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Polymer gel was widely used as water shutoff agent in mature oil fields. And the results of single-phase plugging experiments show that the plugging rate of the polymer gel to the oil phase is lower than that of the water phase. However, the disproportionate permeability reduction (DPR) mechanism of polymer gels still remains controversial. In this paper, we used four gel formulations including polyethyleneimine (PEI) and phenol-formaldehyde crosslinked gel with and without adding laponite to investigate the effect of gel elastic property on the water shutoff mechanism. The result of sand pack flooding experiments shown that the gel with higher elastic modulus has better effects on decreasing water cut and increasing oil recovery. After adding laponite, the elastic modulus of phenol-formaldehyde crosslinked gel increased from 64.2 Pa to 192 Pa, and the elastic modulus of PEI crosslinked gel increased from 27.4 Pa to 36.5 Pa. Compared to the phenol-formaldehyde-HAPM gel, the oil recovery of laponite-phenol-formaldehyde-HPAM gel increased by 5.2% and the maximum water cut decreased by 8.3%. Besides, comparing with PEI-HPAM gel, the oil recovery of laponite-PEI-HPAM gel increased by 2.7% and the water cut dropped by 27.8%. In the meanwhile, the laponite-phenol-formaldehyde-HPAM gel with higher elastic modulus obviously swells in the formation water but almost remains constant in oil at 105°C. The mass of gel soaked in the formation water increased from 42 g to 96 g and the gel volume increased by 300% within 48 hours. This study improves the understanding of the DPR mechanism of polymer gel for water shutoff.

As an effective method to prolong the life of mature field, conformance control in water-injection well has been used wildly. Naturally, effect evaluation of conformance control has attracted great attention because it is an important guideline for the design of later enhanced oil recovery (EOR) plan. Usually, production responses such as excessive water reduction and oil production increment are widely used as the indicators. However, production responses may be unreliable due to the difficulty in determining an effective injection well which is caused by a large number of treated water-injection wells in a well group. Therefore, with the application of fuzzy comprehension evaluation (FCE), five evaluation indexes (injection pressure, injectivity index, slope of hall curve, variation coefficient and homogenization coefficient of injection profile) describe injection responses were selected to establish a new evaluation method in this paper. Based on fuzzy mathematics, FCE reflects the difference of evaluation units. Meanwhile, weights of evaluation indexes were obtained by analytic hierarchy process (AHP), which made the results more convincing. Taking Bai 239 oilfield as an example, the five injection responses indexes were used to assess treatment effect on five water-injection wells by single index evaluation and FCE. The results showed that among the five evaluation indexes mentioned above, the slope of hall curve was the most important factor affected evaluation result. In single index evaluation, opposite results may be produced easily on account of the one-sidedness of single index or human error. Furthermore, we found that effective treatment was a relative concept actually. The result of FCE was consistent with single index evaluation but FCE was more acceptable. This study suggests that FCE could be applied to another field such as water flooding, acidizing and hydraulic fracturing

Abstract Immunotherapy involving immune checkpoint inhibitors (ICIs) for enhancing immune system activation is promising for tumor management. However, the patients’ responses to ICIs are different. Here, we applied a non-negative matrix factorization algorithm to establish a robust immune molecular classification system for colorectal cancer (CRC). We obtained data of 1503 CRC patients (training cohort: 488 from The Cancer Genome Atlas; validation cohort: 1015 from the Gene Expression Omnibus). In the training cohort, 42.8% of patients who exhibited significantly higher immunocyte infiltration and enrichment of immune response-associated signatures were subdivided into immune classes. Within the immune class, 53.1% of patients were associated with a worse overall prognosis and belonged to the immune-suppressed subclass, characterized by the activation of stroma-related signatures, genes, immune-suppressive cells, and signaling. The remaining immune class patients belonged to the immune-activated subclass, which was associated with a better prognosis and response to anti-PD-1 therapy. Immune-related subtypes were associated with different copy number alterations, tumor-infiltrating lymphocyte enrichment, PD-1/PD-L1 expression, mutation landscape, and cancer stemness. These results were validated in patients with microsatellite instable CRC. We described a novel immune-related class of CRC, which may be used for selecting candidate patients with CRC for immunotherapy and tailoring optimal immunotherapeutic treatment.

