Childhood traumatic experiences and complex posttraumatic stress disorder in Chinese adolescents: The mediating role of attachment.

OBJECTIVE: The prevalence of child maltreatment is high in China. Child maltreatment damages children's developing abilities (e.g., emotional functions, self-perception) and is highly associated with a new diagnostic disorder, namely, complex posttraumatic stress disorder (CPTSD). The mechanism of CPTSD is not clear, and attachment might be a crucial factor in the development of CPTSD symptoms. The prevalence of child maltreatment is high in China. Child maltreatment damages children's developing abilities (e.g., emotional functions, self-perception) and is highly associated with a new diagnostic disorder, namely, complex posttraumatic stress disorder (CPTSD). The mechanism of CPTSD is not clear and attachment might be a crucial factor in the development of CPTSD symptoms. To explore the mediating roles of attachment anxiety and attachment avoidance in the relationship between five forms of childhood trauma (i.e., physical abuse, physical neglect, emotional abuse, emotional neglect, sexual abuse) and CPTSD symptoms. METHOD: The present study included 395 adolescents who had experienced at least one type of traumatic childhood experience. RESULTS: Our findings showed that emotional abuse could predict posttraumatic stress disorder and disturbances of self-organization (DSO) symptoms via attachment anxiety. In addition, childhood neglect experiences (i.e., physical and emotional neglect) could predict DSO symptoms via attachment avoidance. CONCLUSIONS: Attachment is an important framework for understanding individuals' CPTSD symptoms following childhood traumatic experiences. Parents and educators should learn effective parenting styles that promote secure attachment, while researchers and clinical practitioners should further explore attachment-based trauma intervention approaches. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Synergistic enhancement of pulsed light-induced H2 photoproduction in Chlamydomonas cells by optimal sulfite concentration and light waveform.

Pulsed light illumination stands out as a noteworthy technique for photosynthetic H2 production, playing a crucial role in eliminating O2 and activating hydrogenase enzymes. However, further improvements are essential to make H2 photoproduction suitable for future commercial applications. In our study, we observed a distinct enhancement in pulsed light-induced H2 photoproduction in the unicellular green alga Chlamydomonas reinhardtii when treated with the optimal concentration of the mild O2 scavenger Na2SO3. This improvement was a result of reduced O2 content, increased hydrogenase enzyme activity, and suppressed H2-uptake activity. Furthermore, our findings indicate that exposing Na2SO3-treated C. reinhardtii to optimal light waveform continues to significantly boost pulsed light-induced H2 photoproduction, attributed to the alleviation of impaired photosystem II activity. Altogether, the combined application of optimal sulfite concentration and light waveform effectively enhances pulsed light-induced photosynthetic H2 production in the green alga C. reinhardtii.

Kriging-based surrogate data-enriching artificial neural network prediction of strength and permeability of permeable cement-stabilized base.

Limited test data hinder the accurate prediction of mechanical strength and permeability of permeable cement-stabilized base materials (PCBM). Here we show a kriging-based surrogate model assisted artificial neural network (KS-ANN) framework that integrates laboratory testing, mathematical modeling, and machine learning. A statistical distribution model was established from limited test data to enrich the dataset through the combination of markov chain monte carlo simulation and kriging-based surrogate modeling. Subsequently, an artificial neural network (ANN) model was trained using the enriched dataset. The results demonstrate that the well-trained KS-ANN model effectively captures the actual data distribution characteristics. The accurate prediction of the mechanical strength and permeability of PCBM under the constraint of limited data validates the effectiveness of the proposed framework. As compared to traditional ANN models, the KS-ANN model improves the prediction accuracy of PCBM's mechanical strength by 21%. Based on the accurate prediction of PCBM's mechanical strength and permeability by the KS-ANN model, an optimization function was developed to determine the optimal cement content and compaction force range of PCBM, enabling it to concurrently satisfy the requirements of mechanical strength and permeability. This study provides a cost-effective and rapid solution for evaluating the performance and optimizing the design of PCBM and similar materials.

