Objective To investigate the effect of cinobufacini on inhibiting colorectal cancer metastasis by regula-ting the polarization of M2 macrophages.Methods THP-1 was induced into M0 type macrophages.The condi-tioned medium of HCT116 cells was collected to stimulate M0 type macrophages.The polarization of M2 type mac-rophages was observed by flow cytometry,real-time quantitative PCR and ELISA experiments.The conditioned me-dium of M0 type macrophages and HCT116-Mφ cells was collected to stimulate HCT116 cells.The ability of migra-tion and invasion was observed by wound healing assay and Transwell assay.The effect of cinobufacini on the via-bility of HCT116 cells was detected by CCK-8 assay.The conditioned medium of HCT116 and HCT116+cinobufa-cini was collected to stimulate M0 type macrophages.The polarization of M2 type macrophages was observed by flow cytometry,real-time quantitative PCR and ELISA experiments.The conditioned media of HCT116-Mφ cells and(HCT116+cinobufacini)-Mφ cells were collected to stimulate HCT116 cells.The changes of migration and inva-sion ability were observed by wound healing assay and Transwell assay.Results After stimulation of M0 type mac-rophages in HCT116 cell conditioned medium,the morphology of M0 macrophages turned into fusiform cells,the proportion of CD11b+CD206+cells increased,and the expression of M2 macrophage markers IL-10 and TGF-β in-creased.The migration and invasion ability of HCT116 cells were significantly enhanced after stimulation in the conditioned medium of HCT1 16-Mφ cells.After the addition of cinobufacini,not only the polarization proportion of M2 macrophages decreased,but also the metastatic effect mediated by M2 macrophages was inhibited.Conclusion HCT116 cells can induce the polarization of M2 macrophages,while cinobufacini can inhibit the tumor metastasis mediated by M2 macrophages by inhibiting the polarization of M2 macrophages.

Objective To investigate the role of bufalin(BU)in inhibiting M2-type macrophage-mediated colorec-tal cancer metastasis.Methods Human acute leukemia mononuclear cells(THP-1)were differentiated into M0 macrophages using phorbol ester induction(PMA)for 48 hours.The M0 macrophages were then treated with IL-4 and IL-13 medium.Surface markers and morphological changes were observed through ELISA,morphology,and RT-qPCR experiments.RT-PCR and ELISA experiments were conducted to detect the surface markers TGF-β and IL-10 of M2 macrophages.The secretion level of IL-6 in the supernatant of M2 macrophages and colorectal cancer cells HCT116 was compared using ELISA.Additionally,the effect of conditioned medium on colorectal cancer cell HCT116 was assessed through Transwell,Wound healing,RT-qPCR,and Western blot experiments.Subsequent-ly,bufalin was added to the conditioned medium and the changes in AKT/PI3K protein,migration,and epithelial-mesenchymal transition ability in HCT116 were observed using Western blot,Transwell,Wound healing and RT-qPCR experiments.Results THP-1 were successfully differentiated into M2 macrophages.The activation of AKT/PI3K protein in HCT116 cells was induced by the secretion of IL-6 from M2 macrophages,which in turn promoted the migration and epithelial-mesenchymal transition ability of the HCT116 cells.The migration and epithelial-mes-enchymal transition mediated by M2 macrophages in HCT116 cells were effectively inhibited by Bufalin.Conclu-sion The release of IL-6 from M2 macrophages activates the AKT/PI3K signaling pathway in colorectal cancer cells,thereby promoting their migration and epithelial-mesenchymal transition capacity.Moreover,bufalin exhibits inhibitory effects on this effect.