Aim: To analyze the clinical phenotype and genetic etiology of three cases of glutaric aciduria type 1 (GA1) in Chinese children. Methods: We performed genetic and metabolic testing using tandem mass spectrometry (MS/MS) and gas chromatography–mass spectrometry (GC/MS), followed by trio whole-exome sequencing (trio-WES) and Sanger sequencing. A literature review on glutaric aciduria type 1 (GA1) in Chinese patients was also conducted. Results: Sequencing results showed each case had compound heterozygous variants in GCDH(NM_000159.4): c.214C > G (p.Arg72Gly) and c.411C > G (p.Tyr137Term) (Case 1), c.214C > G (p.Arg72Gly) and c.1204C > T (p.Arg402Trp) (Case 2), and c.1228G > T (p.Val410Leu) and c.395G > A (p.Arg132Gln) (Case 3). These variants were inherited from their respective parents. Notably, the c.214C > G variant found in two children was a novel variant not previously reported. A review of the literature revealed that, clinically, the majority of patients experienced onset in infancy and early childhood (82%). Additionally, 38.36% were diagnosed through newborn screening, with the primary reasons for the initial visit being delayed development (32.43%) and infections (21.61%). The most common clinical manifestations included increased head circumference (77.19%) and motor developmental delay (65.15%). Biochemically, patients exhibited significant elevations in C5DC (98.51%) and C5DC/C8 (94.87%) in blood, as well as GA (94.37%) and 3OHGA (69.39%) in urine. Radiographically, patients showed a high prevalence of abnormalities in cranial MRI (86.15%) and EEG (73.33%). Genetically, 67 distinct GCDH gene variants were identified among 73 patients, with missense variants being the most prevalent type (73.97%). The most frequent variant was c.1244-2 A > C, observed in 17.12% of cases. Additionally, the majority of variant sites were located in exons 11 (25.37%) and 6 (22.39%). Conclusion: GCDH variants were identified as the causative factors in the three children. The discovery of the novel variant (c.214C > G) expands the spectrum of pathogenic GCDH variants. These findings facilitate the diagnosis and treatment of affected children and provide a basis for genetic counseling and prenatal diagnosis for their families.

Abstract Background To explore and compare the clinical effects of high‐resolution non‐invasive prenatal screening (NIPS‐Plus) for common/uncommon chromosomal aneuploidy and microdeletion/microduplication syndromes (MMS). Methods The current prospective study included a total of 25,380 pregnant women who performed NIPS‐Plus, and amniocentesis was performed on women with MMS with the screening results to diagnose patients with suspected MMS. Results There were 415 samples with positive results for NIPS‐Plus, included 275 with aneuploidy and 140 with MMS. After diagnosis by amniocentesis, 188 cases were confirmed as true positive, included46 cases of T21, 9 cases of T18, 1 case of T13, 34 cases of SCA, 41 cases of other chromosomal euploidy and 57 cases of MMS. In addition, no false negative cases were found, MMS was classified with 5 Mb with the cutoff value, and the PPV of different fragment size was counted, respectively. Conclusion We found that the corresponding PPV was 44.66% with the fragment of copy number variation (CNV) being less than or equal to 5 Mb, and when it was greater than 5 Mb, the PPV was 29.73%, which suggested that NIPS‐Plus was more suitable for screening the PPV of small fragment abnormalities. NIPS‐Plus has a good application effect in routine aneuploidy screening and had the best detection effect for T21; moreover, it performed well in screening of MMS and had better detection effect on MMS with CNV fragment length less than 5 Mb. Based on the current results, we suggested that NIPS‐Plus should be used as a comprehensive elementary prenatal screening method for all pregnant women, but for MMS caused by abnormal large fragment CNV, the detection method and efficiency still need to be improved.