Safety and feasibility of enhanced recovery after surgery-based management model for ambulatory pediatric surgical procedures.

BACKGROUND: There is still some room for optimizing ambulatory pediatric surgical procedures, and the preoperative and postoperative management quality for pediatric patients needs to be improved. AIM: To discuss the safety and feasibility of the enhanced recovery after surgery (ERAS)-based management model for ambulatory pediatric surgical procedures. METHODS: We selected 320 pediatric patients undergoing ambulatory surgery from June 2023 to January 2024 at The First People's Hospital of Liangshan Yi Autonomous Prefecture. Of these, 220 received ERAS-based management (research group) and 100 received routine management (control group). General information, postoperative ambulation activities, surgical outcomes (operation time, postoperative gastrointestinal ventilation time, and hospital stay), postoperative pain visual analogue scale, postoperative complications (incision infection, abdominal distension, fever, nausea, and vomiting), and family satisfaction were compared. RESULTS: The general information of the research group (sex, age, disease type, single parent, family history, etc.) was comparable to that of the control group (P > 0.05), but the rate of postoperative (2 h, 4 h, and 6 h after surgery) ambulation activities was statistically higher (P < 0.01), and operation time, postoperative gastrointestinal ventilation time, and hospital stay were markedly shorter (P < 0.05). The research group had lower visual analogue scale scores (P < 0.01) at 12 h and 24 h after surgery and a lower incidence of total postoperative complications than the control group (P = 0.001). The research group had higher family satisfaction than the control group (P = 0.007). CONCLUSION: The ERAS-based management model was safe and feasible in ambulatory pediatric surgical procedures and worthy of clinical promotion.

SMAD4 endows TGF-ß1-induced highly invasive tumor cells with ferroptosis vulnerability in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy prone to recurrence and metastasis. Studies show that tumor cells with increased invasive and metastatic potential are more likely to undergo ferroptosis. SMAD4 is a critical molecule in the transforming growth factor ß (TGF-ß) pathway, which affects the TGF-ß-induced epithelial-mesenchymal transition (EMT) status. SMAD4 loss is observed in more than half of patients with PDAC. In this study, we investigated whether SMAD4-positive PDAC cells were prone to ferroptosis because of their high invasiveness. We showed that SMAD4 status almost determined the orientation of transforming growth factor ß1 (TGF-ß1)-induced EMT via the SMAD4-dependent canonical pathway in PDAC, which altered ferroptosis vulnerability. We identified glutathione peroxidase 4 (GPX4), which inhibited ferroptosis, as a SMAD4 down-regulated gene by RNA sequencing. We found that SMAD4 bound to the promoter of GPX4 and decreased GPX4 transcription in PDAC. Furthermore, TGF-ß1-induced high invasiveness enhanced sensitivity of SMAD4-positive organoids and pancreas xenograft models to the ferroptosis inducer RAS-selective lethal 3 (RSL3). Moreover, SMAD4 enhanced the cytotoxic effect of gemcitabine combined with RSL3 in highly invasive PDAC cells. This study provides new ideas for the treatment of PDAC, especially SMAD4-positive PDAC.

A new glance at autophagolysosomal-dependent or -independent function of transcriptional factor EB in human cancer.

Autophagy-lysosome system plays a variety of roles in human cancers. In addition to being implicated in metabolism, it is also involved in tumor immunity, remodeling the tumor microenvironment, vascular proliferation, and promoting tumor progression and metastasis. Transcriptional factor EB (TFEB) is a major regulator of the autophagy-lysosomal system. With the in-depth studies on TFEB, researchers have found that it promotes various cancer phenotypes by regulating the autophagolysosomal system, and even in an autophagy-independent way. In this review, we summarize the recent findings about TFEB in various types of cancer (melanoma, pancreatic ductal adenocarcinoma, renal cell carcinoma, colorectal cancer, breast cancer, prostate cancer, ovarian cancer and lung cancer), and shed some light on the mechanisms by which it may serve as a potential target for cancer treatment.

