Inhibition of co-occurring weeds and young sugarcane seedling growth by perennial sugarcane root extract.

Allelopathy is a process whereby a plant directly or indirectly promotes or inhibits growth of surrounding plants. Perennial sugarcane root extracts from various years significantly inhibited Bidens pilosa, Digitaria sanguinalis, sugarcane stem seedlings, and sugarcane tissue-cultured seedlings (P < 0.05), with maximum respective allelopathies of - 0.60, - 0.62, - 0.20, and - 0.29. Allelopathy increased with increasing concentrations for the same-year root extract, and inhibitory effects of the neutral, acidic, and alkaline components of perennial sugarcane root extract from different years were significantly stronger than those of the control for sugarcane stem seedlings (P < 0.05). The results suggest that allelopathic effects of perennial sugarcane root extract vary yearly, acids, esters and phenols could be a main reason for the allelopathic autotoxicity of sugarcane ratoons and depend on the type and content of allelochemicals present, and that allelopathy is influenced by other environmental factors within the rhizosphere such as the presence of old perennial sugarcane roots. This may be a crucial factor contributing to the decline of perennial sugarcane root health.

Direct synthesis of branched amines enabled by dual-catalyzed allylic C─H amination of alkenes with amines.

Direct conversion of hydrocarbons into amines represents an important and atom-economic goal in chemistry for decades. However, intermolecular cross-coupling of terminal alkenes with amines to form branched amines remains extremely challenging. Here, a visible-light and Co-dual catalyzed direct allylic C─H amination of alkenes with free amines to afford branched amines has been developed. Notably, challenging aliphatic amines with strong coordinating effect can be directly used as C─N coupling partner to couple with allylic C─H bond to form advanced amines with molecular complexity. Moreover, the reaction proceeds with exclusive regio- and chemoselectivity at more steric hinder position to deliver primary, secondary, and tertiary aliphatic amines with diverse substitution patterns that are difficult to access otherwise.

Effects of appropriate low-temperature treatment on the yield and quality of pigmented potato (Solanum tuberosum L.) tubers.

Temperature is one of the important environmental factors affecting plant growth, yield and quality. Moreover, appropriately low temperature is also beneficial for tuber coloration. The red potato variety Jianchuanhong, whose tuber color is susceptible to temperature, and the purple potato variety Huaxinyangyu, whose tuber color is stable, were used as experimental materials and subjected to 20 °C (control check), 15 °C and 10 °C treatments during the whole growth period. The effects of temperature treatment on the phenotype, the expression levels of structural genes related to anthocyanins and the correlations of each indicator were analyzed. The results showed that treatment at 10 °C significantly inhibited the potato plant height, and the chlorophyll content and photosynthetic parameters in the leaves were reduced, and the enzyme activities of SOD and POD were significantly increased, all indicating that the leaves were damaged. Treatment at 10 °C also affected the tuberization of Huaxinyangyu and reduced the tuberization and coloring of Jianchuanhong, while treatment at 15 °C significantly increased the stem diameter, root-to-shoot ratio, yield and content of secondary metabolites, especially anthocyanins. Similarly, the expression of structural genes were enhanced in two pigmented potatoes under low-temperature treatment conditions. In short, proper low temperature can not only increase yield but also enhance secondary metabolites production. Previous studies have not focused on the effects of appropriate low-temperature treatment during the whole growth period of potato on the changes in metabolites during tuber growth and development, these results can provide a theoretical basis and technical guidance for the selection of pigmented potatoes with better nutritional quality planting environment and the formulation of cultivation measures.

MV-SHIF: Multi-view symmetric hypothesis inference fusion network for emotion-cause pair extraction in documents.