Exploiting ChatGPT for Diagnosing Autism-Associated Language Disorders and Identifying Distinct Features.

Diagnosing language disorders associated with autism is a complex and nuanced challenge, often hindered by the subjective nature and variability of traditional assessment methods. Traditional diagnostic methods not only require intensive human effort but also often result in delayed interventions due to their lack of speed and specificity. In this study, we explored the application of ChatGPT, a state-of-the-art large language model, to overcome these obstacles by enhancing diagnostic accuracy and profiling specific linguistic features indicative of autism. Leveraging ChatGPT's advanced natural language processing capabilities, this research aims to streamline and refine the diagnostic process. Specifically, we compared ChatGPT's performance with that of conventional supervised learning models, including BERT, a model acclaimed for its effectiveness in various natural language processing tasks. We showed that ChatGPT substantially outperformed these models, achieving over 13% improvement in both accuracy and F1-score in a zero-shot learning configuration. This marked enhancement highlights the model's potential as a superior tool for neurological diagnostics. Additionally, we identified ten distinct features of autism-associated language disorders that vary significantly across different experimental scenarios. These features, which included echolalia, pronoun reversal, and atypical language usage, were crucial for accurately diagnosing ASD and customizing treatment plans. Together, our findings advocate for adopting sophisticated AI tools like ChatGPT in clinical settings to assess and diagnose developmental disorders. Our approach not only promises greater diagnostic precision but also aligns with the goals of personalized medicine, potentially transforming the evaluation landscape for autism and similar neurological conditions.

Unraveling the role of Mn(V)/Mn(III) in the enhanced permanganate oxidation under Vis-LED radiation.

A novel approach of visible light-emitting diode (Vis-LED) radiation was employed to activate permanganate (Mn(VII)) for efficient organic micropollutant (OMP) removal. The degradation rates of OMPs by Vis-LED/Mn(VII) were 2-5.29 times higher than those by Mn(VII) except for benzoic acid and atrazine. Increasing wavelengths (445-525 nm) suppressed the degradation of diclofenac (DCF) and 4-chlorophenol (4-CP) owing to the decreased quantum yields of Mn(VII). Comparatively, light intensity and Mn(VII) dosage had a positive effect on the degradation of DCF and 4-CP. Experimental data revealed that Mn(V) dominated the DCF degradation whereas Mn(III) was the active oxidant in the 4-CP degradation. Mn(V) and Mn(III) formed from the photo-decomposition of Mn(VII), meanwhile, Mn(III) also formed from the Mn(V) photo-decomposition. The increase in solution pH inhibited DCF degradation but had a positive impact on 4-CP degradation, mainly due to the changing speciation of DCF and 4-CP. Inorganic anions (Cl- and HCO3-) had little impact on DCF and 4-CP degradation, while humic acid (HA) showed a positive impact because of the π-π interaction between HA and DCF/4-CP. The transformation products of DCF and 4-CP were identified and transformation pathways were proposed. Finally, the Vis-LED/Mn(VII) exhibited great degradation performance in various authentic waters. Overall, this study boosts the development of Mn(VII)-based oxidation processes.

Matching periodate peak absorbance by far UVC at 222 nm promotes the degradation of micropollutants and energy efficiency.

Periodate (PI)-based advanced oxidation processes have gained increasing interest. This study for the first time elevates the light-activation capacity of PI by using far UVC at 222 nm (UV222/PI) without extra chemical inputs. The effectiveness and the underlying mechanisms of UV222/PI for the remediation of micropollutants were studied by selecting atenolol (ATL) as a representative. PI possessed a high molar absorption coefficient of 9480-6120 M-1 cm-1 at 222 nm in the pH range of 5.0-9.0, and it was rapidly decomposed by UV222 with first-order rate constants of 0.0055 to 0.002 s-1. ATL and the six other organic compounds were effectively degraded by the UV222/PI process under different conditions with the fluence-based rate constants generally two to hundred times higher than by UVA photolysis. Hydroxyl radical and ozone were confirmed as the major contributors to ATL degradation, while direct photolysis also played a role at higher pH or lower PI dosages. Degradation pathways of ATL were proposed including hydroxylation, demethylation, and oxidation. The high energy efficiency of the UV222/PI process was also confirmed. This study provides a cost-effective and convenient approach to enhance PI light-response activity for the treatment of micropollutants.

