Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity. Inactivation or knockdown of USP2 leads to the degradation of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo. Conversely, overexpressing USP2 stabilizes KRAS and partially abrogates GA-induced apoptosis in MM cells. Furthermore, elevated USP2 levels may be associated with poorer prognoses in MM patients. These findings highlight the potential of the USP2/KRAS axis as a therapeutic target in MM, suggesting that strategically inducing KRAS degradation via USP2 inhibition could be a promising approach for treating cancers with KRAS mutations.

【Objective】 To analyze the efficacy and safety of intralesional triamcinolone acetonide in the treatment of mass granulomatous mastitis (GLM). 【Methods】 Retrospective analysis was made on 67 patients with GLM who were treated in Xijing Hospital from July 2021 to May 2022 and met the inclusion criteria. Among them, 31 patients were treated with local injection of triamcinolone acetonide, while 36 ones were treated with oral methylprednisolone. All the included patients underwent surgical treatment after their condition met the surgical criteria, and the follow-up period lasted for up to six months after surgery. The two groups were compared in improvement of symptoms and signs, treatment time, clinical effectiveness and safety, and recurrence rate. 【Results】 The effective rate of triamcinolone acetonide group and methylprednisolone group was 100%, but the clinical cure rate was significantly higher in triamcinolone acetonide group than in methylprednisolone group in stratified analysis (P<0.05). The improvement time of symptoms and signs in triamcinolone acetonide group was significantly shorter than that in methylprednisolone group (P<0.05). The incidence of side effects in triamcinolone acetonide group was also significantly reduced compared to methylprednisolone group (P<0.05). Follow-up for half a year showed no recurrence in both groups. 【Conclusion】 Compared with the traditional oral methylprednisolone group, local injection of triamcinolone acetonide in the treatment of mass granulomatous mastitis can rapidly relieve clinical symptoms and signs, shorten treatment time, and has higher efficiency and fewer side effects. Local injection of hormone combined with surgery is effective in treating mass granulomatous mastitis with low recurrence rate.

Objective:To understand the identification value of pointing gestures in children with autism spectrum disorder(ASD) and its relationship with functional development.Methods:From December 2020 to November 2021, 1 099 children from Children’s Health Care Center of Beijing Children’s Hospital were tested by pointing gestures test, including 942 ASD children and 157 typical developed children.And the data of children's neuropsychological development scale from 800 children aged 1.0-5.9 were collected.SPSS 20.0 was used for statistical analysis. Trend test was used to analyze the distribution of pointing gestures test sensitivity in autistic children, and ANOVA was used to analyze the relationship between pointing gestures test scores and functional development fields.Results:The sensitivity of pointing gestures was 83.5% in children aged 1.0-10.0 years, 76.3%-93.1% in children aged 1.0-4.9 years, and 93.1%-95.1% in children aged 1.0-2.9.With the increase of age, the sensitivity of pointing gestures in autistic children (linear-by-linear association =164.889, P<0.001) and the Yoden index had a decreasing trend. The positive predictive value (91.53%-100.00%) and negative predictive value (75.36%-91.84%) were found in the children aged 1.0-10.0 years.The sensitivity of pointing gestures test was 44.9% in children with mild autism aged 1.0-10.0 years and 46.5%-65.9% in children with mild autism aged from 1.0-3.9 years. The sensitivity of pointing gestures test was 81.5% in children with moderate autism aged from 1.0-10.0 years and 87.3%-97.8% in children with moderate autism aged 1.0-3.9 years. The sensitivity of the pointing gestures test was 97.2% in children with severe autism aged 1.0-10.0 years, and 100.0% in children with severe autism aged 1.0-3.9 years. The sensitivity of the pointing gestures in mild, moderate and severe autism children decreased with age (linear-by-linear association values were 16.725, 64.232, 66.732 respectively, all P<0.001). The children with severe autism mainly scored 2 points (80.3%, 419/522) on the pointing gestures test , and children with moderate autism mainly scored 1 point(64.2%, 170/265) on the pointing gestures test. There were significant differences in functional development among different pointing gestures test groups.Functional development score in the autism children with 0 score of pointing gestures test was significantly higher than those with 1 score and 2 scores of pointing gestures test (all P<0.05). Conclusion:Pointing gestures has good sensitivity in children with autism (especially 1.0-4.9 years of age), and may serve as an objectively observable screening method. The better children with autism score on the pointing gestures, the better their functional development.

