CEAC (oral semustine, etoposide, cytarabine and cyclophosphamide) vs BEAM (carmustine, etoposide, cytarabine, and melphalan) conditioning regimen of autologous stem cell transplantation for diffuse large B-cell lymphoma: a post-hoc, propensity score-matched, cohort study in Chinese patients.

Autologous stem cell transplantation (ASCT) is a salvage therapy for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). We have developed a novel conditioning regimen called CEAC (oral semustine 250 mg/m2 d-6, etoposide 300 mg/m2 d-5 ~ d-2, cytarabine 500 mg/m2 d-5 ~ d-2, and cyclophosphamide 1200 mg/m2 d-5 ~ d-2) In lymphoma patients in China. Here, we conducted a study to compare the conventional BEAM regimen with the CEAC regimen in 110 DLBCL patients. Propensity-score matching was performed in a 1:4 ratio (22 patients received BEAM and 88 received CEAC). Our results showed no significant difference in the overall response rate (95% vs 97%, P = 1.000) and complete response rate (66% vs 73%, P = 0.580) between the two cohorts. The 5-year progression-free survival (PFS), 5-year overall survival (OS), and 5-year cumulative incidence of relapse (CIR) for all patients were 72% (95% CI 62%-82%), 92% (95% CI 86%-97%), and 29% (95% CI 17%-38%), respectively. There was no significant difference in the 5-year PFS (80% vs 70%, P = 0.637), 5-year OS (95% vs 91%, P = 0.496), and 5-year CIR (20% vs 30%, P = 0.733) between cohorts. In terms of safety, the CEAC cohort had a lower incidence rate of grade 1-2 gastrointestinal hemorrhage (P = 0.023) and severe nausea (P = 0.007) compared with the BEAM cohort. In conclusion, the CEAC regimen seems to be a suitable alternative to the BEAM regimen for ASCT in DLBCL patients.

Indole-3-propionic acid alleviates sepsis-associated acute liver injury by activating pregnane X receptor.

BACKGROUND: The morbidity and mortality of sepsis are extremely high, which is a major problem plaguing human health. However, current drugs and measures for the prevention and treatment of sepsis have little effect. Sepsis-associated acute liver injury (SALI) is an independent risk factor for sepsis, which seriously affects the prognosis of sepsis. Studies have found that gut microbiota is closely related to SALI, and indole-3-propionic Acid (IPA) can activate Pregnane X receptor (PXR). However, the role of IPA and PXR in SALI has not been reported. METHODS: This study aimed to explore the association between IPA and SALI. The clinical data of SALI patients were collected and IPA level in feces was detected. The sepsis model was established in wild-type mice and PXR knockout mice to investigate the role of IPA and PXR signaling in SALI. RESULTS: We showed that the level of IPA in patients' feces is closely related to SALI, and the level of IPA in feces has a good ability to identify and diagnose SALI. IPA pretreatment significantly attenuated septic injury and SALI in wild-type mice, but not found in knockout PXR gene mice. CONCLUSIONS: IPA alleviates SALI by activating PXR, which reveals a new mechanism of SALI, and provides potentially effective drugs and targets for the prevention of SALI.

Knockdown of RABL3 suppresses the proliferation and invasion of oral squamous cell carcinoma through inactivating the FAK/AKT pathway.

Rab-like 3 (RABL3) is a member of Rab family that is related with several kinds of cancers. However, the functional roles of RABL3 in oral squamous cell carcinoma (OSCC) remain largely unknown. In the current study, we examined the expression levels of RABL3 in OSCC tissues and cell lines. The results showed that RABL3 expression was markedly increased in OSCC tissues and cell lines. Knockdown of RABL3 significantly suppressed the proliferation, migration and invasion of OSCC cells. Overexpression of RABL3 exhibited opposite effects with RABL3 knockdown. In vivo assay demonstrated that knockdown of RABL3 suppressed the tumorigenesis of OSCC. Moreover, RABL3 regulated the activation of focal adhesion kinase (FAK)/protein kinase B (Akt) signaling pathway in OSCC cells. Inhibition of FAK reversed the effects of RABL3 overexpression on cell proliferation, migration and invasion of OSCC cells. In conclusion, these findings demonstrated that RABL3 acted as an oncogene in OSCC, which was attributed to the regulation of FAK/Akt pathway. Thus, RABL3 may be potential therapeutic target for the treatment of OSCC.

