Colorectal cancer， a leading malignant gastrointestinal tumor globally in terms of incidence and mortality， has seen a consistent annual rise in newly diagnosed cases. While conventional therapies like radiotherapy， chemotherapy， and surgery are available， problems such as lack of early diagnosis， poor prognosis， and drug resistance remain significant burdens for patients. Given the complex and diverse pathogenesis of colorectal cancer， there is an urgent clinical need for safe， effective， reliable， and multi-targeted therapeutic strategies. The Hippo signaling pathway， closely linked to mechanisms like tumorigenesis， cancer cell invasion， migration， and drug resistance， extensively participates in the occurrence and development of colorectal cancer， so targeting the signaling pathway for cancer prevention and treatment has become a crucial research direction in recent years. Traditional Chinese medicine （TCM） offers multi-faceted， multi-pathway， and multi-target advantages and becomes an important therapy for colorectal cancer by enhancing patients' immunity， improving the life quality， and prolonging survival. Studies show that the active components of TCM， including flavonoids， terpenoids， phenols， alkaloids， quinones， lignans， and saponins， as well as TCM compounds such as modified Sijunzi decoction， Jiedu Sangen decoction， Jianpi Jiedu compound， and Quyu Jiedu decoction， exhibit significant targeting effects on the Hippo signaling pathway. These TCMs can exert an anti-colorectal cancer effect through various mechanisms， such as inducing cancer cell autophagy and apoptosis， inhibiting epithelial-mesenchymal transition， reversing drug resistance of the tumor， and blocking the cancer cell cycle. This paper reviewed and analyzed Chinese and international research on the action mechanisms of TCM in regulating the Hippo signaling pathway for the prevention and treatment of colorectal cancer with a comprehensive overview presentation， aiming to provide new references and ideas for the clinical application of TCM and the development of new pharmacological agents in the prevention and treatment of colorectal cancer.

Colorectal cancer， a leading malignant gastrointestinal tumor globally in terms of incidence and mortality， has seen a consistent annual rise in newly diagnosed cases. While conventional therapies like radiotherapy， chemotherapy， and surgery are available， problems such as lack of early diagnosis， poor prognosis， and drug resistance remain significant burdens for patients. Given the complex and diverse pathogenesis of colorectal cancer， there is an urgent clinical need for safe， effective， reliable， and multi-targeted therapeutic strategies. The Hippo signaling pathway， closely linked to mechanisms like tumorigenesis， cancer cell invasion， migration， and drug resistance， extensively participates in the occurrence and development of colorectal cancer， so targeting the signaling pathway for cancer prevention and treatment has become a crucial research direction in recent years. Traditional Chinese medicine （TCM） offers multi-faceted， multi-pathway， and multi-target advantages and becomes an important therapy for colorectal cancer by enhancing patients' immunity， improving the life quality， and prolonging survival. Studies show that the active components of TCM， including flavonoids， terpenoids， phenols， alkaloids， quinones， lignans， and saponins， as well as TCM compounds such as modified Sijunzi decoction， Jiedu Sangen decoction， Jianpi Jiedu compound， and Quyu Jiedu decoction， exhibit significant targeting effects on the Hippo signaling pathway. These TCMs can exert an anti-colorectal cancer effect through various mechanisms， such as inducing cancer cell autophagy and apoptosis， inhibiting epithelial-mesenchymal transition， reversing drug resistance of the tumor， and blocking the cancer cell cycle. This paper reviewed and analyzed Chinese and international research on the action mechanisms of TCM in regulating the Hippo signaling pathway for the prevention and treatment of colorectal cancer with a comprehensive overview presentation， aiming to provide new references and ideas for the clinical application of TCM and the development of new pharmacological agents in the prevention and treatment of colorectal cancer.

Colorectal cancer is a common malignant tumor of the digestive system. In recent years， its incidence rate and mortality are increasing year by year. Due to the complex pathogenesis and poor prognosis of patients， colorectal cancer poses a serious threat to human physical and mental health. Currently， although Western medicine treatment methods can to some extent inhibit tumor growth and alleviate patient symptoms， postoperative recurrence， metastasis， multiple adverse reactions， and susceptibility to drug resistance are prominent issues， resulting in unsatisfactory overall treatment outcomes. Therefore， exploring more efficient and safe treatment methods has become an urgent task. The adenosine monophosphate-activated protein kinase （AMPK） signaling pathway plays a regulatory role in the growth， differentiation， apoptosis， and autophagy of colorectal cancer cells， and is widely involved in the occurrence and development of colorectal cancer. It is considered an important target for colorectal cancer treatment. Traditional Chinese medicine has unique advantages in the treatment of colorectal cancer， as it can exert its effects through multiple mechanisms and pathways. It can prevent postoperative recurrence and metastasis， reduce adverse reactions to radiotherapy and chemotherapy， and improve patients' quality of life. It has become a key means of treating colorectal cancer. Research has shown that active ingredients in traditional Chinese medicine such as flavonoids， polyphenols， terpenes， and esters， as well as traditional Chinese medicine compounds such as Qingjie Fuzheng Granules and some traditional Chinese medicine extracts， have significant regulatory effects on AMPK and its interaction signaling pathways. They exert their anti-colorectal cancer effects by inducing autophagy and apoptosis in colorectal cancer cells， promoting ferroptosis， inhibiting epithelial-mesenchymal transition， reversing drug resistance， and arresting the cell cycle. This article reviewed and summarized the relevant research on traditional Chinese medicine in the treatment of colorectal cancer in recent years， with a focus on the mechanism of traditional Chinese medicine in regulating the AMPK signaling pathway for the treatment of colorectal cancer. It is expected to provide ideas and references for the development of new drugs for clinical anti-colorectal cancer treatment.

