Patterns and driving factors of functional traits of desert species with different elevational distributions in the Tibetan Plateau and adjacent areas.

Variations in functional traits serve as measures of plants' ability to adapt to environment. Exploring the patterns of functional traits of desert plants along elevational gradients is helpful to understand the responses and adaptation strategies of species to changing environments. However, it is unknown whether the relationship between functional traits and elevation is affected by differences in the species' elevational distributions (elevation preference and species' range). Importantly, most researches have concerned with differences in mean trait values and ignored intraspecific trait variation. Here, we measured functional traits of desert plants along a wide elevational gradient in the Tibetan Plateau and adjacent areas and explored functional trait patterns over elevation in species with different elevational distributions. We decomposed trait variation and further investigated characterizations of intraspecific variation. Ultimately, the main drivers of trait variation were identified using redundancy analysis. We found that species' elevational distributions significantly influenced the relationship of functional traits such as plant height, leaf dry matter content, leaf thickness, leaf nitrogen and carbon content with elevation. Species with a lower elevational preference showed greater trait variation than species with a higher elevational preference, suggesting that species that prefer high elevation are more conservative facing environmental changes. We provide evidence that interspecific trait variation in leaf thickness and leaf carbon content decreased with increasing species' range, indicating that increased variations in resistance traits within species make greater responsiveness to environmental changes, enabling species a wider range. Elevation, temperature and precipitation were the main drivers of trait variation in species with a low elevational preference, while the effect of precipitation on trait variation in species with a high elevational preference was not significant. This study sheds new insights on how plants with different elevational distributions regulate their ecological strategies to cope with changing environments.

DNAJC24 acts directly with PCNA and promotes malignant progression of LUAD by activating phosphorylation of AKT.

Heat shock proteins (HSPs) are a group of highly conserved proteins found in a wide range of organisms. In recent years, members of the HSP family were overexpressed in various tumors and widely involved in oncogenesis, tumor development, and therapeutic resistance. In our previous study, DNAJC24, a member of the DNAJ/HSP40 family of HSPs, was found to be closely associated with the malignant phenotype of hepatocellular carcinoma. However, its relationship with other malignancies needs to be further explored. Herein, we demonstrated that DNAJC24 exhibited upregulated expression in LUAD tissue samples and predicted poor survival in LUAD patients. The upregulation of DNAJC24 expression promoted proliferation and invasion of LUAD cells in A549 and NCI-H1299 cell lines. Further studies revealed that DNAJC24 could regulate the PI3K/AKT signaling pathway by affecting AKT phosphorylation. In addition, a series of experiments such as Co-IP and mass spectrometry confirmed that DNAJC24 could directly interact with PCNA and promoted the malignant phenotypic transformation of LUAD. In conclusion, our results suggested that DNAJC24 played an important role in the progression of LUAD and may serve as a specific prognostic biomarker for LUAD patients. The DNAJC24/PCNA/AKT axis may be a potential target for future individualized and precise treatment of LUAD patients.

Long-term prognosis of patients with gallbladder carcinoma after curative-intent resection based on changes in the ratio of carbohydrate antigen 19-9 to total bilirubin (CA19-9/TB): a multicenter retrospective cohort study.

