Self-Assembled STING-Activating Coordination Nanoparticles for Cancer Immunotherapy and Vaccine Applications.

The cGAS-STING pathway plays a crucial role in innate immune activation against cancer and infections, and STING agonists based on cyclic dinucleotides (CDN) have garnered attention for their potential use in cancer immunotherapy and vaccines. However, the limited drug-like properties of CDN necessitate an efficient delivery system to the immune system. To address these challenges, we developed an immunostimulatory delivery system for STING agonists. Here, we have examined aqueous coordination interactions between CDN and metal ions and report that CDN mixed with Zn2+ and Mn2+ formed distinctive crystal structures. Further pharmaceutical engineering led to the development of a functional coordination nanoparticle, termed the Zinc-Mn-CDN Particle (ZMCP), produced by a simple aqueous one-pot synthesis. Local or systemic administration of ZMCP exerted robust antitumor efficacy in mice. Importantly, recombinant protein antigens from SARS-CoV-2 can be simply loaded during the aqueous one-pot synthesis. The resulting ZMCP antigens elicited strong cellular and humoral immune responses that neutralized SARS-CoV-2, highlighting ZMCP as a self-adjuvant vaccine platform against COVID-19 and other infectious pathogens. Overall, this work establishes a paradigm for developing translational coordination nanomedicine based on drug-metal ion coordination and broadens the applicability of coordination medicine for the delivery of proteins and other biologics.

Biomimetic ZrO2-modified seaweed residue with excellent fluorine/ bacteria removal and uranium extraction properties for wastewater purification.

Exploring and developing promising biomass composite membranes for the water purification and waste resource utilization is of great significance. The modification of biomass has always been a focus of research in its resource utilization. In this study, we successfully prepare a functional composite membrane, activated graphene oxide/seaweed residue-zirconium dioxide (GOSRZ), with fluoride removal, uranium extraction, and antibacterial activity by biomimetic mineralization of zirconium dioxide nanoparticles (ZrO2 NPs) on seaweed residue (SR) grafted with oxidized graphene (GO). The GOSRZ membrane exhibits highly efficient and specific adsorption of fluoride. For the fluoride concentrations in the range of 100-400 mg/L in water, the removal efficiency can reach over 99 %, even in the presence of interfering ions. Satisfactory extraction rates are also achieved for uranium by the GOSRZ membrane. Additionally, the antibacterial performance studies show that this composite membrane efficiently removes Escherichia coli (E. coli) and Methicillin-resistant Staphylococcus aureus (MRSA). The high adsorption of F- and U(VI) to the composite membrane is ascribed to the ionic exchange and coordination interactions, and its antibacterial activity is caused by the destruction of bacterial cell structure. The sustainability of the biomass composite membranes is further evaluated using the Sustainability Footprint method. This study provides a simple preparation method of biomass composite membrane, expands the water purification treatment technology, and offers valuable guidance for the resource utilization of seaweed waste and the removal of pollutants in wastewater.

L-lysine supplementation attenuates experimental autoimmune hepatitis in a chronic murine model.

The incidence of autoimmune hepatitis (AIH) has increased significantly worldwide. The present study aims to explore the protective effect of L-lysine supplementation against AIH and to investigate its potential underlying mechanisms. A chronic experimental AIH mouse model was established by repeated tail vein injection of human cytochrome P450 2D6 (CYP2D6) plasmid. Starting from day 14 of the modeling, mice in the CYP2D6-AIH +L-lysine group were given 200 µl of purified water containing 10 mg/kg L-lysine by gavage until day27, once a day, and mice in the healthy control group and model group were given an equal volume of purified water by gavage. Our results showed that L-lysine supplementation partially reversed the liver injury mediated by CYP2D6 overexpression. These effects were consistent with the restraining impacts of L-lysine supplementation on decreasing pro-inflammatory cytokines expression level and CD4+ and CD8+ T lymphocytes infiltration, as well as curbing hepatic oxidative stress. Furthermore, L-lysine supplement relieved liver fibrosis in the context of AIH. In conclusion, L-lysine supplementation attenuates CYP2D6-induced immune liver injury in mice, which may serve as a novel nutrition support approach for AIH.

Enhancing Gastrointestinal Function Recovery in Post-Intestinal Surgery Patients Through Rapid Rehabilitation Nursing Therapy.

