Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Background Atmospheric fine particulate matter (PM_2.5) can disrupt the metabolic homeostasis of the liver and accelerate the progression of liver diseases, but there are few studies on the effects of sub-chronic PM_2.5 exposure on the liver metabolome. Objectives To investigate the effects of sub-chronic exposure to concentrated PM_2.5 on hepatic metabolomics in mice by liquid chromatography-mass spectrometry (LC-MS), and to identify potentially affected metabolites and metabolic pathways. Methods Twelve male C57BL/6J (6 weeks old) mice were randomly divided into two groups: a concentrated PM_2.5 exposure group and a clean air exposure group. The mice were exposed to concentrated PM_2.5 using the "Shanghai Meteorological and Environmental Animal Exposure System" at Fudan University. The exposure duration was 8 h per day, 6 d per week, for a total of 8 weeks. The mice's liver tissues were collected 24 h after the completion of exposure. LC-MS was performed to assess changes in the hepatic metabolome. Orthogonal partial least squares discriminant analysis and t-test were employed to identify differentially regulated metabolites between the two groups under the conditions of variable important in projection (VIP)≥1.0 and P<0.05. Metabolic pathway enrichment analysis was performed using MetaboAnalyst 5.0 software and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results A total of 297 differentially regulated metabolites were identified between the concentrated PM_2.5 exposure group and the clean air group. Among these metabolites, 142 were upregulated and 155 were downregulated. A total of 38 metabolic pathways were altered, with 7 pathways showing significant perturbation (P<0.05). These pathways involved amino acid metabolism, glucose metabolism, nucleotide metabolism, as well as cofactor and vitamin metabolism. The 7 significant metabolic pathways were pantothenic acid and coenzyme A biosynthesis; purine metabolism; amino sugar and nucleotide sugar metabolism; arginine biosynthesis; alanine, aspartate and glutamate metabolism; aminoacyl-tRNA biosynthesis; and fructose and mannose metabolism. Conclusion The results from metabolomics analysis suggest that sub-chronic exposure to PM_2.5 may disrupt hepatic energy metabolism and induce oxidative stress damage. Aspartic acid, succinic acid, ornithine, fumaric acid, as well as purine and xanthine derivatives, were identified as potential early biomarkers of hepatic response to sub-chronic PM_2.5 exposure.

OBJECTIVE To investigate the effects of GSTP1， XRCC1， ABCB1， MTHFR gene polymorphisms on efficacy and toxic effect of chemotherapy regimen containing oxaliplatin in patients with stage Ⅲ and Ⅳ colorectal cancer patients. METHODS Clinical data of 76 patients with stage Ⅲ and Ⅳ colorectal cancer who received chemotherapy regimen containing oxaliplatin （XELOX，FOLFOX） were collected from the Second Affiliated Hospital of Soochow University from September 2018 to March 2020. The correlation of genotypes with progression-free survival （PFS） and toxic effect was analyzed by using univariate and multivariate COX regression model. RESULTS Carriers of the ABCB1 3435T＞C locus C allele （TC/CC） had a significantly higher risk of progression compared to TT genotype patients [HR＝2.39， 95%CI （1.05，5.50）， P＝0.038]. The risk of progression in patients at stage Ⅳ was significantly higher than those at stage Ⅲ [HR＝8.11， 95%CI（3.39，19.40）， P＜0.001]. Chemotherapy regimen， Karnofsky performance status score and tumor site had no significant effect on disease progression （P＞0.05）. Mutations in gene loci were not correlated with adverse reactions （P＞0.05）. CONCLUSIONS Patients carrying ABCB1 TC/CC and receiving chemotherapy regimen containing oxaliplatin have a higher risk of disease progression， which may be associated with longer PFS in patients （TT genotype） with stage Ⅳ colorectal cancer receiving the chemotherapy， while GSTP1， XRCC1， and MTHFR gene polymorphisms have no significant impact.