BACKGROUND: The prognostic value of carbohydrate antigen 19-9 (CA19-9) is known to be affected by elevated bilirubin levels in patients with gallbladder carcinoma (GBC). The clinical significance of changes in the ratio of CA19-9 levels to total bilirubin (TB) levels in patients with GBC after curative-intent resection remains unknown. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative CA19-9/TB ratio in these patients. METHODS: Prospectively colleced data on consecutive patients who underwent curative-intent resection for GBC between January 2015 and December 2020 stored in a multicenter database from 10 hospitals were analysed in this retrospective cohort study. Based on the adjusted CA19-9 defined as the ratio of CA19-9 to TB, and using 2×103 U/µmol as the upper normal value, patients were divided into a normal group (with normal preoperative and postoperative adjusted CA19-9), a normalization group (with abnormal preoperative but normal postoperative adjusted CA19-9), and a non-normalization group (with abnormal postoperative adjusted CA19-9). The primary outcomes were overall survival (OS) and recurrence-free survival (RFS). The log-rank test was used to compare OS and RFS among the groups. The Cox regression model was used to determine factors independently associated with OS and RFS. RESULTS: The normal group (n=179 patients) and the normalization group (n=73 patients) had better OS and RFS than the non-normalization group (n=65 patients) (the 3-year OS rates 72.0%, 58.4% and 24.2%, respectively; the RFS rates 54.5%, 25.5% and 11.8%, respectively; both P<0.001). There were no significant differences between the normal and the normalization groups in OS and RFS (OS, P=0.255; RFS, P=0.130). Cox regression analysis confirmed that the non-normalization group was independently associated with worse OS and RFS. Subgroup analysis revealed that the non-normalization group of patients who received adjuvant therapy had significantly improved OS and RFS as compared to those who did not receive adjuvant therapy (OS, P=0.025; RFS, P=0.003). CONCLUSIONS: Patients with GBC who underwent curative-intent surgical resection with postoperative abnormal levels of adjusted CA19-9 (the CA19-9/TB ratio) were associated with poorer long-term survival outcomes. Adjuvant therapy after surgery improved the long-term outcomes of these patients.

Cost-effectiveness analysis of amivantamab plus chemotherapy versus chemotherapy alone in NSCLC with EGFR Exon 20 insertions.

Objective: Amivantamab plus chemotherapy has been proved to be an efficient treatment strategy for non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertions. The aim of this study was to conduct the cost-effectiveness analysis of amivantamab-chemotherapy compared with chemotherapy alone in NSCLC harboring EGFR exon 20 insertion mutations. Methods: We constructed a Markov model based on the data derived from the PAPILLON trial. We evaluated the cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were used to evaluate the influence of different parameters on this model. Results: Compared with chemotherapy alone, amivantamab combined with chemotherapy treatment gained an incremental effectiveness of 0.473 QALYs and an incremental cost of $361,950.952, which resulted in an ICER of $765,224/QALY. The ICER was much higher than the willingness-to-pay threshold of 15,0000/QALY. One-way sensitivity analysis revealed that amivantamab cost was the leading influential factor in the model. Conclusions: Compared with chemotherapy alone, amivantamab plus chemotherapy is not a cost-effective first-line treatment choice for NSCLC patients with EGFR exon 20 insertions. The costly price of amivantamab is one of the major reasons for the high cost of this combined treatment strategy. Therefore, it is imperative to take into account the high cost of amivantamab in the subsequent clinical application and strive to attain a relative equilibrium between its significant clinical benefit and economic encumbrance.

Ophiasis Alopecia Areata in a Patient With Spondyloarthritis on Secukinumab: A Case Report and Review of the Literature.

Secukinumab (Cosentyx), an interleukin-17A-targeting biological agent, is commonly prescribed for psoriasis, psoriatic arthritis, and spondyloarthritis (SpA). Alopecia areata (AA), an IL-17-mediated autoimmune disorder characterized by nonscarring hair loss, particularly in an ophiasis pattern, represents a rare adverse effect associated with secukinumab therapy. We present a case of a 46-year-old female with SpA undergoing secukinumab treatment, who developed an ophiasis pattern of AA, subsequently experiencing regrowth upon medication discontinuation. The patient's clinical course and treatment response are detailed, alongside a discussion on the potential pathophysiological mechanisms underlying secukinumab-induced AA. Additionally, we provide a review of existing literature, discussing similar cases and proposing hypotheses on the immunological basis of this adverse event. This report underscores the importance of recognizing and managing secukinumab-induced AA, highlighting the need for further investigation and tailored therapeutic approaches in affected patients.