Objective: This study aimed to investigate the efficacy of rapid recovery nursing therapy in enhancing digestive tract function recovery following intestinal surgery. Methods: This study included 100 post-intestinal surgery patients between March 2020 and March 2022. A random table method was used, and patients were assigned to either a control group receiving standard nursing care or an experimental group receiving rapid rehabilitation therapy. A thorough assessment compared different outcomes such as gastrointestinal function recovery, physical recuperation, stress levels, postoperative adverse events, nutritional status, nursing efficacy, and patient satisfaction between the two groups. Results: Compared to the control group, the experimental group exhibited significant improvements in gastrointestinal function and physiological parameters (P < .05). Additionally, the experimental group experienced fewer adverse effects, improved nursing outcomes, and higher patient satisfaction post-treatment (P < .05). Conclusions: Rapid rehabilitation nursing therapy in patients undergoing intestinal surgery substantially enhances digestive tract function and overall patient well-being. It effectively reduces the incidence of postoperative complications, accelerates the patient's recovery process, and improves their quality of life. Patient satisfaction with postoperative fast recovery care was notably high. This rehabilitation approach holds significant promise for patients undergoing intestinal surgery and merits wider adoption.

Dietary oregano essential oil supplementation alters meat quality, oxidative stability, and fatty acid profiles of beef cattle.

This study was conducted to elucidate the effects of oregano essential oil (OEO) supplementation on the meat quality, antioxidant capacity, and nutritional value of the longissimus thoracis muscle in steers. Steers were divided into three groups (n = 9) and fed either a basal diet, or a basal diet supplemented with 130 mg/d OEO, or 230 mg/d OEO for 390 days. The results demonstrated that dietary OEO supplementation increased the total antioxidant capacity and activity of catalase, glutathione peroxidase, and superoxide dismutase, and decreased pH30min, pH24h, cooking loss, and malondialdehyde content. OEO increased the concentrations of polyunsaturated fatty acids and conjugated linoleic acid. In contrast, saturated fatty acids decreased, accompanied by increased essential amino acids, flavor amino acids, and total amino acids in the longissimus thoracis muscle. In summary, dietary OEO supplementation promotes the nutritional and meat quality of beef by maintaining its water-holding capacity and meat color, enhancing its antioxidative capacity, and preventing lipid oxidation.

Repression of ferroptotic cell death by mitochondrial calcium signaling.

The uptake of Ca2+ into and extrusion of calcium from the mitochondrial matrix, regulated by the mitochondrial Ca2+ uniporter (MCU), is a fundamental biological process that has crucial impacts on cellular metabolism, signaling, growth and survival. Herein, we report that the embryonic lethality of Mcu-deficient mice is fully rescued by orally supplementing ferroptosis inhibitor lipophilic antioxidant vitamin E and ubiquinol. Mechanistically, we found MCU promotes acetyl-CoA-mediated GPX4 acetylation at K90 residue, and K90R mutation impaired the GPX4 enzymatic activity, a step that is crucial for ferroptosis. Structural analysis supports the possibility that GPX4 K90R mutation alters the conformational state of the molecule, resulting in disruption of a salt bridge formation with D23, which was confirmed by mutagenesis studies. Finally, we report that deletion of MCU in cancer cells caused a marked reduction in tumor growth in multiple cancer models. In summary, our study provides a first direct link between mitochondrial calcium level and sustained GPX4 enzymatic activity to regulate ferroptosis, which consequently protects cancer cells from ferroptosis.

STING agonist-loaded mesoporous manganese-silica nanoparticles for vaccine applications.

Cyclic dinucleotides (CDNs), as one type of Stimulator of Interferon Genes (STING) pathway agonist, have shown promising results for eliciting immune responses against cancer and viral infection. However, the suboptimal drug-like properties of conventional CDNs, including their short in vivo half-life and poor cellular permeability, compromise their therapeutic efficacy. In this study, we have developed a manganese-silica nanoplatform (MnOx@HMSN) that enhances the adjuvant effects of CDN by achieving synergy with Mn2+ for vaccination against cancer and SARS-CoV-2. MnOx@HMSN with large mesopores were efficiently co-loaded with CDN and peptide/protein antigens. MnOx@HMSN(CDA) amplified the activation of the STING pathway and enhanced the production of type-I interferons and other proinflammatory cytokines from dendritic cells. MnOx@HMSN(CDA) carrying cancer neoantigens elicited robust antitumor T-cell immunity with therapeutic efficacy in two different murine tumor models. Furthermore, MnOx@HMSN(CDA) loaded with SARS-CoV-2 antigen achieved strong and durable (up to one year) humoral immune responses with neutralizing capability. These results demonstrate that MnOx@HMSN(CDA) is a versatile nanoplatform for vaccine applications.