ObjectiveTo explore the changes in volatile components， total polysaccharides， enzyme activity， and chromaticity value of Myristicae Semen Koji（MSK） during the fermentation process， and conduct correlation analysis. MethodsBased on gas chromatography-mass spectrometry（GC-MS）， the changes of volatile components in MSK at different fermentation times were identified. The phenol sulfuric acid method， dinitrosalicylic acid method（DNS）， and carboxymethyl cellulose sodium salt method（CMC-Na） were used to investigate the total polysaccharide content， amylase activity， and cellulase activity during the fermentation process. Visual analysis technology was used to explore the changes in chromaticity values， revealing the fermentation process of MSK and the dynamic changes of various measurement indicators， partial least squares-discriminant analysis（PLS-DA） was used to explore the differential compounds of MSK at different fermentation degrees， and Pearson correlation analysis was used to explore the correlation between volatile components of MSK and total polysaccharides， enzyme activity， and chromaticity values. ResultsA total of 60 volatile compounds were identified from MSK， the relative contents of components such as （+）-α-pinene， β-phellandrene， β-pinene， （+）-limonene， and p-cymene obviously increased， while the relative contents of components such as safrole， methyl isoeugenol， methyleugenol， myristicin， and elemicin significantly decreased. During the fermentation process， the total polysaccharide content showed an upward trend， while the activities of amylase and cellulase showed an initial increase followed by a decrease， and reached their maximum value at 40 h. the overall brightness（L^*） and total color difference（ΔE^*） gradually increased， while the changes in red-green value（a^*） and yellow-blue value（b^*） were not obvious. PLS-DA results showed that MSK could be clearly distinguished at different fermentation times， and 13 differential biomarkers were screened out. Pearson correlation analysis results showed that the contents of α-terpinene， β-phellandrene， methyleugenol， β-cubebene and myristic acid had an obvious correlation with chromaticity values. ConclusionAfter fermentation， the volatile components， total polysaccharides， amylase activity， and cellulase activity of MSK undergo significant changes， and there is a clear correlation between them and chromaticity values， which reveals the dynamic changes in the fermentation process and related indicators of MSK， laying a foundation for the quality control.