Lactate-induced protein lactylation: A bridge between epigenetics and metabolic reprogramming in cancer.

Lactate is not only an endpoint of glycolysis but is gradually being discovered to play the role of a universal metabolic fuel for energy via the 'lactate shuttle' moving between cells and transmitting signals. The glycolytic-dependent metabolism found in tumours and fast-growing cells has made lactate a pivotal player in energy metabolism reprogramming, which enables cells to obtain abundant energy in a short time. Moreover, lactate can provide favourable conditions for tumorigenesis by shaping the acidic tumour microenvironment, recruiting immune cells, etc. and the recently discovered lactate-induced lactylation moves even further on pro-tumorigenesis mechanisms of lactate production, circulation and utilization. As with other epigenetic modifications, lactylation can modify histone proteins to alter the spatial configuration of chromatin, affect DNA accessibility and regulate the expression of corresponding genes. What's more, the degree of lactylation is inseparable from the spatialized lactate concentration, which builds a bridge between epigenetics and metabolic reprogramming. Here, we review the important role of lactate in energy reprogramming, summarize the latest finding of lactylation in tumorigenesis and try to explore therapeutic strategies in oncotherapy that can kill two birds with one stone.

Hernandezine induces autophagic cell death in human pancreatic cancer cells via activation of the ROS/AMPK signaling pathway.

Hernandezine (Her) is a bisbenzylisoquinoline alkaloid extracted from the traditional Chinese herbal medicine Thalictrum glandulosissimum. Evidence shows that Her is a natural agonist of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and induces apoptosis and autophagy in tumor cells. In this study, we investigated the role of autophagy in Her-induced cell death in human pancreatic cancer cell lines. We showed that Her dose-dependently suppressed cell proliferation, promoted autophagy and induced autophagic death in pancreatic ductal adenocarcinoma (PDAC) cell lines Capan-1 and SW1990. The IC50 values of Her in inhibition of Capan-1 and SW1990 cells were 47.7 µM and 40.1 µM, respectively. Immunoblotting showed that Her (1-40 µM) promoted the conversion of LC3-I to LC3-II, and Her exerted concentration-dependent and time-dependent effects on autophagy activation in PDAC cells. In transmission electron microscopy and fluorescence image analysis, we found that autophagic vacuoles were significantly increased in Her-treated cells. Knockdown of ATG5, a key gene in the autophagy pathway, alleviated the activation of autophagy by Her. These results demonstrated that Her induced autophagy in PDAC cells. Intensely activated autophagy could promote cell death. The autophagy inhibitors, BafA1 and HCQ significantly inhibited Her-induced cell death, implying that Her induced autophagic cell death in PDAC cells. Moreover, we showed that Her activated autophagy by increasing the phosphorylation of AMPK and decreasing the phosphorylation of mTOR/p70S6K. Knockdown of AMPKα relieves the autophagic cell death induced by Her. Furthermore, Her concentration-dependently enhanced reactive oxygen species (ROS) generation in PDAC cells. Antioxidants could reduce the phosphorylation of AMPK and suppress autophagic cell death induced by Her. Our study provides evidence for the development of Her as a therapeutic agent for the treatment of pancreatic cancer.

Effect of nursing intervention based on Maslow's hierarchy of needs in patients with coronary heart disease interventional surgery.

