Bone marrow lesion and 5-year incident joint surgery in patients with knee osteoarthritis: a retrospective cohort study.

BACKGROUND: It is beneficial for society to discover the risk factors associated with surgery and to carry out some early interventions for patients with these risk factors. Few studies specifically explored the relationship between bone marrow lesions (BMLs) and long-term incident joint surgery. OBJECTIVE: To investigate the association between BML severity observed in knee osteoarthritis (OA) patients' first MRI examination and incident knee surgery within 5 years. Additionally, to assess the predictive value of BMLs for the incident knee surgery. DESIGN: Retrospective cohort study. METHODS: We identified patients diagnosed with knee OA and treated at our institution between January 2015 and January 2018, and retrieved their baseline clinical data and first MRI examination films from the information system. Next, we proceeded to determine the Max BML grades, BML burden grades and Presence BML grades for the medial, lateral, patellofemoral, and total compartments, respectively. Multi-variable logistic regression models examined the association of the BML grades with 5-year incident knee surgery. Positive and negative predictive values (PPVs and NPVs) were determined for BML grades referring to 5-year incident knee surgery. RESULTS: Totally, 1011 participants (knees) were found eligible to form the study population. Within the 5 years, surgery was performed on 74 knees. Max BML grade 2 and grade 3 of medial, patellofemoral and total compartments were strongly and significantly associated with incident surgery. None of the BML grades from lateral compartment was associated with incident surgery. The PPV was low and NPV was high for BMLs. CONCLUSIONS: BMLs found in the first MRI examination were associated with 5-year incident joint surgery, except for those allocated in lateral compartments. The high NPVs imply that patients without BMLs have a low risk of requiring surgery within 5 years.

Design, synthesis, and biological evaluation of new bis-benzylisoquinoline-based analogues as potential neuromuscular blocking agents.

Neuromuscular blocking agents (NMBAs) are widely used in anesthesia for intubation and surgical muscle relaxation. Novel atracurium and mivacurium derivatives were developed, with compounds 18c, 18d, and 29a showing mivacurium-like relaxation at 27.27 nmol/kg, and 15b, 15c, 15e, and 15h having a shorter duration at 272.7 nmol/kg. The structure-activity and configuration-activity relationships of these derivatives and 29a's binding to nicotinic acetylcholine receptors were analyzed through molecular docking. Rabbit trials showed 29a has a shorter duration compared to mivacurium. This suggests that linker properties, ammonium group substituents, and configuration are crucial for NMBA activity and duration, with compound 29a emerging as a potential ultra-short-acting NMBA.

Effort-reward imbalance and sleep quality in railway locomotive stewards: a cross-sectional study.

OBJECTIVE: To assess the correlation between the effort-reward imbalance (ERI) and sleep quality among railway locomotive stewards. DESIGN: Cross-sectional study. SETTING: Lanzhou Bureau Group, China Railway, between July and August 2022. PARTICIPANTS: Railway locomotive stewards. PRIMARY AND SECONDARY OUTCOME MEASURES: Sleep quality was assessed using the Pittsburgh Sleep Quality Index Scale (PSQI), categorising scores of >14 as poor, 8-14 as fair and <8 as good. RESULTS: A total of 5738 valid questionnaires (mean age of 30.85±6.91 years and 5730 males) were included. The response rate was 92.27%. The PSQI score was 11.52±3.95; 2304 (40.15%) respondents had good sleep quality, 1590 (27.71%) had fair sleep quality and 1844 (32.14%) had poor sleep quality. Stepwise multivariable logistic regression analysis showed that, compared with poor sleep quality, Jiayuguan Locomotive Depot workers (OR 0.775, 95% CI 0.587 to 0.971, p=0.028), electric locomotive drivers (OR 0.499, 95% CI 0.316 to 0.786, p=0.003), passenger train locomotive drivers (OR 0.209, 95% CI 1.313 to 3.337, p=0.002), working <40 hours weekly (OR 2.291, 95% CI 1.686 to 3.112, p<0.001), working 40-50 hours weekly (OR 1.602, 95% CI 1.299 to 1.977, p<0.001), senior titles (OR 0.727, 95% CI 0.570 to 0.928, p=0.010), high effort/low reward (OR 2.812, 95% CI 2.218 to 3.564, p<0.001) and low overcommitment (OR 5.848, 95% CI 4.710 to 7.261, p<0.001) were independently associated with fair sleep quality. Electric locomotive drivers (OR 0.535, 95% CI 0.364 to 0.787, p=0.001), diesel locomotive drivers (OR 0.567, 95% CI 0.348 to 0.924, p=0.023), passenger train locomotive drivers (OR 1.471, 95% CI 1.005 to 2.155, p=0.047), working <40 hours weekly (OR 1.549, 95% CI 1.196 to 2.006, p=0.001), working 40-50 hours weekly (OR 1.340, 95% CI 1.141 to 1.574, p<0.001), high school diploma or less (OR 1.448, 95% CI 1.062 to 1.975, p=0.019), high effort/low reward (OR 1.237, 95% CI 1.006 to 1.521, p=0.044), balanced effort-reward (OR 0.653, 95% CI 0.478 to 0.892, p=0.007) and low overcommitment (OR 2.553, 95% CI 2.224 to 2.931, p<0.001) were independently associated with good sleep quality. CONCLUSION: The results revealed an acceptable ERI and poor sleep quality among railway stewards. ERI was correlated with sleep quality. Health education, lifestyle changes and improved work schedules may help boost sleep quality and well-being among railway locomotive stewards.