Investigation and analysis of the current usage status of OTC drug among Inner Mongolian residents / 中国药房

OBJECTIVE To investigate the current usage status of OTC drug among residents in Inner Mongolia Autonomous Region， and to provide evidence for the science popularization of rational drug use. METHODS By approximate random sampling， the questionnaire survey was conducted with the mini-apps Questionnaire Star among the residents aged 19 and above from 7 league or cities of Inner Mongolia Autonomous Region， in order to investigate the current situation of OTC drug use in the region. RESULTS A total of 611 people filled in the questionnaire， and 571 people filled in the questionnaire effectively， with an effective filling rate of 93.45%. According to the results， 18.7% of residents said they did not understand the concept of OTC drugs， 36.1% of residents said they did not know the OTC drug label， and 65.3% of residents did not know the difference between class A and B OTC drugs in terms of OTC drug awareness. And there were statistically significant differences in the scores of OTC drug awareness among different genders， education levels， monthly income and places of residence （P＜0.05）. When choosing OTC drugs， 23.5% of residents still believed in advertisements or friends’ recommendations； 14.5% of the residents did not read the drug instructions carefully before taking drugs. In terms of drug risk， 5.1% of residents had long-term use of OTC drugs； 8.6% of residents reported taking three or more OTC drugs； 2.1% of residents often added other drugs with the same effect or increased the dosage by themselves. They took traditional Chinese medicine， Mongolian medicine and other preparations while taking OTC drugs， accounting for 19.6%， 22.6% and 13.0% respectively. CONCLUSIONS Residents in Inner Mongolia have low awareness of OTC drugs， and their habits of drug use need to be improved. Repeated drug use and overdose drug use are serious， it is necessary to strengthen the publicity and popularization of rational use of OTC drugs.

Pharmacological activities and pharmacokinetics of liquiritin: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Liquiritin is a flavonoid derived from Radix et Rhizoma Glycyrrhizae, which is a widely used traditional Chinese medicine with the effects of invigorating spleen qi, clearing heat, resolving toxins, and dispelling phlegm to stop coughs. AIM OF THE STUDY: In this review,the pharmacokinetics and pharmacological activities of liquiritin have been summarized. MATERIALS AND METHODS: The information on liquiritin up to 2021 was collected from PubMed, Web of Science, Springer Link, and China National Knowledge Infrastructure databases. The key words were "liquiritin", "nerve", "tumor", "cardiac", etc. RESULTS: The absorption mechanism of liquiritin conforms to the passive diffusion and first-order kinetics while with low bioavailability. Liquiritin can penetrate the blood-brain-barrier. Besides, liquiritin displays numerous pharmacological effects including anti-Alzheimer's disease, antidepressant, antitumor, anti-inflammatory, cardiovascular protection, antitussive, hepatoprotection, and skin protective effects. In addition, the novel preparations, new pharmacological effects,and cdusafty of liquiritin are also discussed in this review. CONCLUSION: This review provides a comprehensive state of knowledge on the pharmacokinetics and pharmacological activities of liquiritin, and makes a forecast for its research directions and applications in clinic.

Optimization of enzymatic synthesis of theaflavins from potato polyphenol oxidase.