BACKGROUND: It is very important to provide effective nursing programs to regulate the physical and mental state of patients and to improve treatment compliance after interventional surgery for coronary heart disease (CHD). AIM: To explore the effect of a nursing intervention based on Maslow's hierarchy of needs theory on patients with CHD undergoing percutaneous coronary intervention. METHODS: Ninety-four patients with CHD undergoing interventional surgery in our hospital from January 2020 to February 2021 were randomly divided into a research group (n = 47) and a control group (n = 47). The control group received routine nursing, and the research group received a nursing intervention based on Maslow's hierarchy of needs theory. The scores of self-efficacy, negative emotion [depression (SDS), anxiety (SAS)], intervention compliance (standardized medication, moderate exercise, healthy diet, and regular review), and nursing satisfaction were calculated before and after intervention for the two groups. RESULTS: Before intervention, there was no significant difference in the scores of disease general management self-efficacy, disease management self-efficacy, and total self-efficacy between the two groups (P = 0.795, 0.479, and 0.659, respectively). After intervention, these three scores in the research group were higher than those in the control group (P < 0.001). Before intervention, there was no significant difference in the scores of SAS and SDS between the two groups (P = 0.149 and 0.347, respectively). After intervention, the scores of SAS and SDS in the research group were lower than those in the control group (P < 0.001). The standardized drug use rate (97.87%), moderate exercise rate (97.87%), healthy diet rate (95.74%), and regular reexamination rate (97.87%) in the research group were higher than those in the control group (85.11%, 82.98%, 80.85%, and 87.23%, respectively) (P = 0.027, 0.014, 0.025, and 0.049, respectively). Nursing job satisfaction in the research group (93.62%) was higher than that in the control group (78.72%) (P = 0.036). CONCLUSION: A nursing program based on Maslow's hierarchy of needs theory can effectively alleviate negative emotion, enhance self-efficacy and intervention compliance, and ensure that the patients are highly satisfied with the nursing work.

Plasma membrane targeted photodynamic O2 economizer for hypoxic tumor therapy.

The development of photodynamic therapy (PDT) is severely limited by short half-life of singlet oxygen (1O2) and the hypoxic microenvironment. In this work, a plasma membrane targeted photodynamic O2 economizer (designated as P-POE) is developed to improve the subcellular delivery of photosensitizers and alleviate the tumor hypoxia for enhanced PDT effect. After self-assembly into nanomicelles, P-POE has a relatively high stability and a favorable photochemical performance, which are conducive to boosting the 1O2 production. Besides, the plasma membrane anchoring of P-POE contributes to enhancing the preferential retention and cellular accumulation of photosensitizers on tumor tissues and cells. More importantly, P-POE-induced mitochondrial respiratory depression is demonstrated to reduce the O2 consumption of tumor cells to relieve the hypoxia. Consequently, P-POE still exhibits a robust PDT effect against hypoxic tumors, which greatly inhibits the proliferation of breast cancer with low adverse reactions. This innovative combination of subcellular targeting and hypoxic alleviation would advance the development of individualized drug delivery systems for photodynamic therapy against hypoxic tumors.

Dataset of full-length transcriptome assembly and annotation of apocynum venetum using pacbio sequel II.

Apocynum venetum, which belongs to Apocynaceae, is widely distributed throughout salt-barren zones, desert steppes, and alluvial flats of the Mediterranean area and Northwestern China. Apocynum venetum has long been used in traditional Chinese medicine because of its anti-inflammation, anti-oxidative, anti-hypertensive, anti-cancer, and bactericidal effects. However, the absence of genetic information on Apocynum venetum is an obstacle to understanding its stress resistance or medicinal function. This work was aimed at generating a full-length transcriptome of Apocynum venetum using Pacific Bioscience (PacBio) Single Molecule Real-Time (SMRT) sequencing technology. A total of 18,524 unigenes were obtained, and 18,136 unigenes were successfully annotated. The raw data were uploaded to SRA database, and the BioProject ID is PRJNA650225. The above data will provide the basis for further exploration and understanding of the molecular mechanism in stress resistance or medicinal function of Apocynum venetum.

Tumor targeted self-synergistic nanoplatforms for arsenic-sensitized photodynamic therapy.

