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Objective To investigate the mutation types of colorectal neuroendocrine tumors(NETs)and better un-derstand the pathogenesis of colorectal nets.Methods Patients undergoing colorectal NETs surgery were recruited,colorectal NETs and corresponding adjacent cancerous tissues were collected,and whole genome sequencing(WGS)was performed and further deeply analyzed.Results WGS sequencing showed that the mutation types of colorectal NETs included single nucleotide mutations,insertion and deletion mutations(InDel,less than 50 bp in length),copy number variations(CNV),and large structural variations(SV,more than 50 bp in length),such as insertion(INS),deletion(DEL),intra chromosomal translocation(ITX),inter chromosomal translocation(CTX)and inversion(INV).Conclusions A large number of somatic mutations occur in colorectal NETs,especially chro-mosome translocation

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Objective To investigate the clinical application of skin bridge preopening window drainage in enhanced recovery of mixed hemorrhoids surgically treated with external dissection and internal ligation.Methods A total of 620 patients with mixed hemorrhoids surgically treated with external dissection and internal ligation were retrospectively analyzed from March 1,2021-February 28,2022.Patients were divided into the observation group(n=304)and the control group(n=316)according to the single and even numbers randomly generated at the time of admission.In the observation group,on the basis of conventional operation and drug treatment in the control group,most of them chose to implement preopening window drainage of the skin bridge according to the intraoperative evaluation of the anal skin bridge according to the unified evaluation criteria.Symptom-sign scoring scale used to evaluate the anal edema and pain after the operation.To compare and analyze differences in anal edema,anal pain and the postoperative hospital stay between the observation group and the control.Results The average daily edema scores of the observation group and the control group were 0.56 and 1.2 points,respectively.The average daily edema score of the observation group was lower than that of the control group,with the statistically significant differences(P＜0.05).The average daily pain scores of the observation group and the control group were 0.6 and 1.201+0.289 points,respectively.The average daily pain score of the observation group was lower than that of the control group,with the statistically significant differences(P＜0.05).The average hospitalization days of the observation group and the control group were 8 days and 10 days,respectively.The average length of stay in the observation group was less than that in the control group,with the statistically significant differences(P＜0.05).Conclusion Skin bridge preopening window drainage can effectively relieve the degree of anal edema and pain in patients with mixed hemorrhoids surgically treated with external dissection and internal ligation,improve clinical efficacy,shorten the postoperative hospital stay.It has practical value and clinical significance for enhanced recovery.

BACKGROUND:It has been shown that neural stem cells can differentiate into neurons,astrocytes,and oligodendrocytes.Mesenchymal stem cells-derived extracellular vesicles have also been shown to cross the blood-brain barrier to reach sites of central nervous injury and promote neural repair.However,it is not clear whether neuron-derived extracellular vesicles promote the differentiation of neural stem cells in a direction that is beneficial for neurogenesis. OBJECTIVE:To investigate whether neuron-derived extracellular vesicles facilitate neural stem cell differentiation towards neurogenesis. METHODS:Neurons and neural stem cells were extracted from neonatal SD rat cerebral cortex by trypsin digestion.Cell supernatants of neurons were collected.Neuron-derived extracellular vesicles were extracted.Neural stem cells cultured for 10 days were co-cultured with neuron-derived extracellular vesicles or PBS for 7 days.Immunoblotting,immunofluorescence,and RT-qPCR were used to detect proteins specifically expressed by neurons,neural stem cells,oligodendrocytes,and astrocytes. RESULTS AND CONCLUSION:The neural stem cells co-cultured with neuron-derived extracellular vesicles showed high expression of neuron-specific proteins and oligodendrocyte-specific proteins including β3-tubulin,neurofilament 200 and myelin basic protein,and low expression of astrocyte-specific protein glial fibrillary acidic protein.These results suggest that neuron-derived extracellular vesicles can promote the differentiation of neural stem cells into neurons and oligodendrocytes and prevent the differentiation of neural stem cells into astrocytes.

