Although NPM1 mutations are frequently found in acute myeloid leukemia patients, therapeutic strategies are scarce and unsuitable for those who cannot tolerate intensive chemotherapy. Here we demonstrated that heliangin, a natural sesquiterpene lactone, exerts favorable therapeutic responses in NPM1 mutant acute myeloid leukemia cells, with no apparent toxicity to normal hematogenous cells, by inhibiting their proliferation, inducing apoptosis, causing cell cycle arrest, and promoting differentiation. In-depth studies on its mode of action using quantitative thiol reactivity platform screening and subsequent molecular biology validation showed that the ribosomal protein S2 (RPS2) is the main target of heliangin in treating NPM1 mutant AML. Upon covalent binding to the C222 site of RPS2, the electrophilic moieties of heliangin disrupt pre-rRNA metabolic processes, leading to nucleolar stress, which in turn regulates the ribosomal proteins-MDM2-p53 pathway and stabilizes p53. Clinical data shows that the pre-rRNA metabolic pathway is dysregulated in acute myeloid leukemia patients with the NPM1 mutation, leading to a poor prognosis. We found that RPS2 plays a critical role in regulating this pathway and may be a novel treatment target. Our findings suggest a novel treatment strategy and lead compound for acute myeloid leukemia patients, especially those with NPM1 mutations.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

Objective:To clarify the relationship between epidermal growth factor receptor (EGFR) mutations and the clinicopathologic features of primary lung adenocarcinomas in Xinjiang.Methods:The mutations of EGFR gene at exons 18 -21 in 59 cases (including 15 cases of Uighur and 44 cases of Han) of lung adenocarcinoma tissues,which were obtained from surgical resection,were detected by amplifica-tion refractory mutation system (ARMS)method.And the relationships among mutations,race and clini-copathologic features were analyzed.Results:The frequencies of EGFR mutations in lung adenocarcinoma were 20% for Uighur,which was lower than that in Han (54.5%),P <0.05.The deletion mutations at exon 19 were seen in 2 of 15 Uighur cases and 9 of 44 Han cases.EGFR mutations were present,inclu-ding exon 21 L858R in one Uighur case and 12 Han cases,exon 18 G719X in two of 44 cases of Han, exon 21 L861Q in one of them.On histological type,the frequencies of EGFR mutation in alveolar pre-dominant adenocarcinoma was 71% (22 /31),which was higher than both that in solid predominant and mucinous carcinoma (6.7%,20% respectively).According to statistic analysis,EGFR mutations were without correlation with the patient’s gender,age,location,gross type,smoking status and lymph node metastasis(P >0.05).EGFR mutation was more frequent in well-differentiated cancer,mainly in acinar carcinoma,while poorly differentiated adenocarcinoma and mucous adenocarcinoma were lower.Conclu-sion:There was a difference of EGFR mutation in primary lung adenocarcinoma between Uighur and Han in Xinjiang,perhaps reflecting ethnic genetic variation,which is worth further analyzing.EGFR mutation was commonly detected in well or middle differentiated adenocarcinoma,mainly in acinar carcinoma.