Development of antitumor agents with high efficiency and low toxicity is one of the most important goals for biomedical research. However, most traditional therapeutic strategies were limited due to their non-specificity and abnormal tumor microenvironments, causing a poor therapeutic efficiency and severe side effects. In this paper, a tumor targeted self-synergistic nanoplatform (designated as PAO@PCN@HA) was developed for chemotherapy sensitized photodynamic therapy (PDT) against hypoxic tumors. The efficient drug loading of phenylarsine oxide (PAO) in porphyrinic metal organic framework of PCN-224 as well as the surface modification of hyaluronic acid (HA) improved the targeted drug delivery and reduced the side effects of PAO at the therapeutic dose. Particularly, PAO as an arsenical-based chemotherapeutic agent could not only induce cell apoptosis by generating reactive oxygen species (ROS), but also regulate tumor microenvironments to improve the PDT effect of PCN-224 by mitigating hypoxia and consuming cellular GSH. Both in vitro and in vivo investigations confirmed an effective self-synergy of PAO@PCN@HA in hypoxic tumor therapy with a low systemic toxicity. This integration of microenvironment adjustment with tumor targeted self-synergistic mechanism might provide a new insight for the development of arsenic-based antitumor strategy for clinical applications.

Self-Delivery Photodynamic Nanoinhibitors for Tumor Targeted Therapy and Metastasis Inhibition.

Simultaneous inhibitions of primary tumor growth and distant metastasis are very critical for cancer patients to improve their survival and cure rates. Although photodynamic therapy (PDT) shows great potential for primary tumor treatment, it often exacerbates hypoxia with a reduced therapeutic efficacy and subsequently contributes to carcinoma progression and metastatic dissemination. To solve these issues, self-delivery photodynamic nanoinhibitors (PNI) are developed for tumor targeted therapy and metastasis inhibition. PNI are composed of a carbonic anhydrase inhibitor (CAi), a hydrophilic poly(ethylene glycol) (PEG) linker, and a hydrophobic photosensitizer protoporphyrin IX (PpIX). Such self-delivery design of PNI avoids the premature release and heterogeneous distribution of CAi and PpIX to enhance the availability and synergism. Briefly, the CAi-based nanoinhibitors improve the selectivity of CAi for specific recognition and inhibition of tumor-associated isoform carbonic anhydrase (CA) IX, which would not only facilitate the targeted drug delivery of PNI but also regulate the hypoxia-induced signaling cascade and PDT resistance. Benefiting from the CA IX inhibition and targeted PDT, PNI exhibit a robust inhibitory effect on primary tumor growth and distant metastasis. This targeted self-delivery strategy sheds light on the photosensitizer-based molecular design to overcome the defect of traditional PDT.

Epigenetics-inspired photosensitizer modification for plasma membrane-targeted photodynamic tumor therapy.

In recent years, epigenetics has attracted great attentions in the field of biomedicine, which is used to denote the heritable changes in gene expression without any variation in DNA sequence, including DNA methylation, histone modification and so on. Inspired by it, a simple and versatile amino acids modification strategy is proposed in this paper to regulate the subcellular distribution of photosensitizer for plasma membrane targeted photodynamic therapy (PDT). Particularly, the plasma membrane anchoring ability and photo toxicity of the photosensitizer against different cell lines could be effectively manipulated at a single amino acid level. Systematic researches indicate that the number and variety of amino acids have a significant influence on the plasma membrane targeting effect of the photosensitizer. Furthermore, after self-assembling into nanoparticles, the obtained nano photosensitizers (NPs) also exhibit a good biocompatibility and plasma membrane targeting ability, which are conducive to enhancing the PDT therapeutic effect under light irradiation. Both in vitro and in vivo investigations confirm a robust tumor inhibition effect of NPs with a good biocompatibility. This epigenetics-inspired photosensitizer modification strategy would contribute to the development of structure-based drug design for tumor precision therapy.

Chimeric peptide engineered exosomes for dual-stage light guided plasma membrane and nucleus targeted photodynamic therapy.