Associations between Atmospheric PM2.5 Exposure and Carcinogenic Health Risks: Surveillance Data from the Year of Lowest Recorded Levels in Beijing, China.

Scant research has pinpointed the year of minimum PM2.5 concentration through extensive, uninterrupted monitoring, nor has it thoroughly assessed carcinogenic risks associated with analyzing numerous components during this nadir in Beijing. This study endeavored to delineate the atmospheric PM2.5 pollution in Beijing from 2015 to 2022 and to undertake comprehensive evaluation of carcinogenic risks associated with the composition of atmospheric PM2.5 during the year exhibiting the lowest concentration. PM2.5 concentrations were monitored gradually in 9 districts of Beijing for 7 consecutive days per month from 2015 to 2022, and 32 kinds of PM2.5 components collected in the lowest PM2.5 concentration year were analyzed. This comprehensive dataset served as the basis for carcinogenic risk assessment using Monte Carlo simulation. And we applied the Positive Matrix Factorization (PMF) method to identity the sources of atmospheric PM2.5. Furthermore, we integrated this source appointment model with risk assessment model to discern the origins of these risks. The findings revealed that the annual average PM2.5 concentration in 2022 stood at 43.1µg/m3, marking the lowest level recorded. The mean carcinogenic risks of atmospheric PM2.5 exposure calculated at 6.30E-6 (empirical 95% CI 1.09E-6 to 2.25E-5) in 2022. The PMF model suggested that secondary sources (35.4%), coal combustion (25.6%), resuspended dust (15.1%), biomass combustion (14.1%), vehicle emissions (7.1%), industrial emissions (2.0%) and others (0.7%) were the main sources of atmospheric PM2.5 in Beijing. The mixed model revealed that coal combustion (2.41E-6), vehicle emissions (1.90E-6) and industrial emissions (1.32E-6) were the main sources of carcinogenic risks with caution. Despite a continual decrease in atmospheric PM2.5 concentration in recent years, the lowest concentration levels still pose non-negligible carcinogenic risks. Notably, the carcinogenic risks associated with metals and metalloids exceeded that of PAHs. And the distribution of risk sources did not align proportionally with the distribution of PM2.5 mass concentration.

Utilizing a structure-based virtual screening approach to discover potential LSD1 inhibitors.

BACKGROUND: Lysine-specific demethylase 1 (LSD1) is highly expressed in a variety of malignant tumors, rendering it a crucial epigenetic target for anti-tumor therapy. Therefore, the inhibition of LSD1 activity has emerged as a promising innovative therapeutic approach for targeted cancer treatment. METHODS: In our study, we employed innovative structure-based drug design methods to meticulously select compounds from the ZINC15 database. Utilizing virtual docking, we evaluated docking scores and binding modes to identify potential inhibitors. To further validate our findings, we harnessed molecular dynamic simulations and conducted meticulous biochemical experiments to deeply analyze the binding interactions between the protein and compounds. RESULTS: Our results showcased that ZINC10039815 exhibits an exquisite binding mode with LSD1, fitting perfectly into the active pocket and forming robust interactions with multiple critical residues of the protein. CONCLUSIONS: With its significant inhibitory effect on LSD1 activity, ZINC10039815 emerges as a highly promising candidate for the development of novel LSD1 inhibitors.