Objective:To investigate the acute gastrointestinal injury (AGI) in patients with extracorporeal membrane oxygenation (ECMO) at the early stage of operation and its influencing factors.Methods:A total of 70 patients with ECMO who were hospitalized in the Emergency Care Unit of Guangxi Zhuang Autonomous Region People's Hospital from September 2020 to December 2021 were retrospectively analyzed, and a total of 70 patients with ECMO who were hospitalized in the emergency care unit of Guangxi Zhuang Autonomous Region People's Hospital from September 2020 to December 2021 were retrospectively analyzed. According to the 2012 guidelines of the European Society of Intensive Care Medicine on the classification of acute gastrointestinal injury in critically ill patients, the patients were divided into AGI group and non-AGI group. The incidence of acute gastrointestinal injury in the early stage was statistically analyzed, and the results of blood gas analysis during ECMO loading and ECMO parameters, hemodynamic indexes and biochemical indexes after ECMO transfer were statistically analyzed. To explore the influencing factors and independent risk factors of AGI in the early stage. In addition, 70 patients were divided into successful group and non-successful group according to whether they were successfully withdrawn. The occurrence of acute gastrointestinal injury between the two groups was compared, and the effect of acute gastrointestinal injury on ECMO patients was analyzed.Results:Among the 70 ECMO patients, the incidence of early AGI was 71.43% (50 cases), and the components of AGI Ⅰ, Ⅱ, Ⅲ and Ⅳ were 18.57% (13 cases), 41.43% (29 cases), 11.43% (8 cases) and 0% (0 cases), respectively. ① Univariate analysis showed that systolic blood pressure, diastolic blood pressure, mean arterial pressure (MAP), vasoactive drug index (VIS), pH, lactic acid and BMI were significantly different between AGI group and non-AGI group when ECMO was used ( P < 0.05). Logistic binary regression analysis showed that BMI was an independent risk factor for early AGI in ECMO patients (ROC area 0.657, 95% confidence interval 0.522-0.791 ( P < 0.05), and Yoden index 0.15). (3) The AGI composition ratio of the unsuccessful group was higher than that of the unsuccessful group ( P < 0.05). Conclusions:Patients with ECMO have a high incidence of AGI in the early stage, mainly occurring in grade I and Ⅱ. Systolic blood pressure, diastolic blood pressure, MAP, VIS, pH, lactic acid and BMI when ECMO is put on are influential factors for the early development of AGI in ECMO patients, among which BMI is an independent risk factor for the early development of AGI in ECMO patients. The occurrence of AGI reduces the probability of successful withdrawal in ECMO patients.

Objective To observe the value of clinical and CT radiomics features for predicting microsatellite instability-high(MSI-H)status of gastric cancer.Methods Totally 150 gastric cancer patients including 30 cases of MSI-H positive and 120 cases of MSI-H negative were enrolled and divided into training set(n=105)or validation set(n=45)at the ratio of 7∶3.Based on abdominal vein phase enhanced CT images,lesions radiomics features were extracted and screened,and radiomics scores(Radscore)was calculated.Clinical data and Radscores were compared between MSI-H positive and negative patients in training set and validation set.Based on clinical factors and Radscores being significant different between MSI-H positive and negative ones,clinical model,CT radiomics model and clinical-CT radiomics combination model were constructed,and their predictive value for MSI-H status of gastric cancer were observed.Results Significant differences of tumor location and Radscore were found between MSI-H positive and negative patients in both training and validation sets(all P＜0.05).The area under the curve(AUC)of clinical model,CT radiomics model and combination model for evaluating MSI-H status of gastric cancer in training set was 0.760,0.799 and 0.864,respectively,of that in validation set was 0.735,0.812 and 0.849,respectively.AUC of clinical-CT radiomics combination model was greater than that of the other 2 single models(all P＜0.05).Conclusion Clinical-CT radiomics combination model based on tumor location and Radscore could effectively predict MSI-H status of gastric cancer.