Targeted delivery of the drug to its therapeutically active site with low immunogenicity and system toxicity is critical for optimal tumor therapy. In this paper, exosomes as naturally-derived nano-sized membrane vesicles are engineered by chimeric peptide for plasma membrane and nucleus targeted photosensitizer delivery and synergistic photodynamic therapy (PDT). Importantly, a dual-stage light strategy is adopted for precise PDT by selectively and sequentially destroying the plasma membrane and nucleus of tumor cells. Briefly, plasma membrane-targeted PDT of chimeric peptide engineered exosomes (ChiP-Exo) could directly disrupt the membrane integrity and cause cell death to some extent. More interestingly, the photochemical internalization (PCI) and lysosomal escape triggered by the first-stage light significantly improve the cytosolic delivery of ChiP-Exo, which could enhance its nuclear delivery due to the presence of nuclear localization signals (NLS) peptide. Upon the second-stage light irradiation, the intranuclear ChiP-Exo would activate reactive oxygen species (ROS) in situ to disrupt nuclei for robust and synergistic PDT. Based on exosomes, this dual-stage light guided subcellular dual-targeted PDT strategy exhibits a greatly enhanced therapeutic effect on the inhibition of tumor growth with minimized system toxicity, which also provides a new insight for the development of individualized biomedicine for precise tumor therapy.

Effect of ß-patchoulene on cerebral ischemia-reperfusion injury and the TLR4/NF-κB signaling pathway.

ß-patchoulene (ß-PAE), an active constituent of the Pogostemon cablin, is well known for its anti-inflammatory and antioxidative functions in various diseases. However, little is known about the impact of ß-PAE on the cerebral ischemia-reperfusion (I/R) injury. The current study aimed to determine the neuroprotective effect of ß-PAE and the underlying mechanisms on cerebral I/R injury. Following pretreatment with ß-PAE (10 mg/kg body weight) by tail intravenous injection for 1 h, Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 2 h and reperfusion for 24 h. The results indicated that pretreatment with ß-PAE could diminish the infarct volume, decrease the brain water content, reduce the neurological deficit score and restore the mitochondrial membrane potential, compared with the untreated I/R injury group. Furthermore, cell apoptosis was markedly suppressed by ß-PAE, and this effect was associated with the decreased apoptosis regulator BAX/apoptosis regulator Bcl-2 expression ratio and caspase-3 activity. In addition, ß-PAE significantly inhibited the release of proinflammatory factors, including tumor necrosis factor-α, interleukin (IL)-1ß and IL-6. Superoxide generation and malondialdehyde levels were reduced while the levels of glutathione peroxidase and superoxide dismutase were elevated following treatment with ß-PAE, indicating the antioxidative role of ß-PAE in cerebral I/R injury. Furthermore, the Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway was inhibited by ß-PAE, as demonstrated by the decreased TLR4 expression and nuclear translocation of p65, and increased IκBα level. Taken together, the results suggested that ß-PAE may exhibit a neuroprotective effect on cerebral I/R injury in rats through inactivating the TLR4/NF-κB signaling pathway.

Ratiometric theranostic nanoprobe for pH imaging-guided photodynamic therapy.

An abnormal pH microenvironment results from the development of tumors, and also affects the therapeutic efficiency of anti-tumor drugs. In this work, a Förster resonance energy transfer (FRET)-based theranostic fluorescent nanoprobe was constructed for simultaneous ratiometric pH sensing and tumor-targeted photodynamic therapy. Based on the FRET process between rhodamine B and protoporphyrin IX (PpIX), the fabricated nanoprobe exhibited excellent pH responsiveness in both solutions and live cells with the ratiometric fluorescence changes. Moreover, this ratiometric pH fluorescent nanoprobe also possessed the capability for pH-responsive singlet oxygen (1O2) generation under light irradiation, guiding robust photodynamic therapy in a pH-dependent manner. Benefiting from the enhanced permeability and retention (EPR) effect, the nanoprobe could significantly inhibit tumor growth and metastasis via targeted photodynamic therapy in vivo. This work presents a novel paradigm for precise tumor theranostics by ratiometric pH fluorescence imaging-guided photodynamic therapy.

