[Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study].

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.

[To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia].

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

A highly distorted ultraelastic chemically complex Elinvar alloy.

The development of high-performance ultraelastic metals with superb strength, a large elastic strain limit and temperature-insensitive elastic modulus (Elinvar effect) are important for various industrial applications, from actuators and medical devices to high-precision instruments1,2. The elastic strain limit of bulk crystalline metals is usually less than 1 per cent, owing to dislocation easy gliding. Shape memory alloys3-including gum metals4,5 and strain glass alloys6,7-may attain an elastic strain limit up to several per cent, although this is the result of pseudo-elasticity and is accompanied by large energy dissipation3. Recently, chemically complex alloys, such as 'high-entropy' alloys8, have attracted tremendous research interest owing to their promising properties9-15. In this work we report on a chemically complex alloy with a large atomic size misfit usually unaffordable in conventional alloys. The alloy exhibits a high elastic strain limit (approximately 2 per cent) and a very low internal friction (less than 2 × 10-4) at room temperature. More interestingly, this alloy exhibits an extraordinary Elinvar effect, maintaining near-constant elastic modulus between room temperature and 627 degrees Celsius (900 kelvin), which is, to our knowledge, unmatched by the existing alloys hitherto reported.

[Distribution of the anterior corneal astigmatism in over 140 000 patients with age-related cataract].

Objective: To analyze the distribution characteristics of the anterior corneal astigmatism in 140 000 cataract patients from 18 hospitals in China. Methods: Retrospective study. A total of 143 889 patients (143 889 right eyes) over the age of 40 years with age-related catarac were admitted to 18 Aier eye hospitals in China from July 2015 to October 2018. The average values of the three measurements of the magnitude of anterior corneal astigmatism, the meridian of corneal astigmatism, anterior chamber depth, corneal refractive power, and axial length measured by IOLMaster 500 were obtained. The data acquisition method of each sub-center was to collect and analyze the electronic case data in accordance with the inclusion and exclusion criteria, and to provide them for the sponsor Wuhan Aier Eye Hospital. Non-normal distribution data are presented as M (P25, P75). Mann-Whitney test, Kruskal-Wallis test, Chi-square test were used to analyze the distribution differences of the magnitude of corneal astigmatism and the meridian of corneal astigmatism in gender, age, anterior chamber depth, corneal refractive power and axial length. Results: Among the 143 889 patients, 84 319 were females and 59 570 were males, the median age was 72 (65, 78) years old, the median corneal astigmatism was 0.84 (0.51, 1.33) D; the corneal astigmatism was ≥0.75 D in 80 895 patients (56.22%) and was ≥1.00 D in 57 304 patients (39.83%). The median corneal astigmatism was 0.87 (0.53, 1.37) D in women and 0.82 (0.50, 1.29) D in men; with statistical difference (U=-14.891; P<0.05). The proportion of with-the-rule (WTR) astigmatism was 33.26% (28 046/84 319) for women and 34.26% (20 408/59 570) for men; The proportion of against-the-rule (ATR) astigmatism was 49.08% (41 385/84 319) for women and 46.91% (27 945/59 570) for men, with statistical difference (χ²=70.913; P<0.05). With the increase of age, the magnitude of corneal astigmatism first decreased from 0.94 (0.57, 1.48) D to 0.75 (0.46, 1.18) D, and then increased to 1.19 (0.74, 1.79) D, with statistical difference (H=1 263.438; P<0.05), and the change was at 61 to 70 years old. With the increase of age, the proportion of WTR astigmatism decreased from 77.50% (396/511) to 12.50% (3/24), the proportion of ATR astigmatism increased from 11.15% (57/511) to 79.07% (34/43), and the proportion of oblique astigmatism changed little from 17.02% (16/94) to 19.92% (245/1 230), the distribution difference was significant (χ²=10 174.496; P<0.05). As the anterior chamber became shallow, the magnitude of corneal astigmatism significantly increased from 0.82 (0.51, 1.31) D to 1.05 (0.61, 1.56) D, and the proportion of ATR astigmatism increased from 47.32% (60 207/127 227) to 51.69% (184/356) (H=409.961, χ²=120.995, both P<0.05). With the corneal refractive power rising, the magnitude of corneal astigmatism increased from 0.80 (0.49, 1.33) D to 0.95 (0.58, 1.53) D, the proportion of ATR astigmatism decreased from 52.84% (4 963/9 392) to 39.97% (9 023/22 577); the difference was significant (H=808.562, χ²=752.147, both P<0.05). When the axial length was>25.00 mm, the magnitude of corneal astigmatism was highest [1.04 (0.62, 1.65) D], and the proportion of ATR astigmatism was also highest [49.00% (10 964/22 376)]; the difference was significant (H=2 071.198, χ²=131.130, all P<0.05). Conclusions: The meridian of corneal astigmatism in middle-aged and elderly cataract patients is mainly ATR astigmatism. With the increasing of age, the magnitude of corneal astigmatism decreases first and then increases. The turning point from the proportion of WTR astigmatism to the proportion of ATR astigmatism is 65 years old. The shallower the anterior chamber is, the more the magnitude of corneal astigmatism and the proportion of ATR astigmatism increase. When the axial length is>25.00 mm, both the magnitude of corneal astigmatism and the proportion of ATR astigmatism reach the peak. (Chin J Ophthalmol, 2021, 57: 56-62).