An Enhanced Indoor Three-Dimensional Localization System with Sensor Fusion Based on Ultra-Wideband Ranging and Dual Barometer Altimetry.

Accurate three-dimensional (3D) localization within indoor environments is crucial for enhancing item-based application services, yet current systems often struggle with localization accuracy and height estimation. This study introduces an advanced 3D localization system that integrates updated ultra-wideband (UWB) sensors and dual barometric pressure (BMP) sensors. Utilizing three fixed UWB anchors, the system employs geometric modeling and Kalman filtering for precise tag 3D spatial localization. Building on our previous research on indoor height measurement with dual BMP sensors, the proposed system demonstrates significant improvements in data processing speed and stability. Our enhancements include a new geometric localization model and an optimized Kalman filtering algorithm, which are validated by a high-precision motion capture system. The results show that the localization error is significantly reduced, with height accuracy of approximately ±0.05 m, and the Root Mean Square Error (RMSE) of the 3D localization system reaches 0.0740 m. The system offers expanded locatable space and faster data output rates, delivering reliable performance that supports advanced applications requiring detailed 3D indoor localization.

Selpercatinib attenuates bleomycin-induced pulmonary fibrosis by inhibiting the TGF-ß1 signaling pathway.

IPF is a chronic, progressive, interstitial lung disease with high mortality. Current drugs have limited efficacy in curbing disease progression and improving quality of life. Selpercatinib, a highly selective inhibitor of receptor tyrosine kinase RET (rearranged during transfection), was approved in 2020 for the treatment of a variety of solid tumors with RET mutations. In this study, the action and mechanism of Selpercatinib in pulmonary fibrosis were evaluated in vivo and in vitro. In vivo experiments demonstrated that Selpercatinib significantly ameliorated bleomycin (BLM)-induced pulmonary fibrosis in mice. In vitro, Selpercatinib inhibited the proliferation, migration, activation and extracellular matrix deposition of fibroblasts by inhibiting TGF-ß1/Smad and TGF-ß1/non-Smad pathway, and suppressed epithelial-mesenchymal transition (EMT) like process of lung epithelial cells via inhibiting TGF-ß1/Smad pathway. The results of in vivo pharmacological tests corroborated the results obtained from the in vitro experiments. Further studies revealed that Selpercatinib inhibited abnormal phenotypes of lung fibroblasts and epithelial cells in part by regulating its target RET. In short, Selpercatinib inhibited the activation of fibroblasts and EMT-like process of lung epithelial cells by inhibiting TGF-ß1/Smad and TGF-ß1/non-Smad pathways, thus alleviating BLM-induced pulmonary fibrosis in mice.

Influences of pretreatment methods on the mechanical and environmental behaviors of PG-GGBS-LM ternary stabilizer.

Phosphogypsum is a kind of acidic industrial byproducts with high content of soluble phosphorus and fluorine pollutants, which requires to be pretreated when used as cementitious material to (partial) replace traditional Portland cement. In this study, five different pretreatment methods were proposed for comparative analysis to examine the pretreatment effect on the mechanical and environmental behaviors of ternary phosphogypsum (PG), ground granulated blast-furnace slag (GGBS), and lime (LM) mixed stabilizer. Series laboratory tests, including unconfined compressive strength (UCS), pH, phosphorus (P)/fluorine (F) leaching, scanning electron microscopy (SEM), and X-ray diffraction (XRD) tests, were conducted to comprehend the macro- and microscopic mechanism. The results show that it is essential to grind raw PG to finer powdered state, so that it reacts more easily and quickly with LM and water. In addition, it was noticed that the UCS and P/F leaching concentration are not only affected by the mixing proportion of the PG-GGBS-LM ternary stabilizer, but also by the curing duration. The UCS increases rapidly from initial curing period and then grows slowly after 28 days of curing. From the perspective of strength evolution, mixing proportion of PG: GGBS: LM = 15:80:5 is optimal, but considering the economy and environmental related issues, PG: GGBS: LM = 30:65:5 was regarded as a more attractive choice. The findings can provide a reference for the selection of pretreatment methods and design of PG-based cementitious materials suited for stabilized soils.

