Refractory or relapsed B lymphoblastic leukemia (B-ALL) patients have a dismal outcome with current therapy. We treated 42 primary refractory/hematological relapsed (R/R) and 9 refractory minimal ...residual disease by flow cytometry (FCM-MRD
) B-ALL patients with optimized second generation CD19-directed CAR-T cells. The CAR-T-cell infusion dosages were initially ranged from 0.05 to 14 × 10
/kg and were eventually settled at 1 × 10
/kg for the most recent 20 cases. 36/40 (90%) evaluated R/R patients achieved complete remission (CR) or CR with incomplete count recovery (CRi), and 9/9 (100%) FCM-MRD
patients achieved MRD
. All of the most recent 20 patients achieved CR/CRi. Most cases only experienced mild to moderate CRS. 8/51 cases had seizures that were relieved by early intervention. Twenty three of twenty seven CR/CRi patients bridged to allogeneic hematopoietic stem cell transplantation (allo-HCT) remained in MRD
with a median follow-up time of 206 (45-427) days, whereas 9 of 18 CR/CRi patients without allo-HCT relapsed. Our results indicate that a low CAR-T-cell dosage of 1 × 10
/kg, is effective and safe for treating refractory or relapsed B-ALL, and subsequent allo-HCT could further reduce the relapse rate.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Monodispersed CoFe
2
O
4
nanoparticles were synthesized by the thermal decomposition of Co and Fe acetylacetonate in octadecene, which contained oleic acid (OA) and oleylamine (OLA). The ...hydrophobicity of the CoFe
2
O
4
nanoparticles was alleviated such that they were water dispersible by encapsulating them with poly(maleic anhydride-
alt
-1-octadecene) (PMAO). The heating ability of these magnetic fluids was assessed by calorimetry measurement of specific absorption rate under an alternating magnetic field of 300 Oe within the frequency interval of 290-450 kHz. The highest value of the specific absorption rate was 297.4 W g
−1
for a sample concentration of 1 mg mL
−1
under an applied field of 300 Oe and frequency of 450 kHz. Linear response theory was used to explain the results. The high specific absorption rate of the nanofluid based on PMAO-encapsulated CoFe
2
O
4
@OA/OLA showed that it may meet the requirements for practical applications in tumor-targeted hyperthermia treatment.
In vitro
cytotoxicity analysis was also performed on Sarcoma 180 cancer cells, and the results showed that these nanoparticles were nontoxic to cells.
OA and OLA coated CoFe
2
O
4
nanoparticles encapsulated with PMAO through hydrophobic interactions were developed for hyperthermia applications.
Objective
To examine the associations between personality traits and suicidal ideation (SI) and attempt (SA) in mood disorder patients and community controls.
Method
We recruited 365 bipolar, 296 ...major depressive disorder patients, and 315 community controls to assess their lifetime suicidality. Participants filled out self‐reported personality questionnaires to collect data of personality traits, including novelty seeking (NS), harm avoidance (HA), extraversion (E), and neuroticism (N). We used logistic regression models adjusted for diagnoses to analyze combinational effects of personality traits on the risk of suicide. Additionally, radar charts display personality profiles for suicidal behaviours by groups.
Results
All personality traits were associated with the risk of suicidality with various effect size, except for E that showed protective effect. High N or HA had prominent and independent risk effects on SI and SA. Combinations of high N and low E, or high HA and NS were the risk personality profiles for suicidality. Higher N scores further distinguished SA from SI in mood disorder patients.
