Xiao Zeng

BACKGROUND: Radiographically, ground-glass nodules (GGN) and part-solid nodules (PSN) in lung adenocarcinoma (LUAD) have significant heterogeneity in their clinical manifestations, biological characteristics, and prognosis. This study aimed to explore the heterogeneity of LUAD in different radiological phenotypes and associated factors influencing tumor evolution. METHODS: We performed single-cell RNA sequencing (scRNA-seq) on tumor tissues from eight and seven cases of GGN- and PSN-LUAD, respectively, at different disease stages, including minimally invasive adenocarcinoma (MIA), invasive adenocarcinoma (IAC), and metastatic lung cancer (MLC). Additionally, we analyzed adjacent normal tissues from four cases. Immunohistochemistry, multiplex immunofluorescence, and external scRNA-seq data were employed to confirm the expression of signature genes as well as the distribution patterns of CXCL9 + TAMs and TREM2 + TAMs. A LUAD mouse model was generated using gene editing, organoid culture, and orthotopic transplantation techniques, and comprehensive analyses such as histopathology, RNA sequencing, and Western blotting were performed to validate key pathways. RESULTS: Diverse cellular compositions were observed in the tumor microenvironment (TME) during GGN- and PSN-LUAD invasion and metastasis. Notably, CXCL9 + and TREM2 + tumor-associated macrophages (TAMs) exhibited the most significant enrichment changes. It was found that GGN-LUAD exhibited a stronger immune response than PSN-LUAD, with increased interaction between CXCL9 + TAMs and CD8 + tissue-resident memory T cells during invasion stage (MIA-IAC). Conversely, greater interactions between TREM2 + TAMs and tumor cells were observed in PSN-LUAD during the MLC stage. Additionally, TREM2 + TAMs were found to differentiate into TREM2 + /SPP1 + and TREM2 + /SPP1- TAMs at different stages, which promotes tumor progression. This study also emphasizes that during the transdifferentiation process of GGN- and PSN-LUAD, IFN-γ activates the STAT1 signaling pathway to regulate the activation of CXCL9 + TAMs, and further recruiting CD8 + Trm cells and activating T cells through MHC class I antigen presentation. The role of the IFN-γ/STAT1 pathway in the occurrence and development of LUAD was further validated by animal experiments. CONCLUSIONS: Our findings offer a potential therapeutic strategy to maintain a dynamic balance within the TME and improve the immunotherapy efficacy by modulating the relative proportions and functional states of CXCL9 + TAMs and TREM2 + TAMs.

OBJECTIVES: This study aimed to examine the long-term efficacy, remission and survival of patients with severe systemic lupus erythematosus (SLE) after the combination treatment with high-dose immunosuppressive therapy (HDIT) and autologous peripheral blood stem cell transplantation (APBSCT). METHODS: Chinese patients with severe SLE receiving combination therapy with HDIT and APBSCT in Peking Union Medical College Hospital were enrolled from July 1999 to October 2005. Disease activity, treatment, and adverse effects of these patients were evaluated. The 10-year overall survival and 10-year remission survival were also analysed. RESULTS: Among the 27 patients, one patient failed to collect enough CD34+ cells and data was missing for two patients. In the end, 24 patients were included in the final analysis. After APBSCT, one patient died, two patients achieved partial remission and 21 (87.5%) achieved remission at 6 months. The median follow-up duration of the 23 patients was 120 months. Fourteen patients had completed a ten-year follow-up. The median proteinuria level of the 14 patients with LN with ten years of follow-up significantly decreased from 4.00 g/24 hours at pre-treatment to 0.00g/24 hours at year 5 and 0.00 g/24 hours at year 10 (both p=0.001). The 10-year overall survival rate and 10-year remission survival rate were both 86.0% (95% CI: 71.1-100.9%). After a median follow-up for 120 months, 16 patients (66.7%) remained in remission, 4 patients were lost to follow-up, 2 patients died and 1 patient remained active. CONCLUSIONS: The combination of HDIT and APBSCT may be an option to improve the survival of severe lupus patients.

AIM: To compare the hemostatic properties of transurethral plasmakinetic resection of the prostate (PKRP) and standard transurethral resection of the prostate (TURP) ex vivo, as perioperative bleeding is still regarded as one of the major complications of transurethral prostatectomy. MATERIALS AND METHODS: Isolated normal saline (NS)-perfused porcine kidneys were used to determine the hemostatic efficacy of PKRP and TURP. The perfusion fluid loss was semiquantitatively measured in relation to tissue ablation for the two techniques and specimens were evaluated histologically. RESULTS: The PKRP group had a significantly smaller loss of NS than the TURP group (4.16 +/- 1.25 and 6.39 +/- 1.05 g/min, respectively, p < 0.01). Compared with the measurements with TURP, the depths of the coagulation zones with PKRP were significantly larger (225.09 +/- 35.77 and 146.84 +/- 18.91 microm, respectively, p< 0.01). CONCLUSIONS: PKRP ex vivo was associated with significantly better hemostasis than TURP.

OBJECTIVE: To analyze the impact of gastrointestinal manifestations on quality of life in patients with systemic sclerosis (SSc) and to provide clinical evidence for their early treatment and health-related management. METHODS: Altogether 65 patients admitted to the Peking Union Medical College Hospital selected from a disease cohort and 127 matched controls were enrolled. A self-assessment questionnaire was completed by all participants. Each participant completed scleroderma gastrointestinal tract 1.0 (SSC-GIT 1.0) questionnaire (including reflux or indigestion, diarrhea, constipation, distention, emotional well-being, and social functioning). Autoimmune antibodies were tested in SSc patients. RESULTS: Among these SSc cases, gastrointestinal manifestations were seen in 84.6%. Reflux/indigestion and diarrhea were more common in SSc patients than in the control group (67.7% vs 27.8%; 27.7% vs 10.2%, P < 0.05). SSc patients had a significantly higher percentage of abnormal social functioning than the control group (33.8% vs 3.9%, P < 0.05). SSc patients with abnormal social functioning and abnormal emotional well-being had worse distention, diarrhea, and constipation statuses. Patients with reflux or indigestion and diarrhea had lower anti-Scl-70 level than those without (both P < 0.05). Patients with distention had higher levels of anti-RNP and anti-SSA than those without distention (both P < 0.05). Patients with diarrhea had higher levels of anti-RNP than those without diarrhea (P = 0.014). CONCLUSIONS: Gastrointestinal involvement is frequent in SSc, with reflux or indigestion as the most common symptom. The impaired quality of life in patients with SSc indicates that early and active management should be considered.