BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

OBJECTIVE To establish and verify the risk prediction models for postoperative multidrug-resistant or-ganisms(MDROs)infections in the liver transplantation patients based on the machine learning algorithms so as to provide bases for identification of the population at high risk of postoperative MDROs infections.METHODS The liver transplantation patients who were retrospectively collected from intensive care Ⅳ database(MIMIC-Ⅳ)and eICU collaborative research database(eICU)were recruited as the research subjects,meanwhile,the patients who underwent liver transplantation in the First Hospital of Shanxi Medical University from Jan.2021 to Jul.2024 were assigned as the external verification group.The variables were selected by Lasso regression,and the models were established based on 7 types of machine learning algorithms such as extreme gradient boosting algorithm and random forest.The predictive performances of the models were evaluated by comparing the areas under receiver operating characteristic(ROC)curves and the accuracy,the characteristic variables were interpreted by Shapley additive explanations(SHAP),and the risk prediction calculator was established.RESULTS A total of 637 pa-tients were finally enrolled in the study,and the incidence of postoperative MDROs infections was 35.79％.Total-ly 15 variables were finally selected for construction of the model.The area under the receiver operating character-istic curve of XGBoost model was 0.82 for the internal test set,0.78 for the external test set;the predictive per-formance of XGBoost model was better than that of the rest of 6 models.SHAP algorithm indicated that the top 5 important predictive factors were as follows:hepatic encephalopathy,length of intensive care unit(ICU)stay,albumin,model of end-stage liver disease(MELD)and total length of hospital stay.CONCLUSION The risk pre-diction models that are established based on the machine learning algorithms have remarkable effect on prediction of the postoperative MDROs infections and can accurately identify the liver transplantation patients at high risk of postoperative MDROs infections,which may provide guidance for the identification of high-risk population and the development of prevention and treatment measures for infections.

OBJECTIVE To establish and verify the risk prediction models for postoperative multidrug-resistant or-ganisms(MDROs)infections in the liver transplantation patients based on the machine learning algorithms so as to provide bases for identification of the population at high risk of postoperative MDROs infections.METHODS The liver transplantation patients who were retrospectively collected from intensive care Ⅳ database(MIMIC-Ⅳ)and eICU collaborative research database(eICU)were recruited as the research subjects,meanwhile,the patients who underwent liver transplantation in the First Hospital of Shanxi Medical University from Jan.2021 to Jul.2024 were assigned as the external verification group.The variables were selected by Lasso regression,and the models were established based on 7 types of machine learning algorithms such as extreme gradient boosting algorithm and random forest.The predictive performances of the models were evaluated by comparing the areas under receiver operating characteristic(ROC)curves and the accuracy,the characteristic variables were interpreted by Shapley additive explanations(SHAP),and the risk prediction calculator was established.RESULTS A total of 637 pa-tients were finally enrolled in the study,and the incidence of postoperative MDROs infections was 35.79％.Total-ly 15 variables were finally selected for construction of the model.The area under the receiver operating character-istic curve of XGBoost model was 0.82 for the internal test set,0.78 for the external test set;the predictive per-formance of XGBoost model was better than that of the rest of 6 models.SHAP algorithm indicated that the top 5 important predictive factors were as follows:hepatic encephalopathy,length of intensive care unit(ICU)stay,albumin,model of end-stage liver disease(MELD)and total length of hospital stay.CONCLUSION The risk pre-diction models that are established based on the machine learning algorithms have remarkable effect on prediction of the postoperative MDROs infections and can accurately identify the liver transplantation patients at high risk of postoperative MDROs infections,which may provide guidance for the identification of high-risk population and the development of prevention and treatment measures for infections.

