Colorectal cancer （CRC） is one of the most common cancers， with its incidence ranking high among cancers. It stands as the second leading cause of cancer-related death worldwide. In the early stages， CRC lacks specific symptoms， and most patients are diagnosed at advanced stages， making it a major research focus in the field of gastrointestinal tumors. Currently， clinical CRC treatments face several common challenges， including high surgical risks， frequent metastasis and recurrence， drug resistance， and significant side effects from chemotherapy and radiation therapy. With the development and application of traditional Chinese medicine （TCM）， it has been found that TCM and its active ingredients can effectively inhibit CRC cell proliferation， invasion， migration， and angiogenesis， and promote apoptosis and autophagy， thereby slowing the progression of CRC. This has become a key focus of CRC treatment research. Salvia Miltiorrhiza has multiple pharmacological effects， including activating blood circulation to dispel blood stasis， unlocking meridians to relieve pain， clearing heat to calm irritability， and cooling blood to reduce abscesses. It contains a variety of chemical components， including diterpenoids， phenolic acids， flavonoids， polysaccharides， nitrogen-containing compounds， steroids， and lactone compounds. This review summarized the molecular mechanisms of Salvia miltiorrhiza and its active ingredients in the treatment of CRC. It is found that these ingredients exert anti-CRC effects through various molecular mechanisms， including cell cycle arrest， promotion of apoptosis， inhibition of cell invasion and migration， induction of autophagy， suppression of tumor angiogenesis， and remodeling of the tumor microenvironment. The review aims to provide new insights for the drug development and clinical application of Salvia miltiorrhiza in CRC treatment.

Objective To establish a rat model of postoperative delirium(POD)induced by cardiopulmonary bypass with human gut microbiota using fecal microbiota transplantation(FMT)technology,and evaluate the model based on bioinformatics,cytokine analysis,and behavioral testing methods.Methods SPF-grade adult male SD rats weighing 400 to 450 g were selected.After under-going a week of Morris water maze training,rats with consistent performance were used to construct pseudo-germ-free rat models.Subsequently,20 successfully modeled rats were randomly divided into two groups:(CON group receiving fecal microbiota filtrate from healthy individuals)and(POD group receiving fecal microbiota filtrate from POD patients).Behavioral tests were conducted two weeks af-ter modeling,and rat feces were collected for metagenomic sequencing.Rats were euthanized by cer-vical dislocation,and blood and brain tissue samples were collected for cytokine and histopathological examinations.Results Compared with the CON group,the POD group exhibited significantly increased relative abundances of Akkermansiaceae,Prevotellaceae,and Akkermansia muciniphila,while the relative abundances of Lactobacillaceae and Mediterraneibacter massiliensis decreased significantly(P＜0.05).Serum levels of interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-α were signif-icantly higher in the POD group than those in the CON group(P＜0.05).Hematoxylin-eosin(HE)staining in the POD group revealed neurons with pyknotic and hyperchromatic nuclei.After modeling,the average latency in the Morris water maze was significantly longer in the POD group than that in the CON group(P＜0.05).Conclusion This study utilizes fecal microbiota trans-plantation technology to establish a rat model of POD induced by cardiopulmonary bypass with hu-man gut microbiota.The changes in gut microbiota structure abundance,levels of POD-related in-flammatory factors,and Morris water maze test results in this model are similar to the clinical mani-festations observed in patients with POD induced by cardiopulmonary bypass.

Vaccination is the most effective measure for reducing and preventing influenza and related complications. In this study, we analyzed the mutation trend and the antigen dominant site changes of the amino acid sequence of hemagglutinin subunit 1 (HA1) of human influenza A virus (IAV) in the northern hemisphere from 2012 to 2022. According to the HA1 sequences of A/Darwin/6/2021 (H3N2) and A/Wisconsin/588/2019 (H1N1) recommended by the World Health Organization in the 2022 influenza season in northern hemisphere, we employed the mosaic algorithm to design three Mosaic-HA1 antigens through stepwise substitution. Mosaic-HA1 was expressed and purified in 293F cells and then mixed with the alum adjuvant at a volume ratio of 1:1. The mixture was used to immunize BALB/c mice, and the immunogenicity was evaluated. Enzyme-linked immunosorbent assay showed that Mosaic-HA1 induced the production of IgG targeting two types of HA1, the specific IgG titers for binding to H3 protein and H1 protein reached 10⁵ and 10³ respectively. The challenge test showed that Mosaic-HA1 protected mice from H3N2 or H1N1. This study designs the vaccines by recombination of major antigenic sites in different subtypes of IAV, giving new insights into the development of multivalent subunit vaccines against influenza.
Animals ; Influenza A Virus, H1N1 Subtype/genetics* ; Influenza A Virus, H3N2 Subtype/genetics* ; Mice, Inbred BALB C ; Mice ; Influenza Vaccines/genetics* ; Hemagglutinin Glycoproteins, Influenza Virus/genetics* ; Humans ; Antibodies, Viral/blood* ; Antigens, Viral/genetics* ; Immunoglobulin G/immunology* ; Female ; Orthomyxoviridae Infections/prevention & control* ; HEK293 Cells