LncRNA UCA1 regulates proliferation, migration and invasion of cervical cancer cells by targeting miR-145.

OBJECTIVE: Finding a key target for the development of cervical cancer is conducive to the treatment of cervical cancer. LncRNA UCA1 plays a role in multiple tumors, such as the digestive tract and bladder. However, whether LncRNA UCA1 plays a role in cervical cancer is unclear. PATIENTS AND METHODS: The tumor tissues (tumor group) and adjacent tissues (normal group) of cervical cancer patients were collected for analysis of expression of LncRNA UCA1 and miR-145 by Real Time-Polymerase Chain Reaction (RT-PCR). Cervical cancer HeLa cell line was cultured and divided into NC group, si-UCA1 group, and si-UCA1+ miR-145 inhibitor group. It was followed by the analysis of LucRNA UCA1 expression by Real Time-PCR, cell proliferation by MTT assay, cell migration and invasion by respective cell scratch, transwell chamber assay, and targeted relationship between UCA1 and miR-145 by Dual-Luciferase activity. RESULTS: LncRNA UCA1 expression was significantly increased in cervical cancer and miR-145 expression was decreased compared with the normal group (p<0.05). There was a negative correlation between them (p<0.05). The downregulation of UCA1 significantly inhibited tumor cell proliferation, migration, and invasion compared with NC group (p<0.05). MiR-145 is the target miRNA of UCA1. The addition of miR-145 inhibitor reversed the effect of UCA1 siRNA on downregulating UCA1 expression, and the difference was statistically significant compared with the si-UCA1 group (p<0.05). CONCLUSIONS: LncRNA UCA1 expression is significantly increased in cervical cancer and miR-145 expression is decreased with a negative correlation between them. Lnc-RNA UCA1 regulates cervical cancer cell proliferation, migration, and invasion by targeting miR-145.

Structural responses of metallic glasses under neutron irradiation.

Seeking nuclear materials that possess a high resistance to particle irradiation damage is a long-standing issue. Permanent defects, induced by irradiation, are primary structural changes, the accumulation of which will lead to structural damage and performance degradation in crystalline materials served in nuclear plants. In this work, structural responses of neutron irradiation in metallic glasses (MGs) have been investigated by making a series of experimental measurements, coupled with simulations in ZrCu amorphous alloys. It is found that, compared with crystalline alloys, MGs have some specific structural responses to neutron irradiation. Although neutron irradiation can induce transient vacancy-like defects in MGs, they are fully annihilated after structural relaxation by rearrangement of free volumes. In addition, the rearrangement of free volumes depends strongly on constituent elements. In particular, the change in free volumes occurs around the Zr atoms, rather than the Cu centers. This implies that there is a feasible strategy for identifying glassy materials with high structural stability against neutron irradiation by tailoring the microstructures, the systems, or the compositions in alloys. This work will shed light on the development of materials with high irradiation resistance.

[Measurement and analysis of tracheal inner diameter in Chinese adults using multi-slice spiral CT, multi-planar reconstruction and special window technique].

