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.

Radiotherapy is a first-line treatment for a variety of malignant tumors by inducing DNA damage to kill tumor cells. However, tumor cells have different sensitivities to radiotherapy, ultimately leading to different therapeutic effects. Histone acetylation, regulated by histone acetyltransferase (HAT) and histone deacetylase (HDAC), is involved in the regulation of cell radiation sensitivity by influencing DNA damage repair. The main mechanisms are recruiting DNA repair related proteins and mediating chromatin dynamic changes. In this article, the role of histone acetylation modification in tumor radiotherapy was reviewed, aming to provide the basis for the radiotherapy sensitization strategy based on histone acetylation.

Objective To investigate the effectiveness and safety of volumetric modulated arc therapy (VMAT) hypofractionated radiotherapy and intensity modulated conformal radiotherapy technique (IMRT) conventional fractionated radiotherapy after breast cancer radical operation.Methods Eighty-five patients with breast cancer modified radical operation admitted and treated in this hospital from March 1,2021 to De-cember 30,2021 were selected as the research subjects and divided into the VMAT group (n=41) and the IM-RT group (n=42) according to the random number table method.The VMAT group adopted the hypofrac-tionated radiotherapy,with the single fractionated dose of 2.9 Gy/frequency and radiotherapeutic total dose of 43.5 Gy/15 frequencies;the IMRT group adopted the IMRT conventional fractionated radiotherapy,with the single fractionated dose of 2.0 Gy/frequency and radiotherapeutic total dose of 50.0 Gy/25 frequencies.The planning target region V95,V110,conformity index,homogeneity index,treatment time,V5,V20,V30,average dose (Dmean) in the affected side lung,humeral head Dmean and heart V30,Dmean were compared between the two groups.Meanwhile,local recurrence,distant metastasis,disease-free survival and acute and chronic radiation injury were compared between the two groups.Results Compared with the IMRT group,V95 in the VMAT was higher,V110 and homogeneity index were lower,the treatment time was shorter,V5 in the affected lung,Dmean and Dmean in the affected humeral head were lower,V30 in the affected lung was higher,heart V30 in the left side breast cancer was lower,heart Dmean in the right side breast cancer was lower,and the differences were statistically significant (P<0.05).All patients survived without local relapse.The distant metastasis rate and disease free survival rate had no statistical difference between the two groups (P>0.05).Follow up lasted for 12 months,the incidence rates of grade Ⅰ-Ⅱ acute radiodermatitis,radiation esophagitis,chronic radioder-matitis and radiation pneumonia had no statistical differences between the two groups (P>0.05).The inci-dence rate of grade Ⅰ-Ⅱ shoulder dysfunction in the VMAT group was lower than that in the IMRT group with statistical difference (P<0.05).No grade Ⅱ and above acute and chronic radiation injury in the two groups occurred.Conclusion VMAT hypofractionated radiotherapy after breast cancer radical operation is safe and effective.

Objective:To investigate the safety and efficacy of robot-guided ventricular partition puncture drainage in severe intraventricular hemorrhage.Methods:A total of 23 patients with severe intraventricular hemorrhage who underwent robot-guided ventricular partition puncture drainage (experimental group) and 19 patients who underwent robot-guided bilateral ventricular puncture drainage (control group) at Department of Neurosurgery, People's Hospital of Baise from January 2021 to December 2021 were included. The differences in residual hematoma volume within 24 h of surgery, drainage tube retention time, mortality rate within 30 d of surgery, incidence of complications (re-bleeding, intracranial infection, pulmonary infection, hydrocephalus) within 6 months of surgery, and scores of Glasgow coma scale (GCS), activity of daily living (ADL), and National Institutes of Health stroke scale (NIHSS) at 6 months after surgery were compared between the 2 groups.Results:Compared with the control group, the experimental group had significantly lower residual hematoma volume within 24 h of surgery ([8.854±3.519] mL vs. [5.668±2.873] mL), shorter drainage tube retention time ([6.580±1.981] d vs. [4.910±2.763] d), lower incidence of hydrocephalus within 6 months of surgery (42.105% vs. 8.696%), and significantly higher GCS and ADL scores and lower NIHSS scores at 6 months after surgery (8.790±2.898 vs. 11.610±2.948; 69.470±12.899 vs. 78.480±12.861; 13.950±5.265 vs. 9.870±4.124, P<0.05). Conclusion:Robot-guided ventricular partition puncture drainage is a safe and effective surgical method for severe intraventricular hemorrhage.