Theaflavin (TF), a chemical component important in measuring the quality of fermented tea, has a strong natural antioxidant effect and many pharmacological functions. Enzymatic oxidation has become a widely used method for preparing TFs at the current research stage. Using plant exogenous polyphenol oxidase (PPO) to enzymatically synthesize TFs can significantly increase yield and purity. In this study, tea polyphenols were used as the reaction substrate to discuss the optimal synthesis conditions of potato PPO enzymatic synthesis of theaflavins and the main products of enzymatic synthesis of TFs. The optimal enzymatic synthesis conditions were as follows: pH of the reaction system was 5.5, reaction time was 150 min, substrate concentration was 6.0 mg/mL, reaction temperature was 20 °C, and the maximum amount of TFs produced was 651.75 µg/mL. At the same time, high-performance liquid chromatography was used to determine the content of theaflavins and catechins in the sample to be tested, and the dynamic changes and correlations of the main catechins and theaflavins in the optimal enzymatic system were analyzed. The results showed that epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG), and epigallocatechin gallate (EGCG) are all the main substrates synthesis of TFs. The main substrate of TFs and its strongest enzymatic catalytic effect on EGCG make theaflavin-3,3'-digallate (TFDG) the most important synthetic monomer. In this study, theaflavins were synthesized by polyphenol oxidase catalysis, which laid a foundation for industrialization of theaflavins.

Effect of music therapy on infants who underwent mechanical ventilation after cardiac surgery.

OBJECTIVE: To investigate the effect of music therapy on infants who underwent mechanical ventilation after cardiac surgery. METHODS: A prospective randomized controlled study was conducted in a provincial hospital in southeast China. The subjects were randomly divided into the music therapy (MT) group and the control group. Both groups were given standardized sedation treatment and routine nursing. Infants in the MT group received 60 min of MT three times a day. The sedation medication, Richmond sedation agitation scale (RASS) score, incidence of delirium, mechanical ventilation duration, length of cardiac intensive care unit (CICU) stay, restraint belt use time, and successful ventilation withdrawal rate were collected. RESULTS: Infants in the control group had a higher total amount of on-demand midazolam (p = .039). Infants in the MT group had a significantly lower incidence of delirium, shorter mechanical ventilation duration, and restraint band use time (p = .047, p = .046, and p = .038, respectively). Although infants in the MT group had a higher success rate of ventilation withdrawal, lower RASS scores, and shorter ICU stay, the difference was not statistically significant (p = .427, p = .585, and p = .068, respectively). CONCLUSION: MT in the ICU can reduce the use of on-demand sedative drugs, shorten mechanical ventilation, and reduce the occurrence of delirium in infants who underwent mechanical ventilation after cardiac surgery. MT is a safe and reliable treatment and worthy of clinical application.

Comparison of the Effectiveness of Music Video Therapy and Music Therapy on Pain after Cardiothoracic Surgery in Preschool Children.

OBJECTIVE: To explore the effects of music video therapy on pain among preschool children after cardiothoracic surgery. METHODS: Patients in the music video therapy (MVT) group received a 30-min music video intervention, while patients in the music therapy (MT) group received a 30-min musical intervention. Both groups were given their respective therapy three times a day for three days. Patients in the control group did not receive MVT or MV. Measures, including pain scores, vital signs (heart rate, mean arterial pressure, respiratory rate, and oxygen saturation), and other postoperative indicators were recorded and analyzed. RESULTS: The MVT group showed a statistically significant decrease in heart rate, mean arterial pressure, and respiratory rate at the first day after surgery and pain scores at the first and second day after surgery compared to the MT group, but no significant difference was identified in oxygen saturation. The postoperative indicators including cumulative capacity of sufentanil use, the length of intensive care unit (ICU) stay, and the length of hospital stay in the MVT group were significantly lower than those in the control group. CONCLUSION: The findings provide further evidence to support the practice of music video therapy as a non-pharmaceutical intervention to reduce postoperative pain, reduce  the dosage of analgesics, shorten the length of ICU and hospital stay in preschool children after the cardiothoracic surgery.

The music video therapy in postoperative analgesia in preschool children after cardiothoracic surgery.

OBJECTIVES: To observe the effect of music video (MV) therapy on early postoperative pain in preschool children after cardiothoracic surgery. METHODS: 116 preschool children undergoing cardiothoracic surgery were randomly divided into the MV and control groups from June 2019 to March 2020. The related vital signs parameters, the Wong-Baker FACES pain rating scale, the FLACC scale, the number of postoperative PCA press and the cumulants of sufentanil use were recorded and analyzed. RESULTS: There were no statistically significant differences in general characteristics and preintervention data between the two groups. However, there were significantly lower in the heart rate, mean arterial pressure, respiratory rate, the number of postoperative PCA press, and the dosage of sufentanil in the MV group than those in the control group after the intervention. The Wong-Baker FACES and FLACC scales in the MV group were significantly lower than those in the control group at the time point of immediately after the first intervention, 1 day, and 2 days after the intervention. The two pain scores showed a downward trend over time, and the corresponding scores in the MV group were better than those in the control group. CONCLUSION: MV therapy can be an effective nonpharmaceutical intervention in the clinical to relieve children's postoperative pain after cardiothoracic surgery.

