Pain is one of the most common symptoms in cancer patients. Apart from causing patients to suffer from unpleasant feelings and negative emotional experiences, uncontrolled pain may also influence patients' function and quality of life, and may be associated with poorer prognosis. Poor management of chronic cancer-related pain may be related to its complicated mechanisms, limitations of current clinical treatment and clinicians' and patients' insufficient understanding of the symptom. Therefore, this review summarizes the definitions, classifications, evaluation and treatment principles of chronic cancer-related pain, and emphasises the importance of multidisciplinary management and patient education in cancer pain management to provide clinicians with the overall idea of pain management in adult cancer patients.

Objective : To explore the mechanism of hippocampal corticotropin-releasing hormone ( CRH) receptor type 1 ( CRHR1 ) in chronic stress-induced learning and memory impairment in early aged mice． Methods: C57BL /6J mice aged 12 －14 months were divided into two groups according to gender，and then divided into wild type (WT) group and hippocampal CRHR1 conditional gene knockout (KN) group according to genotype．Mice in each group were randomly divided into control group and stress group，and the stress group was subjected to chronic unpredictable stress ( CUS ) for 30 days． Genotyping of mice was performed using polymerase chain reaction ( PCR) ，agarose gel electrophoresis and real-time fluorescence quantitative PCR (RT-qPCR) ．The new object rec- ognition experiment and Morris Water maze measured learning and memory ability．Golgi-Cox staining was used to observe damage to hippocampal neuronal dendrites． The protein expressions of target protein of rapamycin (mTOR) ，p-mTOR (Ser2448) ，ribosomal protein S6 kinase ( p70S6K) and p-p70S6K ( Thr389 / Thr412 ) were detected by Western blot．Serum levels of corticotropin releasing hormone ( CRH) were measured by ELISA. Results : Compared to mice without chronic stress，the cognitive coefficient of WT stress groups decreased after chron- ic stress，and the difference was statistically significant (P ＜0. 05) ，while there was no significant difference in cognitive coefficient of KN stress groups before and after chronic stress．Compared with the WT stress group，the escape latency of the WT control group was shortened (P＜0. 05) ，and the number of crossing the platform and tar- get quadrant increased (P ＜0. 01) ，and there was no significant difference in the KN groups above． Compared with the WT control group，the WT stress group had a significant reduction in the neuronal complexity in the hipp- ocampal CA1，CA3 and DG regions (P ＜0. 05) and significant reductions in the expression of p-mTOR and p- p70S6K in the hippocampus (P＜0. 05) ．There was no significant difference in the expression of p-mTOR between the KN stress group and the KN control group (P＞0. 05) ，except that the expression of p-mTOR in the hippocam- pus of the female group decreased (P＜0. 05) ．In addition，the serum level of CRH in the stress group was higher than that in the control group (P＜0. 01) ． Conclusion Hippocampal CRHR1 regulates learning and memory im- pairment and neuronal dendrite damage in early aged mice induced by chronic stress．The mechanism may be that high levels of CRH induced by chronic stress cannot bind to CRHR1 receptor，thereby enhancing the expression of down-regulated mTOR / p70S6K signaling pathway.

Non-alcoholic fatty liver disease is a common chronic liver disease in clinical practice. In recent years, with increasing social attention to the health of women and the elderly, the prevention and treatment of non-alcoholic fatty liver disease after menopause has increasingly become a research hotspot in metabolic diseases. This study explores the pathogenesis and treatment method of non-alcoholic fatty liver disease in postmenopausal women based on the theory of "deficient qi and stagnation" and combined with the physiological and pathological characteristics of postmenopausal women and the Western medicine understanding of non-alcoholic fatty liver disease. We believe that the pathogenesis of non-alcoholic fatty liver disease in postmenopausal women is rooted in the "deficient qi" caused by depletion of liver and kidney essence and blood. The imbalance between the physical and functional aspects of the liver due to this "deficient qi" is the primary factor, while the "stagnation" of phlegm and blood stasis is the manifestation. Furthermore, the "deficient qi" and "stagnation" reinforce each other, with the deficiency leading to stagnation and stagnation exacerbating the deficiency, thus accelerating the progression of the disease. The treatment approach should be one that combines nourishing deficiency and resolving stagnation, addressing both root cause and maifestations. Given the female characteristic of "the liver as the innate organ" and the post-menopausal physiological state of "gradual decline of kidney essence", it is important to focus on nourishing the liver and kidneys, nurturing the liver′s physical body while maintaining its function, and also promoting the circulation of qi, resolving phlegm, and invigorating blood circulation to remove blood stasis. This approach aims to reduce the accumulation of lipids in the liver, offering a new perspective and approach for the treatment of non-alcoholic fatty liver disease in post-menopausal women with traditional Chinese medicine.