Objective: To measure the inner diameter of tracheal(TD) in Chinese adults by multi-slice spiral CT(MSCT), multi-planar reconstruction(MPR) with special window technique and analyze its influencing factors. Methods: A total of 824 normal adults(male 435, female 389) and 16 patients with small peripheral pulmonary nodules(SPN) receiving chest multi-slice spiral CT (MSCT) in the physical examination at the First Affiliated Hospital of Guangzhou Medical University between January, 2014 and December, 2015 were included and their records were retrospectively analyzed. The 16 patients with SPN received bronchoscopy and the images were recorded followed by measurement of tracheal diameter using software. MSCT and MPR images were obtained by the 3Dview software, and the inner diameter of the trachea at 4 horizontal positions were measured by special window technique (window width 500 Hu, window level 100 Hu): thoracic entrance (TD(1)), aortic arch (TD(2)), 2 cm higher than the carina of trachea (TD(3)) and the narrowest trachea (TD(4)). Results: The results of bronchoscopy and software measurement in 16 patients were consistent with those of MSCT and MPR combined with special window technique (P>0.05). The TD at 4 positions in adult males were larger than those of adult females (P<0.01). The TD values at each position for males and females were as follows: (18.9±1.7) and (15.6±1.3) mm (t=30.9, P<0.01) for TD(1), (18.8±1.6) and (16.1±1.2) mm (t=28.0, P<0.01) for TD(2), (19.0±1.6) and (16.3±1.3) mm (t=26.5, P<0.01) for TD(3), (18.4±1.5) and (15.5±1.1) mm (t=31.3, P<0.01) for TD(4), respectively. The age, weight and BMI were not significantly correlated with the tracheal diameter (P>0.05). The height was linearly correlated with the tracheal diameter: for males, TD(1)=0.071× height (cm) + 6.964 (r=0.249, P<0.05), TD(2)=0.064 × height (cm) + 7.898 (r=0.246, P<0.05), TD(3)=0.074 × height (cm) + 6.533 (r=0.279, P<0.05), TD(4)=0.056 × height(cm) + 8.811(r=0.226, P<0.05); while for females, TD(1)= 0.046× height (cm) + 8.331 (r=0.183, P<0.05), TD(2) = 0.058 × height (cm)+ 6.950(r=0.248, P<0.05), TD(3)=0.059 × height (cm)+ 7.052 (r=0.235, P<0.05), TD(4) =0.044× height (cm) + 8.520 (r=0.208, P<0.05). Conclusion: MSCT and MPR combined with special window technique are accurate and feasible for the measurement of adult tracheal diameter. The diameter of the trachea in males is larger than that in females, and it is positively correlated with height, but not with age, body weight and BMI. The tracheal diameter can be evaluated by linear regression equation.

[Efficacy and safety of IA regimen containing different doses of idarubicin in de-novo acute myeloid leukemia for adult patients].

Objective: To investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m(2), 10 mg/m(2) or 12 mg/m(2) as induction chemotherapy for adult patients with de-novo acute myeloid leukemia (AML) . Methods: A total of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multicenter, single-blind, non-randomized, clinical controlled study. To compare the response rate of complete remission (CR) , adverse events between different dose idarubicin combined with cytarabine (100 mg/m(2)) as induction chemotherapy in newly diagnosed patients of adult AML. Results: Of 1 207 evaluable AML patients were assigned to this analysis of CR rate. The CR rates of IDA 8 mg/m(2) group, IDA 10 mg/m(2) group and IDA 12 mg/m(2) group were 73.6% (215/292) , 84.1% (662/787) and 86.7% (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone marrow, FAB classification and risk stratification, the odds ratios (95% CI) of IDA 10 mg/m(2) group and IDA 12 mg/m(2) group were 0.49 (0.34-0.70) and 0.36 (0.18-0.71) , as compared with the IDA 8 mg/m(2) group (P<0.001, P=0.003) . In the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9% (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly, IA regimen with IDA 10 mg/m(2) was the only beneficial factor affecting CR in this group after adjusted for age, blast ratio of bone marrow and FAB classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) . However, the odds ratios (95% CI) of IDA 12 mg/m(2) when compared with the IDA 8 mg/m(2) was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow and FAB classification. The median time (days) of neutrophil count less than 0.5×10(9)/L in IDA 8 mg/m(2) group, IDA 10 mg/m(2) group and IDA 12 mg/m(2) group were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of platelet count lower than 20×10(9)/L were 14 (7-17) , 15 (11-20) and 17 (15-21) , respectively (P=0.001) . The incidences of lung infection in the three groups were 9.8%, 13.5% and 25.2%, respectively (P<0.001) . Conclusions: For young adult patients (aged 18-60 years) with AML in China, intensifying induction therapy with idarubicin 10 mg/m(2) is clinically superior to IDA 8 mg/m(2) and IDA 12 mg/m(2) in favorable intermediate AML subgroup. However, idarubicin 12 mg/m(2) is more suitable to adverse AML subgroup.

[Pulmonary surfactant protein adenosine triphosphate-binding-cassette-A3 gene composite mutations in infant congenital interstitial lung disease: report of a case and review of literature].