ObjectiveTo investigate the protective effect of Rehmanniae Radix iridoid glycosides （RIG） on the kidney tissue of streptozotocin （STZ）-induced diabetic mice and explore the underlying mechanism. MethodsTwelve of 72 male C57BL/6J mice were randomly selected as the normal group， and the remaining 60 mice were fed with a high-fat diet for six weeks combined with injection of 60 mg·kg^-1 STZ for 4 days to model type 2 diabetes mellitus. The successfully modeled mice were randomized into model， metformin （250 mg·kg^-1）， catalpol （100 mg·kg^-1）， low-dose RIG （RIG-L， 200 mg·kg^-1） and high-dose RIG （RIG-H， 400 mg·kg^-1） groups （n=11）. Mice in each group were administrated with corresponding drugs， while those in the normal group and model group were administrated with the same dose of distilled water by gavage once a day. After 8 weeks of intervention， an oral glucose tolerance test （OGTT） was performed， and the area under the curve （AUC） was calculated. After mice were sacrificed， both kidneys were collected. The body weight， kidney weight， and fasting blood glucose （FBG） were measured. Biochemical assays were performed to measure the serum levels of triglycerides （TG）， total cholesterol （TC）， serum creatinine （SCr）， and blood urea nitrogen （BUN）. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the serum level of fasting insulin （FINS）， and the insulin sensitivity index （ISI） and homeostatic model assessment for insulin resistance （HOMA-IR） were calculated. The pathological changes in kidneys of mice were observed by hematoxylin-eosin staining and Masson staining. The immunohistochemical method （IHC） was employed to assess the expression of interleukin-1 （IL-1）， interleukin-6 （IL-6）， tumor necrosis factor-α（TNF-α）， transforming growth factor-β₁ （TGF-β₁）， and collagen-3 （ColⅢ） in the kidney tissue. The protein levels of TGF-β₁， cell signal transduction molecule 3 （Smad3）， matrix metalloproteinase-9 （MMP-9）， and ColⅢ in kidneys of mice were determined by Western blot. ResultsCompared with the normal group， the model group showcased decreased body weight and ISI （P<0.01）， increased kidney weight， FBG， AUC， FINS， HOMA-IR， TC， TG， SCr， and BUN （P<0.01）， glomerular hypertrophy， capsular space narrowing， and collagen deposition in the kidney， up-regulated protein levels of IL-1， IL-6， TNF-α， TGF-β₁， ColⅢ， and Smad3 （P<0.01）， and down-regulated protein level of MMP-9 （P<0.01） in the kidney tissue. Compared with the model group， the treatment groups had no significant difference in the body weight and decreased kidney weight （P<0.05， P<0.01）. The FBG level declined in the RIG-H group after treatment for 4-8 weeks and in the metformin， catalpol， and RIG-L groups after treatment for 6-8 weeks （P<0.01）. The AUC in the RIG-L， RIG-H， and metformin groups decreased （P<0.05， P<0.01）. The levels of TC， SCr， and BUN in the serum of mice in each treatment group became lowered （P<0.05， P<0.01）. The level of TG declined in the RIG-L， RIG-H， and metformin groups （P<0.05， P<0.01）. The serum level of FINS declined in the catalpol， RIG-L， and metformin groups （P<0.01）. Compared with the model group， the treatment groups showed decreased HOMA-IR （P<0.01）， increased ISI （P<0.01）， alleviated pathological changes in the kidney tissue， and down-regulated expression of IL-1 and TGF-β₁. In addition， the protein levels of IL-6， TNF-α， and ColⅢ in the RIG-H and metformin groups and IL-6 and TNF-α in the RIG-L group were down-regulated （P<0.05， P<0.01）， and the protein levels of IL-6， TNF-α， and ColⅢ in the catalpol group and ColⅢ in the RIG-L group showed a decreasing trend without statistical difference. The protein levels of TGF-β₁， Smad3， and ColⅢ in the RIG-H and metformin groups were down-regulated （P<0.01）. Compared with that in the model group， the protein level of MMP-9 was up-regulated in each treatment group （P<0.01）. ConclusionRIG can improve the renal structure and function of diabetic mice by regulating the TGF-β₁/Smads signaling pathway.

Peanut, a major economic and oil crop known for the high protein and oil content, is extensively cultivated in China. Peanut plants have the ability to form nodules with rhizobia, where the nitrogenase converts atmospheric nitrogen into ammonia nitrogen that can be utilized by the plants. Analysis of nodule fixation is of positive significance for avoiding overapplication of chemical fertilizer and developing sustainable agriculture. In this study, AhNIGT1.2, a member of the NIGT family predominantly expressed in peanut nodules, was identified by bioinformatics analysis. Subsequent spatiotemporal expression analysis revealed that AhNIGT1.2 was highly expressed in nodules and showed significant responses to high nitrogen, low nitrogen, high phosphorus, low phosphorus, and rhizobia treatments. Histochemical staining indicated that the gene was primarily expressed in developing nodules and at the connection region between mature nodules and peanut roots. The fusion protein AhNIGT1.2-GFP was located in the nucleus of tobacco epidermal cells. The AhNIGT1.2-OE significantly increased the number of peanut nodules, while AhNIGT1.2-RNAi reduced the number of nodules, which suggested a positive regulatory role of AhNIGT1.2 in peanut nodulation. The AhNIGT1.2-OE in roots down-regulated the expression levels of NRT1.2, NRT2.4, NLP1, and NLP7, which indicated that AhNIGT1.2 influenced peanut nodulation by modulating nitrate transport and the expression of NLP genes. The transcriptome analysis of AhNIGT1.2-OE and control roots revealed that overexpressing AhNIGT1.2 significantly enriched the differentially expressed genes associated with nitrate response, nodulation factor pathway, enzymes for triterpene biosynthesis, and carotenoid biosynthesis. These findings suggest that AhNIGT1.2 play a key role in peanut nodulation by regulating nitrate transport and response and other related pathways. This study gives insights into the molecular mechanisms of nitrogen and phosphorus in regulating legume nodulation and nitrogen fixation, and sheds light on the development of legume crops that can efficiently fix nitrogen in high nitrogen environments.
Arachis/physiology* ; Nitrates/metabolism* ; Plant Proteins/physiology* ; Transcription Factors/metabolism* ; Plant Root Nodulation/physiology* ; Gene Expression Regulation, Plant ; Root Nodules, Plant/metabolism* ; Nitrogen Fixation