Objective To evaluate the effect of temporal resolution of breast dynamic contrast-enhancing (DCE)-MRI on pharmacokinetic parameters and diagnostic performance in benign and malignant breast lesions.Methods Retrospective review was performed on 26 benign and 29 malignant breast lesions which were proven pathologically by surgery or biopsy.Dynamic contrast enhanced breast MRI using a new volume-interpolated-breath-hold examination sequence combining parallel acquisition, Dixon fat separation and time-resolved imaging with interleaved stochastic trajectories (CDT-VIBE) was performed in all patients.The original time resolution of this sequence was 12 s and based on which, dynamic sequences with different temporal resolutions of 24 s, 36 s, 48 s and 60 s were simulated by a sample-removing method and were used for the calculation of pharmacokinetic parameters, including volume transfer constant (Ktrans), constant flux rate (Kep), volume of extravascular extracellular space (Ve) and area under the curve at initial 60 s (iAUC), to observe their changes with different temporal resolution.The repeated measurement of analysis of variance was used to explore significant changes in pharmacokinetics parameters with different temporal resolution.To evaluate the diagnostic efficiency of parameters with different temporal resolution, ROC analysis was performed in accordance with pathological findings.Results With decrease of temporal resolution from 12 to 60 s, there was a significant increase in Ktrans and Kep of benign lesions [Ktrans: (0.147±0.084)/min to (0.170 ± 0.085)/min, Kep: (0.321± 0.176)/min to (0.433± 0.175)/min] and steady decrease in Ktrans and Kep of malignant lesions [Ktrans: (0.373±0.210)/min to (0.259± 0.122)/min, Kep: (0.929 ±0.402)/min to (0.581 ± 0.143)/min];the changes of Ve were less significant and irregular;the values of iAUC decreased both in benign [(9.192± 4.660) to (7.388± 3.065)] and malignant [(20.221±9.876) to (12.850±5.194)] lesions.The changes in all parameters with different time resolution were statistically significant in benign and malignant lesions (all P＜0.05).By pair-wise comparison between different time resolution, the changes of K among 12 s, 24 s and 36 s (all P＜0.05), the changes of Kep between 12 s and others (all P＜0.01), the changes of Ve between 24 s and others (all P＜0.01), and the changes among all pairs of iAUC were significant (all P＜0.05) except for 12 s and 24 s (P=1.000).The best AUC value of Ktrans and Kep between benign and malignant lesions were achieved with 12 s dynamic sequences (0.887, 0.939), and the best AUC value of iAUC was with 24 s sequences (0.877).The AUC values of Ve were between 0.511 to 0.601, which was lower than that of other three parameters.Conclusion A 24 s or higher temporal resolution of DCE-MRI should be able to provide consistent differentiation of pharmacokinetic parameters in benign and malignant breast lesions.

Epstein-Barr Virus Infections ; virology ; Herpesvirus 4, Human ; Humans ; Lymphoma, Large B-Cell, Diffuse ; pathology ; virology

ObjectiveTo comprehend the similarities and differences of postoperative quality of life between mastectomie avec dissection axillaire and modified radical mastectomy among patients with breast cancer,and in order to supply references for establishing corresponding nursing measures. Methods160patients with early breast cancer were selected,40 patients accepted the mastectomie avec dissection axillaire (the conservative group)and 120 patients accepted modified radical mastectomy (the radical group).The quality of life of patients was surveyed with questionnaires. ResultsThe EORTC QLQ-C30 score of the conservative group was not significant than the radical group.The EORTC QLQ-BR 23 score showed that the conservative group had a better self-evaluation of their configuration. ConclusionsThe patients who accepted the mastectomie avec dissection axillaire will live a better life than those who accepted modified radical mastectomy.

Objective To investigate the expression of interleukin-17 (IL-17) and matrix metalloproteinase-9 (MMP-9) in non-small cell lung cancer (NSCLC) and their relationship with pTNM staging.Methods IL-17 and MMP-9 expressions in cancer and adjacent tissues were detected from 102 cases of NSCLC by immunohistochemistry.x2 test was used to compare the ratio of their relationship with the pTNM stage.Results IL-17,MMP-9 expression rates in NSCLC cancer were 73.53 ％ (75/102),60.78 ％ (62/102)respectively,IL-17,MMP-9 expressions in different TNM stages were statistically significant correlated (P ＜ 0.05) respectively.The expression of IL-17 and MMP-9 in NSCLC tumor tissue were related statistically (P ＜ 0.05),and adjacent tissues were not related (P ＞ 0.05).Conclusion IL-17,MMP-9 in NSCLC tissues were significant increased,both may be involved in invasion and metastasis of NSCLC,IL-17 and MMP-9 were correlated in NSCLC tumor tissue but not in adjacent tissues.