MONAI Label: A framework for AI-assisted interactive labeling of 3D medical images.

The lack of annotated datasets is a major bottleneck for training new task-specific supervised machine learning models, considering that manual annotation is extremely expensive and time-consuming. To address this problem, we present MONAI Label, a free and open-source framework that facilitates the development of applications based on artificial intelligence (AI) models that aim at reducing the time required to annotate radiology datasets. Through MONAI Label, researchers can develop AI annotation applications focusing on their domain of expertise. It allows researchers to readily deploy their apps as services, which can be made available to clinicians via their preferred user interface. Currently, MONAI Label readily supports locally installed (3D Slicer) and web-based (OHIF) frontends and offers two active learning strategies to facilitate and speed up the training of segmentation algorithms. MONAI Label allows researchers to make incremental improvements to their AI-based annotation application by making them available to other researchers and clinicians alike. Additionally, MONAI Label provides sample AI-based interactive and non-interactive labeling applications, that can be used directly off the shelf, as plug-and-play to any given dataset. Significant reduced annotation times using the interactive model can be observed on two public datasets.

The inhibitory impact of Schisandrin on inflammation and oxidative stress alleviates LPS-induced acute kidney injury.

Inflammation and oxidative stress (OS) are the major pathogenic characteristics of acute kidney injury (AKI). Studies have shown that Schisandrin (Sch) could regulate inflammatory disease. However, the function and mechanism of Sch in AKI progression are still unknown. Here, we investigated Sch's potential effects and mechanism on mice's renal damage and macrophages induced by lipopolysaccharide (LPS). Sch decreased LPS-induced inflammatory factor production while increasing the activity of related antioxidant enzymes in macrophages and mouse kidney tissues. Hematoxylin and eosin staining revealed that Sch may have the ability to profoundly inhibit inflammatory cell invasion and tissue damage caused by LPS in renal tissue. Furthermore, Western blot and immunohistochemical studies showed that Sch exerted its effects mainly through up-regulation of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 and inhibition of Toll-like receptor 4‒mitogen-activated protein kinases/nuclear factor-kappa B pathways. Collectively, this study illustrates that Sch suppresses LPS-stimulated AKI by descending inflammation and OS, illuminating prospective AKI treatment options.

Photo-assisted natural chalcopyrite activated peracetic acid for efficient micropollutant degradation.

The effective activation of natural chalcopyrite (CuFeS2) on peracetic acid (PAA) to remove organic micropollutants was studied under visible light irradiation. Results showed than an effective sulfamethoxazole (SMX) degradation (95.0 %) was achieved under visible light irradiation for 30 min at pH 7.0. Quenching experiments, electron spin resonance analysis, and LC/MS spectrum demonstrated that HO• and CH3C(O)OO• were the main reactive species for SMX degradation, accounting for 43.3 % and 56.7 % of the contributions, respectively. Combined with X-ray photoelectron spectroscopy analysis, the photoelectrons generated on CuFeS2 activated by visible light enhanced the Fe3+/Fe2+ and Cu2+/Cu+ cycles on the surface, thereby activating PAA to generate HO•/CH3C(O)OO•. The removal rate of SMX decreased with the increase in wavelengths, due to the formation of low energy photons at longer wavelengths. Besides, the optimal pH for degradation of SMX by CuFeS2/PAA/Vis-LED process was neutral, which was attributed to the increasing easily activated anionic form of PAA during the increase in pH and the depletion of Fe species at alkaline conditions. Cl-, HCO3-, and HA slightly inhibited SMX degradation because of reactive species being quenched and/or shielding effect. Furthermore, the degradation efficiency of different pollutants by CuFeS2/PAA/Vis-LED was also measured, and the removal efficiency was different owing to the selectivity of CH3C(O)OO•. Finally, the process exhibited good applicability in real waters. Overall, this study provides new insight into visible light-catalyzed activation of PAA and suggests on further exploration of the intrinsic activation mechanism of PAA.