OBJECTIVE To study the effects of the Mongolian medicine Sugemule-4 on the metabolism of insomnia rats， and to preliminarily explore its possible mechanisms for improving insomnia. METHODS The rat model of chronic stress insomnia was established by tail clipping stimulation and intraperitoneal injection of p-chlorophenyl alanine solution. Twenty-four male rats were randomly divided into the normal group， model group， diazepam group （positive control， 0.92 mg/kg）， and Sugemule-4 group （5.2 g/kg）， with 6 rats in each group. Since the 7th day of tail clipping stimulation， the Sugemule-4 group and diazepam group began to be intragastrically administered with relevant medicine； the normal group and model group were intragastrically administered with an equal volume of distilled water， once a day， for 14 consecutive days. The learning and memory abilities of rats were tested using a water maze experiment， and the non-invasive sleep activity monitoring system was used to monitor the 24- hour sleep time of rats. A metabolomics study was conducted on rat serum and hippocampal tissue by using ultra-high-performance liquid chromatography-tandem mass spectrometry. The multivariate statistical analysis method was adopted to analyze the differential metabolites in serum and hippocampal tissue of rats， and screen for differential metabolites and metabolic pathways among those groups. RESULTS Compared with the normal group， the escape latency of rats in the model group was significantly increased， the times of crossing platforms were significantly reduced， and the percentage of average 24-hour sleep time was significantly reduced （P＜0.05）. Compared with the model group， the levels of the above indicators were significantly reversed in the diazepam group and Sugemule-4 group （P＜0.05）. Metabolomics studies found that a total of 9 differential metabolites were identified in rat serum and hippocampal tissue， including 5-hydroxyindoleacetic acid， canine urate， canine urinary quinolinic acid， 5-hydroxytryptamine， phenol sulfate， 1-carboxyethyltyrosine， 3-（4-hydroxyphenyl） lactate， N-acetyl tyrosine， tyrosine and phenol sulfate， mainly involving 2 metabolic pathways of tryptophan and tyrosine.CONCLUSIONS Sugemule-4 can improve the sleep time and behavioral performance of insomnia rats， and its mechanism may be associated with affecting amino acid metabolic pathways such as tryptophan and tyrosine.

Objective To explore the possibility of MR Ti-mapping imaging technology to provide additional indicators for clinical quantitative evaluation of renal function in children with renal insufficiency.Methods A total of 13 children with renal insufficiency diagnosed and underwent renal function MRI examination were selected(renal insufficiency group),and 23 children with normal renal function were included as the control group.The difference of renal cortex T1 value between the control group and the renal insuffi-ciency group was compared,and the correlation between renal cortex T1 value and biochemical indexes such as serum creatinine(SCr)and cystatin C(CysC)in the renal insufficiency group was analyzed.Results There was significant difference in T1 value of renal cortex between the renal insufficiency group and the control group(P＜0.01).The correlation between T1 value of renal cortex and SCr and CysC in renal insufficiency group was higher(r=0.75,P＜0.01;r=0.68,P＜0.01).Conclusion MR T1-mapping technol-ogy can non-invasively monitor the renal function status of children with renal insufficiency,and has a suggestive value for clinical quantitative evaluation of renal function in children.

The incidence of cancer has remained high in recent years, and anti-tumor treatment methods are emerging. Cancer treatment has undergone significant changes, and the survival rate of patients with cancer has significantly improved. Various types of new anti-tumor treatments may not only treat and control tumor growth but also place patients in critical situations that require treatment by intensive care medical personnel. Patients with cancer are in critical condition mainly due to three reasons: severe cases caused by cancer diseases themselves, complications during the perioperative period, and accompanying diseases and hospital acquired diseases. In the new situation, we should consider patient characteristics, such as abnormal metabolism, abnormal coagulation system, and abnormal immune mechanism, to save them from serious illness. We need to comprehensively evaluate patients with cancer, emphasize the role of the Intensive Care Unit (ICU) treatment platform, and promote the treatment concept of planned transfer to ICU, to improve the success rate and efficiency of treatment. After transferring the patient out of the ICU, the planned follow-up anti-tumor treatment can still be continued as the endpoint of ICU treatment for critically ill patients with cancer. In the future, efforts will be devoted to establishing a discipline and talent echelon with distinctive characteristics of oncology critical care medicine and treating "the critical illness of cancer and the cancer of critical illness".

Colorectal cancer(CRC)is a common malignant tumor of the digestive system.The main treatments for CRC currently include surgical resection,chemotherapy,radiotherapy,and immunotherapy.Immunogenic cell death(ICD)is an important method ofanti-tumortherapy.ICD is a specific type of cell death that involves the release of damage-associated molecular patterns(DAMPs).These DAMPs can be effectively taken up by dendritic cells(DCs),neutrophils,and macrophages,thereby stimulating adaptive immune responses in the body.However,colorectal cancer is considered a"cold tumor"with relatively low immunogenicity,resulting in a low response rate to immunotherapy.Inducing ICD can potentially enhance the immunogenicity of colorectal cancer,leading to long-term tumor control.This review aims to explore the impact of ICD development in colorectal cancer treatment and investigate the potential of ICD inducers in colorectal cancer immunotherapy.