Diffusion-weighted imaging as a follow-up modality for evaluation of major salivary gland function in nasopharyngeal carcinoma patients: a preliminary study.

PURPOSE: To investigate the value of diffusion-weighted imaging (DWI) in assessing dynamic changes of major salivary gland function during follow-up post radiotherapy (RT) in nasopharyngeal carcinoma (NPC) patients. MATERIALS AND METHODS: 31 consecutive patients with pathologically confirmed NPC scheduled for RT underwent six routine follow-up MRI examinations including DWI sequence prior to (pre-RT) and 1, 3, 6, 9, and 12 months post RT. Mean apparent diffusion coefficient (ADC) values of bilateral parotid glands (PGs) and submandibular glands (SMGs) were measured. Objective measurement of salivary flow rate (SFR) under unstimulated (uSFR) and stimulated conditions (sSFR) as well as subjective xerostomia assessment according to a patient-rated questionnaire were conducted before each MRI. Variance analysis was used to evaluate dynamic changes of ADC, SFR and xerostomia questionnaire summary scores (XQ-sum) at different timepoints and the correlation between ADC and XQ-sum. Pearson's correlation test was used to evaluate the correlations between pre- and post-RT changes of ADC (ΔADC) and SFR (ΔSFR) or mean RT dose. RESULTS: At each timepoint, ADCs of PGs were significantly lower than of SMGs, uSFR was significantly lower than sSFR. For both PGs and SMGs, ADCpost-RT were all higher than ADCpre-RT, with significant differences. ADC1m-post-RT initially increased and changed little to ADC3m-post-RT, ADC6m-post-RT, ADC9m-post-RT, and ADC12m-post-RT, then gradually declined over time. The dynamic change trends of SFR were negatively paralleled to those of ADC, while that of XQ-sum was similar. Dose-response relationships were detected between salivary gland mean RT dose and ΔADC. In PGs, negative correlations between ΔsSFR9m-post-RT and ΔADC9m-post-RT, and ΔsSFR12m-post-RT and ΔADC12m-post-RT were detected. In SMGs, negative correlations between ΔsSFR12m-post-RT and ΔADC12m-post-RT, and ΔuSFR12m-post-RT and ΔADC12m-post-RT were also detected. The ADCs of patients with severe subjective xerostomia were significantly higher, while patients with moderate subjective xerostomia presented a tendency toward higher ADCs compared to those with mild xerostomia from 6 to 12 months post RT. CONCLUSION: As part of routine follow-up MRI in NPC patients, DWI might be a promising modality for follow-up assessing the dynamic changes of major salivary gland function and might be more powerful in the late post-RT period.

Nomogram for predicting the risk of postoperative delirium in elderly patients undergoing orthopedic surgery.

OBJECTIVE: To retrospectively analyze the risk factors for postoperative delirium (POD) after orthopedic surgery in elderly patients and establish an individualized nomogram to predict the risk of POD. METHODS: The data of 1011 patients who underwent orthopedic surgery from January 2019 to January 2022 were retrospectively analyzed. Univariate and multivariate logistic analyses were used to screen for independent risk factors. Stepwise regression was conducted to screen risk factors to construct a nomogram to predict the risk of POD after orthopedic surgery in elderly individuals, and nomogram validation analyses were performed. RESULTS: The logistic regression results showed that age (≥ 75 years old vs. < 75 years old; odds ratio (OR) = 2.889; 95% confidence interval (CI), 1.149, 7.264), sex (male vs. female, OR = 2.368; 95% CI, 1.066, 5.261), and preoperative cognitive impairment (yes vs. no, OR = 13.587; 95% CI, 4.360, 42.338) were independent risk factors for POD in elderly patients who underwent orthopedic surgery (P < 0.05). A nomogram was constructed using 7 risk factors, i.e., age, American Society of Anesthesiologists (ASA) classification, sex, preoperative hemoglobin (Hb), preoperative pulmonary disease, cognitive impairment, and intraoperative infusion volume. The area under the curve (AUC) showed good discrimination (0.867), the slope of the calibration curve was 1.0, and the optimal net benefit of the nomogram from the decision curve analysis (DCA) was 0.01-0.58. CONCLUSION: This study used 7 risk factors to construct a nomogram to predict the risk of POD after major orthopedic surgery in elderly individuals, and the nomogram had good discrimination ability, accuracy, and clinical practicability.

