OBJECTIVE To analyze the safety and efficacy of vonoprazan （VPZ） in the treatment of peptic ulcer （PU） and post-endoscopic submucosal dissection （ESD） ulcers， providing evidence-based pharmaceutical evidence for clinical practice and medical decision-making. METHODS Retrieved from CNKI， Wanfang， VIP， CBM， PubMed， Embase， Web of Science， and the Cochrane Library， meta-analyses/systematic reviews related to VPZ in the treatment of PU and post-ESD ulcers were collected. Two researchers independently performed literature screening， data extraction， quality assessment of included studies， and evaluation of literature overlap. By employing the umbrella review analysis， a fresh meta-analysis was conducted on all relevant raw research data when a high degree of overlap was identified among the included studies. RESULTS A total of 17 meta-analyses were included， with quality ranging from high to very low； all outcome measures involved showed a very high level of overlap in the included meta-analyses （corrected covered area： 22.22%-100%）. In the treatment of post-ESD ulcers， compared to proton pump inhibitor （PPI）， VPZ significantly improved the ulcer healing rate at 4 weeks post-ESD [RR＝1.27， 95%CI （1.03， 1.56）， Z＝2.21， P＝ 0.027] and the ulcer contraction rate post-ESD [MD＝0.08， 95%CI （0.00， 0.16）， Z＝2.09， P＝0.037]， while significantly reducing the ulcer recurrence rate in patients with a history of PU [RR＝0.49， 95%CI （0.32， 0.73）， Z＝3.49， P＝0.001]； the delayed bleeding rate in the VPZ group was significantly lower than that in the lansoprazole subgroup [RR＝0.47， 95%CI （0.25， 0.90）， Z＝2.28， P＝0.02]. In the treatment of PU， the incidence of adverse events with VPZ was significantly higher than that with PPI in the duodenal ulcer subgroup [RR＝1.13， 95%CI （1.02， 1.26）， Z＝2.38， P＝0.017]. CONCLUSIONS For post-ESD ulcers， VPZ demonstrates superior therapeutic efficacy compared to PPI and can reduce ulcer recurrence rates in patients with a history of PU. However， it does not offer advantages in terms of safety for duodenal ulcer treatment.

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

Transcatheter arterial embolization (TAE) is the mainstay for treating advanced hepatocellular carcinoma (HCC), and the performance of the embolization material is crucial in TAE. With the development of medical imaging and the birth of "X-ray-free" technologies, we designed a new dual-mode imaging material of dimethoxy tetraphenyl ethylene (DMTPE) via emulsification by mixing poly(N-isopropylacrylamide-co-acrylic acid) (PNA) with lipiodol and fluorocarbons, which was evaluated for temperature sensitivity, stability, and dual-mode visualization in vitro. Additionally, blood vessel casting embolization and renal artery imaging were assessed in healthy rabbits. In a rabbit model with a VX2 tumor, the effectiveness of TAE for treating HCC was examined, with an emphasis on evaluating long-term outcomes of embolization and its effects on tumor growth, necrosis, and proliferation through imaging techniques. In vitro experiments confirmed that the temperature-sensitive dual-oil-phase Pickering emulsion had good flow, stable contrast, and embolism when the oil-to-oil ratio and water-to-oil ratio were both 7:3 ( v/v) and stabilized with 8% PNA. Similarly, in vivo, arterial embolization confirmed the excellent properties of DMTPE prepared at the abovementioned ratios. It was observed that DMTPE not only has an antitumor effect but can also achieve dual imaging using X-rays and ultrasound, making it a promising excellent vascular embolization material for TAE in tumor treatment.

The chemical constituents such as polysaccharides, flavonoids and polyphenols in Sanghuangporus have anti-tumor, anti-inflammatory, anti-oxidation and immune regulation effects. Sanghuangporus and its chemical constituents have shown anti-tumor activity against lung cancer, gastric cancer, liver cancer, colorectal cancer, breast cancer, melanoma, glioma and other malignant tumor cells. The mechanism mainly includes blocking cell cycle, inducing apoptosis and autophagy, inhibiting cell metastasis, immune regulation, etc., and can cooperate with radiotherapy and chemotherapy, targeted therapy, by inducing tumor cell apoptosis, blocking cell cycle, inhibiting inflammatory response, alleviating oxidative stress, etc., in order to play a role in reducing toxicity and increasing efficiency. In the future, small molecules and monomers with anti-tumor activity in Sanghuangporus can be screened. The varieties, producing areas and cultivation methods of Sanghuang would be standardized, and the bioavailability is improved by the development of new dosage forms. Through modern molecular biology and multi-omics techniques, the specific mechanism and target of its anti-tumor effect would be comprehensively explored. Pharmacodynamic toxicology research and large-scale clinical trials would be combined to verify its safety, so as to provide more evidence for its clinical application.

