Qingzao Jiufeitang is a famous classical formula for treating lung injury caused by warm and dryness， included in the Catalogue of Ancient Famous Classical Formulas（The First Batch）. By systematically organizing ancient and modern literature on this formula， this study analyzed and verified the origin， medicinal composition， original plants and processing， dosage and decoction method， efficacy and application of this formula. According to the research， Qingzao Jiufeitang was first recorded in Yimen Falyu in the Qing dynasty， and its creation was mainly inspired by the Ming dynasty physician MIAO Xiyong's idea of the moisturizing drugs with sweet flavour and cold nature. Based on the 2020 edition of the Pharmacopoeia of the People's Republic of China（hereinafter referred to as the Chinese Pharmacopoeia） and the textual research results of modern scholars on traditional Chinese herbal medicines， the botanical sources and processing methods of the herbs in this formula are basically clarified. Among them， Mori Folium， Gypsum Fibrosum， Ginseng Radix et Rhizoma， Sesami Semen Nigrum， Asini Corii Colla， Ophiopogonis Radix and Eriobotryae Folium are consistent with the 2020 edition of the Chinese Pharmacopoeia. The primary source of Glycyrrhizae Radix et Rhizoma is the dried roots and rhizomes of Glycyrrhiza uralensis， family Leguminosae， while the primary source of Armeniacae Semen Amarum is the dried mature seeds of Prunus armeniaca， family Rosaceae. It is recommended to use Gypsum Ustum， stir-fried Sesami Semen Nigrum， stir-fried Armeniacae Semen Amarum， Asini Corii Colla bead， and honey-fried Eriobotryae Folium， and the rest of the raw products. According to the conversion of ancient and modern doses， the recommended dosages are 11.19 g for Mori Folium， 9.33 g for Gypsum Fibrosum， 3.73 g for Glycyrrhizae Radix et Rhizoma， 2.61 g for Ginseng Radix et Rhizoma， 3.73 g for Sesami Semen Nigrum， 4.48 g for Ophiopogonis Radix， 2.61 g for Armeniacae Semen Amarum， 3.73 g for Eriobotryae Folium. The decoction method is to add 300 mL of water， decoct it down to 180 mL， remove the residue， and then add 2.98 g of Asini Corii Colla into the decoction. Take it warm after meals， two to three times a day. Qingzao Jiufeitang has the effects of clearing dryness and moistening the lungs， nourishing Yin and invigorating Qi. In ancient times， it was mainly used to treat stagnation and depression of various Qi， as well as paralysis， asthma and vomiting. In modern clinical practice， it is mostly used to treat diseases in respiratory system， otolaryngology， skin system and digestive system caused by warm-dry impairing lung， deficiency of both Qi and Yin. The above research results can provide a reference for the later development of Qingzao Jiufeitang.

Cancer ranks as the second leading cause of death globally and has surpassed cardiovascular diseases to become the primary cause of mortality in developed countries. Cancer stem cells (CSCs), which play crucial roles in cancer recurrence, metastasis, and drug resistance, have attracted significant attention in targeted therapeutic strategies. Aptamers, with unique three-dimensional structures capable of specifically recognizing the surface markers of CSCs, show promising potential in targeted drug delivery systems. Compared with conventional antibodies, aptamers are praised for small molecular weights, low production costs, and easy chemical modification. This review systematically summarizes recent advances in aptamer research targeting the surface markers of CSCs, with particular emphasis on aptamer-drug conjugate systems targeting the markers including EpCAM, CD133, CD44, and ABCG2. Both in vitro cellular studies and in vivo animal models have demonstrated the definite anti-cancer efficacy of aptamer-based drug delivery systems, which are of great significance to develop novel therapeutic strategies and improving the therapeutic effects of CSC-targeted treatment. Thus, aptamer-based drug delivery system has broad application prospects in the field of precise cancer treatment.
Humans ; Neoplastic Stem Cells/metabolism* ; Aptamers, Nucleotide/therapeutic use* ; Drug Delivery Systems/methods* ; Neoplasms/drug therapy* ; Biomarkers, Tumor/metabolism* ; Animals ; Epithelial Cell Adhesion Molecule ; AC133 Antigen ; Hyaluronan Receptors