The Fukushima Daiichi Nuclear Power Plant accident in Japan resulted in the release of large amounts of radioactive substances into the surrounding environment and caused contamination. In the accident recovery process, Japan had made great efforts in public communication, including the government’s promotion of organization and planning the popularization and publicity of scientific knowledge in various forms, multi-channel information disclosure, and all-round communication and exchange, which can provide a reference for the development of relevant work in China. The nuclear-related public communication work in China can get four enlightenments. Firstly, the public communication system should be improved, and corresponding policies and mechanisms should be clarified. Secondly the popularization of nuclear science knowledge should be taken as the foundation for early and long-term development. Thirdly, the operators of nuclear facilities shall disclose relevant information according to the law and confront the curiosity or doubts of the public. Finally, multi-channel, multi-level and multi-frequency exchanges and interactions should be conducted to seek unity of understanding and balance of interests between the two sides.

Objective:To evaluate the effect of microevolution on phenotypes and drug resistance of the Trichosporon asahii biofilm. Methods:The standard strain of Trichosporon asahii was obtained from the Fungal Biodiversity Institute of the Royal Netherlands Academy of Arts and Sciences, the fluconazole-sensitive primary strain (TO) of Trichosporon asahii was isolated from a case of trichosporonosis diagnosed in the Department of Dermatology, the Seventh Medical Center of Chinese People′s Liberation Army General Hospital in 2000, and the fluconazole-resistant evolved strain (TEVO) of Trichosporon asahii was isolated from the above patient in 2014. Biofilms of the above-mentioned strains were formed in vitro, and tetrazolium salt XTT reduction assay was performed to evaluate growth kinetics of the Trichosporon asahii biofilm, and laser scanning confocal microscopy to determine the thickness of the biofilm; the sessile minimum inhibitory concentrations (SMICs) of fluconazole, itraconazole and voriconazole against the biofilms at different growth stages were determined in vitro for the evaluation of the resistance of the biofilms. One-way analysis of variance was used for comparisons among multiple groups, and Hartley test for testing homogeneity of variance. If the variance was homogeneous, least significant difference test was used for multiple comparisons; if the variance was heterogeneous, Tamhane′ T2 test was used for multiple comparisons. Results:In the adhesion (0 h) and formation stages (4- 24 hours) of the Trichosporon asahii biofilm, the metabolic activity of the evolved strain TEVO was the weakest (adhesion stage: F = 35.705, P < 0.001; formation stage: F = 15.042, P < 0.001) . At 48 hours after adhesion, the biofilms matured, and the TO strain showed the weakest metabolic activity ( F = 10.985, P < 0.001) . In the maturation stage, the biofilm thickness of the TEVO strain (26.1 ± 1.18 μm) was significantly higher than that of the TO strain (22.8 ± 1.73 μm, P = 0.001) , but significantly lower than that of the standard strain (29.5 ± 1.28 μm, P = 0.001) . As drug susceptibility testing showed, the SMICs of azole antifungal agents against the TEVO strain were higher than those against the TO strain in the adhesion and formation stages of the Trichosporon asahii biofilm, and the SMICs of azole antifungal agents against the biofilms of the 3 strains of Trichosporon asahii were all over 1 024 mg/L in the maturation stage of the biofilm. Conclusion:Under the dual pressure of host environment and antifungal drugs, adaptive changes took place in the phenotypes of the Trichosporon asahii biofilm with an increase in the resistance to azole antifungal drugs.

OBJECTIVE: To explore the effects of cumulative noise exposure(CNE) on the intima-media thickness(IMT) of carotid artery in steel workers. METHODS: A cluster random sampling method was used to select 1 437 noise exposed workers in a steel company as study subjects. The CNE was calculated according to the noise intensity of the workplace, and the occupational health check was carried out to construct the structural equation model of noise to IMT. RESULTS: The detection rate of carotid atherosclerosis(CAS) in these 1 437 subjects was 38.3%. The CAS detection rates of steel workers increased with the increasing CNE(P<0.01). The structural equation model had good fitting effect. Path analysis showed CNE can indirectly affect IMT through blood pressure, triglycerides, fasting blood glucose, homocysteine, high-density lipoprotein & apolipoprotein A, low-density lipoprotein & apolipoprotein B. The total effects were-0.375, 0.337, 0.248, 0.117, 0.056, 0.056 and 0.018 respectively. CONCLUSION: CNE can indirectly increase the IMT of steel workers by acting on the proximal cause.