U3 snoRNA inter-regulates with DDX21 in the perichromosomal region to control mitosis.

U3 snoRNA is essential for ribosome biogenesis during interphase. Upon mitotic onset, the nucleolus disassembles and U3 snoRNA relocates to the perichromosomal region (PR) to be considered as a chromosome passenger. Whether U3 controls mitosis remains unknown. Here, we demonstrate that U3 snoRNA is required for mitotic progression. We identified DDX21 as the predominant U3-binding protein during mitosis and confirmed that U3 snoRNA colocalizes with DDX21 in the PR. DDX21 knockdown induces mitotic catastrophe and similar mitotic defects caused by U3 snoRNA depletion. Interestingly, the uniform PR distribution of U3 snoRNA and DDX21 is interdependent. DDX21 functions in mitosis depending on its PR localization. Mechanistically, U3 snoRNA regulates DDX21 PR localization through maintaining its mobility. Moreover, Cy5-U3 snoRNA downsizes the fibrous condensates of His-DDX21 at proper molecular ratios in vitro. This work highlights the importance of the equilibrium between U3 snoRNA and DDX21 in PR formation and reveals the potential relationship between the PR assembly and mitotic regulation.

Solvated Electrons Generated on the Surface of Na-SPHI for Boosting Visible Light Photocatalytic Hydrogen Evolution with Ultra-High AQE.

Enhancing the utilization of visible-light-active semiconductors with an excellent apparent quantum efficiency (AQE) remains a significant and challenging goal in the realm of photocatalytic water splitting. In this study, a fully condensed sulfur-doped poly(heptazine imide) metalized with Na (Na-SPHI) is synthesized by an ionothermal method by using eutectic NaCl/LiCl mixture as the ionic solvent. Comprehensive characterizations of the obtained Na-SPHI reveal several advantageous features, including heightened light absorption, facilitated exciton dissociation, and expedited charge transfer. More importantly, solvated electron, powerful reducing agents, can be generated on the surface of Na-SPHI upon irradiation with visible light. Benefiting from above advantage, the Na-SPHI exhibits an excellent H2 evolution rate of 571.8 µmol·h-1 under visible light illumination and a super-high AQE of 61.7% at 420 nm. This research emphasizes the significance of the solvated electron on the surface of photocatalyst in overcoming the challenges associated with visible light-driven photocatalysis, showcasing its potential application in photocatalytic water splitting.

3D Laser Writing of Low-Loss Cross-Section-Variable Type-I Optical Waveguide Passive/Active Integrated Devices in Single Crystals.

Optical waveguides fabricated in single crystals offer crucial passive/active optical components for photonic integrated circuits. Single crystals possess inherent advantages over their amorphous counterpart, such as lower optical losses in visible-to-mid-infrared band, larger peak emission cross-section, higher doping concentration. However, the writing of Type-I positive refractive index modified waveguides in single crystals using femtosecond laser technology presents significant challenges. Herein, we introduce a novel femtosecond laser direct writing technique that combines slit-shaping with an immersion oil objective to fabricate low-loss Type-I waveguides in single crystals. This approach allows for precise control of waveguide shape, size, mode-field and refractive index distribution, with a spatial resolution as high as 700 nm and a high positive refractive index variation on the order of 10-2, introducing new degrees of freedom to design and fabricate passive/active optical waveguide devices. As a proof-of-concept, we successfully produced a 7 mm-long circular-shaped gain waveguide (∼10 µm in diameter) in an Er3+-doped YAG single crystal, exhibiting a propagation loss as low as 0.23 dB/cm, a net gain of ∼3 dB and a polarization-insensitive character. The newly-developed technique is theoretically applicable to arbitrary single crystals, holding promising potential for various applications in integrated optics, optical communication, and photonic quantum circuits. This article is protected by copyright. All rights reserved.

Optimizing echo state networks for continuous gesture recognition in mobile devices: A comparative study.