[Objective]To identify the relationship between tumor tissue interleukins(ILs)and non-small cell lung cancer(NSCLC)patients with poor response to immune checkpoint blockade(ICB)therapy,and to investigate the differ-ential expression of ILs in tumor of NSCLC patients as well as its effect on ICB response and prognosis.[Methods]A total of 61 patients diagnosed with NSCLC and treated with ICB were retrospectively collected from the data of a previous study.We obtained transcriptome sequencing data from tumor tissues and survival data of the patients before ICB treatment.Us-ing bioinformatics methods,we screened for ILs that significantly affected the efficacy and prognosis of ICB treatment.We evaluated the efficacy of ICB treatment using progressive-free survival(PFS)and assessed the prognosis using overall sur-vival(OS).The Kaplan-Meier survival curve and ROC curve were used to analyze the predictive effect and efficacy of ILs on the efficacy and prognosis of ICB in NSCLC patients.[Results]The results of the univariate Cox regression analysis in our study showed that nine ILs were found to be associated with OS of NSCLC patients treated with ICB at a significance level of P<0.1.Further multivariate analysis revealed that high expression of IL-11,IL-17D,and IL-36A was significant-ly associated with poor prognosis in these patients(P<0.05).The results from the Kaplan-Meier survival curve analysis revealed a significant negative correlation between the high expression of IL-17D and both PFS and OS in NSCLC patients.Specifically,patients with IL-17D high expression had a median PFS of 3.1 months compared with 6.5 months in low ex-pression patients[95%confidence interval(CI)(1.178,3.655),P=0.009].Similarly,the median OS was 9.8 months in the high expression group versus 21.8 months in the low expression group[95%CI(1.116,4.392),P=0.018].ROC curve showed that the prediction performance was favorable[AUCPFS=0.702,95%CI(0.562,0.842),P=0.027;AU-COS=0.684,95%CI(0.550,0.818),P=0.014].Although IL-11 and IL-36A alone were not significant predictors of PFS and OS in NSCLC patients,the median PFS and OS were notably shortened to 2.2 months(P=0.003)and 3.0 months(P<0.001),respectively,when high expression of IL-11 and IL-36A was combined with high expression of IL-17D.The ROC curve analysis demonstrated an improvement in prediction efficiency for both PFS and OS in NSCLC patients[AUCPFS=0.748,95%CI(0.615,0.880),P=0.007;AUCOS=0.703,95%CI(0.573,0.833),P=0.007].[Conclu-sion]The results suggest that high expression of IL-11,IL-17D,and IL-36A is associated with a higher risk of disease progression which correlates to poor PFS and OS in NSCLC patients.

Objective To explore the effectiveness of Guasha therapy with Fufu Tongbian in treating cancer-related insomnia(CRI)and seek a new approach to managing CRI.Methods Sixty patients with CRI who were admitted to the oncology department of our hospital from July 2021 to July 2022 were engaged in the study.The patients were randomly divided equally into two groups by using the PROCPLAN process in SAS software.The patients in the control group were given conventional symptomatic treatment and the patients in the trial group were managed with Guasha therapy with Fufu Tongbian in addition to the conventional symptomatic treatment.The two groups were compared in terms of clinical efficacy as well as scores by the Pittsburgh sleep quality index(PSQI),Hamilton depression scale(HAMD),and Hamilton anxiety scale(HAMA)were compared after 2 courses of treatment.Results All patients had completed the study.The trial group exhibited significantly higher total effective rate and presented significantly lower scores on PSQI,HAMD and HAMA compared to the control group(all P＜0.001).Conclusion Guasha therapy with Fufu Tongbian can improve sleep condition of CRI patients and alleviate their depression and anxiety,thus improving sleep quality of CRI patients.

Objective Comprehensively analyzing the epilepsy-related genes by bioinformatics methods,and to explore their functions based on network and pathway analysis.Methods I Collected epilepsy-related genes through OMIM,DisGeNET,GeneCards databases and literatures deposited in PUBMED.Performed gene ontology(GO)and pathway enrichment analysis using"ClusterProfiler"R package,and the correlation between pathways was identified through pathway crosstalk analysis.Epilepsy-related genes were then mapped to human protein-protein interaction network(PPIN)to obtain epilepsy-specific PPIN,and extracted the hub and potential genes based on network topology.Results A total of 572 epilepsy-related genes were collected,642 significant GO biological process items and 80 Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways,including learning,memory and cognition,were obtained by enrichment analysis.Based on PPIN analysis,10 hub genes of the epilepsy were extracted and most of them are gamma-aminobutyric acid(GABA)receptor genes.By integrating PPIN and WGCNA analysis,17 potential genes were extracted,involving heat shock protein,growth factor receptor binding protein,etc.Conclusion Epilepsy is a complex process,involving the abnormality of multiple functional genes,multiple biological processes and pathways are closely contact through multiple functional genes,and collectively lead to the occurrence of epilepsy.