Improving Lead Phytoremediation Using Endophytic Bacteria Isolated from the Pioneer Plant Ageratina adenophora (Spreng.) from a Mining Area.

This study aimed to isolate and characterise endophytic bacteria from the pioneer plant Ageratina adenophora in a mining area. Seven strains of metal-resistant endophytic bacteria that belong to five genera were isolated from the roots of A. adenophora. These strains exhibited various plant growth-promoting (PGP) capabilities. Sphingomonas sp. ZYG-4, which exhibited the ability to secrete indoleacetic acid (IAA; 53.2 ± 8.3 mg·L-1), solubilize insoluble inorganic phosphates (Phosphate solubilization; 11.2 ± 2.9 mg·L-1), and regulate root ethylene levels (1-aminocyclopropane-1-carboxylic acid deaminase activity; 2.87 ± 0.19 µM α-KB·mg-1·h-1), had the highest PGP potential. Therefore, Sphingomonas sp. ZYG-4 was used in a pot experiment to study its effect on the biomass and Pb uptake of both host (Ageratina adenophora) and non-host (Dysphania ambrosioides) plants. Compared to the uninoculated control, Sphingomonas sp. ZYG-4 inoculation increased the biomass of shoots and roots by 59.4% and 144.4% for A. adenophora and by 56.2% and 57.1% for D. ambrosioides, respectively. In addition, Sphingomonas sp. ZYG-4 inoculation enhanced Pb accumulation in the shoot and root by 268.9% and 1187.3% for A. adenophora, and by 163.1% and 343.8% for D. ambrosioides, respectively, compared to plants without bacterial inoculation. Our research indicates that endophytic bacteria are promising candidates for enhancing plant growth and facilitating microbe-assisted phytoremediation in heavy metal-contaminated soil.

Decreased Ubiquitination and Acetylation of Histones 3 and 4 Are Associated with Obesity-Induced Disorders of Spermatogenesis in Mice.

BACKGROUND: Obesity, a chronic metabolic disorder, is related to cardiovascular diseases, diabetes, cancer, and reproductive disorders. The relationship between obesity and male infertility is now well recognized, but the mechanisms involved are unclear. We aimed to observe the effect of obesity on spermatogenesis and to investigate the role of histone ubiquitination and acetylation modifications in obesity-induced spermatogenesis disorders. METHODS: Thirty male C57BL/6J mice were randomly divided into two groups. The control group was fed with a general maintenance diet (12% fat), while a high-fat diet (HFD) group was fed with 40% fat for 10 weeks; then, they were mated with normal females. The fertility of male mice was calculated, testicular and sperm morphology were observed, and the expression levels of key genes and the levels of histone acetylation and ubiquitination modification during spermatogenesis were detected. RESULTS: The number of sperm was decreased, as well as the sperm motility, while the number of sperm with malformations was increased. In the testes, the mRNA and protein expression levels of gonadotropin-regulated testicular RNA helicase (GRTH/DDX25), chromosome region maintenance-1 protein (CRM1), high-mobility group B2 (HMGB2), phosphoglycerate kinase 2 (PGK2), and testicular angiotensin-converting enzyme (tACE) were decreased. Furthermore, obesity led to a decrease in ubiquitinated H2A (ubH2A) and reduced levels of histone H3 acetylation K18 (H3AcK18) and histone H4 acetylation K5, K8, K12, and K16 (H4tetraAck), which disrupted protamine 1 (Prm1) deposition in testis tissue. CONCLUSION: These results suggest that low levels of histone ubiquitination and acetylation are linked with obesity-induced disorders during spermatogenesis, contributing to a better understanding of obesity-induced damage to male reproduction.