Objective:To evaluate Castor single-branch covered-stent in the treatment of Stanford B aortic dissection(TBAD)with insufficient anchorage zone.Methods:Clinical data of 25 TBAD patients (proximal healthy landing zone ≤15 mm) treated with Castor branched stent-graft at Weifang People's Hospital from Apr 2019 to Sep 2021 were analyzed retrospectively.The stent model was selected according to preoperative CTA examination and intraoperative angiography,the operation result and follow up data were reviewed.Results:The operation success rate was 100%,the mean operative time was (137.8±35.8)min, and the mean blood loss was (52.8±24.5)ml. There were 2 cases of internal leakage (IA) and it was disappeared after balloon dilation, Branched stent stenosis occurred in 2 cases and relieved by balloon dilatation. The mean follow-up time was 14.6 months, and the patency rate of branch stent was 100% during the follow-up period. The true lumen diameter of thoracic aorta was significantly expanded and the false lumen diameter was significantly reduced 3 months after surgery compared with that before surgery ( P<0.05). Conclusion:Castor stenting in the treatment of TBAD with insufficient proximal anchoring area is simple and feasible, with satisfactory short term clinical effect.

Objective:Based on the data of Global Burden of Disease 2019 data, to analyze the past, current, and future burden of disability-adjusted life years (DALYs) in China and compare with the international status.Methods:The total number of DALYs, age-standardized DALY rate, and the composition of different subgroups were extracted and described to analyze the time trend in 2000-2019 and the current situation in 2019 for Chinese female breast cancer. The burden of DALYs in 2050 was predicted by Joinpoint using average annual percent change (AAPC).Results:In 2000-2019, the ranking of DALYs caused by female breast cancer in China rose from the fourth to the second in all female cancers. The total DALYs increased by 48.4%, of which the years lived with disability increased from 4.8% to 8.8%. The age-standardized DALY rate only slightly decreased (AAPC=-0.3%; which increased during 2016-2019, AAPC=1.6%). In 2019, the age-standardized DALY rate for breast cancer in China was 278.0/100 000. The DALYs were 2.88 million (accounting for 14.2% of the global burden and 12.1% of all female cancers burden in China), 26.5% of which attributed known risk factors (overweight and obesity were the largest: 0.34 million DALYs, but some common breast cancer risk factors were not available on the platform, such as menstruation and fertility). In 2050, the prediction suggests that the total DALYs caused by female breast cancer in China will reach 3.80 million person-years-5.16 million person-years, increasing 32.1%-79.4% over 2019. From 2000 to 2019, the peak age of DALYs and DALY rate became older, and the DALYs among females aged 65 years and above increased faster than those younger than 65 years (AAPC were 4.8% and 1.3%, respectively). In 2019, females aged 45-74 (the starting age recommended by local guidelines for breast cancer screening) contributed 74.3% of the total DALYs.Conclusions:Over the past 20 years, the age-standardized DALY rate for breast cancer in female populations in China has not changed obviously. Without the continuous expansion of effective intervention and population aging, the burden of DALYs for female breast cancer in China will increase. DALYs for breast cancer attributed leading risk factors were still limited.

Objective: To investigate the pathogenic characteristics of viral encephalitis in children living in Hebei province. Methods: We randomly collected cerebrospinal fluid specimens from a total of 399 children diagnosed with viral encephalitis in Hebei Children′s Hospital from May to December 2017. Real-time fluorescence quantitative PCR and Sanger sequencing were used to detect viral nucleic acids in cerebrospinal fluid by an automatic laboratory station. Statistical analysis was performed on the experimental data using SPSS 21.0 software and the clinical data were analyzed. Comparison of infection rates of EV encephalitis in different months, using line × column chi-square test. The MRI and EEG positive rates of different viral encephalitis and viral encephalitis patients not infected with the virus were analyzed by Fisher′s exact probability test. The positive rate of infection with different viruses and non-virus agents was analyzed by Fisher′s exact probability test. Results: The result showed that 80 of 399 samples were positive, and the positive rate was 20.05%. It included 22 cases of enterovirus, 4 cases of influenza A virus, 3 cases of mumps virus, 2 cases of herpes simplex virus type 1, 1 case of herpes simplex virus type 2, 4 cases of EB virus, 7 cases of cytomegalovirus, 7 cases of herpes zoster virus, 8 cases of adenovirus, 14 cases of human herpesvirus type 6. Eight cases had combined viral infection. Eight cases had concurrent infections: 3 cases had enterovirus and herpesvirus type 6 concurrent infection, 1 case had enterovirus and Japanese encephalitis virus concurrent infection and 1 case had herpes simplex virus type 2 and adenovirus, 1 case had influenza A virus herpesvirus type 6, 1 case had mumps virus and herpesvirus type 6, 1 case had mumps virus and herpesvirus type 6, 1 case had herpes simplex virus type 1 and herpes zoster virus concurrent infections. Children with EV viral encephalitis in Hebei Province were highly prevalent in May and June (P=0.016). HHV6 virus encephalitis was more susceptible to infection than non-HHV6 virus (P=0.016); The rate of MRI positive findings in patients with different viral encephalitis was not statistically significant (P>0.05). The result of EEG of different viral encephalitis were P>0.05, which was not statistically significant. Conclusions EV was the most common pathogen of children with viral encephalitis in Hebei province. Encephalitis caused by influenza A virus cannot be ignored in clinical practice.