With intensified aging， Alzheimer's disease has become a serious problem in China's health field. In the field of traditional Chinese medicine （TCM）， Alzheimer's disease mainly describes cognitive deficits such as dementia and amnesia. After the inheritance and summary by medical experts of successive generations， the theory of "toxin damaging brain collaterals" has become a mature pathogenesis hypothesis of this disease. Blood stasis， as one of the main viral pathogens， is also closely related to the theory of Alzheimer's disease in modern pharmacology. Chuanxiong Rhizoma is used frequently in clinical prescriptions for Alzheimer's disease. As the main component of Chuanxiong Rhizoma， tetramethylpyrazine has a series of pharmacological effects on the cardiovascular system such as vasodilation， anti-platelet aggregation， anti-atherosclerosis， and anti-myocardial ischemia， which reflects the effects of Chuanxiong Rhizoma in activating blood circulation and removing blood stasis. However， few studies have focused on the effect of tetramethylpyrazine on the pathogenesis of Alzheimer's disease. From the perspective of TCM theory and modern pharmacology， this article discussed the effects of tetramethylpyrazine on the pathology and pathogenesis of Alzheimer's disease from the aspects of cardiovascular function， oxidative stress， inflammatory response， mitochondrial function， and cholinergic system and made prospects for the future application of tetramethylpyrazine to prevent and treat Alzheimer's disease.

Aortic stenosis(AS)is a structural change in aortic valve caused by congenital or acquired factors,and its incidence increases with age.Transcatheter aortic valve replacement(TAVR)is a safe and feasible minimally invasive treatment for severe AS.Since it was first approved by FDA in 2011 for severe AS which cannot be treated surgically,its indications have been extended to AS patients with low to moderate surgical risk.The placed prosthetic valves could compress the atrioventricular conduction system at the aortic root,leading to the development of postoperative cardiac conduction abnormalities,for which permanent pacemaker implantation(PPMI)is a treatment option.And post-TAVR PPMI is closely related to the prognosis of AS patients.Therefore,this article reviews predictors of conduction dysfunction and PPMI after TAVR.

Objective:To establish a nomogram to predict overall survival(OS)of Uterine carcinosarcoma(UCS)patients.Methods:A total of 2635 UCS patients were selected from the Surveillance,Epidemiology and End Results(SEER)database between 2000 and 2020.The patients were randomly divided into a training cohort and a validation cohort in a 7∶3 ratio.Univariate Cox regression analysis,Lasso regression and multivariate Cox analysis was conducted to screen for independent risk factors affecting OS in UCS patients.We established a no-mogram for predicting the 1-and 3-year OS of UCS patients and evaluate the discrimination and calibration of the nomogram using receiver operating characteristic curve(ROC),calibration plots and decision curve analysis(DCA).According to the nomogram scores,patients were divided into low,medium,and high-risk groups and compared with the International Federation of Gynecology and Obstetrics(FIGO)staging system.Results:Age,race,tumor size,tumor stage,surgery,radiotherapy,chemotherapy and lymph node metastasis were identified as independent prognostic factors affecting patient OS(P＜0.05),and the above eight key variables were selected to establish the nomogram for predicting 1-and 3-year OS in UCS patients.The C-index and the area under the ROC curve(AUC)values of both the training and validation cohorts were greater than 0.7,indicating good discriminative capabilities of the nomogram.The calibration curves showed high consistency between the predicted probability and actual survival results.Moreover,the DCA curves suggested the clinical utility and application value of the model were superior to those of the FIGO staging system.The total risk score of each patient was calculated ac-cording to the nomogram model.UCS patients were divided into the low-risk group(score＜80),middle-risk group(score 80-130),and high-risk group(score＞130).Kaplan-Meier survival analysis demonstrated that the nomo-gram had a good ability to identify high-risk individuals.Conclusions;The model is a useful tool for accurately predicting OS in UCS patients and can assist in making individualized interventions by providing valuable prognos-tic information.

Objective:To establish a nomogram to predict overall survival(OS)of Uterine carcinosarcoma(UCS)patients.Methods:A total of 2635 UCS patients were selected from the Surveillance,Epidemiology and End Results(SEER)database between 2000 and 2020.The patients were randomly divided into a training cohort and a validation cohort in a 7∶3 ratio.Univariate Cox regression analysis,Lasso regression and multivariate Cox analysis was conducted to screen for independent risk factors affecting OS in UCS patients.We established a no-mogram for predicting the 1-and 3-year OS of UCS patients and evaluate the discrimination and calibration of the nomogram using receiver operating characteristic curve(ROC),calibration plots and decision curve analysis(DCA).According to the nomogram scores,patients were divided into low,medium,and high-risk groups and compared with the International Federation of Gynecology and Obstetrics(FIGO)staging system.Results:Age,race,tumor size,tumor stage,surgery,radiotherapy,chemotherapy and lymph node metastasis were identified as independent prognostic factors affecting patient OS(P＜0.05),and the above eight key variables were selected to establish the nomogram for predicting 1-and 3-year OS in UCS patients.The C-index and the area under the ROC curve(AUC)values of both the training and validation cohorts were greater than 0.7,indicating good discriminative capabilities of the nomogram.The calibration curves showed high consistency between the predicted probability and actual survival results.Moreover,the DCA curves suggested the clinical utility and application value of the model were superior to those of the FIGO staging system.The total risk score of each patient was calculated ac-cording to the nomogram model.UCS patients were divided into the low-risk group(score＜80),middle-risk group(score 80-130),and high-risk group(score＞130).Kaplan-Meier survival analysis demonstrated that the nomo-gram had a good ability to identify high-risk individuals.Conclusions;The model is a useful tool for accurately predicting OS in UCS patients and can assist in making individualized interventions by providing valuable prognos-tic information.