Disparities in mortality risk after diagnosis of hematological malignancies in 185 countries: A global data analysis.

This study was to report proxy measures for mortality risk in patients with hematological malignancies across 185 countries globally and explore its association with their socioeconomic status and treatment. The incidence, mortality, and 5-year prevalence data were extracted from the GLOBOCAN database. The data regarding the human development index (HDI), gross national income (GNI), vulnerability index, and concordance with cancer Essential Medicines List (EML) were obtained from open-source reports. The ratio of mortality to 5-year-prevalence (MPR) and that of mortality to incidence (MIR) were calculated and age-standardized using Segi's world standard population. Finally, the possible associations were assessed using Pearson correlation analyses. In 2020, the global incidence, mortality, and 5-year prevalence of HMs were 1,278,362, 711,840, and 3,616,685, respectively. Global age-standardized MPR and MIR were 0.15 and 0.44, respectively; they varied significantly among 6 regions, 185 countries, 4 HM types, and 4 HDI groups worldwide. Older populations always had higher ratios. The correlation of MPRs and MIRs with HDI, GNI, and concordance with cancer EML was negative, whereas it was positive with the vulnerability index (lower was better). Increasing access to cancer drugs in resource-limited regions with a focus on vulnerable children may aid in reducing HM-related mortality risk.

Genetic risk, adherence to healthy lifestyle behaviors, and risk of cholelithiasis: A population-based cohort study.

OBJECTIVE: Genetic and lifestyles contribute to cholelithiasis, but the impact of adhering to healthy lifestyle on cholelithiasis risk remains uncertain. We aimed to assess combined lifestyle factors and a polygenic risk score on incident cholelithiasis. METHODS: We utilized cholelithiasis genome-wide association study (GWAS) data from FinnGen study, constructing varied polygenic risk score (PRS), and applied them to 317,640 UK Biobank participants. The relative and absolute risk of incident cholelithiasis associated with six well-established lifestyle risk factors, was evaluated and stratified by PRS (low risk [quintile 1], intermediate risk [quintiles 2-4] and high risk [quintile 5]). Lifestyle score was also categorized into favorable, intermediate, and unfavorable groups. RESULTS: The PRS derived from 13 single nucleotide polymorphisms (p ≤ 5 × 10-6, r2 < 0.001) showed the best performance. A significant gradient of increase in risk of cholelithiasis was observed across the quintiles of the polygenic risk score (p < 0.001). Compared to participants with low genetic risk, those with intermediate or high genetic risk had a 10% (95% confidence interval [CI] = 1.05-1.17) and 24% (95% CI = 1.16-1.32) higher risk of cholelithiasis. An unfavorable lifestyle was associated with an approximately 50% higher risk of cholelithiasis than a favorable lifestyle. Participants with high genetic risk and an unfavorable lifestyle had 98% (Hazard ratio [HR]: 1.98; 95% CI: 1.67-2.35) higher risk of cholelithiasis than those with low genetic risk and a favorable lifestyle. CONCLUSIONS: Our study highlights the importance of lifestyle behaviors intervention on cholelithiasis risk regardless of the genetic risk in White European population.

Vagus nerve stimulation as a promising neuroprotection for ischemic stroke via α7nAchR-dependent inactivation of microglial NLRP3 inflammasome.