Effect of sustained measurable residue disease negativity and post-remission treatment selection on the prognosis of acute lymphoblastic leukemia in adults.

BACKGROUND: To explore the effects of monitoring measurable residual disease and post-remission treatment selection on the clinical outcomes of B-cell acute lymphoblastic leukemia (B-ALL) in adults. METHODS: Between September 2010 and January 2022, adult patients with B-ALL who received combination chemotherapy, with or without allogeneic hematopoietic stem cell transplantation (allo-HSCT), were included in the retrospective study, which was approved by the Ethics Committee and the observation of Declaration of Helsinki conditions. RESULTS: One hundred and forty-three B-ALL patients achieved complete remission (CR) were included in the study, of whom 94 patients (65.7%) received allo-HSCT in first complete remission (CR1). Multivariate analysis showed that the most powerful factors affecting OS were transplantation (hazard ratio [HR] = 0.540, p = 0.037) and sustained measurable residue disease (MRD) negativity (HR = 0.508, p = 0.037). The subgroup analysis showed that the prognosis of the allo-HSCT group was better than that of the chemotherapy group, regardless of whether MRD was negative or positive after two courses of consolidation therapy. After consolidation therapy, the prognosis of patients with positive MRD remained significantly better in the allo-HSCT group than in the chemotherapy group. However, no significant difference was observed in the prognosis between the allo-HSCT and chemotherapy groups with negative MRD after consolidation therapy. CONCLUSIONS: B-ALL patients who achieve sustained MRD negativity during consolidation therapy have excellent long-term outcomes even without allo-HSCT. Allo-HSCT is associated with a significant benefit in terms of OS and DFS for patients who were with positive MRD during consolidation therapy.

Comparison of Stem Cell Transplantation Using Unrelated, Haploidentical, and Sibling Donors for Patients with Acquired Severe Aplastic Anemia: A Single-Center Retrospective Cohort Study.

The preferred donor (haploidentical donor [HID] versus matched unrelated donor [URD]) choice in patients with acquired severe aplastic anemia (SAA) who lack an HLA-matched sibling donor (MSD) and fail upfront immunosuppressive treatment (IST) therapy is unknown. We retrospectively investigated SAA patients (n = 58) who underwent allogeneic stem cell transplantation (allo-SCT) between January 2012 and October 2022. The 5-year overall survival (OS) and 5-year failure-free survival (FFS) were comparable among the URD (n = 8), HID (n = 25), and MSD (n = 25) cohorts (OS: mean, 87.5 ± 11.7% versus 98.0 ± 6.5% versus 83.3 ± 7.6% [P = .926]; FFS: mean, 60.0 ± 18.2% versus 87.0 ± 7.0% versus 78.3 ± 8.6% [P = .222]). Multivariate analysis revealed that primary engraftment failure independently predicted OS and secondary graft failure predicted FFS among SAA patients who underwent allo-SCT, but donor type and age were not predictive of these outcomes. An urgent second SCT for patients with engraftment failure may be an effective salvage treatment. Our findings show that an alternative donor SCT is indicated for eligible SAA patients without an MSD even if age ≥40 years.

Sequential autologous and allogeneic stem cell transplantation for treatment of primary plasma cell leukemia: A case report.

Primary plasma cell leukemia (pPCL) is a rare and aggressive form of plasma cell disorder, which accounts for ~70% of all PCL. Survival of pPCL remains poor, and is related with early mortality. There is no standard therapy for patients with pPCL. In the present study, a 26-year-old man who was diagnosed with pPCL was reported. The patient achieved stringent complete remission to the successful treatment of intensive chemotherapy combined with sequential autologous and allogeneic stem cell transplantation (SCT) followed by maintenance therapy with oral administration of ixazomib, thalidomide and dexamethasone (IRD regimen). Development of complex treatment algorithms that combine novel agents, SCT and post-transplantation remission strategies may translate into survival in patients with pPCL.

Development and validation of a nomogram for prediction of recovery from moderate-severe xerostomia post-radiotherapy in nasopharyngeal carcinoma patients.