Emotion-cause pair extraction (ECPE) is a challenging task that aims to automatically identify pairs of emotions and their causes from documents. The difficulty of ECPE lies in distinguishing valid emotion-cause pairs from many irrelevant ones. Most previous methods have primarily focused on utilizing multi-task learning to extract semantic information solely from documents without explicitly encoding the relations between clauses. We propose a new approach that incorporates textual entailment paradigm aiming to infer the entailment relationship between the original document as the premise and the clauses or pairs described as the hypothesis. Our approach designs label-view hypothesis templates to improve ECPE by filtering out irrelevant emotion and cause clauses. Furthermore, we formulate candidate emotion-cause pairs as hypothesis statements, and define explicit multi-view symmetric templates to capture the emotion-cause relation semantics. The text entailment recognition for ECPE is finally implemented by fusing multi-view semantic information using a simplified capsule network. Our proposed model achieves state-of-the-art performance on ECPE compared to previous baselines. More importantly, this work demonstrates a novel effective way of applying the textual entailment paradigm to ECPE or clause-level causal discovery by designing multi-view hypothesis inference and information fusion.

[A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020]. / 2019­2020å¹´160ä¾‹å„¿ç«¥è‚ºç‚Žé“¾çƒèŒè„‘è†œç‚Žä¸´åºŠæµè¡Œç— å­¦å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To investigate the clinical characteristics and prognosis of pneumococcal meningitis (PM), and drug sensitivity of Streptococcus pneumoniae (SP) isolates in Chinese children. METHODS: A retrospective analysis was conducted on clinical information, laboratory data, and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country. RESULTS: Among the 160 children with PM, there were 103 males and 57 females. The age ranged from 15 days to 15 years, with 109 cases (68.1%) aged 3 months to under 3 years. SP strains were isolated from 95 cases (59.4%) in cerebrospinal fluid cultures and from 57 cases (35.6%) in blood cultures. The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87) and 27% (21/78), respectively. Fifty-five cases (34.4%) had one or more risk factors for purulent meningitis, 113 cases (70.6%) had one or more extra-cranial infectious foci, and 18 cases (11.3%) had underlying diseases. The most common clinical symptoms were fever (147 cases, 91.9%), followed by lethargy (98 cases, 61.3%) and vomiting (61 cases, 38.1%). Sixty-nine cases (43.1%) experienced intracranial complications during hospitalization, with subdural effusion and/or empyema being the most common complication [43 cases (26.9%)], followed by hydrocephalus in 24 cases (15.0%), brain abscess in 23 cases (14.4%), and cerebral hemorrhage in 8 cases (5.0%). Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old, with rates of 91% (39/43) and 83% (20/24), respectively. SP strains exhibited complete sensitivity to vancomycin (100%, 75/75), linezolid (100%, 56/56), and meropenem (100%, 6/6). High sensitivity rates were also observed for levofloxacin (81%, 22/27), moxifloxacin (82%, 14/17), rifampicin (96%, 25/26), and chloramphenicol (91%, 21/23). However, low sensitivity rates were found for penicillin (16%, 11/68) and clindamycin (6%, 1/17), and SP strains were completely resistant to erythromycin (100%, 31/31). The rates of discharge with cure and improvement were 22.5% (36/160) and 66.2% (106/160), respectively, while 18 cases (11.3%) had adverse outcomes. CONCLUSIONS: Pediatric PM is more common in children aged 3 months to under 3 years. Intracranial complications are more frequently observed in children under 1 year old. Fever is the most common clinical manifestation of PM, and subdural effusion/emphysema and hydrocephalus are the most frequent complications. Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates. Adverse outcomes can be noted in more than 10% of PM cases. SP strains are high sensitivity to vancomycin, linezolid, meropenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.

Screening and functional analysis of StMYB transcription factors in pigmented potato under low-temperature treatment.

MYB transcription factors play an extremely important regulatory role in plant responses to stress and anthocyanin synthesis. Cloning of potato StMYB-related genes can provide a theoretical basis for the genetic improvement of pigmented potatoes. In this study, two MYB transcription factors, StMYB113 and StMYB308, possibly related to anthocyanin synthesis, were screened under low-temperature conditions based on the low-temperature-responsive potato StMYB genes family analysis obtained by transcriptome sequencing. By analyzed the protein properties and promoters of StMYB113 and StMYB308 and their relative expression levels at different low-temperature treatment periods, it is speculated that StMYB113 and StMYB308 can be expressed in response to low temperature and can promote anthocyanin synthesis. The overexpression vectors of StMYB113 and StMYB308 were constructed for transient transformation tobacco. Color changes were observed, and the expression levels of the structural genes of tobacco anthocyanin synthesis were determined. The results showed that StMYB113 lacking the complete MYB domain could not promote the accumulation of tobacco anthocyanins, while StMYB308 could significantly promote the accumulation involved in tobacco anthocyanins. This study provides a theoretical reference for further study of the mechanism of StMYB113 and StMYB308 transcription factors in potato anthocyanin synthesis.