Objective To evaluate whether the measurement of tibialis anterior muscle thickness(TA-MT)in sepsis can be used as an alternative method to understand systemic changes in skeletal muscle mass by comparing the trend of ultrasonic measurement of TA-MT with bioelectrical impedance analysis(BIA)in detecting skeletal muscle mass.Methods A single-center prospective study was conducted.The patients with tumor sepsis who were treated in the department of intensive care unit(ICU)of Tianjin Medical University Cancer Hospital from March to December 2022 were selected as the study subjects.The changes of TA-MT within 6 hours after sepsis and 3 days after treatment were measured by ultrasound.The changes of body mass,body mass index(BMI),lean body mass,body fat percentage,body fat,whole body protein,skeletal muscle mass,skeletal muscle index(SMI),arm circumference,right lower limb lean body mass,and body water were measured by BIA.The 28-day prognosis was followed up.The correlation between TA-MT and skeletal muscle indicators measured by BIA was analyzed by Pearson correlation analysis.Results Eventually,40 patients were included.Compared with before treatment,the levels of TA-MT by ultrasound and acute physiology and chronic health evaluationⅡ(APACHEⅡ),sequential organ failure assessment(SOFA)and oxygen metabolism index blood lactic acid(Lac)measured after treatment were significantly reduced[TA-MT(cm):2.31±0.35 vs.2.50±0.36,APACHEⅡscore:11.00±3.18 vs.17.50±5.44,SOFA score:3.28±2.18 vs.6.30±3.11,Lac(mmol/L):1.38±0.35 vs.2.40±1.02,all P＜0.05].Meanwhile,the BIA test showed that body mass,body mass index,lean body mass,body fat percentage,body fat,whole body protein,skeletal muscle mass,SMI,arm circumference,right lower limb lean body mass and body water were also significantly decreased after treatment[body mass(kg):63.87±13.96 vs.66.58±14.95,BMI(kg/m2):22.57±4.37 vs.23.52±4.59,lean body mass(kg):46.32±6.89 vs.49.66±7.84,whole body protein(kg):9.36±1.37 vs.9.93±1.55,skeletal muscle mass(kg):26.23±4.17 vs.27.96±4.72,SMI(kg/m2):7.12±1.04 vs.7.78±1.18,arm circumference(cm):29.41±3.66 vs.30.17±3.59,right lower limb lean body mass(kg):7.21±1.26 vs.7.77±1.42,total body water(L):36.38±5.44 vs.39.11±6.19,all P＜0.05],body fat percentage and body fat were significantly elevated[body fat percentage:(21.96±8.30)%vs.(19.98±8.43)%,body fat(kg):14.81±8.64 vs.14.12±8.81,both P＜0.05].Pearson correlation analysis showed that:the right TA-MT was negatively correlated with the electrical impedance of the right lower extremity(r =-0.445 2,P＜0.001),the right side TA-MT was positively correlated with the right lower limb lean body mass,whole body protein,skeletal muscle mass,SMI and lean body mass(r values were 0.571 4,0.629 9,0.628 3,0.575 9,0.634 4,all P＜0.000 1).Conclusion Significant skeletal muscle depletion can be observed in tumor patients with sepsis,and ultrasound measurement of TA-MT is an effective alternative method to assess systemic skeletal muscle mass trends.