PURPOSE: Aim to create and validate a comprehensive nomogram capable of accurately predicting the transition from moderate-severe to normal-mild xerostomia post-radiotherapy (postRT) in patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: We constructed and internally verified a prediction model using a primary cohort comprising 223 patients who were pathologically diagnosed with NPC from February 2016 to December 2019. LASSO regression model was used to identify the clinical factors and relevant variables (the pre-radiotherapy (XQ-preRT) and immediate post-radiotherapy (XQ-postRT) xerostomia questionnaire scores, as well as the mean dose (Dmean) delivered to the parotid gland (PG), submandibular gland (SMG), sublingual gland (SLG), tubarial gland (TG), and oral cavity). Cox proportional hazards regression analysis was performed to develop the prediction model, which was presented as a nomogram. The models' performance with regard to calibration, discrimination, and clinical usefulness was evaluated. The external validation cohort comprised 78 patients. RESULTS: Due to better discrimination and calibration in the training cohort, age, gender, XQ-postRT, and Dmean of PG, SMG, and TG were included in the individualized prediction model (C-index of 0.741 (95% CI:0.717 to 0.765). Verification of the nomogram's performance in internal and external validation cohorts revealed good discrimination (C-index of 0.729 (0.692 to 0.766) and 0.736 (0.702 to 0.770), respectively) and calibration. Decision curve analysis revealed that the nomogram was clinically useful. The 12-month and 24-month moderate-severe xerostomia rate was statistically lower in the SMG-spared arm (28.4% (0.230 to 35.2) and 5.2% (0.029 to 0.093), respectively) than that in SMG-unspared arm (56.8% (0.474 to 0.672) and 12.5% (0.070 to 0.223), respectively), with an HR of 1.84 (95%CI: 1.412 to 2.397, p = 0.000). The difference in restricted mean survival time for remaining moderate-severe xerostomia between the two arms at 24 months was 5.757 months (95% CI, 3.863 to 7.651; p = 0.000). CONCLUSION: The developed nomogram, incorporating age, gender, XQ-postRT, and Dmean to PG, SMG, and TG, can be used for predicting recovery from moderate-severe xerostomia post-radiotherapy in NPC patients. Sparing SMG is highly important for the patient's recovery.

Overexpression of Sedum SpHMA2, SpHMA3 and SpNramp6 in Brassica napus increases multiple heavy metals accumulation for phytoextraction.

Phytoextraction is an environmentally friendly phytoremediation technology that can reduce the total amount of heavy metals (HMs) in the soil. Hyperaccumulators or hyperaccumulating transgenic plants with biomass are important biomaterials for phytoextraction. In this study, we show that three different HM transporters from the hyperaccumulator Sedum pumbizincicola, SpHMA2, SpHMA3, and SpNramp6, possess Cd transport. These three transporters are located at the plasma membrane, tonoplast, and plasma membrane, respectively. Their transcripts could be strongly stimulated by multiple HMs treatments. To create potential biomaterials for phytoextraction, we overexpressed the three single genes and two combining genes, SpHMA2&SpHMA3 and SpHMA2&SpNramp6, in rapes having high biomass and environmental adaptability, and found that the aerial parts of the SpHMA2-OE3 and SpHMA2&SpNramp6-OE4 lines accumulated more Cd from single Cd-contaminated soil because SpNramp6 transports Cd from root cells to the xylem and SpHMA2 from the stems to the leaves. However, the accumulation of each HM in the aerial parts of all selected transgenic rapes was strengthened in multiple HMs-contaminated soils, probably due to the synergistic transport. The HMs residuals in the soil after the transgenic plant phytoremediation were also greatly reduced. These results provide effective solutions for phytoextraction in both Cd and multiple HMs-contaminated soils.

Association of Gut Microbiota With Intestinal Ischemia/Reperfusion Injury.

Intestinal ischemia/reperfusion (II/R) is a common acute and critical condition in clinical practice with a high mortality rate. However, there is still a lack of effective prevention and treatment measures for II/R injury. The role of the gut microbiota in II/R has attracted widespread attention. Recent evidence has demonstrated that the gut microbiota plays a pivotal role in the occurrence, development, and prognosis of II/R. Therefore, maintaining the homeostasis of gut microbiota and its metabolites may be a potential strategy for the treatment of II/R. This review focuses on the importance of crosstalk between the gastrointestinal ecosystem and II/R to highlight II/R-induced gut microbiota signatures and potential applications of microbial-based therapies in II/R. This will also provide potentially effective biomarkers for the prediction, diagnosis and treatment of II/R.