Evaluation of Clinical Efficacy of Acupuncture and Moxibustion for Asthma: Systematic Review and Meta-Analysis.

Objective: The effectiveness of manual acupuncture for treating bronchial asthma is still debatable and broad, and the effects of different acupuncture points, treatment durations, or illness trajectories have never been rigorously assessed. The objective of this revised systematic review and subgroup meta-analysis of randomized controlled trials (RCTs) is to ascertain the clinical efficacy of manual acupuncture on bronchial asthma and whether these effects varied depending on the acupuncture points, length of treatment, or course of the disease. Materials and methods: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria were followed for creating a systematic review and meta-analysis. From the beginning through March 25, 2022, six electronic databases were checked. For the treatment of asthma, all RCTs contrasting acupuncture therapy along with conventional treatment against conventional treatment alone were chosen. The information was examined using Review Manager version 5.3 and Comprehensive Meta-Analysis version 3. Clinical efficacy (including the effective rate and the recurrence rate) was the primary outcome, and pulmonary function (including FEV1%, PEF) and The secondary results were T-lymphocyte immunity (containing CD3+, CD4+, and CD8+). Based on the acupuncture points, length of therapy, and nature of the condition, subgroup analyses were carried out. Results: There were a total of 21 RCTs that enrolled 2510 individuals. According to the meta-findings, analysis's manual acupuncture in addition to conventional treatment significantly increased the effective rate when compared to conventional treatment alone [OR = 5.14 95% CI 3.58-7.38, P < .00001], lung functions [FEV1% (MD = 6.18, 95% CI 2.40-9.96, P = .001) and PEF (MD = 0.45 95% CI 0.18-0.73, P = .001)], immune functions [CD3+ T lymphocytes (MD = 7.55 95% CI 6.55-8.56, P < .00001), CD4+ T-lymphocytes (MD = 5.11 95% CI 4.09-6.13, P < .00001), T-lymphocyte CD8+ (MD = -0.37.11 95% CI -3.62--2.51, P < .00001)] and noteworthy reduction in the recurrence rate (OR = 0.19 95% CI 0.10-0.38, P < .00001). Results from the subgroup analysis were consistent. Conclusion: Manual acupuncture combined with Western Medicine is more effective than conventional treatment alone for bronchial asthma. Combination therapy can significantly improve clinical efficacy, lung function, and immune function while reducing the relapse rate. But to further support the results of this investigation, high-quality RCTs with long-term outcomes are still required, taking into account the inherent limitations of the included studies. Registration number: PROSPERO (no. CRD42022357805) (https://www.crd.york.ac.uk/prospero/).

Expression and clinical significance of miR-141-5p as a biomarker in the serum of patients with early spontaneous abortion.

AIM: miR-141-5p expression in patients with Early Spontaneous Abortion (ESA) and its correlation with hormone levels during pregnancy were investigated. METHODS: A total of 70 pregnant women with ESA were selected as the research group, and 70 normal pregnant women who chose abortion for non-medical reasons were selected as the Con group. Serum ß-HCG, Progesterone (P), and Estrogen (E2) were detected by enzyme-linked immunosorbent assay. Differentially expressed miRNAs were screened by miRNA microarray analysis. miR-141-5p expression was detected by RT-qPCR, and its correlation with serum ß-HCG, P, and E2 levels was analyzed. The diagnostic value of miR-141-5p for ESA was evaluated by the ROC curve. RESULTS: Serum ß-HCG, P, and E2 were decreased and serum miR-141-5p was increased in patients with ESA. Pearson correlation analysis showed that serum ß-HCG, P, and E2 levels were negatively correlated with miR-141-5p expression levels. ROC curve showed that miR-141-5p had a diagnostic value for ESA. CONCLUSIONS: miR-141-5p is related to hormone levels during pregnancy and is expected to become a new candidate diagnostic marker for ESA.

