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The gravity gradient is the second derivative of gravity potential. A gravity gradiometer can measure the small change of gravity at two points, which contains more abundant navigation and positioning information than gravity. In order to solve the problem of passive autonomous, long-voyage, and high-precision navigation and positioning of submarines, an aided navigation method based on strapdown gravity gradiometer is proposed. The unscented Kalman filter framework is used to realize the fusion of inertial navigation and gravity gradient information. The performance of aided navigation is analyzed and evaluated from six aspects: long voyage, measurement update period, measurement noise, database noise, initial error, and inertial navigation system device level. When the parameters are set according to the benchmark parameters and after about 10 h of simulation, the results show that the attitude error, velocity error, and position error of the gravity gradiometer aided navigation system are less than 1 arcmin, 0.1 m/s, and 33 m, respectively.

This research reports a case of histological transformation from non-small cell lung cancer (NSCLC) to transformed small cell lung cancer (T-SCLC) in a patient undergoing EGFR-tyrosine kinase inhibitors (TKIs). The aggressive characteristics of the tumor diverged significantly from those commonly associated with lung adenocarcinomas, leading to further histological analysis. The subsequent histological examination confirmed the transformation to SCLC, consistent with established mechanisms of acquired resistance in NSCLC. Given the limited therapeutic options, the patient was administered a serplulimab-based immunochemotherapy regimen, achieving a progression-free survival (PFS) of 6 months post-transformation. The study underscores the potential of PD-1 inhibitors, particularly serplulimab, in the treatment landscape for T-SCLC and highlights the need for future comprehensive research.

Ni--TiN coating was prepared by laser cladding on the surface of 40Cr steel which is commonly used to make automotive piston pins. The effect of laser power on the surface morphology, phase composition, microhardness, shear strength, and wear resistance of Ni--TiN coating was studied using scanning electron microscope (SEM), X-ray diffractometer (XRD), microhardness tester, shear strength testing machine, and friction and wear testing machine. The results showed that the Ni--TiN coating cladded at a laser power of 1.5 kW had uniform and compact microstructure with the smallest particle size, and hence it had the highest microhardness (843.2 HV) and shear strength (802.8 MPa), as well as the lowest friction factor (0.44). [ABSTRACT FROM AUTHOR]

Since the first report regarding the successful fabrication of few‐layer transition metal carbides (known as MXenes) of 2011, their intrinsic properties, such as mechanical strength and electrical conductivity, are intensively studied. Though the hydrophilic nature of MXenes is widely reported and utilized to fabricate various functional materials, there is a lack of systematic study with respect to the science behind the wetting phenomena of MXene‐based materials. The goal of this manuscript is to provide some useful guidelines in the design of novel MXene‐based systems with desirable wetting properties by analyzing the current understanding of the wettability of MXenes. Specifically, after the introduction of the fundamental concepts in wetting theory, the wettability of pure MXene films is summarized based on the recently published results from both theoretical and experimental studies. Then, the determining factors in the wetting properties of MXenes associated with surface architectures and chemical compositions are clarified, which is followed by the effect of hybridization strategies discussed in detail. In the end, a summary of the abundant applications relying on the wetting properties of MXene‐based systems is presented along with the current challenges and the corresponding future research directions in this field. [ABSTRACT FROM AUTHOR]

Objective: To explore the effects of methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism on the adverse reactions of high-dose methotrexate (MTX) in pediatric patients with acute lymphoblastic leukemia (ALL)., Methods: A total of 69 children with ALL admitted to the department of Pediatrics of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from November 2018 to October 2020 were included in this study. The clinical data of the children were collected, leukocytes were isolated from their peripheral blood, and MTHFR genotyping was performed by digital fluorescence molecular hybridization techniques. The adverse reactions and plasma drug concentration of MTX were monitored during the chemotherapy. Moreover, the effect of MTHFR gene polymorphism on MTX adverse reactions and plasma drug concentration were analyzed., Results: Among the middle and high risk children, compared with the wildtype group (CC genotype), patients with MTHFR C677T mutations (CT+TT genotypes) had a higher risk of leukopenia ( OR =2.38), neutropenia ( OR =2.2), anemia ( OR =1.83) and hepatoxicity ( OR =1.98). However, no significant difference was found in the MTX plasma concentration between the MTHFR C677T mutantion group and the wildtype group at different timepoints (24 h, 48 h and 72 h). Multivariate analysis revealed that the plasma concentration of MTX (48 h), clinical risk level of ALL and MTHFR C677T gene polymorphism were independent factors for the adverse reactions of high-dose MTX., Conclusion: The MTHFR C677T mutations may be associated with myelosuppression and hepatotoxicity in children with ALL after high-dose MTX treatment.