Objective To investigate the anti-inflammatory effect of 25-OH vitamin D(25-OH-VD)on neonatal infectious pneumonia(NIP)and its mechanism.Methods A total of 65 children with NIP admitted to Chengdu Women and Children's Central Hospital from January 2022 to January 2023 were selected.According to the severity of the disease,they were divided into mild group(n=34)and severe group(n=31),and 60 healthy neonates in the same period were selected as the control group.Serum 25-OH-VD,interleukin-2(IL-2),interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α)and IL-1β levels were measured by ELISA.The expressions of vitamin D receptor(VDR),transforming growth factor-β(TGF-β)/nuolea Yes-associated protein(n-YAP)and nuclear transcriptional coactivator PDZ-binding motif(n-TAZ)pathway related proteins in peripheral blood mononuclear cells were detected by Western blot.NIP in vitro models were established by lipopolysaccharide(LPS)stimulation of human lung epithelial cells,which were divided into control group,LPS group and LPS+VD group.Cell viability was detected by CCK-8 assay.The mRNA expressions of recombinant cytochrome P450 27B1(CYP27B1)and VDR in each group were detected by qRT-PCR.The number of YAP positive nuclei in each group was detected by immunocytochemistry.The nuclear translocation of YAP/TAZ complex in each group was detected by immunofluorescence.The expression of inflammatory factor-related proteins in each group was detected by Western blot.Results Compared with the control group,the serum levels of IL-2(1.91±0.18 μ g/L,2.63±0.27 μg/L vs 1.05±0.12 μg/L),IFN-γ(1.73±0.13 μg/L,2.18±0.19 μg/L vs 1.03±0.07 μg/L),TNF-α(1.79±0.08 μg/L,2.38±0.13 μg/L vs 0.97±0.04 μg/L),IL-1 β(2.18±0.07 μg/L,2.59±0.11μg/L vs 0.96±0.02 μg/L),TGF-β(1.67±0.21,2.43±0.42 vs 1.02±0.04),n-YAP(2.08±0.11,4.23±0.37 vs 0.99±0.02)and n-TAZ(2.47±0.42,4.21±0.58 vs 1.03±0.05)proteins of the children in the mild and severe groups were gradually increased,but the content of 25-OH-VD(12.57±2.21 μg/L,7.85±2.03 μg/L vs 16.76±1.02 μg/L)and the expression of VDR(0.73±0.09,0.51±0.06 vs 1.03±0.08)proteins were gradually decreased,and the differences were significant(F=18.983～56.782,all P＜0.001).Cell experiment results showed that cellular survival rate was lower at 12 h(76.23％±0.73％vs 116.72％±2.14％),24 h(57.23％±0.94％vs 125.76％±1.67％)and 48 h(41.23％±0.56％vs 138.56％±1.35％)in the LPS group compared with the control group(t=10.342,26.562,37.821),but the rate of cytosolic n-YAP positivity(47.35±3.47 vs 12.46±1.34),the rate of nuclear translocation of the YAP/TAZ complex(2.56％±0.32％vs 1.01％±0.06％)(t=46.362,26.921),the protein expression levels of IL-2(2.03±0.09vs 1.03±0.08),IFN-γ(2.07±0.21 vs 1.02±0.04),TNF-α(2.18±0.11 vs 0.99±0.02)and IL-1β(3.17±0.42 vs 1.03±0.05)were up-regulated(t=28.341,26.713,31.235,47.823),with significant differences(all P＜0.001),while there was no significant difference in the mRNA expression of CYP27B1 and VDR(t=0.872,0.786,all P＞0.05).Compared with the LPS group,the cell survival rate at 12h(85.23％±0.36％),24h(79.82％±0.63％)and 48h(76.28％±0.72％)and the mRNA expression of CYP27B1(4.42±0.14)and VDR(5.13±0.56)were elevated in the LPS+VD group,while the nucleus n-YAP positivity(24.41±3.23),nuclear translocation of the YAP/TAZ complex(1.47％±0.26％),IL-2(1.21±0.06),IFN-γ(1.13±0.42),TNF-α(1.03±0.37)and IL-1β(1.61±0.58)protein levels were down-regulated,and the differences were significant(t=7.263,19.892,23.145,27.872,26.982,14.762,13.623,18.273,25.314,27.873,22.134,all P＜0.0 1).Conclusion The serum 25-OH-VD level is related to the severity of NIP.Exogenous VD supplementation may play an anti-inflammatory role in reducing NIP injury by regulating the TGF-β-mediated YAP/TAZ nuclear translocation mechanism.

Objective To explore the clinical effect of nursing intervention program based on social support and information motivation behavioral model for pregnant women with gestational diabetes mellitus(GDM).Methods A total of 104 pregnant women with GDM admitted to Linping District,the Second Affiliated Hospital of Zhejiang University School of Medicine from February 2020 to February 2022 were selected as study objects,and were divided into experimental group and control group by random number table method,with 52 cases in each group.The pregnant women in control group were given routine nursing intervention,and the pregnant women in experimental group were given social support and information motivation behavioral model nursing intervention based on routine nursing.The depression-anxiety-stress scale,disease cognition and health behavior,blood glucose control during pregnancy,perinatal maternal and infant complications and delivery mode were compared between two groups.Results After the intervention,the scores of depression,anxiety,stress,fasting blood glucose,2-hour postprandial blood glucose and glycosylated hemoglobin of pregnant women in experimental group were significantly lower than those in control group,and the scores of disease cognition,health promoting lifestyle profile and vaginal delivery rate were significantly higher than those in control group(P<0.05).The complication rate of pregnant women and perinatal infants in experimental group was significantly lower than that in control group(P<0.05).Conclusion The nursing intervention program based on social support and information motivation behavioral model has good effect on pregnant women with GDM,which can enable pregnant women to obtain more social support,reduce negative emotions,improve health behaviors,promote blood glucose control,and increase the rate of natural childbirth.

Nonalcoholic fatty liver disease(NAFLD),which is a kind of irritable liver injury related to genetic and environmental factors,is considered as the manifestation of metabolic syndrome in the liver.Gut microbiota plays an important role in the intestinal environment.In recent years,increased numbers of studies have suggested that the imbalance of intestinal flora is closely related to NAFLD.This paper is to review the mechanism of gut microbiota in the pathogenesis and progression of NAFLD and to comment on gut microbiota-targeting new treatment of NAFLD by regulating the intestinal flora.