Chemicals possessing reactive electrophiles can denature innate proteins leading to undesired toxicity, and the overdose-induced liver injury by drugs containing electrophiles has been one of the major causes of non-approval and withdraw by the US Food and Drug Administration (FDA). Elucidating the associated proteins could guide the future development of therapeutics to circumvent these drugs' toxicities, but was largely limited by the current probing tools due to the steric hindrance of chemical tags including the common "click chemistry" labels. Taking the widely used non-steroidal anti-inflammatory drug acetaminophen (APAP) as an example, we hereby designed and synthesized an APAP analogue using fluorine as a steric-free label. Cell toxicity studies indicated our analogue has similar activity to the parent drug. This analogue was applied to the mouse hepatocellular proteome together with the corresponding desthiobiotin-SH probe for subsequent fluorine-thiol displacement reactions (FTDRs). This set of probes has enabled the labeling and pull-down of hepatocellular target proteins of the APAP metabolite as validated by Western blotting. Our preliminary validation results supported the interaction of APAP with the thioredoxin protein, which is an important redox protein for normal liver function. These results demonstrated that our probes confer minimal steric perturbation and mimic the compounds of interest, allowing for global profiling of interacting proteins. The fluorine-thiol displacement probing system could emerge as a powerful tool to enable the investigation of drug-protein interactions in complex biological environments.

Objective Through factor analysis of the quantified syndrome information of 558 cases of kidney yang deficiency syndrome,the constructing feature of kidney yang deficiency syndrome was revealed,which provides clinical data support for the objectification,standardization and normalization of kidney Yang deficiency syndrome.Methods Firstly,the frequency analysis of symptoms,tongue and pulse signs of 558 patients with kidney Yang deficiency syndrome was carried out,and then the main syndrome information of the patients with kidney Yang deficiency syndrome was quantified.Finally,the common factors and their representative variables of kidney Yang deficiency syndrome were screened out through factor analysis,and the constructing feature of kidney Yang deficiency syndrome was analyzed combined with TCM syndrome knowledge.Results Eight common factors with eigenvalues greater than 1 were extracted by principal component analysis,and the cumulative contribution rate was 60.483%.After the factor rotation,the representative variables with the absolute value of load coefficient greater than 0.45 in each common factor were selected.The representative variables of F1 are afraid of cold and fond of warmth(0.947)and intolerance to cold(0.932).The representative variables of F2 are waist pain(0.754),waist and knee weakness(0.720)and cold in waist and knees(0.466).The representative variables of F3 are depression(0.749),insomnia(0.711)and diarrhoea(0.470).The representative variables of F4 are thin fur(0.819)and white fur(0.768).The representative variable of F5 are tinnitus and deafness(0.687),frequent nocturnal urination(0.591)and decreased libido(0.587).The representative variables of F6 are pulse sinking(0.766)and pulse weakness(0.736).The representative variables of F7 is thready pulse(0.942).The representative variable of F8 is pale tongue(0.961).External syndrome of disease location involved in these common factors are waist,bone,brain,ear,anterior Yin,posterior Yin and reproductive function.The disease nature involved in these common factors is deficiency and cold.Conclusion The basic constituent units of kidney Yang deficiency syndrome include disease location syndrome elements and disease nature syndrome elements.The disease location is kidney,and the abnormal changes of kidney location are mainly external symptoms of waist,bone,brain,ear,anterior Yin,posterior Yin and reproductive function.Its disease nature is deficiency and cold.Yang deficiency leads to external cold.Yang Qi deficiency can not warm the body surface resulting in the appearance of external cold syndrome.