Objective To summarize the medication law of TCM in the treatment of chronic bronchitis;To provide reference for clinical medication.Methods Medical records of patients with chronic bronchitis who were hospitalized in the Respiratory Department of the First Affiliated Hospital of Henan University of Chinese Medicine from January 1,2016 to December 31,2021 were extracted based on HIS electronic medical record data.After screening,the TCM prescriptions used by patients with chronic bronchitis were input into Excel 2019 to establish a database.Based on the software Lantern 5.0,the latent structure model was learned,hidden variables and explicit variables were obtained,and the model was interpreted.SPSS Modeler 18.0 was used to establish model points with Apriori algorithm for Chinese materia medica with a frequency greater than 6%,to obtain the association rules between drugs,and to analyze the medication law of TCM in treating chronic bronchitis.Results A total of 3 410 cases were included,involving 423 kinds of Chinese materia medica,with a cumulative frequency of 82 766 times.Among them,109 kinds of Chinese materia medica with a frequency of>6 % had a cumulative frequency of 69 845 times.The top five commonly used medicines were Fritillariae Cirrhosae Bulbus,Poria,Atractyodis Macrocephalae Rhizoma,Asteris Radix et Rhizoma,Citri Reticulatae Pericarpium,mainly with medicines of reducing cough and phlegm,antiasthmatic medicine,tonifying deficiency,clearing heat,relieving superficies,promoting blood circulation and removing blood stasis.The medicinal properties were warming,cold and mild,and the main tastes were bitter,sweet and pungent,and the meridians were mainly lung,spleen,liver and stomach meridians.Through analysis of latent structure,49 hidden variables and 149 hidden classes were obtained.Combined with professional knowledge,10 comprehensive clustering models and 21 core formulas were deduced,such as Sangbaipi Decoction,Xuefu Zhuyu Decoction,Xiaoqinglong Decoction,Erchen Decoction,Shashen Maidong Decoction,Liuwei Dihuang Pills,Yinqiao Powder,Zhisou Powder,Yupingfeng Powder,Xuefu Zhuyu Decoction combined with Daotan Decoction,etc.It was concluded that the chronic bronchitis syndrome included phlegm-heat stagnation lung syndrome,qi stagnation blood stasis syndrome,cold fluid attacking lung syndrome,phlegm-dampness accumulation lung syndrome,lung qi and yin deficiency syndrome,kidney yin deficiency syndrome,wind heat attacking lung syndrome,wind cold attacking lung syndrome,lung qi and spleen deficiency syndrome,phlegm stasis interjunction syndrome.A total of 41 strong association rules were screened in the analysis of association rules,including 5 strong association rules for two and 36 strong association rules for three.The high confidence rules were Saposheikovize Radix + Angelicae Sinensis Radix →Atractyodis Macrocephalae Rhizoma,Saposheikovize Radix + Codonopsis Radix → Atractyodis Macrocephalae Rhizoma,Codonopsis Radix + Citri Reticulatae Pericarpium → Atractyodis Macrocephalae Rhizoma;the higher degree of improvement were Bupleuri Radix + Mori Cortex → Scutellariae Radix,Perillae Fructus + Belamcandae Rhizoma → Fritillariae Cirrhosae Bulbus,Armeniacae Semen Amarum + Pinelliae Rhizoma → Citri Reticulatae Pericarpium,etc.Conclusion In the treatment of chronic bronchitis,TCM is mainly used to reduce phlegm,relieve cough and asthma,and the method of promoting blood circulation and removing blood stasis is commonly used to help eliminate phlegm.In addition,TCM pays attention to the application of methods such as tonifying lung and securing the exterior,invigorating spleen and benefiting qi.