Ischemic stroke is a major cause of disability and death worldwide, and its management requires urgent attention. Previous studies have shown that vagus nerve stimulation (VNS) exerts neuroprotection in ischemic stroke by inhibiting neuroinflammation and apoptosis. In this study, we evaluated the timing for VNS intervention in ischemic stroke, and the underlying mechanisms  of VNS-induced neuroprotection. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 60 min. The left vagus nerve at cervical level was exposed and attached to an electrode connected to a low-frequency electrical stimulator. Vagus nerve stimulation (VNS) was given for 60 min before, during and after tMCAO (Pre-VNS, Dur-VNS, Post-VNS). Neurological function was assessed 24 h after reperfusion. We found that all the three VNS significantly protected against the tMCAO-induced injury evidenced by improved neurological function and reduced infarct volume. Moreover, the Pre-VNS was the most effective against the ischemic injury. We found that tMCAO activated microglia in the ischemic core and penumbra regions of the brain, followed by the NLRP3 inflammasome activation-induced neuroinflammation, which finally triggered neuronal death. VNS treatment preserved α7nAChR expression in the penumbra regions, inhibited NLRP3 inflammasome activation and ensuing neuroinflammation, rescuing cerebral neurons. The role of α7nAChR in microglial NLRP3 inflammasome activation in ischemic stroke was further validated using genetic manipulations, including Chrna7 knockout mice and microglial Chrna7 overexpression mice, as well as pharmacological interventions using the α7nAChR inhibitor methyllycaconitine and agonist PNU-282987. Collectively, this study demonstrates the potential of VNS as a safe and effective strategy to treat ischemic stroke, and presents a new approach targeting microglial NLRP3 inflammasome, which might be therapeutic for other inflammation-related diseases.

Treatment outcome, toxicity, and quality of life of patients with bronchus-associated lymphoid tissue lymphoma.

The disease failure patterns and optimal treatment of bronchus-associated lymphoid tissue (BALT) lymphoma are unknown. This retrospective study involved 71 patients with primary BALT lymphoma who had received radiotherapy (RT), surgery, immunochemotherapy (IC), or observation. The median follow-up time was 66 months. The 5-year overall survival and lymphoma-specific survival were 91.2% and 96.1%, respectively, and were not significantly different among treatments. The 5-year cumulative incidence of overall failure for RT, surgery, IC, and observation was 0%, 9.7% (p = .160), 30.8% (p = .017), and 31.3% (p = .039). There was no grade ≥3 toxicity in RT group according to the CTCAE 5.0 reporting system. Quality of life (QoL) was at similarly good levels among the treatment groups. BALT lymphoma had a favorable prognosis but persistent risk of relapse after IC or observation. Given the very low disease failure risk and good QoL, RT remains an effective initial treatment for BALT lymphoma.Key PointsBALT lymphoma has a favorable prognosis but a persistent progression and relapse risk.Radiotherapy is associated with lower failure of disease progression and relapse, low toxicity and good quality of life.

Development and implementation of a high-fidelity simulation training course for medical and nursing collaboration based on the Fink integrated course design model.

Aim: The purpose of this study is to examine the design and implementation of a high-fidelity simulation training course for medical and nursing collaboration, based on the Fink integrated course design model. Additionally, the study aims to validate the teaching effectiveness of the course. Background: Previous empirical studies have highlighted the effectiveness of collaborative healthcare education in institutional teaching and hospital training. However, the development of healthcare collaborative education in China has been slow to develop in China. In recent years, Chinese nursing educators and researchers have shown interest in utilizing high-fidelity simulators for healthcare collaborative education. These simulators help address the limitations of traditional nursing teaching and healthcare separation simulation. Nevertheless, a standardized simulation interprofessional education curriculum is still lacking. Therefore, nursing educators need to develop a standardized high-fidelity simulation training curriculum for healthcare collaboration, guided by established science curriculum development theories. Methods: A high-fidelity simulation training course on healthcare collaboration was designed based on the Fink integrated curriculum design model. The course was taught to 14 nursing students and 8 clinical medicine students from March to July 2022. To comprehensively evaluate the effectiveness of the healthcare collaboration high-fidelity simulation training course, several assessment tools were used. These included course grades, satisfaction and self-confidence scales, simulation teaching practice scales, healthcare collaboration attitude scales, critical thinking skills scales, and semi-structured interviews. Results: After the course was implemented, students demonstrated high overall scores (79.19 ± 5.12) and reported high satisfaction ratings (4.44 ± 0.37). They also exhibited increased self-confidence (4.16 ± 0.33). Additionally, students evaluated all four dimensions of the course teaching practice scale positively. Furthermore, the study demonstrated significant improvements in various aspects, such as attitudes toward medical and nursing collaboration (t = -7.135, P < 0.01), shared education and teamwork (t = -3.247, P = 0.002), job autonomy for nurses (t = -1.782, P = 0.000), and reduced physician dominance (t = -6.768, P = 0.000). The critical thinking skills of the students showed significant improvement, with higher scores in truth-seeking (t = -3.052, P = 0.004), analytical ability (t = -2.561, P = 0.014), systematic ability (t = -3.491, P = 0.001), self-confidence in critical thinking (t = -4.024, P = 0.000), and curiosity (t = -5.318, P = 0.000) compared to their scores before the course (all P < 0.05). The interviews showed that the course's student-centered approach enabled active learning. Students suggested enhancing teaching cases and allocating more time for reflection and summarization. Conclusion: The study successfully designed a high-fidelity simulation training course for healthcare collaboration by utilizing the Fink integrated curriculum design model. The findings provide valuable insights for the development of standardized curricula and healthcare collaboration education in China. Moreover, the course adheres to best practice principles, fostering improved attitudes toward healthcare collaboration and enhancing students' healthcare collaboration and clinical thinking skills.