[Changes in Soil Nitrogen Components and Their Relationship with Environmental Factors with Different Tea Plantation Ages].

Changes in soil nitrogen components in tea gardens affect the soil nitrogen supply capacity and nitrogen cycle. In this study, soil samples were collected from forest land, cultivated land, and tea gardens with different plantation ages (30, 50, and 70 years) to explore the changes in soil nitrogen components and their relationship with physicochemical properties and enzyme activities. The results showed that:① with the increase in tea plantation age, the silt, total phosphorus, and urease and catalase activities gradually increased, whereas the sand, clay, pH, electrical conductivity, soil organic carbon, and the activities of invertase gradually decreased. The alkaline phosphatase activity increased first and then decreased with the increase in tea plantation age, and no significant differences were observed in soil water content and acid phosphatase activity. ② With the increase in tea plantation age, the contents of acid ammonia nitrogen, amino acid nitrogen, and nitrate nitrogen (NO3--N) increased significantly, and the contents of total nitrogen, acid ammonia nitrogen, hydrolyzable unknown nitrogen, and non-hydrolyzable nitrogen in tea gardens were significantly higher than those in forest land. ③ The total phosphorus, alkaline phosphatase, and urease were the main factors affecting soil nitrogen components. Among them, organic nitrogen components were significantly correlated with total phosphorus and alkaline phosphatase, and inorganic nitrogen components were significantly correlated with alkaline phosphatase, whereas total nitrogen had significant correlations with sand, silt, total phosphorus, urease, and alkaline phosphatase.

Time-Course Transcriptomic Analysis Reveals Molecular Insights into the Inflorescence and Flower Development of Cardiocrinum giganteum.

Cardiocrinum giganteum is an endemic species of east Asia which is famous for its showy inflorescence and medicinal bulbs. Its inflorescence is a determinate raceme and the flowers bloom synchronously. Morphological observation and time-course transcriptomic analysis were combined to study the process of inflorescence and flower development of C. giganteum. The results show that the autonomic pathway, GA pathway, and the vernalization pathway are involved in the flower formation pathway of C. giganteum. A varied ABCDE flowering model was deduced from the main development process. Moreover, it was found that the flowers in different parts of the raceme in C. giganteum gradually synchronized during development, which is highly important for both evolution and ecology. The results obtained in this work improve our understanding of the process and mechanism of inflorescence and flower development and could be useful for the flowering period regulation and breeding of C. giganteum.

Synthesis and Herbicidal Activity of 2-(2-Oxo-3-pyridyl-benzothiazol-6-yloxy)hexanoic Acids.

The discovery of a lead compound is fundamental to herbicide innovation, but the limited availability of valuable lead compounds has hindered their development in recent years. By utilizing the structural diversity-oriented inactive group strategy, 3-(2-pyridyl)-benzothiazol-2-one was identified as a promising lead scaffold for herbicides, starting from benzothiazole which is an inactive moiety commonly found in herbicides such as mefenacet, benazolin, benzthiazuron, and fenthiaprop-ethyl. To investigate the structure-activity relationship (SAR) of these chemicals, a series of 2-(2-oxo-3-pyridyl-benzothiazol-6-yloxy)hexanoic acid derivatives (VI01 ∼ VI28) were synthesized through classical nucleophilic SNAr reaction using halogenated pyridines and 6-methoxybenzothiazole-2-one. The chemical structures of all the title compounds were confirmed by NMR and MS analysis. Petri dish assays indicated that many compounds exhibited potent herbicidal activity against both broad-leaf weeds and grass weeds at 1.0 mg/L. The SAR analysis revealed that the presence of a trifluoromethyl group at the 5-position of pyridine is essential for herbicidal activity. Furthermore, carboxylic esters exhibit higher herbicidal activity compared to carboxylic amides and free acids, and the activity decreased with the extension of the carbon chain. The postemergence herbicidal activity of VI03 against 16 species of weeds was tested by pot experiments in a greenhouse. VI03 demonstrated comparable efficacy in controlling broadleaf weeds and superior efficacy in controlling grass weeds compared to carfentrazone ethyl. The present study has unveiled a novel molecular scaffold exhibiting remarkably potent herbicidal activity. These findings are anticipated to provide valuable insights for the advancement of new herbicides and offer an alternative approach for managing resistant weeds.