Objective To analyze the clinical characteristics and screen pathogens and prognosis of anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis in children and so as to improve the diagnosis and treatment of anti-NMDAR encephalitis in children.Methods A retrospective and follow-up analysis of 38 cases of pediatric anti-NMDAR encephalitis was performed,who were admitted to the West China Second University Hospital,Sichuan University from May 2012 to June 2016,and their clinical features,associated pathogen screening,treatment and progno-sis were reviewed.Results Those 38 cases included 14 males and 24 females.The age ranged from 1 year and 10 months to 17 years and 6 months.The most common symptoms were psychiatric symptoms(33 cases),and dyskinesias and movement disorders(33 cases),speech disturbances(31 cases).Twenty-four cases(63.2%)received positive pathogenic screening and only one case had right ovarian mature cystic teratoma.Among them,11 cases had positive mycoplasma pneumonia immunoglobulin M(IgM)antibodies,10 cases had positive virus screening,and 1 case had toxoplasma gondii IgM antibodies positive,and 2 cases had mix infection.Symptoms of one case were relieved after anti-toxoplasma treatment without immunosuppression treatment,and another case had partial symptom relief after mycoplas-ma pneumonia treatment.Thirty-seven cases received immunosuppressant therapy(4 cases were treated with glucocor-ticoid,12 cases were treated with glucocorticoid combined with immune globulin,2 cases were treated with glucocorti-coid combined with plasma exchange,still 19 cases were treated with glucocorticoid combined with immune globulin and plasma exchange).After follow-up for median 12 months,3 cases relapsed,29 cases were fully recovered,5 cases had mild language impairment,2 cases had mild memory impairment,and 2 cases had involuntary movement.Conclusions The most common symptoms of the patients were psychiatric symptoms,dyskinesias and movement disorders,and speech disturbances.Children with anti-NMDAR encephalitis had a low incidence of tumors,while various pathogen infections including mycoplasma pneumonia,virus and toxoplasma gondii,which may trigger abnormal immune response of anti-NMDAR encephalitis.Pathogen screening needs to be done for pediatric anti-NMDAR encephalitis and anti-patho-genic treatment may be helpful for disease remission.

Cardiovascular surgery is a type of high-risk surgery for pressure ulcers. This review summarizes the risk factors of pressure ulcers in patients undergoing cardiovascular surgery, including preoperative, intraoperative and postoperative risk factors. At the same time, it points out that in the present study, there is a dispute about whether the pressure sore is associated with the time of cardiopulmonary bypass and the change of body temperature in patients undergoing cardiovascular surgery. In addition, here is a lack of related research on whether the anticoagulant of protamine has an effect on pressure sores during the operation. This article aims to provide a basis for the clinical observation of the risk factors of pressure sores in cardiovascular surgery.

Objective To investigate differences in the expression of Ras 1,Rac1 and Rho1 genes between yeast and hyphal phases of Trichosporon asahii (T.asahii),and to explore their roles in the formation of hyphae.Methods The yeast phase and hyphal phase of T.asahii were cultured and served as yeast phase group and hyphal phase group respectively.Total RNA was extracted from the 2 groups,and real -time fluorescence-based quantitative PCR (RT-PCR) was performed to measure the mRNA expression of Ras1,Rac1 and Rho1.Results The hyphal formation rate was significantly lower in the yeast phase group than in the hyphal phase group (0.40％ ± 0.53％ vs.99.33％ ± 0.57％,t =13.93,P ＜ 0.05).When the mRNA expression of Ras1,Rac1 and Rho1 in the yeast phase group was all set as 1,that in the hyphal phase group was 25.17 ± 10.99,16.81 ± 7.80,42.61 ± 18.50,respectively,with significant differences between the two groups in the three parameters (t =3.81,3.51,3.90,respectively,all P ＜ 0.05).Conclusion Ras1,Rac1 and Rho1 genes may participate in the regulation of hyphal formation in T.asahii.