Objective: To report a case of the pulmonary surfactant protein(SP) adenosine triphosphate-binding-cassette-A3 (ABCA3) gene mutations in infant congenital interstitial lung disease(ILD), and review the related literature, to investigate the relationships of ABCA3 gene mutation associated with ILD in infants. Method: A 6-months-old boy was hospitalized in the department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University. The clinical, radiological, histological information from transbronchial lung biopsy (TBLB) and genetic testing in this case was analyzed; 12 reports retrieved on literature search at Pubmed, OVID databases from 2004 to 2015 by using the ABCA3 as keyword were reviewed and analyzed. Result: (1)The patient, a 6-months-old boy, had progressive tachypnea and dyspnea since 4 months old. Physical examination on admission revealed respiratory rate of 78 times/min , heart rate of 187 times/min, SpO2 0.93(mask oxygen-inspiration with 6 L/min), scattered fine moist crackles could be heard over the both lungs, clubbing fingers were found. High-resolution computed tomography(HRCT) revealed diffuse ground-glass opacity, interlobular and intralobular septal thickening. Lung biopsies showed evidences of the alveolar cavity atelectatic changes and interstitial fibrosis. SP-A and SP-B were negative in immunohistochemical stainting. SP-related gene sequence analysis found that there was compound heterozygous missense mutation of ABCA3 gene in c. 1942A>G, c.2701-33G>C and c. 991-105C>A. (2)The review of related literature found that totally 12 cases were reported. The main manifestations were progressive tachypnea and dyspnea, age of onset was between birth and 4 years of age. The imaging characteristics of chest HRCT revealed diffuse infiltration or diffuse ground-glass pattern in the lung. PROGNOSIS: 6 cases died, and 6 cases survived, including 4 cases with pulmonary function disturbance to different degrees; 12 cases had ABCA3 gene mutations, 9 cases had composite ABCA3 gene mutations, in 11 cases the mutation occured in the exon of coding region, in 1 case in the intron, 9 cases had heterozygous mutations, 3 cases had homozygous mutations. Conclusion: The main phenotypes of ABCA3 mutation associated with ILD were full term neonatal respiratory distress syndrome or progressive tachypnea or dyspnea unexplained in infants. The chest HRCT showed two diffuse pulmonary interstitial changes. ABCA3 mutation mainly was multi-site composite mutations and heterozygous mutations in the exon of coding region.

Atomic-scale mechanisms of the glass-forming ability in metallic glasses.

The issue, composition dependence of glass-forming ability (GFA) in metallic glasses (MG), has been investigated by systematic experimental measurements coupled with theoretical calculations in Cu-Zr and Ni-Nb alloy systems. It is found that the atomic-level packing efficiency strongly relates to their GFA. The best GFA is located at the largest difference in the packing efficiency of the solute-centered clusters between the glassy and crystal alloys in both MG systems. This work provides an understanding of GFA from atomic level and will shed light on the development of new MGs with larger critical sizes.

CT and MRI findings of thoracic ganglioneuroma.

OBJECTIVE: Thoracic ganglioneuroma is sporadic and rarely reported. Pre-operative misdiagnosis often occurs in clinical practice. To improve diagnostic accuracy and facilitate differential diagnosis, we summarised the CT and MRI findings of thoracic ganglioneuroma. METHODS: 22 cases of thoracic ganglioneuroma confirmed by surgery and pathology were retrospectively analysed in terms of CT (16 cases) and MRI data (6 cases). RESULTS: Of 22 lesions, 19 occurred in the posterior mediastinum, 2 in the lateral pleura and 1 in the right chest. The CT value of the plain scans ranged from 20 to 40 HU (mean 29.1 HU) in 16 cases. Punctate calcification was noted in four cases. Patchy fat density shadow was found in one case. Arterial-phase CT found nearly no enhancement (6 cases) or slight enhancement (10 cases) with a CT value of 0-12 HU (mean 5.8 HU). In the delayed phase, enhancement was strengthened progressively, and CT value of 10-20 HU (mean 13.6 HU) was achieved after 120 s. T(1) weighted images showed homogeneous hypointense signals in five cases and hypointense signals mixed with patchy hyperintense signal shadow in one case. T(2) weighted images demonstrated heterogeneous hyperintense signals in all six cases, of which the whorled appearance was noted in one case. Gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA)-enhanced MRI found mildly heterogeneous enhancement in the arterial phase, and progressive mild enhancement in the delayed phase. CONCLUSION: Thoracic ganglioneuroma shows hypodensity in plain CT. On CT and MRI, non-enhancement or slight enhancement in artery phase and progressive mild enhancement in delay phase are characteristic manifestations of ganglioneuroma in the thorax.

Pressure-induced amorphous-to-amorphous configuration change in Ca-Al metallic glasses.

Pressure-induced amorphous-to-amorphous configuration changes in Ca-Al metallic glasses (MGs) were studied by performing in-situ room-temperature high-pressure x-ray diffraction up to about 40 GPa. Changes in compressibility at about 18 GPa, 15.5 GPa and 7.5 GPa during compression are detected in Ca(80)Al(20), Ca(72.7)Al(27.3), and Ca(66.4)Al(33.6) MGs, respectively, whereas no clear change has been detected in the Ca(50)Al(50) MG. The transfer of s electrons into d orbitals under pressure, reported for the pressure-induced phase transformations in pure polycrystalline Ca, is suggested to explain the observation of an amorphous-to-amorphous configuration change in this Ca-Al MG system. Results presented here show that the pressure induced amorphous-to-amorphous configuration is not limited to f electron-containing MGs.