Hepatocellular carcinoma （HCC） is one of the most common malignant tumors with high incidence and mortality rates worldwide， which brings a huge burden to the physical and mental health and socio-economic life of patients. The adenosine monophosphate-activated protein kinase （AMPK） signaling pathway serves as the regulatory center of cellular energy metabolism and is closely associated with the biological activities of HCC cells， including autophagy， apoptosis， and angiogenesis， and it has become a hot topic in current cancer research. Traditional Chinese medicine drugs are abundant in natural components such as flavonoids， alkaloids， and phenols and have the characteristics of multiple targets， pathways， components， and hierarchies. By targeting the AMPK signaling pathway， these components can be used alone or in combination with conventional antitumor therapies to exert an anti-tumor effect on HCC from various aspects. This article reviews and summarizes the extracts of traditional Chinese medicine that target the AMPK signaling pathway for the prevention and treatment of HCC， in order to provide a theoretical basis and a reference for the clinical application of traditional Chinese medicine in the treatment of HCC and the development of related drugs.

To clarify the epidemiological characteristics of pertussis in children in Hanzhong during the nationwide surge in pertussis, this study retrospectively collected nucleic acid testing data of 4 565 children with pertussis from a tertiary hospital in Hanzhong City from September 2023 to August 2024, and collected demographic and clinical information of confirmed cases for analysis. The results showed that among 4 565 cases tested, there were 1 224 positive cases for pertussis nucleic acid testing, with a total positive rate of 26.81%. Since September 2023, the number of tests and positive cases had continuously increased, reaching a peak in May 2024, with 1 174 samples tested and 319 positive cases. Notably, the number of confirmed cases from April to July 2024 accounted for 82.03% (1 004/1 224) of the total confirmed cases during the study period. Among the 1 224 confirmed cases of pertussis, there were 647 male patients (52.86%) and 577 female patients (47.14%). The highest proportion of cases was found in school-age and preschool children, accounting for 88.81% (1 087/1 224). Among outpatients, school-age and preschool children accounted for 93.44% (897/960), while inpatient cases were mainly preschool, school-age children, and infants (94.32%, 249/264). The positive detection rates of outpatient and inpatient children in the same age group were compared. Except for the infant group, the positive rates of the other four groups were higher than those of the inpatient group (all P<0.05). Among 264 hospitalized children with pertussis, 70 cases (26.52%, 70/264) were infected with Bordetella pertussis alone, and 194 cases (73.48%, 194/264) had co-infections with other pathogens. Rhinovirus, Mycoplasma pneumoniae, and Staphylococcus aureus were the most common pathogens in co-infections.

Abstract Tumor immune escape represents a pivotal determinant of cancer immunotherapy failure. It's mechanistically linked to immunosuppressive tumor microenvironment(TME). The TME comprises tumor cells, immune cells, stromal components and extracellular matrix. These components interact synergistically to suppress antitumor immunity through multiple pathways, thereby promoting immune evasion. As crucial chromosomal stability regulators, centromere proteins(CENPs) remodel the TME via multifaceted mechanisms to potentiate immune evasion. This review synthesizes current knowledge on CENPs' role in tumor immune evasion, offering novel insights for cancer diagnostics and immunotherapy.

Objective:To establish the quality standard of the standard decoction of wine-processed Coptidis Rhizoma by studying the extraction rate, fingerprint and component quantitative analysis.Methods:ccording to the Technical Requirements for Quality Control and Standard Formulation of Chinese Medicine Formula Granules, 15 batches of the standard decoction of wine-processed Coptidis Rhizoma were prepared, and the paste rate was determined; HPLC fingerprints of 15 batches of standard decoction of wine-processed Coptidis Rhizoma were established, and evaluated by combining similarity evaluation, clustering analysis, principal component analysis and orthogonal partial least squares discriminant analysis; the contents of berberine, epiberberine, pamadine, and safranine in the samples of the 15 batches were determined and analyzed their transfer rates.Results:A total of 15 batches of standard decoction samples were calibrated with 11 common peaks, referring to the recognition of 8 components. The similarity between the samples and the control product was greater than 0.900; the clustering analysis could cluster the 15 batches of samples into 2 classes; the results of the principal component analysis showed that the cumulative variance contribution rate of the 3 principal component factors was 89.388%; the OPLS-DA screened out the 3 components of the quality difference; the 15 batches of samples out of the paste rate was 15.7% -20.8%, and the mass fractions of berberine, epiberberine, safranine, and palmatine were 18.47%-24.38%, 2.82%-3.49%, 5.08%-6.69%, and 4.84%-6.68%, respectively, with transfer rates of 41.7%-61.7%, 46.9%-68.7%, 39.8%-61.5%, and 43.8%-65.2%.Conclusion:The fingerprint and content determination method established in this study is accurate, stable, simple, and can be used for the quality control and evaluation of the standard decoction of wine-processed Coptidis Rhizoma.