A biomimetic cascade nanoreactor for tumor targeted starvation therapy-amplified chemotherapy.

Targeted drug delivery with precisely controlled drug release and activation is highly demanding and challenging for tumor precision therapy. Herein, a biomimetic cascade nanoreactor (designated as Mem@GOx@ZIF-8@BDOX) is constructed for tumor targeted starvation therapy-amplified chemotherapy by assembling tumor cell membrane cloak and glucose oxidase (GOx) onto zeolitic imidazolate framework (ZIF-8) with the loading prodrug of hydrogen peroxide (H2O2)-sensitive BDOX. Biomimetic membrane camouflage affords superior immune evasion and homotypic binding capacities, which significantly enhance the tumor preferential accumulation and uptake for targeted drug delivery. Moreover, GOx-induced glycolysis would cut off glucose supply and metabolism pathways for tumor starvation therapy with the transformation of tumor microenvironments. Importantly, this artificial adjustment could trigger the site-specific BDOX release and activation for cascade amplified tumor chemotherapy regardless of the complexity and variability of tumor physiological environments. Both in vitro and in vivo investigations indicate that the biomimetic cascade nanoreactor could remarkably improve the therapeutic efficacy with minimized side effects through the synergistic starvation therapy and chemotherapy. This biomimetic cascade strategy would contribute to developing intelligent drug delivery systems for tumor precision therapy.

Mitochondria and plasma membrane dual-targeted chimeric peptide for single-agent synergistic photodynamic therapy.

Mitochondria and cell membrane play important roles in maintaining cellular activity and stability. Here, a single-agent self-delivery chimeric peptide based nanoparticle (designated as M-ChiP) was developed for mitochondria and plasma membrane dual-targeted photodynamic tumor therapy. Without additional carrier, M-ChiP possessed high drug loading efficacy as well as the excellent ability of producing reactive oxygen species (ROS). Moreover, the dual-targeting property facilitated the effective subcellular localization of photosensitizer protoporphyrin IX (PpIX) to generate ROS in situ for enhanced photodynamic therapy (PDT). Notably, plasma membrane-targeted PDT would enhance the membrane permeability to improve the cellular delivery of M-ChiP, and even directly disrupt the cell membrane to induce cell necrosis. Additionally, mitochondria-targeted PDT would decrease mitochondrial membrane potential and significantly promote the cell apoptosis. Both in vitro and in vivo investigations indicated that this combinatorial PDT in mitochondria and plasma membrane could achieve the therapeutic effect maximization with reduced side effects. The single-agent self-delivery system with dual-targeting strategy was demonstrated to be a promising nanoplatform for synergistic tumor therapy.

A Theranostic Nanoprobe for Hypoxia Imaging and Photodynamic Tumor Therapy.

Hypoxia is a common feature for most malignant tumors, which was also closely related to the oxygen-dependent photodynamic therapy. Based on Förster resonance energy transfer (FRET), a smart nanoprobe (designated as H-Probe) was designed in this paper for hypoxia imaging and photodynamic tumor therapy. Due to the FRET process, H-Probe could respond to hypoxia with a significant fluorescence recovery. Moreover, abundant in vitro investigations demonstrated that the photosensitizer of PpIX in H-Probe could generate large amounts of singlet oxygen to kill cancer cells in the presence of oxygen and light with appropriate wavelength. Also, intravenously injected H-Probe with light irradiation achieved an effective tumor inhibition in vivo with a reduced side effect. This original strategy of integrating hypoxia imaging and tumor therapy in one nanoplatform would promote the development of theranostic nanoplatform for tumor precision therapy.

A Self-Delivery Chimeric Peptide for Photodynamic Therapy Amplified Immunotherapy.

