Craniopharyngioma is a rare benign tumor mainly occurs in the hypothalamus region of children. Patients may have a long survival after surgery. Tumors or operations may lead to hypothalamic syndrome, hypopituitarism, obesity, and a disturbed electrolytes metabolism. Multidisciplinary medical teams are required to conduct a long-term hormonal therapy and follow-up management. This consensus is aiming for providinge recommendations for perioperative management, obesity, hormonal replacement therapy, linear growth promotion and pubertal development for pediatric patients.

Objective To verify the effect of bone marrow mesenchymal stem cells (BM-MSCs) in alleviating immune senescence, and to explore the main immune cell population improved by BM-MSCs. Methods Mouse spleen lymphocytes were isolated and stimulated to proliferate for 7 days for constructing a replicative aging model. Flow cytometry was used to detect the p16ink4a(p16) and p21cip1(p21) expression by T cell subpopulation in the young control group, the replicative senescence control group and the BM-MSCs co-cultured group. Results In the replicative senescence model of T lymphocytes, it was observed that CD8⁺T cells senescent significantly as compared with CD4⁺T cells after continuous proliferation. Among the naive cells and effector cell subsets of CD8⁺T cells, effector cell senescence was the most significant. BM-MSCs co-culture had no significant effect on senescent effector cells, and mainly alleviated the senescence of CD8⁺T cells by delaying the senescence of naive T cells(P＜0.01,P＜0.001). Conclusions BM-MSCs co-culture can alleviate the replicative senescence phenotype of T cells and has a more significant anti-senescence effect on CD8⁺T cells by inhibiting the initial senescence of T cells as a major mechcanism.

Objective To establish a multi-state Markov model of systemic lupus erythematosus(SLE) for patients in China and to explore the transition rule of organ damage accumulation and possible factors affecting the transition between states. Methods A retrospective cohort study was conducted using the data from CSTAR. The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index(SDI) was divided into five irreversible disease states(SDI=0, 1, 2, ≥3, and death, marked as S0, S1, S2, S3, Death). The R “mstate” package was used for statistical analysis. Results This study included 23 926 cases of SLE patients with cumulative follow-up of 12 030 visits. Among these patients, 21 070 patients had no any organ damage at baseline. At the follow-up period, the transition probabilities of organ damage of S0→S1, S1→S2, S2→S3, S3→Death were 7.01%, 12.58%, 10.64%, and 12.19%, respectively. The multi-state Markov model showed that age, gender, disease duration, SLEDAI score, corticosteroid dosage, and involvement of major organs were associated with the transition of organ damage status, each 1 year increased was associated with a 2%~3% increase in risk of damage accumulation risk(P＜0.01). Also, neurological(S0→S1:HR=1.34;S1→S2:HR=1.53;S2→S3:HR=1.73), cardiopulmonary(S0→S1:HR=3.66;S1→S2:HR=1.51;S2→S3:HR=1.52), renal(S0→S1:HR=1.24)and hematological involvement(S0→S1:HR=1.24)might be the risk factors. Conclusions The probability of organ damage accumulation in SLE patients increases over time. Therefore, in the early stage of the disease, the involvement of important organs needs to be minimized and the treatment strategy should be dynamically adjusted at different stages of treatment.

In the context of an aging society, the number of elderly cancer patients is constantly increasing, and geriatric oncology has garnered significant attention in recent years. Given the heterogeneity in the health status of older patients, it has become increasingly important to provide individualized diagnosis, treatment, follow-up, and care. Thus, it must be emphasized the Comprehensive Geriatric Assessment (CGA) for elderly patients, which encompasses their physical function, nutritional status, cognitive function, emotional state, comorbidities, polypharmacy, social situation, and treatment preferences. This article provides consensus recommendations on CGA tools for elderly patients prior to anticancer treatment, offering valuable references and insights for clinical practice in China.