OBJECTIVE: To investigate whether gut microbiota disturbance after cardiopulmonary bypass (CPB) contributes to the development of perioperative neurocognitive disorders (PND). METHODS: Fecal samples were collected from healthy individuals and patients with PND after CPB to prepare suspensions of fecal bacteria, which were transplanted into the colorectum of two groups of pseudo-germ-free adult male SD rats (group NP and group P, respectively), with the rats without transplantation as the control group (n=10). The feces of the rats were collected for macrogenomic sequencing analysis, and serum levels of IL-1β, IL-6 and TNF-α were measured with ELISA. The expression levels of GFAP and p-Tau protein in the hippocampus of the rats were detected using Western blotting, and the cognitive function changes of the rats were assessed with Morris water maze test. RESULTS: In all the 3 groups, macrogenomic sequencing analysis showed clustering and clear partitions of the gut microbiota after the transplantation. The relative abundances of Klebsiella in the control group (P < 0.005), Akkermansia in group P (P < 0.005) and Bacteroides in group NP (P < 0.005) were significantly increased after the transplantation. Compared with those in the control group, the rats in group NP and group P showed significantly decreased serum levels of IL-1β, IL-6 and TNF-α and lowered expression levels of GFAP and p-Tau proteins (all P < 0.05). Escape platform crossings and swimming duration in the interest quadrant increased significantly in group NP (P < 0.05), but the increase was not statistically significant in group N. Compared with those in group P, the rats in group NP had significantly lower serum levels of IL-1β, IL-6 and TNF-α and protein expressions of GFAP and p-Tau (all P < 0.05) with better performance in water maze test (P < 0.05). CONCLUSION In patients receiving CPB, disturbances in gut mirobiota contributes to the development of PND possibly in relation with inflammatory response.
Male ; Animals ; Rats ; Rats, Sprague-Dawley ; Cardiopulmonary Bypass ; Gastrointestinal Microbiome ; Interleukin-6 ; Tumor Necrosis Factor-alpha ; Neurocognitive Disorders

The constitutive androstane receptor (CAR, NR3I1) belongs to nuclear receptor superfamily. It was reported that CAR agonist TCPOBOP induces hepatomegaly but the underlying mechanism remains largely unknown. Yes-associated protein (YAP) is a potent regulator of organ size. The aim of this study is to explore the role of YAP in CAR activation-induced hepatomegaly and liver regeneration. TCPOBOP-induced CAR activation on hepatomegaly and liver regeneration was evaluated in wild-type (WT) mice, liver-specific YAP-deficient mice, and partial hepatectomy (PHx) mice. The results demonstrate that TCPOBOP can increase the liver-to-body weight ratio in wild-type mice and PHx mice. Hepatocytes enlargement around central vein (CV) area was observed, meanwhile hepatocytes proliferation was promoted as evidenced by the increased number of KI67

Objective:The current systematic review aims to evaluate the effectiveness and quality of interventions on depressive symptoms of informal caregivers of people with dementia in China and to provide evidences regarding protocols for the most effective interventions.Methods:A systematic literature search of Chinese and English databases was performed, covering randomized controlled trails published up to March 2019. The papers for final review were selected based on the inclusion and exclusion criteria. Data were extracted and analyzed with RevMan 5.3, after a quality appraisal of the included studies.Results:A total of 17 papers were identified as eligible for descriptive analysis and 14 of the papers provided estimates for meta-analysis, with 991 participants. An overall mean reduction in depression was identified among the participants of intervention group, compared to those in the control group ( SMD value was -0.75, 95% CI -0.88 - -0.62, P<0.01). Psychotherapeutic ( SMD value was -0.59, 95% CI -0.78 - -0.40, P<0.01) and psychoeducational interventions ( SMD value was -0.84, 95% CI -1.02 - -0.67, P<0.01) showed significant reductions of depressive symptoms among the caregivers. In addition, Evidence exists for the effectiveness across from the short-term ( SMD value was -0.54, 95% CI -0.82 - -0.26, P<0.01), medium-term ( SMD value was -0.68, 95% CI -0.83 - -0.52, P<0.01) to the long-term interventions ( SMD value was -0.80, 95% CI -1.08 - -0.53, P<0.01). Conclusion:Interventions targeting to reduce depressive symptoms are effective among informal caregivers of persons with dementia in China. However, insufficient evidences are found regarding the most effective protocols and more high-quality studies are needed for the target population.