Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective To analyze the stress distributions of two root canal preparation shapes of oval root canals with micro-crack.Methods Twenty single-canal mandibular premolars with oval canals were expanded to create micro-cracks.Roots were sectioned after staining.The generation and distribution of dentin micro-cracks were observed under microscope.Then a finite element(FE)model of sectioned enlarged oval canal roots with micro-cracks was established.The stress distribution of micro-crack and root were analyzed under lateral loading.Results Cracks always appeared in the buccolingual sides of oval canal roots and extended from the intracanal wall to the root surface.This was consistent with the stress concentration on the buccolingual side of the root canal wall shown by FE analysis.When micro-cracks occurred,stresses were transferred to the crack tip and the peak values increased sharply nearly 5 times.This made the cracks propagate easily along this direction,especially in the long axis direction of the tooth.Conclusions The presence of micro-cracks does not change the general stress concentration on root with two preparation morphologies of oval canals.However,the micro-crack causes an extreme stress concentration in the crack tip.This may be the mechanism of rapid propagation of microcracks into vertical root fracture,and dentists need to pay high attention.

Objective:To understand the current situation of care needs for disabled elderly people, analyze the impact of the family environment and community services on the care needs and care pathways of older people with disabilities and to formulate effective interventions.Methods:A cross-sectional survey was conducted from August 2022 to March 2023 in five tertiary-level hospitals in Tangshan city. The survey included 332 elderly people who were disabled before hospitalization and their primary caregivers, who were selected using a convenience sampling method. The survey investigated their general information, degree of disability, family members′ support, children′s filial piety and old age ethical level, family relationships, and the care needs of the elderly people who were disabled. SPSS 22.0 was used for one-way and correlation analyses as well as multiple linear regression analyses, and AMOS 22.0 was used for the development of structural equations for path analysis.Results:Among 332 disabled elderly individuals, there were 166 males and 166 females each. The care needs score for elderly people with disabilities was 101.54 ± 16.38. The care needs of this population can be influenced by several factors, including the level of disability, number of chronic conditions, presence of chronic pain, filial piety and old age ethical level of caregivers, family relationships, and the availability of care services in the community or village. These factors had direct effects of 0.468, 0.155, -0.083, -0.350, -0.094, and 0.104, respectively.Chronic diseases and chronic pain indirectly affected the demand for care through the degree of incapacity (with respective indirect effect values of 0.065 and 0.049). Additionally, the demand for care was indirectly influenced by the level of filial piety and ethics of the caregiver through the degree of incapacity and the family relationships (an indirect effect value of -0.162).Conclusions:The care needs of the disabled elderly are high, and the personal physiology, family environment and community support of the disabled elderly will directly or indirectly affect their care needs. Therefore, many factors should be considered comprehensively considered to improve the quality of care of the disabled elderly.

Objective To observe the correlations of pontine biological indicators on fetal brain median sagittal MRI with gestational week.Methods Data of head MRI of 226 normal fetuses without obvious abnormalities of central nervous system(normal group)and 17 fetuses with abnormalities(abnormal group)at gestational age of 23 to 38 weeks were retrospectively analyzed.Pontine biological indicators based on median sagittal MRI were obtained,including pons anteroposterior diameter(PAD),total pons area(TPA),pontine basal anteroposterior length(AP),pontine basal cranio-caudal length(CC),basis pontis area(BPA)and pontine angle of midbrain(MAP).According to the gestational week,the fetuses of normal group were divided into 8 subgroups.The distributing ranges of pontine biological indicators at different gestational weeks were analyzed,and the correlations of pontine biological indicators with gestational week in normal group were explored,and the developmental status of fetal pons in abnormal group were assessed.Results In normal group,PAD,TPA,AP,CC and BPA all showed linear positive correlation(r=0.887,0.914,0.787,0.866,0.865,all P＜0.001),while MAP was not significantly correlated with gestational week(P＞0.05).Among 17 fetuses in abnormal group,abnormal PAD or TPA was found each in 8 fetuses,abnormal AP was observed in 14,abnormal CC was noticed in 3 and abnormal BPA was found in 11 fetuses.Conclusion Fetal pontine biological indicators such as PAD,TPA,AP,CC and BPA on median sagittal MRI were positively correlated with gestational week,hence being able to be used for evaluating fetal pontine development.

Objective To explore whether 5/6 nephrectomy can establish a rat model of chronic renal failure-in-duced sarcopenia.Methods The rats were randomly divided into control group,sham operation group and 5/6 ne-phrectomy model group.Chronic renal failure and sarcopenia were further verified.Results Compared with the sham group:① In the model group,the qualitative analysis of urinary protein,serum creatinine,blood urea nitrogen and serum uric acid levels were increased(P＜0.05);② In the model group,the degree of renal fibrosis and the rate of apoptosis were high(P＜0.05);③ In the model group,the muscle strength and function declined(P＜0.05);④ In the model group,the degree of muscle fibrosis was obvious(P＜0.05).Conclusion Through the 5/6 nephrectomy method,an animal model of chronic renal failure-induced sarcopenia can be established,which provides an experimental basis for further prevention and treatment of this disease.