Crosstalk between gut microbiota and renal ischemia/reperfusion injury.

Renal ischemia-reperfusion injury (IRI) is the main cause of acute kidney injury and the cause of rapid renal dysfunction and high mortality. In recent years, with the gradual deepening of the understanding of the intestinal flora, exploring renal IRI from the perspective of the intestinal flora has become a research hotspot. It is well known that the intestinal flora plays an important role in maintaining human health, and dysbiosis is the change in the composition and function of the intestinal tract, which in turn causes intestinal barrier dysfunction. Studies have shown that there are significant differences in the composition of intestinal flora before and after renal IRI, and this difference is closely related to the occurrence and development of renal IRI and affects prognosis. In addition, toxins produced by dysregulated gut microbes enter the bloodstream, which in turn exacerbates kidney damage. This article reviews the research progress of intestinal flora and renal IRI, in order to provide new treatment ideas and strategies for renal IRI.

The Acute Toxicities and Efficacy of Concurrent Chemotherapy With Docetaxel Plus Cisplatin, or Docetaxel, or Cisplatin and Helical Tomotherapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma: A Randomized Single-Center Phase II Trial.

Objective: The objective of this trial is to evaluate and compare the acute toxicity in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) treated with docetaxel plus cisplatin, or docetaxel, or cisplatin concurrently with helical tomotherapy during concurrent chemoradiotherapy (CCRT). Methods: In a prospective, single-center, open-label, randomized phase II study, after 2 cycles of induction chemotherapy with docetaxel plus cisplatin regimen, 125 patients with LA-NPC (stage III and IVA, UICC eighth) diagnosed pathologically from June 2017 to November 2019 were randomized into CCRT with docetaxel plus cisplatin group (25 patients), CCRT with docetaxel group (50 patients), and CCRT with cisplatin group (50 patients). The incidence of grade 3 or 4 acute toxicities and clinical efficacy were analyzed among the 3 groups. Results: Safety evaluation was completed in all the 125 patients, during the CCRT period, 66.4% of patients completed 3 cycles of chemotherapy, 24.0% completed 2 cycles of chemotherapy, and 9.6% completed 1 cycle of chemotherapy according to the research plan. The incidence of grade 3 or 4 acute toxicity in CCRT with docetaxel plus cisplatin (DP), docetaxel (D), and cisplatin (P) groups was 88.0%, 72.0%, and 56.0%, respectively. The incidence of grade 3 or 4 acute toxicities in the DP group was significantly higher than that in the D and P groups (P = .015), no significant difference was detected between the D and P groups (P = .096). The most common toxicities were mucositis (40.0%), leukopenia (29.6%), neutropenia (26.4%), and pharyngo-esophagitis (12.0%); compared to D and P groups, DP group did not significantly improved the 3-year overall survival (96.0% vs 87.0% and 87.6%), progression-free survival (92.0% vs 79.7% and,76.9%), locoregional failure-free survival (96.0% vs 91.8% and 92.7%), and distant failure-free survival (100% vs 90.0% and 89.0%), there were no significant difference in survival data among the 3 groups (all P > .05). Conclusions: Higher survival benefits did not achieve from intensified CCRT with DP, CCRT with P or D obtained similar short-term survival outcomes with similar acceptable toxicities in LA-NPC patients.

Moderate hypofractionated helical tomotherapy for older patients with localized prostate cancer: long-term outcomes of a phase I-II trial.