Discovery of novel inhibitors against main protease (Mpro) of SARS-CoV-2 via virtual screening and biochemical evaluation.

SARS-CoV-2 is the pathogen that caused the global COVID-19 outbreak in 2020. Promising progress has been made in developing vaccines and antiviral drugs. Antivirals medicines are necessary complements of vaccines for post-infection treatment. The main protease (Mpro) is an extremely important protease in the reproduction process of coronaviruses which cleaves pp1ab over more than 11 cleavage sites. In this work, two active main protease inhibitors were found via docking-based virtual screening and bioassay. The IC50 of compound VS10 was 0.20 µM, and the IC50 of compound VS12 was 1.89 µM. The finding in this work can be helpful to understand the interactions of main protease and inhibitors. The active candidates could be potential lead compounds for future drug design.

1ß-OH-arenobufagin induces mitochondrial apoptosis in hepatocellular carcinoma through the suppression of mTOR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Chansu, dried secretions from Bufonidae, has long been used for cancer treatment as a traditional Chinese medicine. In searching for effective anti-hepatoma agents from Chansu, our preliminary drug screening found that a bufadienolide, namely 1ß-hydroxyl-arenobufagin (1ß-OH-ABF), displays anti-hepatoma activities. However, the anti-hepatoma effects and molecular mechanisms of 1ß-OH-ABF have not been defined. AIM OF THE STUDY: To evaluate the anti-hepatoma activity of 1ß-OH-ABF against liver cancer Hep3B and HepG2 cells in vitro and in vivo, as well as explore the underlying mechanisms. MATERIALS AND METHODS: The anti-proliferative effects of 1ß-OH-ABF on liver cancer Hep3B, HepG2, HuH7, SK-HEP-1 and normal hepatocyte LO2 cells were examined by MTT assay and colony formation assay. Hoechst 33258 staining and Annexin V-FITC/PI staining assay were used to analyze apoptosis induced by 1ß-OH-ABF. The collapse of the mitochondrial membrane potential (ΔΨm) was detected by JC-1 staining assay. Western blotting was used to examine the expression levels of targeted proteins. The role of mTOR in 1ß-OH-ABF-induced apoptosis was investigated using small interfering RNA (siRNA) transfection. Zebrafish xenograft model was established to evaluate the anti-hepatoma effects of 1ß-OH-ABF in vivo. RESULTS: We found that 1ß-OH-ABF inhibits the proliferation of Hep3B, HepG2, HuH7, SK-HEP-1 cells but has little cytotoxicity towards LO2 cells. 1ß-OH-ABF induces mitochondria dysfunction and triggers mitochondria apoptotic pathway, which is accompanied by the loss of ΔΨm, upregulation and translocation of Bax, as well as cleavages of caspase-9, caspase-3 and PARP. Mechanistically, 1ß-OH-ABF markedly decreases the expression level of p-AKT/AKT and p-mTOR (Ser2248 and Ser2481)/mTOR in a time-dependent manner. Inhibition of mTOR by siRNA strengthens 1ß-OH-ABF-mediated apoptosis. Critically, 1ß-OH-ABF shows a marked in vivo anti-hepatoma effect on human Hep3B cell xenografts in zebrafish model. CONCLUSION: 1ß-OH-ABF induces mitochondrial apoptosis through the suppression of mTOR signaling in vitro and in vivo, indicating that 1ß-OH-ABF may serve as a potential agent for the treatment of liver cancer.