Objective: To investigate the clinical characteristics and treatment of pneumocystis carinii pneumonia (PCP) in children with acute lymphoblastic leukemia (ALL), in order to improve the early diagnosis and effective treatment., Methods: Clinical data of five children with ALL developing PCP in the post-chemotherapy granulocyte deficiency phase were analyzed retrospectively. The clinical manifestations, laboratory tests, imaging findings, treatment methods and effect were summarized., Results: The male-to-female ratio of the five children was 1∶4, and the median age was 5.5 (2.9-8) years old. All patients developed PCP during granulocyte deficiency phase after induction remission chemotherapy. The clinical manifestations were generally non-specific, including high fever, tachypnea, dyspnea, non-severe cough, and rare rales in two lungs (wet rales in two patients). Laboratory tests showed elevated C-reactive protein (CRP), serum procalcitonin (PCT), (1,3)-β-D-glucan (BDG), lactate dehydrogenase (LDH) and inflammatory factors including IL-2R, IL-6 and IL-8. Chest CT showed diffuse bilateral infiltrates with patchy hyperdense shadows. Pneumocystis carinii(PC) was detected in bronchoalveolar lavage fluid (BALF) or induced sputum by high-throughput sequencing in all patients. When PCP was suspected, chemotherapy was discontinued immediately, treatment of trimethoprim-sulfame thoxazole (TMP-SMX) combined with caspofungin against PC was started, and adjunctive methylprednisolone was used. Meanwhile, granulocyte-stimulating factor and gammaglobulin were given as the supportive treatment. All patients were transferred to PICU receiving mechanical ventilation due to respiratory distress during treatment. Four children were cured and one died., Conclusion: PCP should be highly suspected in ALL children with high fever, dyspnea, increased LDH and BDG, and diffuse patchy hyperdense shadow or solid changes in lung CT. The pathogen detection of respiratory specimens should be improved as soon as possible. TMP/SMZ is the first-line drug against PCP, and the combination of Caspofungin and TMP/SMZ treatment for NH-PCP may have a better efficacy. Patients with moderate and severe NH-PCP may benefit from glucocorticoid.

β-thalassemia is a monogenetic inherited hemolytic anemia, which results in a series of pathophysiological changes due to partial or complete inhibition of the synthesis of β-globin chain. The curative therapy for this disease is to reconstitute hematopoiesis, and transplantation with genetically modified autologous hematopoietic stem cells can avoid the major difficulties of traditional allogeneic hematopoietic stem cell transplantation，such as HLA matching and immune rejection. β-thalassemia gene therapy strategies mainly include gene integration and genome editing. The former relies on the development of lentiviral vectors and adds a fully functional HBB gene to the chromosome; the latter rapidly develops with the research of specific nuclease which can repair the HBB gene in situ. In this review, the latest progress of the two strategies in gene therapy of β-thalassemia is summarized.

Objective: To investigate the values of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), red cell osmotic fragility test(ROFT) and hemoglobin A2(HbA 2 ) in screening of α-thalassemia in Guangdong area., Methods: A total of 285 peripheral blood samples in patients treated in our hospital from January 2017 to December 2017 were collected. The detection of thalassemia gene was used as the gold standard, while blood routine examination, hemoglobin electrophoresis, and red cell osmotic fragility test were simultaneously performed. The optimal cut-off values in MCV, MCH, ROFT and HbA 2 in α-thalassemia were determined by receiver operator characteristic curve (ROC curve)., Results: The most common types of α-thalassemia gene was --SEA/αα (54.59%). Compared with the control group, the differences in MCV, MCH, ROFT and HbA 2 showed statistically significantce between different types of α-thalassemia (P<0.05). The best cut-off values of MCV, MCH, ROFT, and HbA 2 in the diagnosis of α-thalassemia were 81.45 fl, 27.35 pg, 79.95%, and 2.55% respectively., Conclusion: For different laboratories, the cut-off values need to be established for screening α-thalassemia suitable in their own local region．The values of MCV, MCH, ROFT and HbA 2 shows higher accuracy and sensitivity in the diagnosis of α-thalassemia. It is recommended to use MCV<81.45fl, MCH<27.35 pg, ROFT<79.95% and HbA 2 <2.55% as the standards for screening α-thalassemia in Guangdong area.