A prospective phase II clinical trial of total neoadjuvant therapy for locally advanced gastric cancer and gastroesophageal junction adenocarcinoma.

To investigate the safety and efficacy of the neoadjuvant chemoradiotherapy (NCRT) followed by neoadjuvant consolidation chemotherapy (NCCT) and surgery for locally advanced gastric cancer (GC) or gastroesophageal junction (GEJ) adenocarcinoma. Patients diagnosed as locally advanced GC or Siewert II/III GEJ adenocarcinoma with clinical stage T3-4 and/or N positive were prospectively enrolled. Patients underwent NCRT (45 Gy/25 fractions) with concurrent S-1, followed by NCCT (4 to 6 cycles of the SOX regimen) 2 to 4 weeks after NCRT. Gastric cancer radical resection with D2 lymph node dissection was performed 4 to 6 weeks after the total neoadjuvant therapy. The study was conducted from November 2019 to January 2023, enrolling a total of 46 patients. During the NCRT, all patients completed the treatment without dose reduction or delay. During the NCCT, 32 patients (69.6%) completed at least 4 cycles of chemotherapy. Grade 3 or higher adverse events in NCRT (5 cases) were non-hematological. During the course of NCCT, a notable occurrence of hematological toxicities was observed, with grade 3 or higher leukopenia (9.7%) and thrombocytopenia (12.2%) being experienced. A total of 28 patients (60.9%) underwent surgery, achieving R0 resection in all cases. A significant proportion of cases (71.4%) exhibited pathological downstaging to ypT0-2, while 10 patients (35.7%) demonstrated a pathologic complete response (pCR). The total neoadjuvant therapy comprising NCRT followed by NCCT and surgery demonstrates a low severe adverse reactions and promising efficacy, which could be considered as a viable treatment for locally advanced GC or GEJ adenocarcinoma.Trial registration: Clinicaltrials.gov (registration number: NCT04062058); the full date of first trial registration was 20/08/2019.

The effect of nitrogen input on N2O emission depends on precipitation in a temperate desert steppe.