Continuous gesture recognition can be used to enhance human-computer interaction. This can be accomplished by capturing human movement with the use of the Inertial Measurement Units in smartphones and using machine learning algorithms to predict the intended gestures. Echo State Networks (ESNs) consist of a fixed internal reservoir that is able to generate rich and diverse nonlinear dynamics in response to input signals that capture temporal dependencies within the signal. This makes ESNs well-suited for time series prediction tasks, such as continuous gesture recognition. However, their application has not been rigorously explored, with regard to gesture recognition. In this study, we sought to enhance the efficacy of ESN models in continuous gesture recognition by exploring diverse model structures, fine-tuning hyperparameters, and experimenting with various training approaches. We used three different training schemes that used the Leave-one-out Cross-validation (LOOCV) protocol to investigate the performance in real-world scenarios with different levels of data availability: Leaving out data from one user to use for testing (F1-score: 0.89), leaving out a fraction of data from all users to use in testing (F1-score: 0.96), and training and testing using LOOCV on a single user (F1-score: 0.99). The obtained results outperformed the Long Short-Term Memory (LSTM) performance from past research (F1-score: 0.87) while maintaining a low training time of approximately 13 seconds compared to 63 seconds for the LSTM model. Additionally, we further explored the performance of the ESN models through behaviour space analysis using memory capacity, Kernel Rank, and Generalization Rank. Our results demonstrate that ESNs can be optimized to achieve high performance on gesture recognition in mobile devices on multiple levels of data availability. These findings highlight the practical ability of ESNs to enhance human-computer interaction.

The AGAMOUS-LIKE 16-GENERAL REGULATORY FACTOR 1 module regulates axillary bud outgrowth via catabolism of abscisic acid in cucumber.

Lateral branches are important components of shoot architecture and directly affect crop yield and production cost. Although sporadic studies have implicated abscisic acid (ABA) biosynthesis in axillary bud outgrowth, the function of ABA catabolism and its upstream regulators in shoot branching remain elusive. Here, we showed that the MADS-box transcription factor AGAMOUS-LIKE 16 (CsAGL16) is a positive regulator of axillary bud outgrowth in cucumber (Cucumis sativus). Functional disruption of CsAGL16 led to reduced bud outgrowth, whereas overexpression of CsAGL16 resulted in enhanced branching. CsAGL16 directly binds to the promoter of the ABA 8'-hydroxylase gene CsCYP707A4 and promotes its expression. Loss of CsCYP707A4 function inhibited axillary bud outgrowth and increased ABA levels. Elevated expression of CsCYP707A4 or treatment with an ABA biosynthesis inhibitor largely rescued the Csagl16 mutant phenotype. Moreover, cucumber General Regulatory Factor 1 (CsGRF1) interacts with CsAGL16 and antagonizes CsAGL16-mediated CsCYP707A4 activation. Disruption of CsGRF1 resulted in elongated branches and decreased ABA levels in the axillary buds. The Csagl16 Csgrf1 double mutant exhibited a branching phenotype resembling that of the Csagl16 single mutant. Therefore, our data suggest that the CsAGL16-CsGRF1 module regulates axillary bud outgrowth via CsCYP707A4-mediated ABA catabolism in cucumber. Our findings provide a strategy to manipulate ABA levels in axillary buds during crop breeding to produce desirable branching phenotypes.

The rising roles of exosomes in the tumor microenvironment reprogramming and cancer immunotherapy.

Exosomes are indispensable for intercellular communications. Tumor microenvironment (TME) is the living environment of tumor cells, which is composed of various components, including immune cells. Based on TME, immunotherapy has been recently developed for eradicating cancer cells by reactivating antitumor effect of immune cells. The communications between tumor cells and TME are crucial for tumor development, metastasis, and drug resistance. Exosomes play an important role in mediating these communications and regulating the reprogramming of TME, which affects the sensitivity of immunotherapy. Therefore, it is imperative to investigate the role of exosomes in TME reprogramming and the impact of exosomes on immunotherapy. Here, we review the communication role of exosomes in regulating TME remodeling and the efficacy of immunotherapy, as well as summarize the underlying mechanisms. Furthermore, we also introduce the potential application of the artificially modified exosomes as the delivery systems of antitumor drugs. Further efforts in this field will provide new insights on the roles of exosomes in intercellular communications of TME and cancer progression, thus helping us to uncover effective strategies for cancer treatment.