Objective:To investigate the status quo of pain management for cancer patients in hospice care wards of community health service centers.Methods:The electronic medical records of 373 cancer patients admitted in hospice wards of Kangjian Community Health Center of Xuhui District and Jinshanwei Town Community Health Center of Jinshan District from January 2015 to July 2021 were collected. The characteristics of cancer pain, the use of analgesic drugs, the effects of analgesic drugs and its influencing factors were analyzed.Results:The incidence of cancer pain in 373 patients was 93.0% (347/373), and the proportion of moderate to severe cancer pain was 55.6% (193/347). Analgesics were used in 304 patients, among whom 233 (76.6%) patients used oral analgesics, 297 (97.7%) used on time, 97.6%(285/292) used sustained-release opioids, and 94 (30.9%) used combinedly. Breakout pain occurred in 100 cases (32.9%), all of which was controlled with immediate-release morphine. Cancer pain was not relieved in 132 cases (43.42%), and multivariate logistic regression analysis showed that the pain degree on admission (moderate: OR=3.69, 95 %CI:2.09-6.49; severe: OR=5.52, 95 %CI:2.43-12.53), the presence of burst pain ( OR=3.28, 95 %CI:1.77-6.06), the type of analgesics used (non-steroidal+weak opioids: OR=0.39, 95 %CI:0.20-0.76; nonsteroidal+strong opioids: OR=0.20, 95 %CI:0.08-0.51) and the adverse reactions ( OR=1.92, 95 %CI:1.03-3.60) were the influencing factors of pain relief in cancer pain patients (all P<0.05). Conclusion:The pain of cancer patients admitted to community palliative care wards cannot be ignored. Although most cancer pain patients use analgesic drugs in a standard way, there are still a high proportion of patients whose pain is not controlled. Various factors affect the effect of analgesic treatment.

Few studies have described the key features and prognostic roles of lung microbiota in patients with severe community-acquired pneumonia (SCAP). We prospectively enrolled consecutive SCAP patients admitted to ICU. Bronchoscopy was performed at bedside within 48 h of ICU admission, and 16S rRNA gene sequencing was applied to the collected bronchoalveolar lavage fluid. The primary outcome was clinical improvements defined as a decrease of 2 categories and above on a 7-category ordinal scale within 14 days following bronchoscopy. Sixty-seven patients were included. Multivariable permutational multivariate analysis of variance found that positive bacteria lab test results had the strongest independent association with lung microbiota (R² = 0.033; P = 0.018), followed by acute kidney injury (AKI; R² = 0.032; P = 0.011) and plasma MIP-1β level (R² = 0.027; P = 0.044). Random forest identified that the families Prevotellaceae, Moraxellaceae, and Staphylococcaceae were the biomarkers related to the positive bacteria lab test results. Multivariable Cox regression showed that the increase in α-diversity and the abundance of the families Prevotellaceae and Actinomycetaceae were associated with clinical improvements. The positive bacteria lab test results, AKI, and plasma MIP-1β level were associated with patients' lung microbiota composition on ICU admission. The families Prevotellaceae and Actinomycetaceae on admission predicted clinical improvements.
Acute Kidney Injury/complications* ; Bacteria/classification* ; Chemokine CCL4/blood* ; Community-Acquired Infections/microbiology* ; Humans ; Lung ; Microbiota/genetics* ; Pneumonia, Bacterial/diagnosis* ; Prognosis ; RNA, Ribosomal, 16S/genetics*

Objective To investigate the effect of Liu-Shen-Wan on transplanted tumors in mice with colon cancer based on the polarization of M2 macrophages in the tumor microenvironment. Methods We established a subcutaneous transplantation tumor model of mice with CT26 colon cancer. Mice were randomly divided into vehicle, oxaliplatin, and oxaliplatin combined with Liu-Shen-Wan groups. Treatment was administered for three weeks, and tumor volume was measured. All mice were weighed during the administration. After the end of the treatment, the mice were dissected and tumors were photographed and weighed. Spleen index was calculated. The expression levels of IFN-γ and IL-12P40 in serum and related blood biochemical indices were measured. The expression levels of M2 macrophage polarization indices, namely, IL-10 and TGF-β, in serum and tumor tissues were detected. The infiltration degree of M2 macrophages in each group was observed by immunohistochemical experiments. Results The tumor volume and mouse weight in the oxaliplatin combined with Liu-Shen-Wan group significantly decreased compared with those in the vehicle group. The spleen index increased, and the expression levels of IFN-γ and IL-12P40 in serum also significantly increased. The mice had no obvious side effects after the drug treatment. In addition, the expression levels of IL-10 and TGF-β in the serum and tissues of mice in the oxaliplatin combined with Liu-Shen-Wan group significantly decreased. The expression levels of CD68 and CD206 in tumor tissues also decreased. Conclusion The anti-tumor effect of Liu-Shen-Wan on the transplanted tumors of mice with colon cancer is related to the inhibition of M2 macrophage polarization in the tumor microenvironment.