Research Progress on Combined Immunotherapy for Microsatellite Stable Colorectal Cancer / 肿瘤防治研究

In recent years, immunotherapy has achieved great progress in the treatment of malignant tumors and has enriched the treatment mode of many types of malignant tumors. Colorectal cancer is a common tumor worldwide. Immune checkpoint inhibitor therapy for patients with metastatic colorectal cancer (mCRC) featuring DNA mismatch repair deficiency/high microsatellite instability has significant clinical benefits, but approximately 95% of patients with mCRC are DNA mismatch repair proficient/microsatellite stable (MSS). These patients have poor response to immunotherapy. Therefore, strategies to improve the efficacy of immunotherapy in patients with this type of tumor have attracted considerable attention. This article reviews the research progress on combined immunotherapy for MSS mCRC.

Short-term outcome of programmed cell death protein1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high risk factors / 中华胃肠外科杂志

Objective: Total neoadjuvant chemoradiotherapy is one of the standard treatments for locally advanced rectal cancer. This study aims to investigate the safety and feasibility of programmed cell death protein 1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high-risk factors. Methods: A descriptive cohort study was conducted. Clinicopathological data of 24 patients with locally advanced middle-low rectal cancer with high-risk factors receiving PD-1 antibody combined with neoadjuvant chemoradiotherapy in Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital between January 2019 and April 2021 were retrospectively analyzed. Inclusion criteria: (1) rectal adenocarcinoma confirmed by pathology; patient age of ≥ 18 years and ≤ 80 years; (2) the distance from low margin of tumor to anal verge ≤ 10 cm under sigmoidoscopy; (3) ECOG performance status score 0-1; (4) clinical stage T3c, T3d, T4a or T4b, or extramural venous invasion (EMVI) (+) or mrN2 (+) or mesorectal fasciae (MRF) (+) based on MRI; (5) no evidence of distant metastases; (6) no prior pelvic radiation therapy, no prior chemotherapy or surgery for rectal cancer; (7) no systemic infection requiring antibiotic treatment and no immune system disease. Exclusion criteria: (1) anticipated unresectable tumor after neoadjuvant treatment; (2) patients with a history of a prior malignancy within the past 5 years, or with a history of any arterial thrombotic event within the past 6 months; (3) patients received other types of antitumor or experimental therapy; (4) women who were pregnant or breast-feeding; (5) patients with any other concurrent medical or psychiatric condition or disease; (6) patients received immunotherapy (PD-1 antibody). The neoadjuvant therapy consisted of three stages: PD-1 antibody (sintilimab 200 mg, IV, Q3W) combined with CapeOx regimen for three cycles; long-course intensity modulated radiation therapy (IMRT) with gross tumor volume (GTV) 50.6 Gy/CTV 41.8 Gy/22f; CapeOx regimen for two cycles after radiotherapy. After oncological evaluation following the end of the third stage of treatment, surgery or watch and wait would be carried out. Surgical safety, histopathological changes and short-term oncological outcome were analyzed. Results: There were 15 males and 9 females with a median age of 65 (47-78) years. Median distance from the lower margin of the tumor to the anal verge was 4 (3-7) cm. The median maximal diameter of the tumor was 5.1 (2.1-7.5) cm. Twenty patients were cT3, 4 were cT4, 8 were cN1, 5 were cN2a, 11 were cN2b. Ten cases were MRF (+) and 10 were EMVI (+). All the patients were mismatch repair proficient (pMMR). During the neoadjuvant treatment period, 6 patients (25.0%) developed grade 1-2 treatment-related adverse events, including 3 immune-related adverse events. As of April 30, 2021, 20 patients (83.3%, 20/24) had received surgical resection, including 19 R0 resections and 16 sphincter-preservation operations. Morbidity of postoperative complication was 25.0% (5/20), including 2 cases of Clavien-Dindo grade II (1 of anastomotic bleeding and 1 of pseudomembranous enteritis), 3 cases of grade I anastomotic stenosis. Pathological complete response (pCR) rate was 30.0% (6/20) and major pathological response rate was 20.0% (4/20). None of Ras/Raf mutants had pCR or cCR (0/5), while 6 of 17 Ras/Raf wild-type patients had pCR and 3 had cCR, which was significantly higher than that of Ras/Raf mutants (P<0.01). Nine of 16 patients with Ras/Raf wild-type and differentiated adenocarcinoma had pCR or cCR. Among other 4 patients without surgery, 3 patients preferred watch and wait strategy because their tumors were assessed as clinical complete response (cCR), while another one patient refused surgery as the tumor remained stable. After a median follow-up of 11 (6-24) months, only 1 patient with signet ring cell carcinoma had recurrence. Conclusions: PD-1 antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced rectal cancer has quite good safety and histopathological regression results. Combination of histology and genetic testing is helpful to screen potential beneficiaries.