Objective To develop and validate a deep learning model for automatic identification of liver CT contrast-enhanced phases.Methods A total of 766 patients with liver CT contrast-enhanced images were retrospectively collected.A three-phase classification model and an arterial phase(AP)classification model were developed,so as to automatically identify liver CT contrast-enhanced phases as early arterial phase(EAP)or late arterial phase(LAP),portal venous phase(PVP),and equilibrium phase(EP).In addition,221 patients with liver CT contrast-enhanced images in 5 different hospitals were used for external validation.The annotation results of radiologists were used as a reference standard to evaluate the model performances.Results In the external validation datasets,the accuracy in identifying each enhanced phase reached to 90.50%-99.70%.Conclusion The automatic identification model of liver CT contrast-enhanced phases based on residual network may provide an efficient,objective,and unified image quality control tool.

Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity. However, no reliable method is currently available to assess its impact on delivery performance. In this study, a biomimetic nasal model based on three-dimensional (3D) reconstruction and three-dimensional printing (3DP) technology was developed for visualizing the deposition of drug powders in the nasal cavity. The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females. The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test. The experimental device produced the most satisfactory results with five spray times. Furthermore, particle sizes and spray angles were found to significantly affect the experimental device's performance and alter drug distribution, respectively. Additionally, mometasone furoate (MF) nasal spray (NS) distribution patterns were investigated in a goat nasal cavity model and three male goat noses, confirming the in vitro and in vivo correlation. In conclusion, the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.

Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

Liver failure （LF） is a great trouble to the majority of patients due to its severe onset， many complications， difficult treatment， poor prognosis and other characteristics. This disease is liver injury caused by infection， hepatotoxic substances， autoimmunity， circulation disorders and other factors. It is a group of common clinical symptoms mainly manifested by coagulation disorders， jaundice， hepatic encephalopathy， ascites， and so on. In traditional Chinese medicine， it falls under the categories of "tympanites"， "jaundice" and other diseases. At present， the research progress of Western medicine in the treatment of LF is slow， and its clinical application effect is still not ideal. In contrast， traditional Chinese medicine has a long history in the treatment of this disease， with over thousands of years of clinical practice and verification. It is characterized by exact efficacy and fewer side effects. The pathological mechanism of LF is extremely complex， involves a variety of signaling pathways， and is mainly related to inflammation， oxidative stress， liver fibrosis， cell apoptosis and other processes. In recent years， many studies have shown that traditional Chinese medicine can intervene in the occurrence and development of LF by mediating relevant signaling pathways in vivo， but there is still a lack of relevant summary. Therefore， this review summarized several signaling pathways related to the intervention of traditional Chinese medicine in LF by referring to and sorting out relevant literature worldwide， including nuclear factor kappa B （NF-κB）， mitogen-activated protein kinase （MAPK）， phosphatidylin-ositol-3-kinase/protein kinase B （PI3K/Akt）， transforming growth factor-β/ drosophila mothers against decapentaplegic proteins （TGF-β/Smads）， and nuclear factor erythroid 2-related factor 2/heme oxygenase-1 （Nrf2/HO-1）， and elaborated the specific mechanism of their intervention in LF. This paper aims to provide practical and effective pathways and corresponding mechanisms for the treatment of LF by traditional Chinese medicine， and to provide new ideas and a theoretical basis for the clinical treatment of LF and further scientific research.