A membrane-associated phosphoswitch in Rad controls adrenergic regulation of cardiac calcium channels.

The ability to fight or flee from a threat relies on an acute adrenergic surge that augments cardiac output, which is dependent on increased cardiac contractility and heart rate. This cardiac response depends on ß-adrenergic-initiated reversal of the small RGK G protein Rad-mediated inhibition of voltage-gated calcium channels (CaV) acting through the Cavß subunit. Here, we investigate how Rad couples phosphorylation to augmented Ca2+ influx and increased cardiac contraction. We show that reversal required phosphorylation of Ser272 and Ser300 within Rad's polybasic, hydrophobic C-terminal domain (CTD). Phosphorylation of Ser25 and Ser38 in Rad's N-terminal domain (NTD) alone was ineffective. Phosphorylation of Ser272 and Ser300 or the addition of 4 Asp residues to the CTD reduced Rad's association with the negatively charged, cytoplasmic plasmalemmal surface and with CaVß, even in the absence of CaVα, measured here by FRET. Addition of a posttranslationally prenylated CAAX motif to Rad's C-terminus, which constitutively tethers Rad to the membrane, prevented the physiological and biochemical effects of both phosphorylation and Asp substitution. Thus, dissociation of Rad from the sarcolemma, and consequently from CaVß, is sufficient for sympathetic upregulation of Ca2+ currents.

Characterization of m6A methylation modifications in gastric cancer.

Widely recognized as an essential epitranscriptomic modification, RNA N6-methyladenosine (m6A) is involved in both physiological and pathological processes. Here, we want to investigate m6A modification's potential roles in gastric cancer. Gastric cancer samples were selected from TCGA-STAD and GEO (GSE84426, GSE84433) datasets. Based on 18 regulators of m6A, m6A modification patterns were thoroughly evaluated in gastric cancer samples. Principal component analysis algorithms were used to construct the m6Ascore, using which, m6A modification features in tumor somatic mutations and immune checkpoint blockade therapy were analyzed. 34 gastric cancer samples were collected to verify the effectiveness of the m6Ascore. Here, we determined three different m6A modification patterns. m6Acluster-C modification pattern presented immune activation-associated enrichment pathways and have significant survival advantages. Then, in gastric cancer, m6Ascore could act as an independent prognostic biomarker. A significant survival benefit was exhibited in patients with high m6Ascore. Moreover, the modification signature of m6A uncovered in this study would help to predict immune checkpoint blockade therapy's responses. In conclusion, our discoveries all pointed to the fact that modification patterns of m6A were linked to the TME. Moreover, evaluation of individual tumor's m6A modification pattern will help to guide immunotherapy strategies that shows more therapeutic effects.

Dopant effect on the optical and thermal properties of the 2D organic-inorganic hybrid perovskite (HDA)2PbBr4.

Lead-based two-dimensional organic-inorganic hybrid perovskites (2D HOIPs) are popular materials with various optical properties, which can be tuned through metal ion doping. Due to the size and valence misfit, metal ion dopants in 2D lead-based HOIPs are still limited. In this work, Mn2+, Sb3+ and Bi3+ are doped into 2D (HDA)2PbBr4 (HDA = protonated dopamine) successfully. As a result, the dopants in 2D (HDA)2PbBr4 can induce their characteristic optical spectra, which is studied at different temperatures and excitation powers. The temperature-dependent energy transfer in the Mn-doped sample has been clarified, in which abnormal phenomena including negative thermal quenching have been observed. In addition, the dopant ions can impact the phase transition temperatures of the samples, especially lowering their crystallization temperatures greatly. The mussel-inspired organic cation, feasible metal ion regulation, and superior stability provide (HDA)2PbBr4 potential for further applications.