The 2021 edition of the international World Allergy Organization (WAO)/European Academy of Allergy and Clinical Immunology (EAACI) guideline for the management of hereditary angioedema (HAE) is mainly based on high-quality randomized controlled trials. It provides clinical classification for HAE and offers graded recommendations for on-demand therapy, short-term prophylactic therapy, and long-term prophylactic therapy. Additionally, it provides management strategies for people with different HAE types. This article focused on the interpretation of short-term, long-term prophylactic therapy and on-demand therapy for HAE, supplemented with the latest clinical evidence, aiming to provide references for the long-term management of HAE.

The 2021 edition of the international World Allergy Organization (WAO)/European Academy of Allergy and Clinical Immunology (EAACI) guideline for the management of hereditary angioedema (HAE) is mainly based on high-quality randomized controlled trials. It provides clinical classification for HAE and offers graded recommendations for on-demand therapy, short-term prophylactic therapy, and long-term prophylactic therapy. Additionally, it provides management strategies for people with different HAE types. This article focused on the interpretation of short-term, long-term prophylactic therapy and on-demand therapy for HAE, supplemented with the latest clinical evidence, aiming to provide references for the long-term management of HAE.

WUSCHEL-related homebox (WOX) gene family is a type of plant specific transcription factor, and belongs to the homeobox (HB) transcription factor superfamily. WOX genes play an important role in plant development, such as stem cell regulation and reproductive progress, and have been identified in many plant species. However, the information of mungbean VrWOX genes is limited. In this study, we identified 42 VrWOX genes in mungbean genome using Arabidopsis AtWOX genes as BLAST queries. VrWOX genes are unevenly distributed on 11 mungbean chromosomes, and chromosome 7 contains the most VrWOX genes. VrWOX genes are classified into three subgroups, the ancient group, the intermediate group and the modern/WUSCHEL group, which contains 19, 12 and 11 VrWOX members, respectively. Intraspecific synteny analysis revealed 12 VrWOX duplicated gene pairs in mungbean. Mungbean and Arabidopsis thaliana have 15 orthologous genes, and mungbean and Phaseolus vulgaris have 22 orthologous genes, respectively. The gene structure and conserved motif are different among VrWOX genes, indicating their functional diversity. The promoter regions of VrWOX genes contain different number and type of cis-acting elements, and VrWOX genes show distinct expression levels in eight mungbean tissues. Our study investigated the bioinformation and expression profiles of VrWOX genes, and provided essential information for further functional characterization of VrWOX genes.
Vigna/genetics* ; Fabaceae/genetics* ; Transcription Factors/genetics* ; Plants

FRMD6, a member of the 4.1 ezrin-radixin-moesin domain-containing protein family, has been reported to inhibit tumor progression in multiple cancers. Here, we demonstrate the involvement of FRMD6 in lung cancer progression. We find that FRMD6 is overexpressed in lung cancer tissues relative to in normal lung tissues. In addition, the enhanced expression of FRMD6 is associated with poor outcomes in patients with lung squamous cell carcinoma (n = 75, P = 0.0054) and lung adenocarcinoma (n = 94, P = 0.0330). Cell migration and proliferation in vitro and tumor formation in vivo are promoted by FRMD6 but are suppressed by the depletion of FRMD6. Mechanistically, FRMD6 interacts and colocalizes with mTOR and S6K, which are the key molecules of the mTOR signaling pathway. FRMD6 markedly enhances the interaction between mTOR and S6K, subsequently increasing the levels of endogenous pS6K and downstream pS6 in lung cancer cells. Furthermore, knocking out FRMD6 inhibits the activation of the mTOR signaling pathway in Frmd6^-/- gene KO MEFs and mice. Altogether, our results show that FRMD6 contributes to lung cancer progression by activating the mTOR signaling pathway.

The chemical complexity of traditional Chinese medicines (TCMs) makes the active and functional annotation of natural compounds challenging. Herein, we developed the TCMs-Compounds Functional Annotation platform (TCMs-CFA) for large-scale predicting active compounds with potential mechanisms from TCM complex system, without isolating and activity testing every single compound one by one. The platform was established based on the integration of TCMs knowledge base, chemome profiling, and high-content imaging. It mainly included: (1) selection of herbal drugs of target based on TCMs knowledge base; (2) chemome profiling of TCMs extract library by LC‒MS; (3) cytological profiling of TCMs extract library by high-content cell-based imaging; (4) active compounds discovery by combining each mass signal and multi-parametric cell phenotypes; (5) construction of functional annotation map for predicting the potential mechanisms of lead compounds. In this stud TCMs with myocardial protection were applied as a case study, and validated for the feasibility and utility of the platform. Seven frequently used herbal drugs (Ginseng, etc.) were screened from 100,000 TCMs formulas for myocardial protection and subsequently prepared as a library of 700 extracts. By using TCMs-CFA platform, 81 lead compounds, including 10 novel bioactive ones, were quickly identified by correlating 8089 mass signals with 170,100 cytological parameters from an extract library. The TCMs-CFA platform described a new evidence-led tool for the rapid discovery process by data mining strategies, which is valuable for novel lead compounds from TCMs. All computations are done through Python and are publicly available on GitHub.