In this paper, a self-delivery chimeric peptide PpIX-PEG8 -KVPRNQDWL is designed for photodynamic therapy (PDT) amplified immunotherapy against malignant melanoma. After self-assembly into nanoparticles (designated as PPMA), this self-delivery system shows high drug loading rate, good dispersion, and stability as well as an excellent capability in producing reactive oxygen species (ROS). After cellular uptake, the ROS generated under light irradiation could induce the apoptosis and/or necrosis of tumor cells, which would subsequently stimulate the anti-tumor immune response. On the other hand, the melanoma specific antigen (KVPRNQDWL) peptide could also activate the specific cytotoxic T cells for anti-tumor immunity. Compared to immunotherapy alone, the combined photodynamic immunotherapy exhibits significantly enhanced inhibition of melanoma growth. Both in vitro and in vivo investigations confirm that PDT of PPMA has a positive effect on anti-tumor immune response. This self-delivery system demonstrates a great potential of this PDT amplified immunotherapy strategy for advanced or metastatic tumor treatment.

ROS-driven and preferential killing of HepG2 over L-02 cells by a short-term cooperation of Cu(II) and a catechol-type resveratrol analog.

This study was aimed at understanding why dietary polyphenols with a catechol skeleton tend to exhibit cancer chemopreventive activity by using a catechol-type stilbene (3,4-DHS) as a model molecule. Only a short-term cooperation of 3,4-DHS and exogenous Cu(II) exhibited a strong preferential ability to kill HepG2 cells over normal L02 cells. Mechanism studies reveal that this 3,4-DHS/Cu(II) system could produce extracellularly reactive oxygen species (ROS) and o-quinone through two sequential proton loss electron transfer followed by diffusion of ROS into cells, leading to higher intracellular accumulation of ROS, preferential disruption of redox homeostasis and more effective mitochondria-dependent apoptosis as well as necrosis of HepG2 cells than L-02 cells. This work provides further evidence that dietary catechol-type molecules show chemopreventive activity by virtue of their copper-dependent prooxidant action.

Model-based evaluation of 5 Chinese medicine recipes in the treatment of H5N1 influenza virus infection in BALB/c mice.

OBJECTIVE: To investigate whether Chinese medicine (CM) recipes could ameliorate H5N1 influenza virus infection in BALB/c mice model. METHODS: BALB/c mice were orally administrated with 5 CM recipes (removing toxin, tonifying qi, cooling blood, laxation, and compound recipes), oseltamivir, or saline solution respectively for 5 consecutive days after the infection of H5N1 influenza virus. Series of indices were employed to evaluate the amelioration of the 5 CM recipes on infection, including clinical assessment, gross observation, histopathologic findings, cytokine levels and viral burden in the lungs. RESULTS: Two CM recipes (cooling blood and compound recipes) could postpone the death period of the mice infected with high-dose H5N1 influenza virus (P< 0.05). And for the mice infected with low-dose H5N1 influenza virus, CM recipes could significantly reduce the mortality and inhibit viral proliferation in the lungs as compared with the control group (P<0.05). There was no significant difference in lung coefficients between the treatment and the control groups, but histopathological findings in the lungs were improved in CM recipes groups compared to control group findings. A transient increase was observed in pro-inflammatory and anti-inflammatory cytokines during the first 6 days of infection. The levels of interleukin (IL)-12p40 and interferon-gamma of the treatment groups were significantly lower than that of the control group at day 3 post-infection (P<0.05), while only compound recipe were significantly lower in level of tumor necrosis factor alpha than the control (P<0.05). The level of IL-10 of the control was higher than others, and the differences between the control and cooling blood, removing toxin recipes were significant (P<0.05). CONCLUSIONS: Results of this study suggested the potentials of the CM recipes in ameliorating influenza virus infection by suppressing viral proliferations, improving histopathological lesions, and inhibition of over expression of inflammatory cytokines.