ObjectiveTo investigate the effect and mechanism of transplantation of human umbilical cord mesenchymal stem cell （hUC-MSC） with overexpression of the Numb gene in the treatment of cholestatic liver fibrosis （CLF）. MethodsThe technique of lentiviral transfection was used to induce the overexpression of the Numb gene in hUC-MSC （hUC-MSC^Numb-OE）， and hUC-MSC transfected with empty vector （hUC-MSC^OE-EV） was used as negative control. Bile duct ligation （BDL） was performed to establish a rat model of CLF， and then the rats were randomly divided into BDL group， hUC-MSC group， hUC-MSC^OE-EV group， and hUC-MSC^Numb-OE group， while a sham-operation group was also established. The rats in the intervention groups were given a single splenic injection of the corresponding cells after BDL， and samples were collected at the end of week 4. Related indicators were measured， including serum biochemistry， liver histopathology， the content of hydroxyproline （Hyp） in the liver， hepatic stellate cell activation， ductular reaction， liver regeneration， and the expression levels of key molecules in the Numb-p53 signaling axis. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the BDL group， the hUC-MSC group and the hUC-MSC^OE-EV group had significant reductions in the levels of serum biochemical parameters （aspartate aminotransferase， gamma-glutamyl transpeptidase， total bile acid， total bilirubin， and direct bilirubin）， liver fibrosis markers （the content of Hyp and the expression levels of alpha-smooth muscle actin， tumor necrosis factor-α， and transforming growth factor-beta 1）， and ductular reaction markers （the expression levels of CK7 and CK19） （all P <0.05）， and compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significantly greater improvements in the above indicators （all P <0.05）. In addition， compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significant improvements in the expression levels of liver regeneration-related markers （albumin and hepatocyte nuclear factor 4α） and the molecules associated with the Numb-p53 signaling axis （Numb， pNumb， Mdm2， and p53） （all P <0.05）. ConclusionOverexpression of the Numb gene can enhance the therapeutic effect of hUC-MSC on CLF， possibly by activating the Numb-PTB^L-p53-HNF4α axis， promoting the hepatic differentiation of hUC-MSCs and subsequently enhancing liver regeneration.

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.

Liver cancer， as a malignant tumor with high incidence and mortality worldwide， has shown a year-by-year increase in both incidence and mortality in China. Currently， Western medicine has achieved certain efficacy in the clinical management of liver cancer in terms of inhibiting tumor growth， alleviating patient symptoms， and delaying disease progression. However， its limitations cannot be ignored. Significant side effects， increasingly severe drug resistance， and limited improvement in patient survival collectively make the overall therapeutic outcomes fall short of ideal expectations. Therefore， exploring more effective and safer treatment strategies has become a critical issue that urgently needs to be addressed in the field of oncology. The adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway plays a central regulatory role in the physiological processes of liver cancer cells， including proliferation， differentiation， apoptosis， and autophagy， and is considered a key molecular target for anti-liver cancer therapy. Traditional Chinese medicine （TCM）， characterized by its multi-pathway and multi-mechanism synergistic effects， has become an important component of the current comprehensive treatment system for liver cancer. Among these， TCM monomeric compounds， owing to their well-defined chemical structures and precisely analyzable pharmacological mechanisms， represent an important breakthrough in anti-liver cancer drug development. Studies have shown that various TCM monomeric compounds， including flavonoids， alkaloids， polyphenols， saponins， terpenoids， and quinones， can regulate the AMPK/mTOR signaling pathway and its upstream and downstream protein expression. Through these mechanisms， they induce autophagy and apoptosis in liver cancer cells， inhibit aerobic glycolysis， reverse drug resistance， promote ferroptosis， block epithelial-mesenchymal transition， and inhibit angiogenesis， thereby effectively suppressing the growth and metastasis of liver cancer cells. Based on this， this article systematically reviews recent studies on TCM monomeric compounds in the treatment of liver cancer， and further analyzes in depth their mechanisms in regulating the AMPK/mTOR signaling pathway， so as to provide ideas and references for the development of new anti-liver cancer drugs.