Objective To target at the NKG2A-HLA-E inhibitory axis, a pluripotent stem cell(iPSC)-derived genetically engineered natural killer cells(NK cells) with NKG2A knockout (NKG2A KO-iNK) were prepared and then their tumor-killing efficacy was evaluated in vitro. Methods NKG2A was knocked out in iPSCs using gene-editing technology. These cells were then differentiated into NKG2A KO-iNK cells. Surface markers at each differentiation stage were analyzed by flow cytometry. Western blot confirmed NKG2A knockout, and flow cytometry assessed expression of activating receptors (NKG2D) and natural cytotoxicity receptors (NKp30, NKp44, NKp46) in NKG2A KO-iNK cells. Cytotoxic activity against tumor cell lines with varying human leukocyte antigen E (HLA-E) expression level was evaluated via lactate dehydrogenase (LDH) release assay. Results Co-transfection of iPSCs with Cas9 protein and three small-guide RNAs (sgRNAs) targeting at exons 1 and 2 of the KLRC1 gene (encoding NKG2A) successfully generated monoclonal NKG2A-knockout iPSCs (NKG2A KO-iPSCs) with a single T-base insertion in exon 1. During iPSC differentiation into NK cells, CD34 expression reached 30%-50% at the embryoid body (EB) stage (day 8), while CD56 and CD16 expression exceeded 80% by day 28. Western blot confirmed complete NKG2A knockout in NKG2A KO-iNK cells. Flow cytometry revealed comparable expression level of activating receptor NKG2D and cytotoxicity receptors (NKp30, NKp44, NKp46) between NKG2A KO-iNK and wild-type iNK (WT-iNK) cells. The LDH assay results indicated that the cytotoxic activity of NKG2A KO-iNK cells against the HLA-E highly-expressed B-cell precursor leukemia cell line Nalm6 cells was significantly higher than that of WT-iNK cells, while there was no significant difference between them and human myeloma cell line H929 cells with low HLA-E expression and human hepatocellular carcinoma cell line HepG2 cells with almost no HLA-E expression. Interferon-γ (IFN-γ) pretreatment up regulated HLA-E expression in Nalm6 cells, further amplifying NKG2A KO-iNK-mediated cytotoxicity. Conclusions By disrupting the NKG2A-HLA-E inhibitory axis, NKG2A KO-iNK cells exhibit markedly enhanced in vitro cytotoxicity against HLA-E-high tumor cells. This result highlights their potential function as a novel adoptive cell therapy strategy for cancers reliant on HLA-E-mediated immune evasion.

Objective To construct an in vitro research model for studying human liver regeneration based on human pluripotent stem cells (hPSCs)-derived hepatocyte-like organoid (HLO). Methods The hPSCs-derived HLO was obtained by inducing differentiation and the regeneration model after liver injury was constructed by adding acetaminophen (APAP) at fixed time points in HLO culture conditions to simulate acute liver injury. Subsequently, HLO with catenin/cadherin-associated protein beta 1(CTNNB1) knockout, a key gene regulating liver regeneration, was constructed using CRISPR/Cas9 gene editing technology, and regeneration experiments with APAP injury were performed. HLO as a model for liver regeneration studies was further evaluated by morphological observation, RT-qPCR, Western blot and pathological analysis. Results Morphology evidence as well as expres-sion of marker genes showed that hPSCs-derived HLO was able to initiate a post-injury regeneration response after APAP treatment. CTNNB1-deficient HLO showed delayed recovery in dimension and down-regulated or delayed expression of related genes during post-injury regeneration as compared to control HLO. Conclusions A HLO-based hPSCs-derived human liver regeneration model is successfully constructed, which can be used for gene function studies during liver regeneration.

Objective To establish human colorectal cancer(CRC) organoids and to evaluate the efficacy of chemotherapy drugs. Methods Patient-derived CRC cells were cultured to form organoids. The CRC organoids and original tissues were stained with molecular markers of CRC immunohishtochemically. CRC organoids were used to test drug sensitivity and different concentrations of chemotherapy drugs 5-fluorouracil, oxaliplatin and irinotecan were given respectively; Organoid activity before and after drug treatment was measured by 3D cell viability assay. Results The patient-derived organoids(PDO) from 5 CRC tissues were successfully established. The expression of CK20, Ki67 and Villin proteins was similar in organoids and in original tumor. The organoids retained histologcial features similar to those of the original tumors. Different PDO showed differential sensitivity to different chemotherapy drugs. Conclusions CRC-PDO can dispaly their different sensitivities to different chemotherapy drugs, and could provide valuble reference for personalized treatment for CRC patients.