BACKGROUND: Our previous study showed that two different regimens of moderate hypofractionated radiotherapy (HFRT) delivered with helical tomotherapy (HT) are well tolerated in older prostate cancer patients. We provide a longterm efficacy and toxicity after > 7 years of follow-up. PATIENTS AND METHODS: The study recruited 33 patients from February 2009 to July 2011 (76 Gy/34F; Group-1); and 34 from July 2011 to February 2014 (71.6 Gy/28F; 50.4 Gy/25F for the risk of pelvic lymph nodes involvement (LNI) >15%; Group-2). The primary outcomes were biochemical failure (BF), biochemical failure and clinical disease failure (BCDF), progression-free survival (PFS), overall survival (OS), late genitourinary (GU) and gastrointestinal (GI) toxicity. RESULTS: The average ages of two groups were 80 and 77 years and the proportions of patients with LNI > 15% were 69.7% and 73.5%, respectively. At the final follow-up in February 2020, 27.3% and 20.6% cases experienced BF, with a median time until BF of 3.3 years. A total of 38.8% patients reached primary endpoints, in which 18 deaths were reported BCDF events (45.5% vs. 32.4%, p = 0.271). There was no significant difference in 7-year PFS (68.6% vs. 74.8%, p = 0.591), BCDF (45.5% vs. 32.4%, p = 0.271) and OS (71.9% vs. 87.5%, p = 0.376) for full set analysis and for subgroup analysis (all p > 0.05). The incidence of grade ≥ 2 late GU (6.2% vs. 6.3%, p = 0.127) and GI toxicities (9.4% vs. 15.6%, p = 0.554) was comparable. CONCLUSIONS: In older patients with localized prostate cancer, two moderate hypofractionated regimens were all well tolerated with similar, mild late toxicities and satisfactory survival, without necessity of prophylactic pelvic node irradiation.

Sparing submandibular gland to alleviating acute xerostomia in patients with nasopharyngeal carcinoma treated with helical tomotherapy: Evaluation by diffusion kurtosis imaging.

PURPOSE: To identify the clinical significance of sparing submandibular glands (SMG) for the amelioration of acute xerostomia using diffusion kurtosis imaging (DKI) in nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy (HT). MATERIALS AND METHODS: The prospective study enrolled 42 participants treated with HT. All patients underwent five times of DKI scans before HT (pre-HT), in the middle of the HT course (mid-HT), immediately after HT (post-HT), and 1 months (1m-HT), 3 months post-HT(3m-HT). Mean diffusion (MD) and mean kurtosis (MK) of SMG, parotid glands (PG) and sublingual glands (SLG), saliva flow rate measures under resting (uSFR) and stimulated condition (sSFR), and xerostomia questionnaire scores (XQ) were recorded. Comparisons between the SMG-spared and -unspared groups were analyzed using two-factor repeated-measures ANOVA for the group as the inter-subject factor and the time as the intra-subject factor. RESULTS: When sparing SMG, the dose of spared-SMG and ipsilateral SLG was lower compared to that of unspared glands (p < 0.001). MD of spared-SMG and ipsilateral SLG in SMG-spared group were lower than that of SMG-unspared group (the simple effect for the group, p-value at mid-HT, post-HT, 1m- and 3m-HT was 0.014, 0.011, 0.000 and 0.000, respectively), MK of spared-SMG was higher conversely (the main effect for the group, p < 0.001), while uSFR and sSFR were significantly lower in SMG-unspared group (the main effect for the group, p = 0.002, and p = 0.045, respectively). No significant differences were detected in MK of SLG, MD/MK of PG, and XQ between the two groups (the main effect for the group, p values were 0.9, 0.37, 0.15, 0.86, respectively). There were significant differences in the effect of the time for all MD/MK of the salivary glands and for uSFR, sSFR, and XQ between the SMG-spared and -unspared groups (p values were all <0.001). CONCLUSION: Sparing SMG is of great clinical significance in alleviating acute xerostomia for NPC patients treated by helical tomotherapy as evaluated by diffusion kurtosis imaging and saliva flow rate.

Heavy metal transporters: Functional mechanisms, regulation, and application in phytoremediation.

Heavy metal pollution in soil is a global problem with serious impacts on human health and ecological security. Phytoextraction in phytoremediation, in which plants uptake and transport heavy metals (HMs) to the tissues of aerial parts, is the most environmentally friendly method to reduce the total amount of HMs in soil and has wide application prospects. However, the molecular mechanism of phytoextraction is still under investigation. The uptake, translocation, and retention of HMs in plants are mainly mediated by a variety of transporter proteins. A better understanding of the accumulation strategy of HMs via transporters in plants is a prerequisite for the improvement of phytoextraction. In this review, the biochemical structure and functions of HM transporter families in plants are systematically summarized, with emphasis on their roles in phytoremediation. The accumulation mechanism and regulatory pathways related to hormones, regulators, and reactive oxygen species (ROS) of HMs concerning these transporters are described in detail. Scientific efforts and practices for phytoremediation carried out in recent years suggest that creation of hyperaccumulators by transgenic or gene editing techniques targeted to these transporters and their regulators is the ultimate powerful path for the phytoremediation of HM contaminated soils.