Nitrous oxide (N2O) is the third most important greenhouse gas, and can damage the atmospheric ozone layer, with associated threats to terrestrial ecosystems. However, to date it is unclear how extreme precipitation and nitrogen (N) input will affect N2O emissions in temperate desert steppe ecosystems. Therefore, we conducted an in-situ in a temperate desert steppe in the northwest of Inner Mongolia, China between 2018 and 2021, in which N inputs were combined with natural extreme precipitation events, with the aim of better understanding the mechanism of any interactive effects on N2O emission. The study result showed that N2O emission in this desert steppe was relatively small and did not show significant seasonal change. The annual N2O emission increased in a non-linear trend with increasing N input, with a much greater effect of N input in a wet year (2019) than in a dry year (2021). This was mainly due to the fact that the boost effect of high N input (on June 17th 2019) on N2O emission was greatly amplified by nearly 17-46 times by an extreme precipitation event on June 24th 2019. In contrast, this greatly promoting effect of high N input on N2O emission was not observed on September 26th 2019 by a similar extreme precipitation event. Further analysis showed that soil NH4+-N content and the abundance of ammonia oxidizing bacteria (amoA (AOB)) were the most critical factors affecting N2O emission. Soil moisture played an important indirect role in regulating N2O emission, mainly by influencing the abundance of amoA (AOB) and de-nitrification functional microorganisms (nosZ gene). In conclusion, the effect of extreme precipitation events on N2O emission was greatly increased by high N input. Furthermore, in this desert steppe, annual N2O flux is co-managed through soil nitrification substrate concentration (NH4+-N), the abundance of soil N transformation functional microorganisms and soil moisture. Overall, it was worth noting that an increase in extreme precipitation coupled with increasing N input may significantly increase future N2O emissions from desert steppes.

Optimizing the prognostic capacity of baseline 18F-FDG PET/CT metabolic parameters in extranodal natural killer/T-cell lymphoma by using relative and absolute thresholds.

Objectives: To investigate the prognostic capacity of baseline 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) metabolic parameters in extranodal natural killer/T-cell lymphoma (ENKTCL), and the influence of relative thresholds (RT) and absolute thresholds (AT) selection on prognostic capacity. Materials and methods: Metabolic tumor volume (MTV)-based parameters were defined using RTs (41 % or 25 % of maximum standardized uptake value [SUVmax]), ATs (SUV 2.5, 3.0, 4.0, or mean liver uptake) in 133 patients. Metabolic parameters were classified into avidity-related parameters (SUVmax, mean SUV [SUVmean], standard deviation of SUV [SUVsd]), volume-related parameters (RT-MTV), and avidity- and volume-related parameters (total lesion glycolysis [TLG] and AT-MTV). The prognostic capacity of the metabolic parameters and the effects of different threshold types (RT vs. AT) were evaluated. Results: All metabolic parameters were moderately associated with prognosis. However, the area under the receiver operating characteristic curve of MTV and TLG was slightly higher than that of avidity-related parameters for predicting 5-year progression-free survival (PFS) (0.614-0.705 vs. 0.563-0.609) and overall survival (OS) (0.670-0.748 vs. 0.562-0.593). Correlations of MTV and avidity-related parameters differed between RTs (r < 0.06, P = 0.324-0.985) and ATs (r 0.56-0.84, P ≤ 0.001). AT-MTV was the optimal predictor for PFS and OS, while RT-TLG was the optimal predictor for PFS, and the combination of RT-MTV with SUVmax was the optimal predictor for OS. Conclusion: The incorporation of volume and avidity significantly improved the prognostic capacity of PET in ENKTCL. Composite parameters that encompassed both avidity and volume were recommended.

High incidence of gallstones after Roux-en-Y reconstruction gastrectomy in gastric cancer: a multicenter, long-term cohort study.