Discovery of N-benzyl-6-methylpicolinamide as a potential scaffold for bleaching herbicides.

BACKGROUND: In pesticide research, bleaching herbicides have always been a hot topic. Our previous research showed that N-(4-fluorobenzyl)-2-methoxybenzamide is an innovative lead compound for bleaching herbicides. RESULTS: A total of 40 derivatives of picolinamides were prepared and evaluated for their herbicidal activity by Petri dish tests and postemergence trials. The structure-activity relationship (SAR) revealed that introducing electron-withdrawing groups at the 3- or 4-positions of the benzyl significantly enhances herbicidal activity. Furthermore, ZI-04 induced similar symptoms such as bleaching effect in treated weeds and accumulation of biosynthetic precursors for carotenoids as observed with diflufenican. ZI-04 also exhibited significant cross-resistance to diflufenican and had a lower resistance risk than diflufenican. CONCLUSION: N-benzyl-6-methylpicolinamides were discovered as a novel scaffold for bleaching herbicides. The accumulation of phytoene, phytofluene and ζ-Carotene in radish cotyledons, and cross-resistance observed with diflufenican, showed that title compounds can interfere with carotenoid biosynthesis. © 2024 Society of Chemical Industry.

[Efficacy and Prognosis of Chemotherapy Regimen Containing BTK Inhibitor in Treatment of Recurrent/Refractory Mantle Cell Lymphoma].

OBJECTIVE: To investigate the efficacy and prognosis of chemotherapy regimen containing Bruton's tyrosine kinase (BTK) inhibitor in the treatment of relapsed/refractory mantle cell lymphoma (R/R MCL). METHODS: The clinical data of 134 patients with R/R MCL were collected and analyzed retrospectively. The clinical characteristics of patients and effect of chemotherapy regimen on efficacy, overall survival (OS) and progression-free survival (PFS) were observed. RESULTS: The median age of the patients was 58(56-61) years old, and male to female ratio was about 2.9∶1. Patients with Ann Arbor stage III-IV accounted for 77.6%, extranodal involvement > 2 for 43.3%, bone marrow involvement for 60.4%, gastrointestinal involvement for 24.6%, and hepatosplenomegaly for 38.1%. The median follow-up time was 30 (2-103) months, overall response rate (ORR) was 41.8%, 3-year PFS was not reached, and 3-year and 5-year OS rate was 62.7% and 53.8%, respectively. The ORR of BTK inhibitor group was 56.9%, which was higher than 32.5% of non-BTK inhibitor group (P =0.006). The difference was statistically significant in PFS between the two groups (P =0.002), but was not in OS (P>0.05). The difference was statistically significant in OS between classical and special morphology (P < 0.001), but was not in PFS (P >0.05). Ki-67 was an influencing factor for OS and PFS. Multivariate analysis showed that Ki-67, B symptoms, MIPI score, and Ann Arbor stage were independent prognostic factors affecting patients' OS. The second-line treatment regimen was an independent prognostic factor affecting patients' PFS. CONCLUSIONS: The chemotherapy regimen containing BTK inhibitors can effectively improve the efficacy and prolong the PFS of R/R MCL patients. Ki-67, B symptoms, MIPI score, and Ann Arbor stage are independent prognostic factors for R/R MCL patients.