Objective To investigate the changes of mitochondrial respiratory function during myocardial fibrosis in mice with myocardial infarction (MI) and its correlation with the increase of glycolytic flux. Methods Forty C57BL/6N mice were randomized into two equal groups to receive sham operation or ligation of the left anterior descending coronary artery to induce acute MI. At 28 days after the operation, 5 mice from each group were euthanized and left ventricular tissue samples were collected for transcriptomic sequencing. FPKM method was used to calculate gene expression levels to identify the differentially expressed genes (DEGs) in MI mice, which were analyzed using GO and KEGG databases to determine the pathways affecting the disease process. Heat maps were drawn to show the differential expressions of the pathways and the related genes in the enrichment analysis. In primary cultures of neonatal mouse cardiac fibroblasts (CFs), the changes in mitochondrial respiration and glycolysis levels in response to treatment with the pro-fibrotic agonist TGF-β1 were analyzed using Seahorse experiment. Results The mouse models of MI showed significantly increased diastolic and systolic left ventricular diameter (P<0.05) and decreased left ventricular ejection fraction (P<0.0001). A total of 124 up-regulated and 106 down-regulated DEGs were identified in the myocardial tissues of MI mice, and GO and KEGG enrichment analysis showed that these DEGs were significantly enriched in fatty acid metabolism, organelles and other metabolic pathways and in the mitochondria. Heat maps revealed fatty acid beta oxidation, mitochondrial dysfunction and increased glycolysis levels in MI mice. In the primary culture of CFs, treatment with TGF-β1 significantly reduced the basal and maximum respiratory levels and increased the basal and maximum glycolysis levels (P<0.0001). Conclusion During myocardial fibrosis, energy metabolism remodeling occurs in the CFs, manifested by lowered mitochondrial function and increased energy generation through glycolysis.

Objective To explore the clinical efficacy of Xuanfei Liyan decoction in treating post-infectious cough(PIC)with wind-heat invading lung syndrome.Methods A total of 60 patients with PIC were selected from January 2023 to January 2024 in Lishui Hospital of Traditional Chinese Medicine and were classified into 30 cases each in groups of control and observation by using method of randomized numerical table.The control group was given western medicine compound methenamine,and observ groups was given Xuanfei Liyan decoction,one dose per day,and the course of treatment for both groups was a week.After continuous treatment for one week,the efficacy of two groups were evaluated,and the Chinese medicine symptom scores and visual analogue scores before and after treatment were assessed.Results The therapeutic efficacy of observation group was higher than that of control group(P＜0.05).The Chinese medicine symptom scores and visual analogue scale of two groups were lower than those before treatment,and the decline levels of observation group were more favourable than those of control group(P＜0.05).Conclusion Xuanfei Liyan decoction was clinically effective in treatment of PIC and the wind-heat invading lung syndrome.

Objective To observe the value of pleuracentesis and catheterization combined with persistent vacuum aspiration for treating pneumothorax caused by microwave ablation(MWA)of pulmonary nodules.Methods Totally 21 patients who underwent pleuracentesis and catheterization combined with persistent vacuum aspiration since pneumothorax caused by MWA of pulmonary nodules were enrolled,and the efficacy and safety of pleuracentesis and catheterization combined with persistent vacuum aspiration were observed.Results The success rate and effective rate of pleuracentesis and catheterization combined with persistent vacuum aspiration were both 100%(21/21).The incidence of pleural effusion and hemoptysis was 14.29%(3/21)and 9.52%(2/21),respectively,while no other complication occurred.Three months after treatment,complete remission of pulmonary nodule was observed in 71.43%(15/21)cases,while partial remission was noticed in 28.57%(6/21)cases,and the total effective rate and local control rate of pulmonary nodules were both 100%(21/21).Conclusion Pleuracentesis and catheterization combined with persistent vacuum aspiration was safe and effective for treating pneumothorax caused by MWA of pulmonary nodules.

Objective:To explore the heterogeneity among keloids before and after radiotherapy and identify the changes of key cell subpopulations and their interactions utilizing single cell RNA sequencing technology.Methods:Four patients provided a total of 12 samples, each consisting of keloid tissue before and after radiotherapy and the normal skin tissue adjacent to the untreated keloid. The keloid was divided into left and right sides from the midline, and the left-side keloid was fractionally irradiated with 20 Gy electron beam in total in 4 consecutive days. The right-side keloid was irradiated with 10 Gy in 2 fractions before surgery and 10 Gy in 2 fractions after surgery.Results:A total of 25 573 fibroblasts were analyzed and categorized into nine subgroups (fibroblasts 1-9). The proportion of fibroblast-2 increased after radiotherapy ( t=4.70, P<0.05). The number of classical monocytes and macrophages increased after radiotherapy, but there was no significant difference due to the shorter time of sample taking at 2 d after radiotherapy ( P>0.05). Macrophages (4 723 cells) were further divided into four categories. CellPhoneDB analysis showed that type-3 macrophages interacted significantly more closely with fibroblasts than type-1 and type-2 macrophages. The most prominent signaling pathways for the interactions between type-3 macrophages and major fibroblast subtypes were the collagen signaling pathway and the chemerin signaling pathway. These interactions were more pronounced in the keloid samples after radiotherapy. Conclusions:The interactions between type-3 macrophages and fibroblasts (such as fibroblast-2) may serve as an important point for future studies on radio-sensitization of keloids.