Objective:To evaluate clinical prognosis and prognostic factors of patients with early stage (Ⅰ stage) and locally advanced (Ⅱ/Ⅲ stage) lung cancer treated with carbon ion radiotherapy (CIRT).Methods:Clinical data, treatment, adverse reactions, survival and so on of 54 lung cancer patients who received CIRT and follow-up in the Heavy Ion Center of Wuwei Cancer Hospital of Gansu Province from March 2020 to September 2022 were retrospectively analyzed. The survival curve was plotted using Kaplan-Meier method. Difference tests were performed using log-rank test. Logistic regression analysis was used to identify prognostic factors.Results:According to inclusion and exclusion criteria, 54 patients were enrolled in the study, including 10 patients with early stage lung cancer and 44 patients with locally advanced lung cancer. The median follow-up time for 10 patients with early stage lung cancer was 11.0 (6.75, 17.25) months, and the median dose of irradiation was 60 Gy [relative biological effect (RBE)]. Upon the last follow-up, 3 patients had complete response (CR) and 3 patients had partial response (PR). Four patients had stable disease (SD) and no progressive disease (PD). The 1-year and 2-year local control rates (LCR), progression-free survival (PFS) rates and overall survival (OS) rates were 100%. During treatment and follow-up, 2 patients developed grade 1 radiation pneumonia, 1 case of grade 2 radiation pneumonia, 1 case of chest wall injury (chest wall pain), and there were no adverse reactions greater than grade 2. The median follow-up time of 44 patients with locally advanced stage was 12.5 (4.25, 21.75) months, and the median irradiation dose was 72 Gy (RBE). Thirty-two (73%) patients received concurrent chemotherapy during treatment, 20 (45%) patients received sequential chemotherapy after treatment, 14 (32%) patients received immune maintenance therapy and 3 (7%) patients obtained PD and received targeted drugs. Upon the last follow-up, 3 (7%) patients had CR, 17 (39%) patients had PR, 19 (43%) patients obtained SD, and 5 (11%) patients had PD. The 1-year and 2-year LCR were 96.0% and 87.3%, 90.9% and 84.1% for the 1-year and 2-year PFS rates, and 93.2% and 86.4% for the 1-year and 2-year OS rates, respectively. The median OS and PFS of patients were not reached. Multivariate logistic regression analysis showed that maintenance therapy after radiotherapy ( P=0.027) and clinical target volume (CTV) irradiation volume ( P=0.028) were the factors affecting PFS. Simultaneous chemoradiotherapy ( P=0.042) and maintenance therapy after radiotherapy ( P=0.020) were the factors affecting OS. And gross tumor volume (GTV) ≥215 ml ( P=0.068) might be an independent risk factor for grade 2 and above radiation pneumonia. Conclusions:The domestic carbon ion system has definite clinical effect and controllable toxic and side effects in the treatment of early stage and locally advanced lung cancer. The combination of synchronous chemotherapy and further maintenance treatment can significantly improve clinical prognosis of patients without significantly increasing the risk of toxic and side effects.

OBJECTIVE To explore the protective effects and potential mechanisms of Hirudo on mice with non-alcoholic fatty liver disease （NAFLD） in mice. METHODS The male ApoE－/－ mice were randomly divided into the model group and Hirudo low- dose and high-dose groups （0.45， 0.9 g/kg）， with 10 mice in each group； another 10 wild-type male C57BL/6J mice were chosen as the control group. The control group was fed with basal maintenance chow and the remaining groups were fed with high-fat chow for 12 weeks to establish the NAFLD model. Each administration group was given corresponding solution intragastrically， once a day， for 8 consecutive weeks. In the 13th week， the body weight and liver weight of mice in each group were measured after the last medication， and the liver index was calculated； the serum levels of nuclear factor-κB （NF-κB）， tumor necrosis factor-α （TNF- α）， interleukin-1β （IL-1β）， IL-6， total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C） and high-density lipoprotein cholesterol （HDL-C） were detected； the liver pathomorphological changes were observed； the protein expressions of peroxisome proliferator-activated receptor γ（PPARγ） and silence information regulator type 1 （SIRT1） were detected. RESULTS Compared with the control group， the liver tissue of mice in the model group showed more fat vacuoles and infiltration of inflammatory cells， with significant lipid accumulation； the body weight， liver weight and liver index of the mice， and serum levels of NF-κB， TNF-α， IL-1β， IL-6， TC， TG and LDL-C significantly increased， while the serum level of HDL-C， the protein expressions of PPARγ and SIRT1 in liver tissues significantly decreased （P＜0.01）. Compared with the model group， the pathological changes in liver tissue of mice were all relieved in Hirudo low-dose and high-dose groups； the body weight， liver weight and liver index， the serum levels of NF-κB， TNF-α， IL-1β， IL-6， TC， TG and LDL-C decreased significantly， while the serum level of HDL-C， the protein expressions of PPARγ and SIRT1 in liver tissue all increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Hirudo can regulate liver lipid metabolism and inhibit inflammation by activating the protein expressions of PPARγ and SIRT1， thus having a significant ameliorative effect on NAFLD.

