Objective To clarify the expression and distribution of brain⁃derived neurotrophic factor (BDNF) in the cerebrum of plateau yaks and cattle, and to explore the relationship between BDNF function and the adaptability of altitude hypoxia. Methods Five yaks and five cattles were selected.The content and distribution of BDNF in frontal lobe, temporal lobe, parietal lobe, occipital lobe, cerebrum white matter and hippocampus of yak and cattle were analyzed by Real⁃time PCR, Western blotting and Immunohistochemistry. Results Real⁃time PCR result showed that BDNF mRNA expression in the cerebrum of yaks and cattles was highest in temporal cortex, followed by hippocampus, parietal cortex, occipital cortex and frontal cortex, and lowest in white matter. Western blotting results showed that the content of BDNF protein in the cerebrum of yaks was the highest in temporal cortex,followed by hippocampus. The content of BDNF protein in other tissues was parietal cortex, frontal cortex and cerebrum white matter, and the content of BDNF protein was the lowest in occipital cortex. The content of BDNF protein intlecerebrum of cattles was the highest in the temporal cortex, followed by the hippocampus. The content of BDNF protein in other tissues was parietal cortex, occipital cortex and frontal cortex in descending order, and the protein content in cerebrum white matter was the lowest. Immunohistochemical results showed that the positive expression of BDNF protein in the cerebrum of yaks and cattles was basically similar, mainly distributed in the granulosa cells and glial cells in the frontal cortex, temporal cortex, parietal cortex and occipital cortex, glial cells in cerebrum white matter, pyramidal cell layer and polyform cell layer in the hippocampus. There was the small amount of distribution in Martinotti cells and the molecular layer of hippocampus in the cerebral cortex. Conclusion BDNF mRNA and protein are distributed and expressed in different brain regions of yaks and cattles, but the expression level different, which is speculated to be closely related to the specific functions of different cerebrum regions. The expression level of the cerebrum of yak is higher than that of cattle except occipital cortex, suggesting that it is related to the altitude hypoxic environment. BDNF may play an important role in enhancing hypoxic tolerance and protecting internal environmental homeostasis in the process of animal adaptation to hypoxic environment.

The essence of cirrhosis is the over-repairing reaction of liver tissue damage in the process of chronic liver disease.During repair,the liver parenchyma is gradually replaced by fibrosis tissue,resulting in changes in liver tissue morphology,followed by portal hypertension and other related manifestations.Liver failure are serious disorder of liver functions(synthesis,metabolism,transformation,regeneration,etc.)caused by various factors,often mainly manifested as jaundice,coagulation disfunction,hepatic encephalopathy,ascites,etc.The naming and typing of the two are different,and they can exist independently of each other or intersect with each other.In recent years,with the in-depth exploration of cirrhosis and liver failure,many new definitions and classification methods have been put forward in the research.However,due to the confusion of classification methods,there is still a lack of summary,so this article briefly reviews the current progress of clinical classification of liver cirrhosis and liver failure and their differences and intersections.

Humans ; Cardiovascular Diseases ; Enhancer of Zeste Homolog 2 Protein/metabolism* ; Histones ; Methyltransferases

AIM To investigate the effects of Zhuangyao Shuanglu Tongnao Formula on neuronal apoptosis in rats with cerebral ischemia-reperfusion injury based on the study of oxidative stress and inflammatory response.METHODS The rats were randomly divided into the sham operation group,the model group,the edaravone group(3.0 mg/kg),the low,medium and high dose groups(9.0,18.0,36.0 g/kg)of Zhuangyao Shuanglu Tongnao Formula,with 18 rats in each group.The middle cerebral artery occlusion/reperfusion was conducted by thread embolism method to simulate cerebral ischemia reperfusion injury in rats followed by 6 days corresponding drugs administration.Subsequently,the rats had their neurological function deficit scored by Zeal Longa scoring method;their sizes of cerebral infarction areas measured by TTC staining;their pathological damage and apoptosis of neurons in hippocampal CA1 area of ischemic penumbra of the brain tissue detected by HE staining and TUNEL staining;their SOD activity and levels of GSH,MDA,IL-6,IL-1β,TNF-α in brain tissue detected by kits;and their protein expressions of Bax,Bcl-2,caspase-3,cleaved-capase-3,TLR4,NF-κB p65,Nrf2,HO-1 in rat brain tissue determined by Western blot.RESULTS Compared with the model group,the groups intervened with edaravone,medium and high dose of Zhuangyao Shuanglu Tongnao Formula displayed improvements in the scores of nerve function defects,the rate of cerebral infarction,the rate of neuronal apoptosis,the levels of IL-6,IL-1β,TNF-α and MDA in the ischemic penumbra of brain tissues,the protein expressions of Bax and TLR4,the ratio of cleaved-capase-3/caspase-3 and p-NF-κB p65/NF-κB p65(P＜0.05),the levels of GSH,the activity of SOD and the protein expressions of Bcl-2,Nrf2 and HO-1(P＜0.05).CONCLUSION Being an inhibitor of oxidative stress and inflammatory response,Zhuangyao Shuanglu Tongnao Formula can alleviate brain injury in rats with cerebral ischemia reperfusion injury through the inhibition of neuronal apoptosis and improvement of neural function mediated by the inhibition of TLR4/NF-κB signal pathway and activation of Nrf2/HO-1 signal pathway.