AbstractObjective: To investigate the effect of ALAS2 downregulation on the expression of BNIP3L and erythroid differentiation in K562 cells., Methods: The expression of ALAS2 was down-regulated by transfection of lentivirus, then quantitative real-time PCR was performed to detect the transfection efficiency. Flow cytometry analysis was applied to evaluate apoptosis of cells, erythroid differentiation, mitochondrial membrane potential and reactive oxygen species (ROS) level. Western blot was used to detect the BNIP3L expression, Co-immunoprecipitation was performed to analyze the relationship between ALAS2 and BNIP3L., Results: Compared with sh-NC group, knockdown of ALAS2 induced downregulation of BNIP3L mRNA and protein expression(P<0.01) and erythroid related transcription factors GATA1, Nrf2 expression, as well as reduction of ROS level(P<0.05). Mitochondrial membrane potential of control (sh-NC) group was lower than that of shALAS2 group(P<0.05), but there was no significant change of cell apoptotic rate in two groups. CD71highCD235ahigh + CD71lowCD235ahigh cells of sh-NC and shALAS2 groups were 53.5%, 92.9% at 96 h after hemin induction, respectively. No direct action between ALAS2 and BNIP3L was observed., Conclusion: The intracellular heme level can affect the expression of BNIP3L which may be related with the regulation of ROS and transcription factors GATA1 and Nrf2. Higher BNIP3L facilitates cell differentiation but lower BNIP3L is favorable for cells survival.

Objective: To evaluate the thrombus length on CT perfusion imaging and to assess its predictive value for recanalization and clinical outcome after intravenous thrombolysis therapy (IVT)., Methods: Fifty-six consecutive acute ischemic stroke patients with proximal middle cerebral artery (M1 segment) occlusion underwent CT perfusion imaging examination before IVT between June 2009 and May 2015. The onset-to needle time was (214.3 ± 82.0) min, and the pretreatment NIHSS score of patients was 13 (IQR 8-17). The thrombus length was determined as the distance between the proximal and distal thrombus end delineated on dynamic angiography, which was reconstructed from CT perfusion source images. Recanalization was evaluated according to Arterial Occlusive Lesion (AOL) scale, and functional outcome was based on modified Rankin scale (mRS) 3 months after IVT. Logistic regression model was used to investigate the relationship between thrombus length and recanalization, and the optimal cut-off points were determined by receiver operating characteristic curve (ROC)., Results: Among 56 patients, 42 (75%) achieved recanalization 24 h after IVT with mean thrombus length of (9.0 ± 4.7) mm; and 14 (25%) patients remained occlusion with mean thrombus length of (10.0 ± 5.4) mm. Logistic regression analysis demonstrated that thrombus length was an independent predictor for both recanalization (OR=0.869; 95% CI:0.764-0.987; P=0.031) and unfavorable outcome (OR=1.180;95% CI:1.023-1.362; P=0.023). Thrombus length of 11.3 mm was identified as the optimal cut-off value for recanalization (AUC=0.697, sensitivity 71.4%, specificity 76.2%), while thrombus length of 9.9 mm was the optimal cut-off value for unfavorable functional outcome (AUC=0.689, sensitivity 64.7%, specificity 71.4%)., Conclusion: The thrombus length evaluated on CT perfusion imaging is an effective predictor for recanalization and unfavorable outcome after IVT in acute ischemic stroke patients with middle cerebral artery occlusion.

This research was aimed to explore the effects of blocking B7/CD28 and CD40/CD154 co-stimulatory signals on engraftment of hematopoietic stem cell in the sensitized recipient so as to provide the experimental evidence for the treatment of sensitized recipient's immune rejection after clinical allogeneic hematopoietic stem cell transplantation (HSCT). The BALB/c mice were divided into 4 groups: (1)mice sensitized on 7 day before transplant; (2)mice were sensitized on 7 day before transplant, and injected CTLA4Ig+anti-CD154 applied; (3)normal mice injected by corresponding isotype control IgG of CTLA4Ig and anti-CD154; (4)normal blank control mice. Each group had 15 mice. On day 0, mice of each group were irradiated lethally 8 Gy by linear accelerator, and the bone marrow cells of C57BL/6 labeled by fluorescence staining were injected via the tail vein. The fluorescent cell level in peripheral blood and organ tissue at different time points were detected by flow cytometry (FCM) for homing assessment. Survival rates and hematopoietic reconstitution were also monitored and recorded. The results showed that application of CTLA4Ig anti-CD154 could promote implantation of allogeneic HSC in sensitized recipients, induce the immune tolerance, prolong their survival time and accelerate the hematopoietic reconstitution within 28 days, compared with the sensitized group. It is concluded that applying CTLA4Ig and anti-CD154 can enhance the engraftment of HSCT and induce immune tolerance in the sensitized recipient after allogeneic HSCT and accelerate the hematopoietic reconstitution.