A comparative study of functional MRI in predicting response of regional nodes to induction chemotherapy in patients with nasopharyngeal carcinoma.

Purpose: To identify and compare the value of functional MRI (fMRI) in predicting the early response of metastatic cervical lymph nodes (LNs) to induction chemotherapy (IC) in nasopharyngeal carcinoma (NPC) patients. Methods: This prospective study collected 94 metastatic LNs from 40 consecutive NPC patients treated with IC from January 2021 to May 2021. Conventional diffusion-weighted imaging, diffusion kurtosis imaging, intravoxel incoherent motion, and dynamic contrast-enhanced magnetic resonance imaging were performed before and after IC. The parameter maps apparent diffusion coefficient (ADC), mean diffusion coefficient (MD), mean kurtosis (MK), Dslow, Dfast, perfusion fraction (PF), Ktrans, Ve, and Kep) of the metastatic nodes were calculated by the Functool postprocessing software. All LNs were classified as the responding group (RG) and non-responding group (NRG) according to Response Evaluation Criteria in Solid Tumors 1.1. The fMRI parameters were compared before and after IC and between the RG and the NRG. The significant parameters are fitted by logistic regression analysis to produce new predictive factor (PRE)-predicted probabilities. Logistic regression analysis and receiver operating characteristic (ROC) curves were performed to further identify and compare the efficacy of the parameters. Results: After IC, the mean values of ADC, MD, and Dslow significantly increased, while MK, Dfast, and Ktrans values decreased dramatically, while no significant difference was detected in Ve and Kep. Compared with NRG, PF-pre and Ktrans-pre values in the RG were higher statistically. The areas under the ROC for the pretreatment PF, Ktrans, and PRE were 0.736, 0.722, and 0.810, respectively, with the optimal cutoff value of 222 × 10-4, 934 × 10-3/min, and 0.6624, respectively. Conclusions: The pretreatment fMRI parameters PF and Ktrans showed promising potential in predicting the response of the metastatic LNs to IC in NPC patients. Clinical Trial Registration: This study was approved by the ethics board of the Chinese PLA General Hospital, and registered on 30 January 2021, in the Chinese Clinical Trial Registry; http://www.chictr.org.cn/showproj.aspx?proj=121198, identifier (ChiCTR2100042863).

Application of Diffusion Kurtosis Imaging in Evaluating Acute Xerostomia in Nasopharyngeal Carcinoma Treated With Induction Chemotherapy Plus Concurrent Chemoradiotherapy.

Purpose: The aim of this study was to identify the efficacy of diffusion kurtosis imaging (DKI) in tracking and monitoring the dynamic change of parotid glands (PGs), submandibular glands (SMGs), sublingual glands (SLGs), and acute xerostomia in nasopharyngeal carcinoma (NPC) patients treated with induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT). Methods: The prospective study recruited 42 participants treated with IC+CCRT. All patients underwent DKI scanning six times: before IC, before RT, in the middle of the RT course, immediately after RT, and 1 and 3 months post-RT. Mean diffusion coefficient (MD) and mean kurtosis (MK) of PG, SMG, SLG, saliva flow rate measured under resting (uSFR) and stimulated condition (sSFR), and xerostomia questionnaire (XQ) scores were recorded. Results: At each time point, sSFR was significantly higher than uSFR (p < 0.05 for all). MD of the salivary glands and XQ scores increased over time while MK, uSFR, and sSFR decreased. After IC, the significant differences were detected in MD and MK of bilateral SMG and MK of the left SLG (p < 0.05 for all), but not in MD and MK of PG, uSFR, sSFR, and XQ scores. After RT, sSFR at 1m-RT decreased significantly (p = 0.03) while no significant differences were detected in uSFR and XQ scores. Moderate-strong correlations were detected in ΔMD-PG-R%, ΔMK-PG-R%, ΔMD-PG-L%, ΔMK-PG-L%, ΔMD-SMG-R%, ΔMK-SMG-R%, ΔMD-SMG-L%, ΔMK-SMG-L%, and ΔMD-SLG-R%, with correlation coefficients (p < 0.05 for all) ranging from 0.401 to 0.714. ΔuSFR% was correlated with ΔMD-SMG% (p = 0.01, r = -0.39), ΔMD-SLG% (p < 0.001, r = -0.532), and ΔMK-SMG% (p < 0.001, r = -0.493). ΔsSFR% correlated with ΔMD-PG% (p = 0.001, r = -0.509), ΔMD-SMG% (p = 0.015, r = -0.221), and ΔMK-PG% (p < 0.001, r = 0.524). ΔXQ% was only correlated with ΔMK-PG% (p = 0.004, r = 0.433). Conclusion: DKI is a promising tool for tracking and monitoring the acute damage of PG, SMG, and SLG induced by IC+CCRT in NPC patients.