Boosted Second Harmonic Generation and Cascaded Sum Frequency Generation from a Surface Crystallized Glass Ceramic Microcavity.

The development of novel materials and structures for efficient second-order nonlinear micro/nano devices remains a significant challenge. In this study, the remarkable enhancement of second-harmonic generation (SHG) and cascaded sum frequency generation in whispering gallery mode microspheres made of surface-crystallized glass with a 6-µm Ba2TiSi2O8 crystal layer are demonstrated. Attributed to the core-shell design, the Ba2TiSi2O8 located on the surface can be efficiently coupled with whispering gallery modes, resulting in a highly efficient micron-scale cavity-enhanced second-order optical nonlinearity. Greatly enhanced SHG of the microcavity is observed, which is up to 80 times stronger than that of a non-resonant sample. Furthermore, owing to the wavelength non-selectivity of random quasi-phase matching, ultra-wideband SHG with a strong response ranging from 860 to 1600 nm and high-contrast polarization characteristics is demonstrated. The glass-ceramic-based microsphere cavity also boosts the cascading optical nonlinearity, manifested by a two-magnitude enhancement of cascaded sum frequency generation. This work delineates an efficient strategy for boosting nonlinear optical response in glass ceramics, which will open up new opportunities for applications in photonics and optical communications.

Two-Dimensional Os2Se3 Nanosheet: A Ferroelectric Metal with Room-Temperature Ferromagnetism.

Two-dimensional (2D) ferroelectric metals (FEMs) possess intriguing characteristics, such as unconventional superconductivity and the nonlinear anomalous Hall effect. However, their occurrence is exceedingly rare due to mutual repulsion between ferroelectricity and metallicity. In addition, further incorporating other features like ferromagnetism into FEMs to enhance their functionalities poses a significantly greater challenge. Here, via first-principles calculations, we demonstrate a case of an FEM that features a coexistence of room-temperature ferromagnetism, ferroelectricity, and metallicity in a thermodynamically stable 2D Os2Se3. It presents a vertical electric polarization of 3.00 pC/m that exceeds those of most FEMs and a moderate polarization switching barrier of 0.22 eV per formula unit. Moreover, 2D Os2Se3 exhibits robust ferromagnetism (Curie temperature TC ≈ 527 K) and a sizable magnetic anisotropy energy (-30.87 meV per formula unit). Furthermore, highly magnetization-dependent electrical conductivity is revealed, indicative of strong magnetoelectric coupling. Berry curvature calculation suggests that the FEM might exhibit nontrivial band topology.

Carbon nanotube-encapsulated Co/Co3Fe7 heterojunctions as a highly-efficient bifunctional electrocatalyst for rechargeable zinc-air batteries.

In oxygen electrocatalysis, how to rationally design low-cost catalysts with reasonable structure and long-term stability is a crucial issue. Here, an in-situ growth strategy is used to construct a shaped structure encapsulating a uniformly-dispersed Co/Co3Fe7 heterojunction in nitrogen-doped carbon nanotubes (Co/Co3Fe7@NCNTs). Hollow CoFe layered-double-hydroxide prisms act as sacrifices for in-situ growth of Co/Co3Fe7 nanoparticles, which also catalyze the growth of bamboo-like NCNTs. Tubular structure not only accelerates the charge transfer through the interactions between Co and Co3Fe7, but also limits the aggregation of the particles, thereby promoting the 4e- oxygen reduction/evolution reactions (ORR/OER) kinetics and stabilizing the bifunctional activity. Co/Co3Fe7@NCNTs-800 (pyrolyzed at 800 °C) shows exceptional ORR activity (half-wave potential of 0.89 V) and methanol tolerance. Meanwhile, Co/Co3Fe7@NCNTs-800 shows a small OER overpotential of 280 mV, which increases by only 9 mV after 1000 cyclic voltammetry (CV) cycles. The outstanding bifunctionality (potential gap of 0.62 V) is ascribed to the electronic structure modulation at the Co/Co3Fe7 heterointerface. Notably, it also has a high performance as an air-cathode for rechargeable zinc-air battery, showing high power density (165 mW cm-2) and specific capacity (770.5 m Ah kg-1). This work provides a new reference for promoting the development of alloy catalysts with heterogeneous interfaces.