Expert consensus on the diagnosis, treatment, and prevention of respiratory syncytial virus infections in children.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5 years, representing a major global healthcare burden. There is a great unmet need for new agents and universal strategies to prevent RSV infections in early life. A multidisciplinary consensus development group comprising experts in epidemiology, infectious diseases, respiratory medicine, and methodology aims to develop the current consensus to address clinical issues of RSV infections in children. DATA SOURCES: The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, and the Cochrane Library, using variations in terms for "respiratory syncytial virus", "RSV", "lower respiratory tract infection", "bronchiolitis", "acute", "viral pneumonia", "neonatal", "infant" "children", and "pediatric". RESULTS: Evidence-based recommendations regarding diagnosis, treatment, and prevention were proposed with a high degree of consensus. Although supportive care remains the cornerstone for the management of RSV infections, new monoclonal antibodies, vaccines, drug therapies, and viral surveillance techniques are being rolled out. CONCLUSIONS: This consensus, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of RSV infections. Further improvements in the management of RSV infections will require generating the highest quality of evidence through rigorously designed studies that possess little bias and sufficient capacity to identify clinically meaningful end points.

Clinical features and demographic characteristics of gestational trophoblastic neoplasia: Single center experience and the SEER database.

The aim of this study was to analyze the clinical features and demographic characteristics of gestational trophoblastic neoplasia (GTN) patients, specifically choriocarcinoma (CC), placental site trophoblastic tumour (PSTT), and epithelioid trophoblastic tumor (ETT). We utilized data from a local hospital and the SEER database, as well as survival outcomes of CC in SEER database. Additionally, we used multiple risk factors to create a prognostic nomogram model for CC patients. The study included GTN patients from the SEER database between 1975 and 2016 as well as those from the First Affiliated Hospital of Xi 'an Jiaotong University between January 2005 and May 2022. Related factors of patients were compared using the chi-square (χ2) or Fisher's exact test. For assessing overall survival we employed the Kaplan-Meier method and log-rank test. To construct the nomogram, we used Cox regression. Statistically significant differences were found between CC and PSTT/ETT patients in terms of surgery in local hospital, as well as age and year of diagnosis in the SEER database. Moreover, significant differences were observed between low and high (HR) /ultra-high risk (UHR) groups regarding FIGO stage, surgery and chief complaint at the local hospital, and FIGO stage, surgery and unemployment in the SEER database. The Cox regression analysis confirmed that age, race, surgery, marital status, FIGO stage, and unemployment were correlated with CC prognosis. Furthermore, the analysis showed that patients aged 40 years or older and those with FIGO Ⅲ/Ⅳ were independent prognostic factors of CC. The study indicates that atypical symptoms or signs may be the main reasons for HR /UHR patients to seek medical treatment. Therefore, providing multidisciplinary care is recommended for CC patients experiencing psychological distress due to unfavorable marital status or unemployment.

Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of YK-029A in Treatment-Naive Patients With Advanced NSCLC Harboring EGFR Exon 20 Insertion Mutations: A Phase 1 Trial.

INTRODUCTION: Treatment options for treatment-naive patients with advanced NSCLC harboring EGFR exon 20 insertion (ex20ins) mutations are limited. This study evaluated the safety, tolerability, and pharmacokinetics of YK-029A, a third-generation EGFR tyrosine kinase inhibitor, and the preliminary efficacy of YK-029A in treatment-naive patients with EGFR ex20ins mutation. METHODS: This multicenter, dose-escalation, and dose-expansion phase 1 clinical trial enrolled patients with NSCLC harboring EGFR mutations. During the dose-escalation phase, YK-029A was orally administered using the traditional 3+3 principle at 50, 100, 150, 200, and 250 mg/d. In the dose-expansion phase, treatment-naive patients with EGFR ex20ins mutations were enrolled and administered YK-029A 200 mg/d. The primary end point was safety and tolerability. RESULTS: The safety analysis included 108 patients. No dose-limiting toxicity was observed, and the maximum tolerated dose was not reached. The most common treatment-emergent adverse events were anemia (50.9%), diarrhea (49.1%), and rash (34.3%). There was minimal drug accumulation after multiple doses. A total of 28 treatment-naive patients with EGFR ex20ins mutations were enrolled in the dose-expansion and 26 were included in the efficacy analysis. According to the independent review committee evaluation, the objective response rate was 73.1% (95% confidence interval: 52.21%-88.43%), and the disease control rate was 92.3% (95% confidence interval: 74.87%-99.05%). CONCLUSIONS: YK-029A was found to have manageable safety and be tolerable in patients with NSCLC harboring EGFR mutations and have promising antitumor activity in untreated patients with EGFR ex20ins mutations.