Conclusion
Introvert personality traits showed independent risk effects on suicidality regardless of diagnosis status. Among high‐risk individuals with suicidal thoughts, higher neuroticism tendency is further associated with increased risk of suicide attempt.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Objective To evaluate the interaction of articular cartilage (AC) and subchondral bone (SB) through analysis of osteoarthritis (OA)-related genes of site-matched tissue. Design We developed a ...novel method for isolating site-matched overlying AC and underlying SB from three and four regions of interest respectively from the human knee tibial plateau ( n = 50). For each site, the severity of cartilage changes of OA were assessed histologically, and the severity of bone abnormalities were assessed by microcomputed tomography. An RNA isolation procedure was optimized that yielded high quality RNA from site-matched AC and SB tibial regions. Quantitative polymerase chain reaction (Q-PCR) analysis was performed to evaluate gene expression of 61 OA-associated genes for correlation with cartilage integrity and bone structure parameters. Results A total of 27 (44%) genes were coordinately up- or down-regulated in both tissues. The expression levels of 19 genes were statistically significantly correlated with the severity of AC degeneration and changes of SB structure; these included: ADAMTS1 , ASPN , BMP6 , BMPER , CCL2 , CCL8 , COL5A1 , COL6A3 , COL7A1 , COL16A1 , FRZB , GDF10 , MMP3 , OGN , OMD , POSTN , PTGES , TNFSF11 and WNT1. Conclusions These results provide a strategy for identifying targets whose modification may have the potential to ameliorate pathological alterations and progression of disease in both AC and SB simultaneously. In addition, this is the first study, to our knowledge, to overcome the major difficulties related to isolation of high quality RNA from site-matched joint tissues. We expect this method to facilitate advances in our understanding of the coordinated molecular responses of the whole joint organ.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Chronic inflammation plays an important role in cancer development and progression. Cyclooxygenases-2 (COX-2) is a key enzyme in generating prostaglandins causing inflammation, is often found to be ...overexpressed in prostate cancer (PCa) and is correlated with PCa cell invasion and metastasis. We aim to investigate the molecular mechanism of how COX-2 promotes PCa cell invasion and metastasis and to evaluate the effect of COX-2 inhibitors in a selected model of PCa progression. Our results showed that the expression of COX-2 and Interleukin 1β (IL-1β) was upregulated in highly invasive PCa cells and was correlated with the activated levels of membrane-anchored serine protease matriptase. The expression levels of COX-2 were increased and were correlated with matriptase levels in PCa specimens. Moreover, results showed that COX-2 overexpression or a COX-2 product Prostaglandin E
(PGE
) caused an increase in matriptase activation and PCa cell invasion, whereas COX-2 silencing antagonized matriptase activation and cell invasion. In addition, the inhibition of COX-2-mediated matriptase activation by Celebrex and sulindac sulfide suppressed the androgen-independent and COX2-overexpressing PCa PC-3 cell invasion, tumor growth and lung metastasis in an orthotopic xenograft model. Our results indicate that COX-2/matriptase signaling contributes to the invasion, tumor growth and metastasis of COX-2-overexpressing and androgen-independent PCa cells.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objectives
The impact of electrolyte imbalance on clinical outcomes after acute ischemic stroke (AIS) is still not understood. We investigated the association between hypochloremia and hyponatremia ...upon hospital admission and in‐hospital mortality in AIS patients.
Materials and methods
A total of 3314 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included in this study. Hypochloremia was defined as having a serum chloride concentration <98 mmol/L and hyponatremia as having a serum sodium concentration <135 mmol/L. The Cox proportional hazard model was used to examine the effect of hypochloremia and hyponatremia on all‐cause in‐hospital mortality in AIS patients.
Results
During hospitalization, 118 patients (3.6%) died from all causes. Multivariable model adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, serum sodium, and other potential covariates showed that hypochloremia was associated with a 2.43‐fold increase in the risk of in‐hospital mortality (hazard ratio HR 2.43; 95% confidence interval CI, 1.41‐4.19; P=.001). However, no significant association between hyponatremia (P=.905) and in‐hospital mortality was observed. Moreover, the multivariable analysis found that serum chloride (HR=0.92, 95% CI 0.88‐0.98; P=.004) but not serum sodium (P=.102) was significantly associated with in‐hospital mortality.
Conclusions
Hypochloremia at admission was independently associated with in‐hospital mortality in AIS patients.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The occurrence of the β (bcc) to αm (hcp) massive transformation in Ti–6Al–4V (wt.%) during additive manufacturing (AM) by selective electron beam melting (SEBM) has been identified. A variety of ...patch-shaped massive grains including both grain boundary (GB)-crossing and non-GB-crossing instances were characterised and their formation temperature and growth rate were estimated. In contrast to conventional Ti–6Al–4V, the massive grains in SEBM-fabricated Ti–6Al–4V consist of ultrafine lamellar α and β phases (100 nm wide β strips) due to in-situ decomposition of the massive grains during AM. The resulting ultrafine α-β lamellae obey the typical Burgers orientation relationship established for the lamellar α-β structure in conventional Ti–6Al–4V. These findings show that the β (bcc) to αm (hcp) massive transformation significantly contributes to development of the Ti–6Al–4V microstructure during AM by SEBM, providing an alternative microstructural design strategy for AM of Ti–6Al–4V and other titanium alloys.
(a) EBSD colour inverse pole figure (IPF) showing both non-GB-crossing (i.e.③) and GB-crossing (i.e. ④ and ⑤) massive phase grains. (b) Multiple-spot TEM BF image showing the ultra-fine α-β microstructures within the massive phase grain. The inset in (a) is an EBSD band-contrast map showing the original prior-β GB. The side arrow in (a) represents the SEBM building direction. Display omitted
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In the paper, a general thin plate theory including surface effects, which can be used for size-dependent static and dynamic analysis of plate-like thin film structures, is proposed. This theory is a ...modification and generalization of the thin plate model in Lim, C.W., He, L.H., 2004. Size-dependent nonlinear response of thin elastic films with nanoscale thickness. Int. J. Mech. Sci. 46, 1715–1726. With the general theory, the governing equations of Kirchoff and Mindlin plate models including surface effects are derived, respectively. Some numerical examples are provided to verify the validities of the theory.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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