ObjectiveTo analyze the characteristics of kidney Yang deficiency syndrome in different stages and time evolution of chronic kidney disease （CKD） to explore the evolution patterns of kidney Yang deficiency syndrome in CKD. MethodThe evidence information of 256 patients with CKD was collected from October 2020 to September 2022 according to relevant standards， and the "Kidney Yang Deficiency Syndrome Evaluation Scale for Chronic Kidney Disease" was developed. With SPSS Statistics 20.0， SPSS Modeler 18.0， Gephi 0.9.2， and R 4.2.1， the syndrome information of CKD patients at various stages and the syndrome changes after one year were statistically analyzed using complex network analysis， association rule analysis， probability transition matrix analysis， and chi-square test， and the kidney Yang deficiency syndrome of patients at various stages was comprehensively evaluated. ResultIn the CKD population， the proportion of females with kidney Yang deficiency syndrome was higher than that of males （P<0.01）， and the proportion of people over 65 years old was higher than in people under 65 years old. The proportion of people with kidney Yang deficiency syndrome increased with the progression of kidney disease， and the proportion of Ⅳ-Ⅴ CKD patients with kidney Yang deficiency syndrome was higher than that of Ⅰ-Ⅱ CKD patients （P<0.01）. From Ⅰ CKD to Ⅴ CKD， the frequency of dull tongue continued to increase， and the frequency of enlarged tongue and tooth-marked tongue continued to increase after Ⅲ CKD. The frequency of thick coating and greasy coating ranked in the top 3 of frequency distribution in Ⅴ CKD. After Ⅲ CKD， the top 3 tongue characteristics were weak pulse， deep pulse， and thready pulse， all of which were characteristics of kidney Yang deficiency syndrome. Complex network analysis of the tongue and pulse showed that the core tongue and pulse characteristics of patients with end-stage CKD were tooth-marked tongue with white coating and deep and thready pulse. The results of symptom frequency analysis and complex network analysis showed that aversion to cold and preference for warmth， weakness of the knees， and cold extremities were the top 3 symptoms in Ⅰ-Ⅲ CKD patients with kidney Yang deficiency syndrome， and in Ⅳ-Ⅴ CKD， the manifestations of the syndrome of Yang deficiency and water diffusion， such as drowsiness and fatigue， edema， and frequent urination at night became characteristic symptoms. The scores of edema， pale complexion， soreness and weakness of the waist and knees， loose stools， and mental depression symptoms， as well as the total score of kidney Yang deficiency syndrome gradually increased with disease progression， with statistical differences between different stages of CKD （P<0.05， P<0.01）. The frequency analysis of disease-related syndrome elements showed that the frequencies of Yang deficiency syndrome， phlegm-dampness syndrome， blood stasis syndrome， and turbidity-toxin syndrome gradually increased with disease progression， and there were statistically significant differences in the distribution between different stages of CKD （P<0.05， P<0.01）. The results of complex network analysis showed that Yang deficiency syndrome was the core syndrome element throughout all stages of CKD and was the main syndrome element type of CKD， while phlegm-dampness syndrome， blood stasis syndrome， and turbidity-toxin syndrome were gradually revealed in the middle and late stages of CKD. In the CKD population with kidney-Yang deficiency syndrome， the distribution of phlegm-dampness syndrome， blood stasis syndrome， and turbidity-toxin syndrome as concurrent syndromes in different CKD stages had statistically significant differences （P<0.05， P<0.01）. The association rule analysis showed that as the disease progressed， associations between the concurrent syndromes， such as phlegm-dampness syndrome， blood stasis syndrome， turbidity-toxin syndrome， and fluid retention syndrome， and kidney-Yang deficiency syndrome were gradually enhanced. The comparison of the changes in CKD with kidney Yang deficiency syndrome within one year showed that the disease location was centered on the kidney and transmitted between the spleen， stomach， heart， and liver. There is a 23.81% probability of kidney-Yang deficiency syndrome transforming into Qi deficiency syndromes （Qi deficiency in the spleen and kidney， Qi deficiency in the liver， and Qi deficiency in the heart）， 23.79% into Yin deficiency syndromes （Yin deficiency in the liver and kidney， Qi and Yin deficiency， and Yin deficiency in the liver and stomach）， and 9.52% into dampness syndromes （phlegm-dampness internal obstruction and wind-dampness obstruction）. In contrast， 20% of spleen and kidney Qi deficiency syndrome transformed into kidney Yang deficiency syndrome， and 33.33% of Qi deficiency and blood stasis syndrome transformed into kidney Yang deficiency syndrome. ConclusionAs Ⅰ CKD progresses to Ⅴ CKD， the severity of kidney Yang deficiency syndrome gradually increases， and the syndrome characteristics of kidney Yang deficiency become pronounced. Furthermore， the pathogenic factors， such as phlegm-dampness， blood stasis， and turbidity-toxin， gradually increase. With the change of time， kidney Yang deficiency syndrome in CKD tends to evolve into syndromes related to Qi deficiency， Yin deficiency， and dampness. The discovery of these rules provides a theoretical basis and reference guidance for the treatment of CKD based on syndrome differentiation.