Low-dose aspirin for prevention of cardiovascular mortality in patients with type 2 diabetes and chronic kidney disease: A real-world nationwide cohort study.

AIMS/INTRODUCTION: Cardiovascular mortality risk is elevated among patients with diabetes and concurrent chronic kidney disease. However, controversy surrounds the use of aspirin for primary prevention within this population. This study aims to assess the effectiveness and safety of low-dose aspirin for primary prevention in patients with diabetes and pre-end-stage renal disease. MATERIALS AND METHODS: This was a retrospective population-based cohort study using the National Health Insurance Research Database in Taiwan. The study included adults with type 2 diabetes who were enrolled in the pre-end-stage renal disease pay-for-performance program and had no atherosclerotic cardiovascular disease. We used propensity score analysis to control baseline characteristics between the two groups. Clinical outcomes including cardiovascular mortality, all-cause mortality, major bleeding, and renal disease progression were compared between patients who first received aspirin and those who did not. RESULTS: Between January 2012 and December 2015, a total of 2,155 low-dose aspirin users and 6,737 nonaspirin users were identified. Following propensity score adjustment, aspirin use exhibited a comparable risk of cardiovascular death compared with nonaspirin users (adjusted hazard ratio [aHR] 1.12; 95% confidence interval [CI] 0.65-1.95; P = 0.681). The risk of all-cause mortality was similar between the two groups (aHR 1.07; 95% CI 0.92-1.24; P = 0.385). Similar risks were observed in terms of major bleeding and renal disease progression. CONCLUSIONS: In patients with diabetes and pre-end-stage renal disease who lacked atherosclerotic cardiovascular disease, low-dose aspirin did not demonstrate a reduction in mortality. These findings do not support the use of aspirin for primary prevention in this high-risk population.

Expression and clinical significance of miR-141-5p as a biomarker in the serum of patients with early spontaneous abortion

Abstract Aim miR-141-5p expression in patients with Early Spontaneous Abortion (ESA) and its correlation with hormone levels during pregnancy were investigated. Methods A total of 70 pregnant women with ESA were selected as the research group, and 70 normal pregnant women who chose abortion for non-medical reasons were selected as the Con group. Serum β-HCG, Progesterone (P), and Estrogen (E2) were detected by enzyme-linked immunosorbent assay. Differentially expressed miRNAs were screened by miRNA microarray analysis. miR-141-5p expression was detected by RT-qPCR, and its correlation with serum β-HCG, P, and E2 levels was analyzed. The diagnostic value of miR-141-5p for ESA was evaluated by the ROC curve. Results Serum β-HCG, P, and E2 were decreased and serum miR-141-5p was increased in patients with ESA. Pearson correlation analysis showed that serum β-HCG, P, and E2 levels were negatively correlated with miR-141-5p expression levels. ROC curve showed that miR-141-5p had a diagnostic value for ESA. Conclusions miR-141-5p is related to hormone levels during pregnancy and is expected to become a new candidate diagnostic marker for ESA.

Engineered stem cell-based strategy: A new paradigm of next-generation stem cell product in regenerative medicine.

Stem cells have garnered significant attention in regenerative medicine owing to their abilities of multi-directional differentiation and self-renewal. Despite these encouraging results, the market for stem cell products yields limited, which is largely due to the challenges faced to the safety and viability of stem cells in vivo. Besides, the fate of cells re-infusion into the body unknown is also a major obstacle to stem cell therapy. Actually, both the functional protection and the fate tracking of stem cells are essential in tissue homeostasis, repair, and regeneration. Recent studies have utilized cell engineering techniques to modify stem cells for enhancing their treatment efficiency or imparting them with novel biological capabilities, in which advances demonstrate the immense potential of engineered cell therapy. In this review, we proposed that the "engineered stem cells" are expected to represent the next generation of stem cell therapies and reviewed recent progress in this area. We also discussed potential applications of engineered stem cells and highlighted the most common challenges that must be addressed. Overall, this review has important guiding significance for the future design of new paradigms of stem cell products to improve their therapeutic efficacy.

