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We studied the characteristics of contrast-enhanced ultrasound (CEUS) in renal pelvic urothelial carcinomas and explored its performance in assessing microvessel density (MVD) of tumor tissues. We retrospectively analyzed the characteristics of 125 cases, which were confirmed pathologically to be renal pelvic urothelial carcinomas using CEUS. We performed CEUS and found that most tumors presented with an enhanced mode of "slow-in (mean = 16.7 ± 2.6 s, range: 12-25 s), hypo-enhancement and fast-out (mean = 69.3 ± 16.2 s, range: 42-113 s)." However, the wash-in pattern, homogeneity and wash-out pattern observed with CEUS was not correlated with pT stage and grade (p0.05). But advanced-pT-stage and high-grade tumors had a higher peak enhancement than early-pT-stage and low-grade tumors (p0.01). Peak enhancement obtained with CEUS can be used to evaluate the pT stage and grade of renal pelvic urothelial carcinomas more effectively. The MVD of those tissues was observed using immunohistochemical staining of cluster of differentiation 34 (CD34). MVD in the advanced-pT-stage and high-grade groups was significantly higher than that in the early-pT-stage and low-grade groups (p0.01). As tumor pT stage and grade improved, CEUS peak enhancement intensity and MVD of tumors also exhibited an upward trend. CEUS peak enhancement intensity has the potential to determine MVD of renal pelvic urothelial carcinomas.

OBJECTIVE: To explore the characteristics of immune function of healthy full-term infants at the age of 3 months, and to analyze the relationship of immune function with feeding pattern and sex. METHODS: A total of 84 healthy full-term infants born in four hospitals in Beijing and Hohhot, China were prospectively recruited. Their feeding patterns remained unchanged within 4 months after birth. They were divided into a breast-feeding group and a milk powder feeding group according to their feeding patterns. At the age of 3 months after birth, peripheral venous blood samples of the two groups were collected to evaluate cellular immunity and humoral immunity and perform routine blood test. The laboratory indices were compared between infants with different feeding patterns and sexes. RESULTS: Compared with the milk powder feeding group, the breast-feeding group had significantly lower proportion of T cell second signal receptor CD28, immunoglobulin M, and proportion and absolute count of neutrophils (P

To compare gut microbiota of healthy infants that were exclusively breast-fed or formula-fed, we recruited 91 infants, who were assigned into three different groups and fed by breast milk (30 babies), formula A (30 babies) or formula B (31 babies) exclusively for more than 4 months after birth. Faecal bacterial composition was tested. Among different groups, α diversity was lower in breast-fed group than formula-fed groups in 40 days of age, but increased significantly in 6 months of age. The Bifidobacterium represented the most predominant genus and Enterobacteriaceae the second in all groups. In 40 days of age, Bifidobacterium and Bacteroides were significantly higher, while Streptococcus and Enterococcus were significantly lower in breast-fed group than they were in formula A-fed group. Lachnospiraceae was lower in breast-fed than formula B-fed group. Veillonella and Clostridioides were lower in breast-fed than formula-fed groups. In 3 months of age there were less Lachnospiraceae and Clostridioides in breast-fed group than formula-fed groups. There were also significant differences of microbiota between formula A-fed and formula B-fed groups. Those differences may have impacts on their long-term health.

Immunotherapy has emerged as an effective therapeutic strategy for various cancers, including colorectal cancer (CRC), but only a subset of MSI-H patients can benefit from such therapy. Patched1 (PTCH1) is a frequently altered gene in CRCs and its mutations contribute to unregulated Hedgehog (Hh) signaling. In the study, we evaluated the association of PTCH1 mutations with CRC immunity based on our single-center cohort and multiple cancer genomic datasets. Among 21 enrolled patients, six (28.6%) harbored a PTCH1 mutation based on WES analyses. In CRC patients, the PTCH1 mutation subgroup experienced a higher durable clinical benefit rate than the PTCH1 wild-type subgroup (100% vs. 40%, P = 0.017). In addition, patients with the PTCH1 mutation experienced greater progression-free survival (PFS, P = 0.037; HR, 0.208) and overall survival (OS, P = 0.045; HR, 0.185). A validation cohort from the MSKCC also confirmed the correlation between PTCH1 mutation and better prognosis (P = 0.022; HR, 0.290). Mechanically, diverse antitumor immune signatures were more highly enriched in PTCH1-mutated tumors than in PTCH1 wild-type tumors. Furthermore, PTCH1-mutated tumors had higher proportions of CD8 + T cells, activated NK cells, and M1 type macrophage infiltration, as well as elevated gene signatures of several steps in the cancer-immunity cycle. Notably, the PTCH1 mutation was correlated with tumor mutational burden (TMB), loss of heterozygosity score, and copy number variation burden. Our results show that the mutation of PTCH1 is a potential biomarker for predicting the response of CRC patients to immunotherapy.

With the expanding use of immune checkpoint inhibitors (ICIs) in gastrointestinal (GI) cancer, the occurrence of acquired resistance (AR) has gradually emerged. However, the progression patterns and survival of patients with AR to ICIs are still unknown.To explore the characteristics and prognosis of AR after ICI therapy in patients with advanced GI cancer.This cohort study screened patients with advanced GI cancer treated with ICIs between January 14, 2016, and December 31, 2020, at Peking University Cancer Hospital. Initial response was defined as complete response, partial response, or stable disease longer than 6 months as assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Progression was also based on Response Evaluation Criteria in Solid Tumors version 1.1. Progression or death after the initial response was defined as AR. Oligoprogression of AR was defined as 2 or more disease sites progression. The current status of AR in GI cancer and the patterns of AR and its prognosis were evaluated. The site of AR and subsequent management were also assessed. Data were analyzed from June to August 2021.Patients in the cohort were treated with mono-ICI or combination therapy.Kaplan-Meier analyses and log-rank tests were conducted for overall survival analyses. Univariate and multivariate Cox analyses were conducted to determine the prognostic implications of each variable.Of the 1124 patients who received ICIs, 373 (33.2%) patients (282 men [75.6%]; median [IQR] age, 62 [54-68] years) achieved an initial response, and 173 (46.4%) patients (137 men [79.2%]; median [IQR] age, 61 [54-67] years) developed AR. Almost all patients (167 patients [96.5%]) developed AR within 24.0 months. Progression patterns of AR were most commonly oligoprogression (122 patients [70.5%]) rather than polymetastatic progression (38 patients [22.0%]) and were associated with a good prognosis (38.5 vs 14.0 months; hazard ratio, 0.37; 95% CI, 0.18-0.74; P .001). Lymph nodes (101 patients [58.4%]) appeared to be the most common site of AR. Management after AR was mainly systemic therapy (96 patients [55.5%]).Oligoprogression was the most common pattern of AR progression, and lymph nodes were the most susceptible site for AR. Further study will be needed to determine the most favorable management for AR.