Dynamic multicolor emissions of multimodal phosphors by Mn2+ trace doping in self-activated CaGa4O7.

The manipulation of excitation modes and resultant emission colors in luminescent materials holds pivotal importance for encrypting information in anti-counterfeiting applications. Despite considerable achievements in multimodal and multicolor luminescent materials, existing options generally suffer from static monocolor emission under fixed external stimulation, rendering them vulnerability to replication. Achieving dynamic multimodal luminescence within a single material presents a promising yet challenging solution. Here, we report the development of a phosphor exhibiting dynamic multicolor photoluminescence (PL) and photo-thermo-mechanically responsive multimodal emissions through the incorporation of trace Mn2+ ions into a self-activated CaGa4O7 host. The resulting phosphor offers adjustable emission-color changing rates, controllable via re-excitation intervals and photoexcitation powers. Additionally, it demonstrates temperature-induced color reversal and anti-thermal-quenched emission, alongside reproducible elastic mechanoluminescence (ML) characterized by high mechanical durability. Theoretical calculations elucidate electron transfer pathways dominated by intrinsic interstitial defects and vacancies for dynamic multicolor emission. Mn2+ dopants serve a dual role in stabilizing nearby defects and introducing additional defect levels, enabling flexible multi-responsive luminescence. This developed phosphor facilitates evolutionary color/pattern displays in both temporal and spatial dimensions using readily available tools, offering significant promise for dynamic anticounterfeiting displays and multimode sensing applications.

A Dual-mode platform for the rapid detection of Escherichia coli O157:H7 based on CRISPR/Cas12a and RPA.

Escherichia coli O157:H7 (E. coli O157:H7) is a foodborne pathogenic microorganism that is commonly found in the environment and poses a significant threat to human health, public safety, and economic stability worldwide. Thus, early detection is essential for E. coli O157:H7 control. In recent years, a series of E. coli O157:H7 detection methods have been developed, but the sensitivity and portability of the methods still need improvement. Therefore, in this study, a rapid and efficient testing platform based on the CRISPR/Cas12a cleavage reaction was constructed. Through the integration of recombinant polymerase amplification and lateral flow chromatography, we established a dual-interpretation-mode detection platform based on CRISPR/Cas12a-derived fluorescence and lateral flow chromatography for the detection of E. coli O157:H7. For the fluorescence detection method, the limits of detection (LODs) of genomic DNA and E. coli O157:H7 were 1.8 fg/µL and 2.4 CFU/mL, respectively, within 40 min. Conversely, for the lateral flow detection method, LODs of 1.8 fg/µL and 2.4 × 102 CFU/mL were achieved for genomic DNA and E. coli O157:H7, respectively, within 45 min. This detection strategy offered higher sensitivity and lower equipment requirements than industry standards. In conclusion, the established platform showed excellent specificity and strong universality. Modifying the target gene and its primers can broaden the platform's applicability to detect various other foodborne pathogens.

Optimization of Preparation Conditions for Quercetin Nanoliposomes Using Response Surface Methodology and Evaluation of Their Stability.

Quercetin is a flavonol compound with excellent biological activities. However, quercetin exhibits poor stability and solubility in water, which limits its application. In this study, quercetin nanoliposomes (QUE-NL-1) were prepared using an ultrasonic thin-film dispersion method, and the preparation conditions were optimized using response surface methodology. The optimal conditions for preparing QUE-NL-1 were as follows: an evaporation temperature of 35 °C, a drug concentration of 0.20 mg/mL, and a lipid bile ratio of 4:1. The encapsulation rate of QUE-NL-1 is (63.73 ± 2.09)%, the average particle size is 134.11 nm, and the average absolute value of the zeta potential is 37.50 and PDI = 0.24. By analyzing the storage temperature, storage time, and leakage rate of QUE-NL-1 in simulated gastrointestinal fluid, it was found that quercetin exhibits good stability after embedding and can achieve sustained release in intestinal juice. In addition, the cytotoxicity of QUE-NL-1 was not significant, and the survival rate of Caco-2 cells was >90% when the concentration range of QUE-NL-1 was 0.1-0.4 mg/mL. This study provides an efficient method for preparing QUE-NL-1 with small particle sizes, good stability, and high safety, which is of great significance for expanding the application range of quercetin.