Objective:To investigate the effects of carnosine on lipopolysaccharide(LPS)-induced inflammasome activation and pyroptosis in microglia,and to clarify its mechanism.Methods:Activation model of microglia was established by LPS(10 ng/ml).CCK-8 assay was used to detect cell activity of microglia treated with different concentrations of carnosine(0.2,1,5,20,50 mmol/L)for 6 h,and the cell activity of microglia pretreated with different concentrations of carnosine for 0.5 h and then stimulated with LPS for 6 h,to screen a suitable concentration.Then microglia were divided into control group,carnosine group(5 mmol/L),LPS group,and LPS+carnosine group:cell morphological changes in each group were observed under an inverted phase contrast microscope;levels of IL-1β,TNF-α and IL-6 in microglial culture medium were measured by ELISA;propidium iodide(PI)staining was used to detect py-roptotic cells;immunofluorescence was used to observe protein expression of Nod-like receptor protein 3(NLRP3).Results:Com-pared with control group,cell viability of microglia in LPS group was significantly decreased(P<0.01),the shape of microglia was mostly"amoeboid",levels of IL-1β,TNF-α and IL-6 in microglial culture medium were significantly increased(P<0.01),the posi-tive rate of PI and the number of NLRP3 positive cells were significantly increased(P<0.01).Compared with LPS group,cell viability of microglia in LPS+carnosine group was significantly increased(P<0.01),the number of"amoeboid"microglia was decreased,levels of IL-1β,TNF-α in microglial culture medium were significantly decreased(P<0.01),and the level of IL-6 was decreased(P<0.05),the positive rate of PI and the number of NLRP3 positive cells were both significantly decreased(P<0.01).Conclusion:Carnosine can inhibit LPS-induced microglia activation and inflammasome activation,thereby inhibiting cell pyroptosis and the release of inflammato-ry factors.

Objective To investigate the inhibitory effect of gallic acid(GA)on lipopolysaccharide(LPS)-induced inflammatory responses in human THP1 macrophages.Methods THP1 monocytes were differentiated into macrophages with phorbol myristate acetate.A macrophage inflammation model was established with LPS induction,and GA was added at different concentrations.The safe concentrations of LPS and GA for THP1 cells were screened using the CCK-8 method,and a normal group,model group(100 μg/L LPS),and GA group(100 μg/L LPS+different concentrations of GA)were set up.ELISA was used to detect the levels of interleukin(IL)-6,tumor necrosis factor-α(TNF-α),and IL-1β in the cell culture media of each group.The microplate method was used to detect lactate dehydrogenase(LDH)activity and NO content in the cell cultures,and fluorescence staining was used to detect the reactive oxygen species(ROS)levels,cell damage,and changes in mitochondrial transmembrane potential in each group.Western blot was performed to detect the levels of cyclooxygenase-2(COX-2),HMGB1,c-Jun amino-terminal kinase(JNK),extracellular-regulated protein kinase(ERK),P38 mitogen-activated protein kinase(P38),nuclear transcription factor-KB(NF-κB),NOD-like receptor protein 3(NLRP3),Caspase-1,IL-1β,and gasdermin D(GSDMD).Results Compared with the normal group,the model cell group's secretion of IL-6,TNF-α,IL-1β,and NO was increased(P＜0.05);the secretion of COX-2,HMGB1,p-ERK,p-JNK,and p-P38 and expression of p-NF-KB,NLRP3,Caspase-1,IL-1β were elevated(P＜0.05);expression of GSDMD protein activation fragment was reduced(P＜0.05);ROS generation and cellular damage were significantly increased;mitochondrial transmembrane potential was significantly lower;and LDH activity was elevated(P＜0.05).In comparison with the model group,the GA group cells'secretion of IL-6,TNF-α,IL-1β,and NO was decreased(P＜0.05);expression of COX-2,HMGB1,p-ERK,p-JNK,p-P38,p-NF-κB,NLRP3,Caspase-1,and IL-1β was decreased(P＜0.05);GSDMD protein activation fragment expression level was increased(P＜0.05);ROS generation and cellular damage were decreased;mitochondrial transmembrane potential gradually increased;and LDH activity was decreased(P＜0.05).Conclusions GA had an inhibitory effect on the LPS-induced inflammatory response in THP1 macrophages,and its anti-inflammatory mechanism may involve the MAPK and NF-κB signaling pathways.