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 evaluate th e effects of comprehensive drug cost control in China ，and to provide reference for further improving the effects of cost control. METHODS Entropy method was used to establish a comprehensive evaluation index system of the comprehensive drug cost control effect from the respective of drug price control ability ，drug cost control ability and patient affordability. The comprehensively evaluate the effects of drug cost control in 31 provinces （autonomous regions and municipalities）during 2016-2020. The k-means cluster method was used to analyze the effects of comprehensive drug cost control in various provinces. RESULTS & CONCLUSIONS During the period of 2016-2020，the total score of comprehensive drug cost control effect of 31 provinces were 14.64，16.71，17.58，17.57，17.88，respectively. The results of cluster analysis were similar to the ranking of entropy method. Medical and health system reform policy had entered a stable period after achieving phased results ； the effects of comprehensive drug cost control was characterized by regional steps in 31 provinces；the effects of comprehensive drug cost control were better in developed coastal areas and some provinces and cities of western regions ，followed by provinces and cities in central China ；however，comprehensive drug cost control in 3 provinces of northeast China showed poor effect. The effects of comprehensive drug cost control in pilot cities of comprehensive medical reform were significantly improved. It is suggested that the successful experience of pilot cities of comprehensive medical reform should be promoted nationwide ，and policies such as volume-based drug procurement ，medical insurance drug price negotiation ，and diagnosis-related groups / diagnosis-intervention packet payment method reform should be further deepened.

The role of skin microbiota in the occurrence of rosacea remains unclear. This review summarizes several important skin microorganisms that have been reported to be possibly related to the occurrence of rosacea, including Demodex, Bacillus oleronius, Propionibacterium acnes, Corynebacterium kroppenstedtii, etc., and further elaborates on the potential mechanisms of action.

Objective:To explore the effects of different temperature settings on patients with acute hypoxic respiratory failure (AHRF) during application of high-flow nasal cannula (HFNC) .Methods:A total of 90 patients with AHRF who were admitted to the Department of Critical Care Medicine of Zhejiang Hospital and underwent HFNC from January 2019 to May 2020 were selected as research objects by the convenient sampling method. The patients were randomly divided into 3 groups by the random number table method, namely, group A (T=31 ℃) , group B (T=34 ℃) and group C (T=37 ℃) , with 30 cases in each group. The VAS and Borg Scale were used to compare the comfort and dyspnea of patients of 3 groups, and to compare the satisfaction of patients of 3 groups.Results:After applying HFNC for 2 h and 12 h, the scores of VAS and Borg Scale in group B were lower than those in groups A and C, and the differences were statistically significant ( P<0.01) . The VAS scores of the three groups after applying HFNC for 12 h were higher than that after applying HFNC for 2 h, and the scores of Borg Scale were lower than that after applying HFNC for 2 h, and the differences were statistically significant ( P<0.05) . The satisfaction of patients in group B was higher than that in group A and C, and the differences were statistically significant ( P< 0.01) . Conclusions:Different temperature settings of HFNC will affect the comfort, dyspnea and satisfaction of AHRF patients. Among them, 34 ℃ is a more suitable temperature. As time progresses, nursing staff should intervene in time to maintain the comfort of patients, reduce the degree of dyspnea and provide guidance for the clinical application of HFNC.

Objective:To study the clinical features of children with Prader-Willi syndrome(PWS).Methods:Eighteen cases of PWS were collected from July 2016 to November 2018 in Shenzhen Maternal and Child Healthcare Hospital, Southern Medical University.The clinical data of children with PWS were analyzed retrospectively.Results:There were 12 males and 6 females in 18 cases with PWS.The diagnosis age ranged from 25 days to 9.5 years old [(3.09±3.02) years old]. Among them, 11 cases were in infancy (≤3 years old) and 7 cases after infancy (>3 years old). The main clinical features of infants with PWS were 11 cases of gonadal dysplasia (100.0%), 11 cases of psychomotor retardation (100.0%), 10 cases of hypotonia (90.1%), 6 cases of feeding difficulty and weak cry (54.5%). After infancy the main clinical features included 7 cases of psychomotor retardation (100.0%), 5 cases of hyperphagia(71.4%), 5 cases of obesity (71.4%), 5 cases of abnormal behavior problems (71.4%) and 4 cases of visual problems (57.1%). The clinical features of all patients throughout the developmental stage were as follows: decreased fetal movement, hypoplasia, neonatal hypotonia, weak cry, feeding difficulty, psychomotor delay, hyperphagia, obesity, abnormal behavior problems, and so on.Conclusions:The clinical features of PWS vary with age.The main clinical features in the infancy are hypotonia, weak cry, difficulty feeding and gonadal dysplasia.After infancy, there are hyperphagia, obesity, behavior and visual problems.And psychomotor retardation is present in the whole developmental stage of children with PWS.Early diagnosis and treatment are important for improving the prognosis of PWS.