Analysis of chemical composition of volatile oil in Ramulus Mori by GC-MS / 国际药学研究杂志

Objective To extract the volatile oil of Ramulus Mori and analyze the chemical composition of the volatile oil. Methods The volatile oil of Ramulus Mori was extracted by simultaneous distillation extraction(SDE)and direct distillation extraction(DDE)method, and the chemical composition was identified by GC-MS. Results Nineteen compounds were identified in the volatile oil extracted by SDE, which accounted for 94.49% of the total amount of detection. There were alkyl, acids, aldehydes, ketones, esters, alcohols and other substances in the volatile oil. And 16 compounds were determined in the volatile oil extracted by DDE, accounting for 97.12% of the total amount detected. There were furan, carboxylic acids, esters, aldehydes, alcohols, phenols, ketones, alkene and acyl halide. The chemical compositions of the volatile oil extracted by SDE were more than those extracted by DDE. Conclusion The chemical constituents of volatile oil of Ramulus Mori can be more fully identified by the combination of the two extraction methods.

Mapeamento da antiga cobertura vegetal de várzea do Baixo Amazonas a partir de imagens históricas (1975-1981) do Sensor MSS-Landsat / Mapping ancient vegetation cover of the Amazon floodplain using historical MSS/Landsat images (1975-1981)

Este estudo apresenta um mapa da cobertura vegetal da planície de inundação do Rio Amazonas entre as cidades de Parintins (AM) e Almeirim (PA), com base em imagens Landsat-MSS adquiridas entre 1975 e 1981. O processamento digital dessas imagens envolveu a transformação para imagens-fração de vegetação, solo e água escura (sombra), seguido da aplicação de técnicas de segmentação e classificação por região. O mapa resultante da classificação foi organizado em quatro classes de cobertura do solo: floresta de várzea, vegetação não-florestal de várzea, solo exposto e água aberta. A precisão do mapa foi estimada a partir de dois tipos de informações coletadas em campo: 1) pontos de descrição: para validação das classes de cobertura não sujeitas a grandes alterações, como é o caso dos corpos d'água permanentes, e identificação de indicadores dos tipos de cobertura original presentes na paisagem na ocasião da obtenção das imagens (72 pontos); 2) entrevistas com moradores antigos para a recuperação da memória sobre a cobertura vegetal existente há 30 anos (44 questionários). Ao todo foram coletadas informações em 116 pontos distribuídos ao longo da área de estudo. Esses pontos foram utilizados para calcular o Índice Kappa de concordância entre os dados de campo e o mapa resultante da classificação automática, cujo valor (0,78) indica a boa qualidade do mapa de cobertura vegetal da várzea. Os resultados mostram que a região possuía uma cobertura florestal de várzea de aproximadamente 8.650 km2 no período de aquisição das imagens.

This study presents a vegetation map of the Amazon River floodplain between the towns of Parintins (AM) and Almeirim (PA), based on Landsat-MSS scenes from 1975 to 1981. Digital processing involved the transformation of multispectral images into fraction-images of vegetation, soil and dark water (shadow), followed by the application of segmentation and region-classification techniques. The resulting map was organized four classes of land cover types: floodplain forest, non-forest floodplain vegetation, bare soil, and open water. Map accuracy was estimated from two types of ground data 1) sample points describing ground cover classes not subjected to major changes, such as permanent water bodies, and identifying indicators of the 30 year old vegetation type landscape (72 points); 2) interviews with community early residents for memory recovery of information on the vegetation cover existing in the 1970 (44 interviews). Altogether, 116 information points was collected along the study area. These points were used to calculate the Kappa Index for agreement between the four field-verified classes and the automatic classification, with value (0.78) indicates the good quality of the floodplain vegetation cover map. The region had 8650 km2 coverage of floodplain forest at the time of image acquisition.

A Winged-Helix Transcription Factor Foxg1 Induces Expression of Mss4 Gene in Rat Hippocampal Progenitor Cells

Foxg1 (previously named BF1) is a winged-helix transcription factor with restricted expression pattern in the telencephalic neuroepithelium of the neural tube and in the anterior half of the developing optic vesicle. Previous studies have shown that the targeted disruption of the Foxg1 gene leads to hypoplasia of the cerebral hemispheres with severe defect in the structures of the ventral telencephalon. To further investigate the molecular mechanisms by which Foxg1 plays essential roles during brain development, we have adopted a strategy to isolate genes whose expression changes immediately after introduction of Foxg1 in cultured neural precursor cell line, HiB5. Here, we report that seventeen genes were isolated by ordered differential displays that are up-regulated by over-expression of Foxg1, in cultured neuronal precursor cells. By nucleotide sequence comparison to known genes in the GeneBank database, we find that nine of these clones represent novel genes whose DNA sequences have not been reported. The results suggest that these genes are closely related to developmental regulation of Foxg1.

A Case of Marshall-Smith Syndrome

Marshall-Smith syndrome is characterized by a triad of facial dysmorphism, failure to thrive and accelerated osseous maturation. We report a one-month-old male infant with of this rare syndrome, with laryngeal anomalies who died at 6 months of age with pneumonia. This is the first case of Marshall-Smith syndrome in Korea.