OBJECTIVE To analyze the accumulation law of saponins during growth in Paris polyphylla Smith var. chinensis (Franch.) Hara, determine the content of the main saponins in different cultivation years, age groups, cultivation modes and provenances. METHODS The content of 5 kinds saponins(I, II, VI, VII, H) was simultaneous determined by HPLC. RESULTS The total saponins in P. polyphylla Smith var. chinensis (Franch.) Hara were mainly composed of saponin VII and H, supplemented by saponin VI, I and II. The content of saponins(I, II, VII) was significantly different among different cultivation years rhizome, while it reached the standard of Chinese Pharmacopoeia 2020 Edition after 6 years old, 8-year-old rhizome was the highest. The saponins(I, II, VII) content in 4a rhizome and 5a rhizome was significant higher than others, and it ranged from 0.354% to 0.765% in different cultivation modes, from high to low as follows: coniferous forest>bamboo forest>broadleaf forest>greenhouse. In different provenances, it ranged from 0.592% to 0.741%, reached the highest level in Qingyuan Baikan, and was slightly lower than the standard of Chinese Pharmacopoeia 2020 Edition in Sanming Fujian. CONCLUSION There are remarkable correlations among saponins accumulation amounts and cultivation years, age groups, cultivation modes and provenances, which can provide reference for the artificial culvication of P. polyphylla Smith var. chinensis (Franch.) Hara.

Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.Methods Fluorescent microspheres (100 nm, 3 μm, and 10 μm) were given once at a dose of 200 mg/(kg·body weight). The fluorescence intensity (FI) in observed organs was measured using the IVIS Spectrum at 0.5, 1, 2, and 4 h after administration. Histopathology was performed to corroborate these findings.Results In the 100 nm group, the FI of the stomach and small intestine were highest at 0.5 h, and the FI of the large intestine, excrement, lung, kidney, liver, and skeletal muscles were highest at 4 h compared with the control group (P < 0.05). In the 3 μm group, the FI only increased in the lung at 2 h (P < 0.05). In the 10 μm group, the FI increased in the large intestine and excrement at 2 h, and in the kidney at 4 h (P < 0.05). The presence of nano-/microplastics in tissues was further verified by histopathology. The peak time of nanoplastic absorption in blood was confirmed.Conclusion Nanoplastics translocated rapidly to observed organs/tissues through blood circulation;however, only small amounts of MPs could penetrate the organs.

The imprint desorption electrospray photoionization mass spectrometry was employed to locally image the spatial distribution of chemical components in dried tobacco leaves after initial curing. The relative content distribution of different chemical components was obtained in tobacco leaves. The application of imprinting method could transfer tobacco internal compounds to the surface of porous polytetrafluoroethylene plate,which realized the detection and visual analysis of tobacco internal substances. Besides,the imprint desorption electrospray ionization/post-photoionization (Imprint DESI/PI) mass spectrometry imaging technique had the advantages of non-polarity discrimination,soft ionization and high ionization efficiency for plant samples,and could simultaneously detect and image rich compounds in tobacco samples. A total of 40 kinds of chemical components including alkaloids,amino acids,sugars,acids,ketones and phenols were identified based on high resolution mass spectrometry. The results showed that the representative chemical components of tobacco,such as alkaloids,amino acids and sugars,were mainly distributed near the leaf tip from the vertical analysis and at the left and right leaf edges from the horizontal analysis. Amadori compound (1-Deoxy-1-L-proline-d-fructose) was detected,and the content of Amadori was found to be consistent with that of free amino acid (proline). In addition,the technique was further used to study the climate spot disease area of tobacco,and it was found that the compounds had specific distribution in the climate spot area,which further proved the superiority of this method in studying the growth stress of tobacco leaves.