BACKGROUND: Roux-en-Y reconstruction is a common anastomosis technique during gastrectomy in gastric cancer. There is a lack of studies on gallstones after Roux-en-Y reconstruction gastrectomy. This study investigated the incidence and potential risk factors associated with gallstones after Roux-en-Y reconstructive gastrectomy in gastric cancer. METHODS: The study analyzed data from gastric cancer who underwent radical gastrectomy and Roux-en-Y reconstruction at two hospitals between January 2014 and December 2020. The patients fall into distal and total gastrectomy groups based on the extent of gastrectomy. The cumulative event probability curve was plotted using the Kaplan-Meier, and differences in gallstone between groups were evaluated using the Log-Rank. Propensity score matching was applied to construct a balanced total versus distal gastrectomies cohort. A Cox regression was employed to analyze the risk factors for gallstones after Roux-en-Y reconstructive gastrectomy in gastric cancer. Further subgroup analysis was performed. RESULTS: Five hundred thirty-one patients were included in this study, 201 in the distal gastrectomy group and 330 in the total gastrectomy. During the follow-up, gallstones occurred in 170 cases after gastrectomy, of which 145 cases accounted for 85.29% of all stones in the first two years after surgery. Then, to reduce the impact of bias, a 1:1 propensity score matching analysis was performed on the two groups of patients. A total of 344 patients were evaluated, with each subgroup comprising 172 patients. In the matched population, the Cox regression analysis revealed that females, BMI ≥23 kg/m 2 , total gastrectomy, No.12 lymph node dissection, and adjuvant chemotherapy were risk factors for gallstones after Roux-en-Y reconstructive gastrectomy. Subgroup analysis showed that open surgery further increased the risk of gallstones after total gastrectomy. CONCLUSION: The incidence of gallstones increased significantly within 2years after Roux-en-Y reconstructive gastrectomy for gastric cancer. Patients with these risk factors should be followed closely after gastrectomy to avoid symptomatic gallstones.

CD19-specific CAR-T Cell Treatment of 115 Children and Young Adults with Acute B Lymphoblastic Leukemia: Long-Term Follow-up.

Purpose: Chemotherapy has been the primary treatment for patients with B-cell acute lymphoblastic leukemia (B-ALL). However, there are still patients who are not sensitive to chemotherapy, including those with refractory/relapse (R/R) disease and those experiencing minimal residual disease (MRD) re-emergence. Chimeric antigen receptor-T lymphocytes (CAR-T) therapy may provide a new treatment option for these patients. Materials and Methods: Oure institution conducted a single-arm prospective clinical trial (ChiCTR-OPN-17013507) using CAR-T-19 to treat R/R B-ALL and MRD re-emergent patients. One hundred and fifteen patients, aged 1-25 years (median age 8 years), were enrolled, including 67 R/R and 48 MRD re-emergent CD19-positive B-ALL patients. Results: All patients achieved morphologic CR, and within one month after infusion, 111 out of 115 (96.5%) patients achieved MRD-negative CR. With a median follow-up time of 48.4 months, the estimated 4-year leukemia-free survival (LFS) rate and overall survival (OS) rate were (68.7±4.5) % and (70.7±4.3) %, respectively. There were no significant differences in long-term efficacy observed among patients with different disease statuses before infusion (4-year OS: MRD re-emergence vs. R/R B-ALL, 70.6±6.6% vs. 66.5±6.1%, p=0.755; 4-year LFS: MRD re-emergence vs. R/R B-ALL, 67.3±7.0% vs. 63.8±6.2%, p=0.704). R/R B-ALL patients bridging to transplantation after CAR-T treatment had a superior OS and LFS compared to those who did not. However, for MRD re-emergent patients, there was no significant difference in OS and LFS, regardless of whether they underwent HSCT or not. Conclusion: CD19 CAR-T therapy effectively and safely cures both R/R B-ALL and MRD re-emergent patients.

Regulatory effects of natural products on N6-methyladenosine modification: A novel therapeutic strategy for cancer.

N6-methyladenosine (m6A) is considered to be the most common and abundant epigenetics modification in messenger RNA (mRNA) and noncoding RNA. Abnormal modification of m6A is closely related to the occurrence, development, progression, and prognosis of cancer. m6A regulators have been identified as novel targets for anticancer drugs. Natural products, a rich source of traditional anticancer drugs, have been utilized for the development of m6A-targeting drugs. Here, we review the key role of m6A modification in cancer progression and explore the prospects and structural modification mechanisms of natural products as potential drugs targeting m6A modification for cancer treatment.