OBJECTIVETo explore the experimental basis of the "water metabolism theory" in traditional Chinese medicine by observing the changes of aquaporin-1 in the lung, spleen and kidney.

METHODSRat models of Kidney Yang Deficiency induced by gavage with 2% adenine suspension for 4 weeks were treated with cistanches decoction for 6 weeks. Urinary 17-hydroxy cortisol, urine creatinine, urine osmolality value content, and aquaporin-1 mRNA and protein expressions in the lung, spleen and kidney tissues were detected after the treatment.

RESULTSTreatment with adenine induced Kidney Yang Deficiency in rats by causing a reduction in urinary 17-hydroxy cortisol, urine creatinine and urine osmolality. Aquaporin-1 mRNA expression in the spleen and kidney were down-regulated after adenine treatment. Compared with the rat models, intervention with cistanche significantly increased aquaporin-1 mRNA expression in the lung and kidney tissues. Adenine resulted in increased aquaporin-1 protein expression in the lung, spleen and kidney of the rats, while cistanche intervention lowered its expression in lung and kidney tissues.

CONCLUSIONThe lung, spleen, kidneys are involved in water metabolism, and aquaporin-1 is one of its molecular basis. Cistanche can increase aquaporin-1 expressions, which is also regulated by other factors.

Adenine ; pharmacology ; Animals ; Aquaporin 1 ; metabolism ; Cistanche ; chemistry ; Kidney ; metabolism ; Lung ; metabolism ; Male ; Medicine, Chinese Traditional ; Rats ; Rats, Wistar ; Spleen ; metabolism ; Yang Deficiency ; metabolism

Objective To investigate subtype of HPV infection among women at age of 25 to 54 years in Beijing. Methods From Sept. 2006 to Dec. 2008, 5552 reproductive women at age of 25 to 54 years classified into each 5-year as group were screened. Each participant completed a questionnaire and a sample of exfoliated cervical cells for liquid-based cytology and HPV subtype gene testing was performed.Results The overall prevalence of HPV was 6.68% (371/5552). High-risk HPV and Low-risk HPV prevalence were 5.76% (320/5552) and 2.00% (111/5552), respectively. The most common HPV types were HPV16 (2.61%, 145/5552), HPV58 (0. 97%, 54/5552), HPV33 (0.85%, 47/5552), HPV43 (0.74% ,41/5552) and HPV56(0.70% ,39/5552). There were two peaks of HPV prevalence: groups of 30 -34 years and 40 -44 years. Conclusion The most common HPV subtypes in Beijing were HPV 16,58, 33 and 43 and HPV prevalence showed a bi-medal age-specific curve.

Purpose To study the clinicopathological features, immunophenotype and differential diagnosis of proximal epithelioid sarcoma (PES).Methods The clinical, radiological and pathological features were reviewed in 6 cases of PES.Results The patients consisted of five males and one female with ages ranging from 32 to 74 years (mean 56 years). Clinically, the tumor mass were progressively-growing solitary nodules with the fuctional disorder and pain. The sites of the tumor involvement were buttock (1 case), thigh (2 cases), iliac spine (1 case), lumbar spine (1 case) and anterior sacrum (1 case). Histologically, the tumors were mainly consisted of epithelioid cells with round or oval nuclei, prominent nucleoli and eosinophilic cytoplasm, some tumor cells appeared rhabdoid features. Immunohistochemically, the tumor cells were positive for vimentin (6/6), CK (5/6), EMA (6/6),β-catenin (6/6), CD99 (5/6), and CD34 (4/6), but negative for S-100 protein, HMB 45, CD 117 and CD 31.Conclusion PES is a distinctive moderate grade malignant tumor with prominent epithelioid and rhabdoid cells appearance.The differential diagnoses include the tumors that have similar cellular appearance with PES, and immunohistochemical staining is useful for diagnosis and differential diagnosis.