Objective To compare the pathological diagnosis rate, number of punctures, and applicability to different lesion locations between a fork-tip biopsy needle and a conventional needle. Methods A retrospective collection of data was conducted on 137 patients who underwent endoscopic ultrasound (EUS)-guided fine needle biopsy (novel needle group, n=12) or aspiration (conventional needle group, n=125) at Zhongshan Hospital, Fudan University from January to August 2023. After propensity score matching at a ratio of 1∶5, there were 12 patients in the novel needle group and 60 patients in the conventional needle group. The pathological diagnosis rate and number of punctures were compared between the two groups. The stratified analyses on the size and location of lesions were performed. Results After matching, the pathological diagnosis rate was 91.7% (11/12) in the novel needle group, with a median of 2 punctures; the rate was 61.7% (37/60) in the conventional needle group, with a median of 3 punctures. No statistically significant differences in pathological diagnosis rate and number of punctures were observed between the two groups. Subgroup analysis showed that for lesions ≥20 mm, there was no significant difference in the number of punctures between the novel and conventional needles. The novel needle achieved a significantly higher pathological diagnosis rate for subepithelial tumors compared with the conventional needle (100.0% vs 30.4%, P＝0.019), whereas no significant differences were found for pancreatic masses or lymph node lesions. Conclusions Compared with EUS-guided aspiration using the conventional needle, EUS-guided biopsy using the novel fork-tip needle shows a trend toward a higher pathological diagnosis rate, with particular advantages in subepithelial tumors.

Liver cancer， as a malignant digestive tract tumor with high incidence and mortality rates globally， has witnessed continuous increases in both incidence and mortality in recent years. Although modern medical treatment methods have achieved certain results in disease control， the treatment of liver cancer remains challenging due to the low early diagnosis rate， obvious toxic and side effects， and widespread drug resistance. Against this backdrop， exploring more efficient and safer treatment strategies is of utmost urgency. The Hippo cascade signaling pathway plays a crucial regulatory role in processes such as the proliferation， differentiation， apoptosis， and invasion of liver cancer cells. It is extensively involved in the occurrence and development of liver cancer， serving as an important target for anti-liver cancer treatment research. Traditional Chinese medicine （TCM） can exert anti-liver cancer effects through multiple approaches， mechanisms， and pathways. It has shown remarkable efficacy in preventing postoperative recurrence and metastasis of liver cancer， reducing adverse reactions of radiotherapy and chemotherapy， and improving the quality of life， thus becoming a key component of comprehensive liver cancer treatment. Studies have confirmed that the TCM active components including flavonoids， alkaloids， terpenoids， polyphenols， saponins， and quinones， as well as the TCM compound prescriptions such as compound Banmao capsules， Erzhu Jiedu decoction， Pianzaihuang， and Zhenggan prescription， can effectively regulate the Hippo signaling pathway. They exert significant anti-liver cancer effects through multiple mechanisms， such as inducing autophagy and apoptosis of liver cancer cells， improving macrophage polarization， blocking epithelial-mesenchymal transition， inhibiting glycolytic metabolism， promoting immune cell activation， reversing tumor drug resistance， and arresting the cell cycle. This study used "liver cancer" "Hippo" "signaling pathway" and "traditional Chinese medicine" as the main keywords to search multiple literature databases， including PubMed， CNKI， and VIP. By discussing and analyzing the mechanisms of TCM in regulating the Hippo signaling pathway for the treatment of liver cancer in the past five years， this paper aims to provide ideas and references for the research and development of new anti-liver cancer drugs in clinical practice.