Anatomic prognostic factors and their potential roles in refining M1 classification for de novo metastatic nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: To identify anatomic prognostic factors and their potential roles in refining M1 classification for de novo metastatic nasopharyngeal carcinoma (M1-NPC). MATERIALS AND METHODS: All M1-NPC treated with chemotherapy and/or radiotherapy between 2010 and 2019 from two centers (training and validation cohort) were included. The prognostic value of metastatic disease extent and involved organs for overall survival (OS) were assessed by several multivariable analyses (MVA) models. A new M1 classification was proposed and validated in a separate cohort who received immuno-chemotherapy. RESULTS: A total of 197 M1-NPC in the training and 307 in the validation cohorts were included for M1 subdivision study with median follow-up of 46 and 57 months. MVA model with "≤2 organs/≤5 lesions" as the definition of oligometastasis had the highest C-index (0.623) versus others (0.606-0.621). Patients with oligometastasis had better OS versus polymetastasis (hazard ratio [HR] 0.47/0.63) while liver metastases carried worse OS (HR 1.57/1.45) in MVA in the training/validation cohorts, respectively. We proposed to divide M1-NPC into M1a (oligometastasis without liver metastases) and M1b (liver metastases or polymetastasis) with 3-year OS of 66.5%/31.7% and 64.9%/35.0% in the training/validation cohorts, respectively. M1a subset had a better median progress-free survival (not reach vs. 17 months, p < 0.001) in the immuno-chemotherapy cohort (n = 163). CONCLUSION: Oligometastasis (≤2 organs/≤5 lesions) and liver metastasis are prognostic for M1-NPC. Subdivision of M1-NPC into M1a (oligometastasis without liver metastasis) and M1b (liver metastasis or polymetastasis) depicts the prognosis well in M1-NPC patients who received immuno-chemotherapy.

[Evaluation of the Short-Term Efficacy and Safety of Orelabrutinib Combined with High-Dose Methotrexate in the First-line Treatment of Elderly Patients with High Risk Primary Central Nervous System Lymphoma].

OBJECTIVE: To explore the short-term efficacy and adverse reactions of orelabrutinib combined with high-dose methotrexate (HD-MTX) in the first-line treatment of elderly high-risk primary central nervous system lymphoma (PCNSL), as well as the survival of patients. METHODS: Twenty-five elderly patients with high-risk primary central nervous system diffuse large B-cell lymphoma admitted to Fujian Provincial Hospital from June 2016 to June 2022 were enrolled in this study, and complete clinical data from all patients were collected retrospectively, and the cut-off for follow-up was December 2022. 15 patients had received temmozolomide combined with HD-MTX regimen for at least four cycles, sequential lenalidomide maintenance therapy, while 10 patients had received orelabrutinib combined with HD-MTX regimen for at least four cycles, sequential orelabrutinib maintenance therapy. The short-term efficacy and adverse reactions of the two groups of patients after treatment were observed. Kaplan-Meier was used to analyze the progression-free survival (PFS) and time to progression (TTP). RESULTS: The objective response rate (ORR) and 2-year median FPS of orelabrutinib combined with HD-MTX regimen group were similar to the temozolomide combined with HD-MTX regimen group (ORR: 100% vs 66.7%; 2-year median PFS: 16 months vs 15 months, P>0.05). The 2-year median TTP of the orelabrutinib+HD-MTX regimen group was better than that of the temozolomide+HD-MTX regimen group (not reached vs 12 months, P<0.05). There were no significant differences in adverse reactions such as gastrointestinal reactions, bone marrow suppression, liver and kidney damage, cardiotoxicity, pneumonia and bleeding between these two groups (P>0.05). CONCLUSION: For elderly patients with high-risk PCNSL, orelabrutinib combined with HD-MTX has reliable short-term efficacy, good safety, and tolerable adverse reactions, which is worthy of clinical promotion.