Objective To study the clinical effect of probiotics in the treatment of non-alcoholic fatty liver disease (NAFLD). Methods A total of 200 patients with NAFLD were randomly divided into 4 groups: control group (routine treatment group) and combined treatment group A, B and C. Each group had equal patients. The control group received orally polyene phosphatidylcholine capsules; whereas combined group A, B and C were given orally the live"combined Bifidobacterium Lactobacillus and Enterococcus powder","two live combined Bacillus subtilis and Enterococcus", and the both probiotics respectively. The duration of treatment was 1 month. Laboratory parameters were evaluated before treatment and thirtieth day after treatment, including cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol(LDL-C), alanine aminotransferase(ALT), aspartate aminotransferase (AST), fasting blood glucose (FPG), serum high molecular weight adiponectin (HMW-APN) and serum TNFα. Meanwhile the faece sample was collected for routine test and bacterial culture. Liver ultrasound scan was done in all patients. Results In terms of blood lipids and blood glucose, each group improved after treatment with significant differences(P<0.05)except for HDL-C. As for liver function, serum ALT and AST decreased after treatment in each group; especially in combined group C which were lower than those of control group [(33.7±7.6) U/L vs. (45.0±8.5) U/L; (22.0±1.6) U/L vs. (29.4±3.7) U/L; P<0.05]. TNFα levels decreased after treatment in each group, in addition the values in combined group C was significantly lower than that of control group[(0.51 ± 0.27) μg/L vs. (0.82 ± 0.28) μg/L, P<0.05]. Serum HMW-APN increased after treatment in each group, and the HMW-APN in combined C group was significantly higher than that of control group[(9.28 ± 3.72) μg/L vs. (7.87 ± 3.96)μg/L, P<0.05].(5)After treatment, all groups showed improvement of fatty liver by ultrasound, but the difference between groups was not statistically significant.(6)Compared with before treatment, fecal flora in combined groups was all reduced (P<0.01), but it was comparable before and after treatment in control group. Conclusions Probiotics improve intestinal microecological system in NAFLD patients via inhibiting TNFα and enhancing adiponectin, possibly resulting in regulating blood glucose, lipid metabolism, and protecting liver injury from NAFLD.

Objective To observe the effect of enteral nutrition therapy on metabolic status and adiponectin levels in elderly patients with metabolic syndrome (MS) complicated with nonalcoholic fatty liver disease (NAFLD).Methods 92 elderly hospitalized patients with mild to moderate non-alcoholic fatty liver disease underwent enteral nutrition (EN,n=46) and total parenteral nutrition (TPN,n=46) for 2 months.Body mass index,triceps skin-fold thickness,waist hip ratio,serum high-molecular weight (HMW) form of adiponectin,fasting blood glucose,postprandial 2-hour blood glucose,glycosylated hemoglobin,plasma insulin,alanine aminotransferase,aspartate aminotransferase,γ-glutamyltransferase,total bilirubin,direct bilirubin,total cholesterol,triglyceride,low density lipoprotein cholesterol,high density lipoprotein cholesterol,the blood pressure and liver ultrasound test were detected.The insulin resistance (HOMA-IR) was used to assess insulin resistance.Results In pre-versus post-treatment,serum level of HMW adiponectin [(6.8 ± 4.0) μg/L vs.(7.1 ± 3.9) μg/L,P ＞ 0.05 in enteral nutrition],and [(6.8 ± 3.5) μg/L vs.(5.0 ± 1.1)μg/L(P＜0.05)] in parenteral nutrition were found.The significantly decreased body mass index in the obese patients (P＜0.05),significantly improved values of 2-hour blood glucose,glycated hemoglobin,liver function,triglycerides,low-density lipoprotein cholesterol levels (all P＜0.05),and no obvious change in HOMA-IR were found after two months of enteral nutrition treatment.There were no significant changes in indicators mentioned above in TPN group after 2 months of treatment.Conclusions Enteral nutrition therapy can improve the glucose metabolism,lipid metabolism,the non-alcoholic fatty liver disease and body mass index,affect the level of adiponectin in the elderly patients with MS and NAFLD.It is vital to body metabolism.

Objective To investigate the clinical value of 3.0T MRI for hilarcholangioc-arcinoma diagnosis.Methods T Totally48 hilarcholangiocarcinoma patients from October 2011 to June 2015 underwent diagnoses by 3.0T MRI and 64-slice spiral CT,and then the diagnosing results were compared with those by surgery and pathological examination to determine the value of 3.0T MRI for hilarcholangiocarcinoma diagnosis.Results 3.0T MRI had the positioning accuracy (100％) and qualitative accuracy (95.83％) significantly higher than the positioning accuracy (79.17％) and qualitative accuracy (81.25％) (P＜0.05).In case of hepatic duct dilatation,CT found 35 cases of hilar masses,14 cases of lymphoma,5 cases of hepatic duct wall invasion and 9 cases of portal vein invasion,while 3.0T MRI displayed 44 cases of hilar masses,26 cases of lymphoma,13 cases of hepatic duct wall invasion and 30 cases of portal vein invasion.Conclusion 3.0T MRI has high positioning and qualitative accuracies when used to diagnosing hilarcholangiocarcinoma,behaves well in displaying hepatic duct dilatation,high resolution of soft tissues,and thus is worthy promoting clinically.