Objective To estimate prenatal diagnoses strategy with abnormal results of non-invasive prenatal testing (NIPT) based on a case of mosaic for trisomy 22.Methods The pregnanct woman was recruited from Department of Prenatal Diagnosis Center of Xinhua Hospital.Ultrasound scans suggested fetal nuchal translucency was 3.5 mm.Peripheral venous blood was drawn from the pregnant woman for NIPT at 12+2 weeks gestation.For further prenatal diagnosis, amniocentesis was conducted at 16+2 weeks gestation, and karyotype analysis combination with chromosome microarray analysis (CMA) was executed to analysis amniocytes.Results NIPT results suggested that chromosome 21, 18 and 13 were normal and supplementary reports suggested that chromosome 22 were slightly above the normal range.Karyotype analyzed 35 cultured cells.Each of them revealed a normal female karyotype.However, CMA results suggested that chromosome 22 gain mosaic and its copy number was 2.26.The fetus was diagnosed as high possibility of mosaic for trisomy 22.Conclusions Combined with the NIPT results, which was slightly gain mosaic of chromosome 22, a prenatal diagnosis strategy were proposed.When NIPT results suggest chromosomal abnormities, karyotype analysis combination with CMA to diagnose were recommended.

Insertional mutagenesis is a widely used method to determine the function(s) of a gene. To study the function(s) of the gene nsdAmgh in Streptomyces roseoflavus, a homologous recombination vector pSRNA2500 was structured in this paper. The recombination donor vector was then transformed into Strempomyces roseoflavus strain Men-myco-93-63 by conjugative transfer. The transformants were subjected to selection under the pressure of high temperature and appropriate antibiotics. As a result, several disrupted mutants of nsdAmgh gene, with a phenotype of Am(s)Km(r), were isolated and verified using PCR and Dot-blotting and Southern blotting hybridization methods. Functional analysis showed that the disrupted mutants of nsdAmgh had a two-fold higher inhibition against Verticillium dahlia Kleb than that of the wild strain Men-myco-93-63, which all will provide a new study route for future research about positive and negative regulator in Men-myco-93-63.
Genes, Bacterial ; Genetic Vectors ; Mutagenesis, Insertional ; Polymerase Chain Reaction ; Streptomyces ; genetics

Objective:To explore the mediating effect of inferiority feelings on the relationship between child-hood trauma and fear of intimacy in college students.Methods:Totally 420 college students (72 males and 324 fe-males,aged 18 to 24)from Langfang Normal School were assessed with the Feelings of Inadequacy Scale(FIS), Childhood Trauma Questionnaire(CTQ)and Fear-of-Intimacy Scale(FIS).The regression analysis and Bootstrap were used to test the mediating effect of inferiority feelings on the relationship between childhood trauma and fear of intimacy.Results:The total scores of CTQ and the scores of 4 childhood trauma factors were positively correla-ted with fear of intimacy score and feeling of inferiority score(r =0.18 -0.55,Ps <0.05).Feeling of inferiority scores were positively correlated with fear of intimacy scores (r =0.24 -0.44,Ps <0.05).The childhood trauma was positively associated with fear of intimacy (β=0.31,P <0.01).In addition,feeling of inferiority fully media-ted the relationship between childhood trauma and fear of intimacy,the value of mediating effect was 34%.Conclu-sion:Feeling of inferiority may play a mediating role between childhood trauma and fear of intimacy in college students.

To improve the part of the hardware about Xin Hua SL-IC model X-ray radiotherapy simulative position finder, using CR and PACS, so that located-picture shooting for the simulative position finder have been realized digital upgrade.
Automatic Data Processing ; Radiographic Image Enhancement ; Radiotherapy ; methods ; Tomography, Spiral Computed ; methods