Phase 1/2 multicenter trial of acalabrutinib in Chinese patients with relapsed/refractory mantle cell lymphoma.

Acalabrutinib studies have limited Asian participation. This phase 1/2 study (NCT03932331) assessed acalabrutinib in Chinese patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL). Primary endpoint was blinded independent central review (BICR)-assessed overall response rate (ORR). Overall, 34 patients were enrolled. Most patients were men (88%); median age was 63 years and 59% had ≥3 prior treatments. Median treatment duration was 14 months (range, 1-24). Any-grade adverse events (AEs) and grade ≥3 AEs occurred in 85.3% and 44.1% of patients, respectively. AEs causing treatment discontinuation were aplastic anemia, thrombocytopenia, and gastrointestinal infection (n = 1 each). Fatal AEs occurred in 2 patients (aplastic anemia and multiple organ dysfunction syndrome [n = 1 each]). BICR-assessed ORR was 82.4% (95% confidence interval [CI]: 65.5, 93.2); 12 (35.3%) patients achieved complete response. Estimated 12-month OS was 84.5% (95% CI: 66.6, 93.3). Acalabrutinib yielded tolerable safety and high response rates in Chinese patients with R/R MCL.

Comparison of bicarbonate Ringer's solution with lactated Ringer's solution among postoperative outcomes in patients with laparoscopic right hemihepatectomy: a single-centre randomised controlled trial.

The study was aimed to investigate the positive impact of bicarbonate Ringer's solution on postoperative outcomes in patients who underwent laparoscopic right hemihepatectomy. Patients in the two groups were infused with lactated Ringer's solution (LRS, n = 38) and the bicarbonate Ringer's solution (BRS, n = 38) at a rate of 5 ml·kg-1·h-1. The stroke volume was monitored and 200 ml of hydroxyethyl starch with 130/0.4 sodium chloride injection (Hes) of a bolus was given in the first 5-10 min. The main outcome was to test lactic acid (LAC) concentration before and after surgery. The concentrations of LAC in the LRS group were higher than in the BRS group at 2 h after operation began, at the end of the operation and 2 h after the operation. Overall, the parameters including pH, base excess (BE), HCO3-, aspartate transaminase (AST) and alanine transaminase (ALT) were improved. The values of bilirubin in the LRS group were higher and albumin were lower than in the BRS group at post-operation 1st and 2nd day (P<0.05). The time of prothrombin time (PT) and activated partial thromboplastin time (APTT) in the LRS group were longer than that in the BRS group at post-operation 1st and 2nd day (P<0.05). Likewise, the concentrations of Mg2+, Na+ and K+ also varied significantly. The length of hospital was reduced, and the incidence of premature ventricular contractions (P = 0.042) and total complications (P = 0.016) were lower in group BRS. TRIAL REGISTRATION: The study was registered at clinicalTrials.gov with the number ChiCTR2000038077 on 09/09/2020.

Synthesis and Characterization of Poly(butylene glycol adipate-co-terephthalate/diphenylsilanediol adipate-co-terephthalate) Copolyester.

The copolyester poly(butylene glycol adipate-co-terephthalate/diphenylsilanediol adipate-co-terephthalate) (PBDAT) was synthesized by the melt polycondensation method using terephthalic acid, adipic acid, 1,4-butanediol, and diphenylsilylene glycol as the raw materials. The molecular chain structure, thermal properties, thermal stability, mechanical properties, and degradation behaviors of the copolyesters were investigated. The results showed that the prepared PBDAT copolyesters exhibited good thermal stability and mechanical properties. With the increase in diphenylsilanediol (DPSD) content, the thermal stability of PBDAT and the melting temperature both increased. The tensile strength and elastic modulus of PBDAT also exhibited an increasing tend. When the DPSD content was 12.5% (PBDAT-12.5), the tensile strength, the elastic modulus, and elongation at break were 30.56 MPa, 238 MPa, and 219%, respectively. With the increase in diphenylsilanediol content, the hydrophilicity of PBDAT decreased, but PBDAT still shows good degradability and the thermal degradation T5% temperature was 355 °C. The thermal degradation of PBDAT was also improved.