Objective:To investigate the clinical and genetic characteristics and predictive role of the severe liver disease phenotype in patients with hepatolenticular degeneration (HLD).Methods:Inpatients with HLD confirmed at Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine from January 1989 to December 2022 were selected as the research subjects. Clinical classification was performed according to the affected organs. Patients with liver disease phenotypes were classified into the liver disease group and further divided into the severe liver disease group and the ordinary liver disease group. The clinical characteristics and genetic variations were compared in each group of patients. The predictive indicators of patients with severe liver disease were analyzed by multiple regression. Statistical analysis was performed using the t-test, Mann-Whitney U test, or χ2 test according to different data. Results:Of the 159 HLD cases, 142 were in the liver disease group (34 in the severe liver disease group and 108 in the ordinary liver disease group), and 17 were in the encephalopathy group. The median age of onset was statistically significantly different between the liver disease group and the encephalopathy group [12.6 (7.0, 13.3) years versus 16.9 (11.0, 21.5) years, P<0.01]. 156 ATP7B gene mutation sites were found in 83 cases with genetic testing results, of which 54 cases carried the p.Arg778Leu gene mutation (allele frequency 46.2%). Compared with patients with other types of gene mutations ( n=65), patients with homozygous p.Arg778Leu mutations ( n=18) had lower blood ceruloplasmin and albumin levels, a higher prognostic index, Child-Pugh score, an international normalized ratio, and prothrombin time ( P<0.05). Hemolytic anemia, corneal K-F ring, homozygous p.Arg778Leu mutation, and multiple laboratory indexes in the severe liver disease group were statistically significantly different from those in the ordinary liver disease group ( P<0.05). Multivariate logistic regression analysis showed that the predictive factors for severe liver disease were homozygous p.Arg778Leu mutation, total bilirubin, and bile acids ( ORs=16.512, 1.022, 1.021, 95% CI: 1.204-226.425, 1.005-1.039, and 1.006-1.037, respectively, P<0.05). The drawn ROC curve demonstrated a cutoff value of 0.215 3, an AUC of 0.953 2, and sensitivity and specificity of 90.91% and 92.42%, respectively. Conclusion:Liver disease phenotypes are common in HLD patients and have an early onset. Total bilirubin, bile acids, and the homozygous p.Arg778Leu mutation of ATP7B is related to the severity of liver disease in HLD patients, which aids in predicting the occurrence and risk of severe liver disease.

A retrospective analysis was conducted on three patients with primary myelofibrosis who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from 2020 to 2023. They subsequently developed poor graft function. The patients received selected donor CD34 + cell boosts as salvage therapy. There were two male patients and one female patient, with a median age of 68 (39-69) years. The median time from allo-HSCT to the selected donor CD34 + cell boost was 83 (56-154) days. The median infusion of selected donor CD34 + cells was 7.67 (7.61-9.06) ×10 6/kg, with a CD34 + cell purity of 97.76% (96.50%-97.91%) and a recovery rate of 70% (42%-75%) . Hematological recovery was achieved in two cases. No acute GVHD was observed in any of the three patients. One case of moderate oral chronic GVHD was noted. Selected donor CD34 + cell boosts for the treatment of poor graft function after allo-HSCT in primary myelofibrosis was effective and no severe acute or chronic GVHD was observed.

BACKGROUND:Mesenchymal stem cells are susceptible to senescence during in vitro expansion,which greatly hinders their application in vivo and in vitro.How to improve the replicative senescence of mesenchymal stem cells is an urgent problem to be solved in tissue engineering. OBJECTIVE:To determine whether vascular endothelial growth factor combined with basic fibroblast growth factor can improve the aging of bone marrow mesenchymal stem cells caused by replicative passage. METHODS:Rat bone marrow mesenchymal stem cells were extracted by whole bone marrow adhesion method.Passage 2 cells were selected as normal control group.Passage 7 and later algebraic cells were selected as aging model group.Vascular endothelial growth factor(50 μg/L),basic fibroblast growth factor(10 μg/L),and their combination were administered.Cell proliferation was detected by CCK-8 assay.Cell senescence was observed by β-galactosidase activity staining.Cytoskeleton size and colony formation ability were observed by phalloidine staining and Giemsa staining,respectively,and the levels of senescence-related genes P16,P21,and P53 were detected by qRT-PCR.Gene expression levels of P16,P21,and P53 were tested by qRT-PCR. RESULTS AND CONCLUSION:(1)Vascular endothelial growth factor combined with basic fibroblast growth factor could promote the proliferation of aged bone marrow mesenchymal stem cells,which began to enter the plateau stage on day 9,and the absorbance value of the combined intervention group was significantly higher than that of the model group on day 9(P<0.05).(2)The phenotypic markers of the cells in the combined intervention group did not change,and the cell morphology changed from broad to slender.(3)Compared with the model group,the positive rate of β-galactosidase was significantly decreased(P<0.01);the number of nuclei increased(P<0.001);the total area of cytoskeleton increased(P<0.01);colony formation ability was enhanced(P<0.05);expression level of P16 was decreased(P<0.01)in the combined intervention group.These results indicate that vascular endothelial growth factor combined with basic fibroblast growth factor can improve the senescence of bone marrow mesenchymal stem cells caused by replicative passage without changing the cell phenotype.

