas segmentation has been widely applied to the analysis of brain MR images. However, the state-of-the-art techniques in multi-atlas segmentation, including both patch-based and learning-based methods, are strongly dependent on the pairwise registration or exhibit huge spatial inconsistency. The paper proposes a new segmentation framework based on supervoxels to solve the existing challenges of previous methods. The supervoxel is an aggregation of voxels with similar attributes, which can be used to replace the voxel grid. By formulating the segmentation as a tissue labeling problem associated with a maximum-a-posteriori inference in Markov random field, the problem is solved via a graphical model with supervoxels being considered as the nodes. In addition, a dense labeling scheme is developed to refine the supervoxel labeling results, and the spatial consistency is incorporated in the proposed method. The proposed approach is robust to the pairwise registration errors and of high computational efficiency. Extensive experimental evaluations on three publically available brain MR datasets demonstrate the effectiveness and superior performance of the proposed approach.