Research Progress on G2/M Arrest in Breast Cancer Cells by Active Compounds of Traditional Chinese Medicine / 中国实验方剂学杂志

The global incidence of breast cancer has increased year by year. Breast cancer has the highest mortality rate in female patients with malignant tumors. Traditional Chinese medicine（TCM） has made great contribution to health of human being， improving the overall curative effect， reducing the patients' pain， improving the quality of life and alleviating adverse reactions in patients. TCM and its active compounds can inhibit the proliferation of breast cancer cells by inducing cell cycle arrest， invasion， metastasis and reversing multidrug resistance. The effect of the compounds in TCM is obvious on inducing the arrest of the breast cancer cells cycle. It′s a novel method to fight against breast cancer by influencing the progress of the breast cancer cell cycle and inducing the cell cycle arrest in breast cancer cells. Lots of studies have shown that the G2/M phase checkpoint which transition from gap-phase （G2 phase） to mitotic phase （M phase） in the cell cycle is the key point for cell survival or death. Many antitumor drugs can inhibit the proliferation of tumor cells through the cell cycle arrest. We summarized the domestic and foreign literatures in recent years， and comprehensively explained the research progress on the related regulatory molecules in G2/M arrest. In addition， we summarized and sorted out the researches on the methods and ways of alkaloids， polysaccharides， terpenes， flavonoids， saponins and other active compounds of TCM in inducing the G2/M arrest of human breast cancer cells. By summarizing the active compounds of various Chinese medicines in inducing G2/M arrest of breast cancer cells， and reviewing the research progress on mechanism of active TCM compounds for inhibiting the proliferation of breast cancer cells， we will， in this paper， investigate the mechanism of active TCM compounds for inhibiting the proliferation of breast cancer cells through inducing G2/M arrest of human breast cancer cells， so as to provide a scientific basis for in-depth research on the anti-breast cancer mechanism of the active compounds in TCM.

Comprehensive analysis of key biomarkers, immune infiltration and potential therapeutic agents for ulcerative colitis.

AIMS: There has been an increasing trend towards the ulcerative colitis (UC) incidence worldwide. The present study aimed to explore novel biomarkers and potential therapeutic agents for UC. MATERIALS AND METHODS: Differentially expressed genes (DEGs) among UC and healthy control samples were identified by GEO2R online tool. Functional analysis was performed and protein-protein interaction networks were constructed. The hub genes were explored by Cytoscape, and quantitative real-time-PCR (qRT-PCR) was used to valid their expression in clinical samples. ImmuCellAI was utilized to analyze the fraction of 24 types of immune cells. The L1000 platform was applied to determine potential agents for UC treatment. The dextran sulfate sodium (DSS)-induced colitis model was used to identify the therapeutic effect of meclofenamic acid. KEY FINDINGS: A total of 270 DEGs were identified among UC and healthy control samples. Functional analysis indicated that the DEGs were primarily enriched in several immune response and digestion pathways. A proportion of 18 immune-cell types was found to be significantly altered between UC and healthy control samples. 10 compounds were predicted to have therapeutic potentials for treating UC. Among them, we selected meclofenamic acid to identify its therapeutic effect on UC treatment by animal experiments. SIGNIFICANCE: The current study comprehensively analyzed the DEGs and immune infiltration in UC, as well as screened for potential agents for UC treatment.

Superconductivity enhancement in phase-engineered molybdenum carbide/disulfide vertical heterostructures.

Stacking layers of atomically thin transition-metal carbides and two-dimensional (2D) semiconducting transition-metal dichalcogenides, could lead to nontrivial superconductivity and other unprecedented phenomena yet to be studied. In this work, superconducting α-phase thin molybdenum carbide flakes were first synthesized, and a subsequent sulfurization treatment induced the formation of vertical heterolayer systems consisting of different phases of molybdenum carbide-ranging from α to γ' and γ phases-in conjunction with molybdenum sulfide layers. These transition-metal carbide/disulfide heterostructures exhibited critical superconducting temperatures as high as 6 K, higher than that of the starting single-phased α-Mo2C (4 K). We analyzed possible interface configurations to explain the observed moiré patterns resulting from the vertical heterostacks. Our density-functional theory (DFT) calculations indicate that epitaxial strain and moiré patterns lead to a higher interfacial density of states, which favors superconductivity. Such engineered heterostructures might allow the coupling of superconductivity to the topologically nontrivial surface states featured by transition-metal carbide phases composing these heterostructures potentially leading to unconventional superconductivity. Moreover, we envisage that our approach could also be generalized to other metal carbide and nitride systems that could exhibit high-temperature superconductivity.

[Time selection and course of treatment of cerebral resuscitation with hyperbaric oxygen].