Food toxicology plays a crucial role in supporting scientific and technical aspects of food safety risk assessment.However,traditional methods relying on animal testing are becoming increas-ingly inadequate for identifying and evaluating emerging foods and unknown risks.There is a strong push worldwide towards the development of new approach methodologies(NAMs)based on non-animal testing methods.Policies and regulations related to NAMs are being standardized gradually in the European Union,the United States,and China.Some progress has also been made in applying these methodologies in food toxicology research in China.For instance,within the"Food Toxicology Program"at the National Center for Food Safety Risk Assessment,high-content and high-throughput in vitro hazard identification models employing model organisms like human macrophages,hepatocytes,adipocytes,embryonic stem cells,and zebrafish,as well as Toxicological Thresholds of Concern and quantitative in vitro to in vivo extrapolation based on physiologically-based toxicokinetic models have been estab-lished and applied.Nonetheless,new toxicological hazard identification technologies still face challenges such as inadequate elucidation of toxic mechanisms,insufficient collaborative research efforts,and inef-ficient translation of these findings into practical applications.

Objective:To explore the characteristics of gray matter volume (GMV) and structural covariant network (SCN) in patients with cerebral small vessel disease (CSVD) related cognitive impairment.Methods:This was a cross-sectional study. Ninety-eight patients with CSVD who attended Wuxi People′s Hospital of Nanjing Medical University between October 2021 and December 2022 were prospectively included. The patients were evaluated using the cognitive status assessment scale and were categorized into 57 cases in the CSVD with cognitive impairment group and 41 cases in the CSVD without cognitive impairment group according to the presence or absence of cognitive impairment. 3D-T 1WI structural image data were collected, and GMV differences between the two groups were compared by SPM 12 toolbox and CAT12 toolkit. At the same time, Pearson correlation analysis was also performed to analyze the GMV of differences between the 2 groups and cognitive status assessment scale scores. The BCT software package based on MATLAB platform was used to construct the GMV-related structural covariant network (SCN), and the graph theory method was utilized for SCN analysis to calculate the area under the curve (AUC) of the global and local parameters within the set sparsity range, and the permutation test was used to compare the differences in the AUC of the 2 groups. Results:In the CSVD with cognitive impairment group, GMV in bilateral hippocampus, parahippocampal gyrus, fusiform gyrus, and left amygdala was significantly lower than that in the CSVD without cognitive impairment group (family wise error corrected P<0.05), and the GMV in these regions had correlation with cognitive status assessment scale ( P<0.05). At the global network level of the SCN, the area under the curve (AUC) of the characteristic path length was significantly higher in the CSVD with cognitive impairment group than in the CSVD without cognitive impairment group ( P=0.023), while the AUC of global efficiency was significantly lower in CSVD with cognitive impairment group than in the CSVD without cognitive impairment group ( P=0.005). At the local level, the nodal degree and nodal efficiency of the left putamen were significantly decreased in the CSVD with cognitive impairment group compared to the CSVD without cognitive impairment group (false discovery rate corrected P<0.05). Conclusions:GMV reduce in patients of CSVD with cognitive impairment in the bilateral hippocampus, parahippocampal gyrus, fusiform gyrus, and left amygdala. In the structural covariance network, characteristic path length increase while global efficiency reduce, and node degree and nodal efficiency of the left putamen reduce.

Objective:To summarize the best evidence for the application of massage in the management of meibomian gland dysfunction (MGD) -related dry eye.Methods:A systematic search was conducted in databases and websites including UpToDate, BMJ Best Clinical Practice, Joanna Briggs Institute Evidence-Based Healthcare Center database, National Guideline Clearinghouse, Medlive, PubMed, China National Knowledge Infrastructure, and WanFang data. The search covered literature on massage for MGD-related dry eye, including clinical decisions, best practices, evidence summaries, guidelines, expert consensus, systematic reviews, and randomized controlled trials. The search period extended to December 2023. Two researchers independently evaluated the quality of the literature and extracted and summarized the evidence.Results:A total of nine articles were included: three guidelines, four expert consensus papers, and two systematic reviews. Twenty-five pieces of best evidence were summarized from six aspects: massage practitioners, massage methods and indications, massage instruments and devices, massage duration and frequency, combination therapy, and the safety and efficacy of massage.Conclusions:This study summarizes the best evidence for applying massage in MGD-related dry eye. It is recommended that healthcare professionals apply this evidence in combination with clinical context and patient preferences.