Objective To address the challenges of fragmented multi-omics data and insufficient integrated analysis in silicosis research, we aim to construct a comprehensive data platform that supports systematic analysis of multi-level molecular alterations in fibrotic lung tissues and facilitates rapid identification of therapeutic targets. Methods We systematically integrated transcriptomic, single-cell transcriptomic, quantitative proteomic, post-translational modification-specific proteomic, and metabolomic data from human and mouse silicotic and control lung tissues. By leveraging bioinformatics tools including DESeq2, Seurat, and CellChat, we developed a web-based visualization platform enabling data visualization and interactive analysis. Results We successfully constructed SilicosisOmics (https://respir.pumc.edu.cn/SilicosisOmics/), a comprehensive multi-omics data platform for silicosis research. The platform integrated five types of omics data derived from both silicotic and non-diseased lung tissues across human and mouse species. SilicosisOmics provided not only online search functionality for static visualization of gene expression and single-cell clustering but also interactive analytical tools supporting user-customized analyses including differential gene expression, pathway enrichment, and cell-cell interaction studies. Conclusions The SilicosisOmics platform offers systematic multi-omics data resources and user-friendly analytical tools for silicosis and pulmonary fibrosis research, thereby facilitating the advancement of mechanistic studies, target discovery, and subsequent translational research.

Objective To screen the soluble hemagglutinin (HA) recombinant protein derived from B/Victoria lineages of influenza virus that possess hemagglutination activity. Methods Based on the B/Darwin/7/2019 (B/Victoria) strain, HA mutant genes BV-T1, BV-T2, and BV-T3 were obtained by fusing the leucine zipper GCN4pII and GCN4pLL trimerization motifs(T1 and T2), and bacteriophage T4 Foldon trimerization motifs(T3) to the C-terminus of the HA ectodomain. HA ectodomain mutant gene BV-ecto was also constructed as a control. These genes were inserted into pFastBac1 vector. The proteins were expressed using baculovirus-Sf9 insect cell expression system and culture supernatants of infected cells were harvested. Recombinant proteins were purified by Strep-Tactin affinity chromatography and subsequently characterized for their oligomerization degree and hemagglutination activity. Results All four mutant proteins were solubly expressed in the culture supernatant. BV-T2 and BV-T3 exhibited a high trimerization form, while BV-T1 formed predominantly trimers with minor low-order oligomers. BV-ecto existed as a monomer.BV-T1 and BV-T2 exhibited hemagglutination activity, in contrast, BV-T3 and BV-ecto lacked hemagglutination activity. Conclusions The soluble BV-T2 mutant protein present efficient trimer- ization and possesses hemagglutination activity.The leucine zipper trimerization motif GCN4pLL is suitable for the soluble expression of B/Victoria lineage HA recombinant protein and thus provides a reference for the development of soluble recombinant protein vaccines against B/Victoria virus.

Objective To evaluate the clinical significance of local radiotherapy(LT) in oligo-residual lesions of advanced non-small cell lung cancer(NSCLC) treated with tyrosine kinase inhibitors(TKIs). Methods A retrospective study was conducted in 61 patients with stage Ⅳ NSCLC who developed oligo-residual disease after TKI therapy at Peking Union Medical College Hospital from February 2018 to May 2024. The patients were stratified into two groups: the LT group(n=31, receiving local consolidative therapy or ablation while continuing systemic therapy) and the non-LT group(n=30, receiving systemic therapy alone). Progression-free survival(PFS), overall survival(OS), and treatment-related safety were compared between the groups. Results The LT group showed a prolonged PFS compared to the non-LT group(31 vs. 23 months, P= 0.171), although the difference did not reach statistical significance. Patients undergoing LT also had a longer median OS(54 vs. 42 months, P=0.713), although the difference did not achieve statistical significance. A total of 7 patients(22.6%) in the local radiotherapy group developed radiation pneumonitis of any grade, including 4 patients(12.9%) with grade 1 pneumonitis and 3 patients(9.7%) with grade 2 pneumonitis.Univariate and multivariate analyses indicated that the number of metastatic lesions, sex, ECOG performance status, targeted therapy regimen, and best response to targeted therapy were factors associated with patient prognosis. Among these variables, ECOG performance status and smoking status were identified as independent predictors of PFS. Conclusions In NSCLC patients with oligo-residual lesions after TKI therapy, LT preliminarily appears to prolong progression-free survival without significantly increasing treatment-related adverse events.