OBJECTIVE: To explore the effect of treatment opportunity and course of hyperbaric oxygen (HBO) on the curative effect of cerebral resuscitation patients after successful cardiopulmonary resuscitation (CPR). METHODS: Eighty-nine patients who underwent cerebral resuscitation after CPR admitted to the second department of the First Hospital of Jilin University from June 2015 to June 2019 were enrolled. All patients underwent conventional drug therapy after admission, and HBO therapy was added on the basis of conventional drug therapy at different intervention times, and all patients received at least 3 courses of HBO treatment. Glasgow coma scale (GCS) score and amplitude-integrated electroencephalography (aEEG) score on different treatment opportunity (i.e. intervention of HBO within 12 hours, 12-72 hours, 4-7 days, 8-21 days after successful CPR) and different course of HBO (i.e. 1, 2 and 3 courses of treatment) were recorded. Repeated measurement analysis of variance was used to assess whether the treatment opportunity or course of treatment affects the GCS score and aEEG score. Then, paired sample t test was used to further analyze the results of repeated measurement analysis of variance and evaluate the specific effect of treatment course or intervention time on the efficacy. RESULTS: A total of 89 patients were enrolled. 8, 20, 33 and 28 patients started HBO treatment at < 12 hours, 12-72 hours, 4-7 days and 8-21 days after successful CPR. (1) GCS score: repeated measurement analysis of variance (the Greenhouse-Geisser correction method was used) showed that the effect of course of HBO treatment on GCS score was statistically significant (F = 71.735, P = 0.000). The interaction between the duration of HBO treatment and the timing of intervention was not statistically significant (F = 0.455, P = 0.817). Paired sample t test showed that the means of GCS scores before HBO treatment and treatment 1, 2, 3 courses were 3.56, 4.80, 5.55 and 6.49 respectively, and the difference of pairwise pairing between different groups were statistically significant (all P < 0.01). (2) aEEG score: repeated measurement analysis of variance (the Greenhouse-Geisser correction method was used) showed that the effect of course of HBO treatment on aEEG score was statistically significant (F = 96.965, P = 0.000).The interaction between the duration of HBO treatment and the timing of intervention was not statistically significant (F = 1.735, P = 0.112). Paired sample t test showed that the means of aEEG scores before HBO treatment and treatment 1, 2, 3 courses were 1.71, 2.21, 2.52 and 3.03 respectively (all P < 0.01). CONCLUSIONS: The effect of HBO on cerebral resuscitation after CPR is obvious. The longer the course of HBO is, the more significant the effect of cerebral resuscitation is. Within 21 days after successful CPR, the treatment opportunity of HBO had no significant effect on the effect of cerebral resuscitation.

Platycodin D alleviates liver fibrosis and activation of hepatic stellate cells by regulating JNK/c-JUN signal pathway.

Liver fibrosis is involved in the progression of most chronic liver diseases. Even though we have made a huge progress in order to understand the pathogenesis of liver fibrosis, however, there is still a lack of productive treatments. Being a traditional Chinese medicine, Platycodin D (PD), an oleanane kind of triterpenoid saponin has been put to extensive use for treating different kinds of illnesses that include not just anti-nociceptive, but also antiviral, anti-inflammatory, and anti-cancer for thousands of years. Nonetheless, there has been no clarification made for its effects on the progression of liver fibrosis. In this manner, we carried out in vitro studies for the purpose of investigating the anti-fibrosis impact of PD. Activation of hepatic stellate cells was evaluated by means of the detection of the proliferation of HSCs and the expression of specific proteins. We discovered the fact that PD had the potential of activating HSCs. Thereafter, we detected the apoptosis and autophagy of the HSCs; as the results suggested, PD induced apoptosis and autophagy of the HSCs. It augmented the expression level of apoptotic proteins that included Bax, Cytochrome C (cyto-c), cleaved caspase3 and cleaved caspase9, in addition to the autophagy relevant proteins, for instance, LC3II, beclin1, Atg5 and Atg9. Further research was carried out for the investigation of the underlying molecular mechanism, and discovered that PD promoted the phosphorylation of JNK and c-Jun. Treating the JNK inhibitor P600125 inhibited the effect of PD, confirming the impact of PD on the regulation of JNK/c-Jun pathway. Thus, we speculated that PD alleviates liver fibrosis and activation of hepatic stellate via promoting phosphorylation of JNK and c-Jun and further altering the autophagy along with apoptosis of HSCs.