Objective: To explore the effect of cluster skin management (SSKIN) on reducing the incidence of stress skin injury in children with congenital heart disease during perioperative period. Methods: Delphi method was used to establish cluster skin management specialty to formulate SSKIN. Skin outcomes of 863 children before SSKIN implementation (control group) and 819 children after SSKIN implementation (experimental group) were analyzed and compared through personnel training, program application and supervision. Results: The incidence of stress skin injury, stage I stress skin injury and occipital pressure injury were 5.1% (44/863), 4.4% (38/863), 2.5% (22/863) in the control group and 2.3% (19/819), 2.2% (18/819), 0.7% (6/819) in the experimental group, respectively. There were significant differences between the two groups (χ² = 8.999, 6.350, 8.472, P < 0.01 or 0.05). The incidence of stress skin injury in delayed chest closure and continuous positive airway pressure were 27.9%(17/61), 23.4%(18/77) in the control group and 11.5%(6/52), 8.9%(7/79) in the experimental group, respectively. There were significant differences between the two groups(χ²=4.618, 6.105, P<0.05). Conclusions The SSKIN is effective at prevent congenital heart disease patients with high risk of stress skin injury. It can improve the skin outcomes in children.

Objective: To improve the clinical outcomes and critical care quality for pediatric extracorporeal membrane oxygenation (ECMO), the multidisciplinary team including doctors, nurses and respiratory therapist designed a daily checklist for patients with ECMO and evaluated the effect of the checklist. Methods: A daily checklist for ECMO patients was designed based on the expert consensus and multi-centers relevant researches. ECMO patients from January 2015 and May 2017 in the pre-application group, while the other patients from June 2017 to December 2018 in the post-application group were compared in the clinical outcomes. Results: All 78 pediatric patients used the venoarterial extracorporeal membrane oxygenation (VA-ECMO) including 27 patients in the pre-application group and the other 51 patients in the post-application group. The mortality rate was 49.02%(25/51) in the post-application group and 81.48%(22/27) in the pre-application group, the differences were significant (χ²=7.768, P=0.005). The rates of central line-associated bloodstream infection, pressure injury and the body weight change was 2/5, 4/5, -2.70(-3.50--2.05) in the pre-application group and 3.85%(1/26), 26.92%(7/26), -0.09(-1.00-0.00) in the post-application group,the differences were significant (χ²=4.505, 5.161, Z=3.252, P<0.05 or 0.01). Conclusions It is helpful for clinical staff to follow up the progress of the multiple organs when using the daily checklist, to facilitate team communication for, and to improve nursing management through setting the daily targets for individual VA-ECMO patients.

Objective To investigate CT features of multifoeal lung adenocarcinoma (MLA) with ground glass opacity and the relationships with pathology.Methods Totally 16 cases (36 lesions) of MLA confirmed by pathology were collected.Based on pathology,the lesions were divided into pre-invasive lesion group (n =7),minimally invasive adenocarcinoma (MIA) group (n=20) and invasive adenocarcinoma (IAC) group (n =9).CT features of all three groups were analyzed and compared with pathology.Results Among 36 lesions,there were 19 lesions (52.78％) with round shape,19 (52.78％) with lobulation,12 (33.33％) with spiculation sign,13 (36.11％) with vacuole sign,12 (33.33％)with blood vessel cluster sign,and 32 lesions (88.89％) with well-defined interface.Seven pre-invasive lesions (7/7,100％) were all pure ground glass opacity (pGGO),while 12 lesions (12/20,60.00％) were pGGO in MIA group,other 8 lesions (8/20,40.00％) were mixed ground glass opacity (mGGO).Only 1 lesion (1/9,11.11％) in IAC group was pGGO,other 8 lesions (1/9,88.89％) were mGGO.There were significant differences of pGGO,spiculation sign,vacuole sign and blood vessel cluster sign among 3 groups (all P＜0.05).There were significant differences of pGGO,spiculation sign and blood vessel cluster sign between pre-invasive lesion and IAC group (P=0.001,0.003,0.001).Significant differences were found in spiculation sign,vacuole sign and blood vessel cluster sign between MIA and IAC group (P=0.014,0.014,0.001).Conclusion CT findings of multiple ground glass opacity are helpful to diagnosis of MLA before surgery.