First case report of a NUP98-PMX1 rearrangement in de novo acute myeloid leukemia and literature review.

BACKGROUND: The nucleoporin 98 (NUP98)-paired related homeobox 1 (PMX1) fusion gene, which results from t(1;11)(q23;p15), is rare in patients with acute myeloid leukemia (AML). Currently, only two cases of chronic myeloid leukemia in the accelerated phase or blast crisis and three cases of therapy-related AML have been reported. Here, we first report a patient with de novo AML carrying the NUP98-PMX1 fusion gene. CASE PRESENTATION: A 49-year-old man diagnosed with AML presented the karyotype 46,XY,t(1;11)(q23;p15)[20] in bone marrow (BM) cells. Fluorescence in situ hybridization analysis using dual-color break-apart probes showed the typical signal pattern. Reverse transcription-polymerase chain reaction (RT-PCR) analysis suggested the presence of the NUP98-PMX1 fusion transcript. The patient received idarubicin and cytarabine as induction chemotherapy. After 3 weeks, the BM aspirate showed complete remission, and the RT-PCR result for the NUP98-PMX1 fusion gene was negative. Subsequently, the patient received three cycles of high-dose Ara-c as consolidation chemotherapy, after which he underwent partially matched (human leukocyte antigen-DP locus mismatch) unrelated allogeneic hematopoietic stem cell transplantation (HSCT). The follow-up period ended on September 30, 2020 (6 months after HSCT), and the patient exhibited no recurrence or transplantation-related complications. CONCLUSION: This is the first report of a patient with de novo AML carrying the NUP98-PMX1 fusion gene. The reported case may contribute to a more comprehensive profile of the NUP98-PMX1 rearrangement, but mechanistic studies are warranted to fully understand the role of this fusion gene in leukemia pathogenesis.

A Risk Prediction Model by LASSO for Radiation-Induced Xerostomia in Patients With Nasopharyngeal Carcinoma Treated With Comprehensive Salivary Gland-Sparing Helical Tomotherapy Technique.

OBJECTIVE: This study aimed to develop a least absolute shrinkage and selection operator (LASSO)-based multivariable normal tissue complication probability (NTCP) model to predict radiation-induced xerostomia in patients with nasopharyngeal carcinoma (NPC) treated with comprehensive salivary gland-sparing helical tomotherapy technique. METHODS AND MATERIALS: LASSO with the extended bootstrapping technique was used to build multivariable NTCP models to predict factors of patient-reported xerostomia relieved by 50% and 80% compared with the level at the end of radiation therapy within 1 year and 2 years, R50-1year and R80-2years, in 203 patients with NPC. The model assessment was based on 10-fold cross-validation and the area under the receiver operating characteristic curve (AUC). RESULTS: The prediction model by LASSO with 10-fold cross-validation showed that radiation-induced xerostomia recovery could be predicted by prognostic factors of R50-1year (age, gender, T stage, UICC/AJCC stage, parotid Dmean, oral cavity Dmean, and treatment options) and R80-2years (age, gender, T stage, UICC/AJCC stage, oral cavity Dmean, N stage, and treatment options). These prediction models also demonstrated a good performance by the AUC. CONCLUSION: The prediction models of R50-1year and R80-2years by LASSO with 10-fold cross-validation were recommended to validate the NTCP model before comprehensive salivary gland-sparing radiation therapy in patients with NPC.