AIM To explore the effect of Compound Fo'ercao Mixture on TLR4/MyD88/NF-κB signaling pathway in a rat model of chronic obstructive pulmonary disease(COPD).METHODS Rats were randomly divided into the blank group(n=10),and the model group(n=50)for the establishment of a rat model of COPD by 12-week cigarette smoke exposure combined with intratracheal injection of LPS.The successful rat models were randomly divided into the model group,the dexamethasone group(0.5 mg/kg)and the low,medium and high dose Compound Fo'ercao Mixture groups(6.8,13.6 and 27.2 g/kg),with 10 rats in each group.After 24 weeks of drug intervention,the rats had their lung function detected by animal lung function meter;their pathological changes of lung tissue observed by HE staining;their serum TNF-α,IL-1β,IL-6,and MDA levels and SOD activity detected by ELISA;their pulmonary mRNA expressions of TLR4,MyD88,NF-κB and caspase-3 detected by RT-qPCR;and their pulmonary protein expressions of TLR4,MyD88,NF-κB and TNF-α detected by Western blot.RESULTS Compared with the blank group,the model group displayed obviously pulmonary ventilation dysfunction,damaged lung tissue and bronchus,decreased SOD activity(P＜0.01);increased serum TNF-α,IL-1β,IL-6 and MDA levels(P＜0.01);and increased pulmonary expressions of TLR4,MyD88,NF-κB and caspase-3 mRNA and TLR4,MyD88,NF-κB and TNF-α proteins(P＜0.01).Compared with the model group,all Compound Fo'ercao Mixture groups shared improvement in lung function indices levels and lung tissue damage;decrease in the levels of serum TNF-α,IL-1β,IL-6 and MDA(P＜0.05,P＜0.01);and decrease in the pulmonary expressions of TLR4,MyD88,NF-κB and caspase-3 mRNA and TLR4,MyD88,NF-κB and TNF-α protein(P＜0.05,P＜0.01)in a dose-dependent manner.CONCLUSION Compound Fo'ercao Mixture can improve the lung dysfunction and pathological injury in a rat model of COPD,and its mechanism may be associated with the regulated TLR4/MyD88/NF-κB signaling pathway.

This study using maltodextrin as raw material, 1%-5% polyvinylpyrrolidone K30 as template agent, 1%-5% ammonium bicarbonate as pore-forming agent, curcumin and ibuprofen as model drugs. Porous maltodextrin was prepared by template and pore-forming agent methods, respectively. The structure and drug delivery behavior of porous maltodextrin prepared by different technologies were comprehensively characterized. The results showed that the porous maltodextrin prepared by pore-forming agent method had larger specific surface area (6.449 4 m²·g^-1) and pore size (32.804 2 nm), which was significantly better than that by template agent method (3.670 2 m²·g^-1, 15.278 5 nm). The adsorption kinetics between porous maltodextrin prepared by pore-forming agent method and curcumin were suitable for quasi-first order adsorption kinetic model, and that between porous maltodextrin and ibuprofen were suitable for quasi-second order adsorption kinetic model. While the adsorption kinetics between porous maltodextrin prepared by template agent method and two model drugs were both suitable for the quasi-first order adsorption kinetic model. In addition, the dissolution behavior analysis showed that the porous maltodextrin prepared by the two technologies can significantly improve the dissolution behavior of insoluble drugs, and the drug release was both carried out by diffusion mechanism, which suitable for the Peppas kinetic release model, but the porous maltodextrin prepared by template agent method had a faster release rate. The change of nozzle diameter had no significant effect on the adsorption process and drug release behavior of porous maltodextrin. In conclusion, the porous maltodextrins prepared by two different technologies were both beneficial to the delivery of insoluble drugs, and the template agent method was the best for delivery of insoluble drugs. This study can provide theoretical basis for the preparation of porous particles, promote the application of porous particles in insoluble drugs, and improve the bioavailability of insoluble drugs.

Humans ; Cardiovascular Diseases ; Enhancer of Zeste Homolog 2 Protein/metabolism* ; Histones ; Methyltransferases

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

The expression level of NOD-like receptors(NLRP3)inflammasome is significantly elevated in breast cancer tissues,and a high level of NLRP3 inflammasomes is closely associated with breast cancer metastasis.Activation of NLRP3 inflammasome can induce the release of inflammatory factors into the tumor microenvironment(TME).These inflammatory factors,by signaling to cancer cells,reshape the TME to promote tumor growth and invasion,ultimately facilitating the process of epithelial-mesenchymal transition.This equips cancer cells with the ability to establish distant metastases and increase the formation of metastatic lesions.This review addresses the current research status and prospects of NLRP3 inflammasomes in the breast cancer TME and their role in breast cancer metastasis.The goal is to provide new insights for the study of breast cancer metastasis mechanisms and treatment strategies.

Therapeutic mRNA vaccine for tumors attracted much attention as a new type of tumor treatment,and most products are in the preclinical and clinical research stage,and there has not post-market drug.However,the non-clinical evaluation of therapeutic mRNA vaccines for tumors is more complicated,due to their target features,mechanisms,delivery patterns,and the cross-species differences of immune system.The choice of animal model is not only content of the clinical effectiveness,and it was a key factor of toxicity assessment.In this work,the challenges for non-clinical evaluation of therapeutic mRNA vaccines for tumors are discussed,and the compliant requirements are reviewed,and the general considerations are suggested.