Objective:To analyze the colonization rate and molecular types of Staphylococcus aureus (SA) on the tracheotomy wounds of neonates at early postoperative stage in neonatal intensive care unit (NICU). Methods:This was a case series study. Patients who were admitted and underwent tracheotomy in NICU of Beijing Children′s Hospital, Capital Medical University from January 1 st 2020 to December 31 st 2023 were enrolled. Swabs on the skin around the incision or on the nasal mucosa were collected and cultured at 24, 72 and 168 h after operation. Coagulase test and Staphytect Plus kits were used for SA identification. The nuc gene amplification and molecular types of SA were assessed by PCR. The patients were divided into SA colonization group and non-colonization group based on the presence or absence of SA colonization, and into infection group and non-infection group based on the presence or absence of infection. Demographic data, hospitalization information, colonization and infection status of SA were collected from the digital medical record system of the hospital. Differences between groups were analyzed using the independent sample t test or Fisher exact test. Results:Totally 19 patients were enrolled, among whom 13 were male. The gestation age was 39.0 (38.1, 40.0) weeks, and the birth weight was 3 150 (2 600, 3 400) g. Tracheotomy was done at 8.2(4.1, 19.6) days after diagnosis and indication confirmed. Corrected gestational age of patients on the operation day was 43.6 (42.2, 45.4) weeks. The NICU stay time was (34.0±3.1) days. SA colonization was confirmed around the incision of 8 patients. Out of the 18 strains of colonized bacteria, 10 were methicillin-resistant Staphylococcus aureus (MRSA). The most common molecular type of MRSA was ST59-SCCmec Ⅳ-t437 strain (8 strains). A total of 10 patients presented typical clinical manifestations of bacterial infection at the lungs, 3 patients in the blood stream and 2 patients in the central nervous system. Among 10 patients with bacterial infection, 3 patients were MRSA positive by boby fluid culture and affected by the ST59-SCCmec Ⅳ-t437 strain. The infection rate was different between patients with or without SA colonization on the tracheotomy incision (7/8 vs. 3/11, P=0.020). Conclusions:The colonization rate and infection rate were high on the tracheotomy incision in neonates. The major type was MRSA, and the most common molecular strain was ST59-SCCmec Ⅳ-t437 .

OBJECTIVE To identify core genes associated with the treatment of coronary heart disease （CHD） with Tongmai yangxin pills， and predict their potential immunological and metabolic mechanisms. METHODS Mendelian randomization （MR） analysis was conducted using protein quantitative trait loci （pQTL） data from the UK Biobank and Icelandic，and data from genome- wide association study to screen core genes related to Tongmai yangxin pills in the treatment of CHD. Gene expression changes were further validated using transcriptomic sequencing data. Mediation analyses of immune cells and plasma metabolites were subsequently performed to explore the downstream regulatory networks of these core genes. RESULTS A total of 62 positive pQTL genes showed significant causal associations with CHD. MR analysis combined with transcriptomic sequencing validation identified three core genes FAM3D，OXT， and ENPP5-associated with Tongmai yangxin pills in the treatment of CHD. The transcriptomic sequencing results showed that after treatment with Tongmai yangxin pills， the expression levels of FAM3D and OXT were significantly reduced （P＜0.01）， while the expression level of ENPP5 was significantly increased （P＜0.05）. Mediation analyses between immune cells and plasma metabolites indicated that these genes may positively or negatively regulate CHD through immune pathways involving regulatory T cells and myeloid dendritic cells expressing CD11c and CD62L， as well as through metabolic pathways related to lipid and fatty acid metabolism， cholesterol metabolism， and bile acid metabolism. CONCLUSIONS This study identified FAM3D，OXT， and ENPP5 as core genes associated with the treatment of CHD by Tongmai yangxin pills， which may exert therapeutic effects via modulation of immune cells and plasma metabolic pathways involving fatty acids and bile acids.

Natural products (NPs) are an important source of new drugs for the treatment of stroke. Identifying cellular targets for bioactive molecules is a major challenge and critical issue in the development of new drugs for stroke. Small-molecule probes play a unique role in target discovery. However, drawbacks to these probes include non-specificity, unstable activity, and difficulty in synthesis. Small-molecule probes based on NPs at least partially compensate for these shortcomings. NPs feature rich chemical and structural diversity, biocompatibility, and unique biological activities. These features could be exploited to provide new ideas and tools for target discovery. Small-molecule probes based on NPs provide a precise and direct search for interacting protein targets of NPs-active small molecules. This review explores the properties of small-molecule probes based on NPs and their applications in mechanistic studies of stroke and other diseases. We hope that this review will bring new perspectives to the mechanistic study of NPs-active small molecules and accelerate the translation of these ingredients into drug candidates for the treatment of stroke.