Contributions of individual qSOFA elements to assessment of severity and for prediction of mortality.

BACKGROUND: The quick sequential [sepsis-related] organ failure assessment (qSOFA) acts as a prompt to consider possible sepsis. The contributions of individual qSOFA elements to assessment of severity and for prediction of mortality remain unknown. METHODS: A total of 3974 patients with community-acquired pneumonia were recruited to an observational prospective cohort study. The area under the receiver operating characteristic curve (AUROC), odds ratio, relative risk and Youden's index were employed to assess discrimination. RESULTS: Respiratory rate ≥22/min demonstrated the most superior diagnostic value, indicated by largest odds ratio, relative risk and AUROC, and maximum Youden's index for mortality. However, the indices for altered mentation and systolic blood pressure (SBP) ≤100 mm Hg decreased notably in turn. The predictive validities of respiratory rate ≥22/min, altered mentation and SBP ≤100 mm Hg were good, adequate and poor for mortality, indicated by AUROC (0.837, 0.734 and 0.671, respectively). Respiratory rate ≥22/min showed the strongest associations with SOFA scores, pneumonia severity index, hospital length of stay and costs. However, SBP ≤100 mm Hg was most weakly correlated with the indices. CONCLUSIONS: Respiratory rate ≥22/min made the greatest contribution to parsimonious qSOFA to assess severity and predict mortality. However, the contributions of altered mentation and SBP ≤100 mm Hg decreased strikingly in turn. It is the first known prospective evidence of the contributions of individual qSOFA elements to assessment of severity and for prediction of mortality, which might have implications for more accurate clinical triage decisions.

Respiratory rate ≥22/min demonstrated the most superior diagnostic value.Respiratory rate ≥22/min showed the strongest association with severity.Respiratory rate ≥22/min, altered mentation and SBP ≤100 mm Hg predicted mortality well, adequately and poorly, respectively.

Process Condition Optimization and Structural Feature Analysis of Humic Acid Extraction from Weathered Lignite.

In this study, response surface methodology (RSM) was adopted to investigate the optimization of process conditions for extracting humic acid (HA) from coal, aiming to enhance the yield of humic acid. Additionally, UV-vis spectroscopy, FTIR, XRD, TG-DTG, CP/MAS13CNMR, XPS, and molecular fluorescence were utilized to examine the properties of HAs. The extraction time significantly influenced the yield from Lishi weathered lignite, while the liquid-solid ratio had a significant impact on the yield from Wuhai weathered lignite. The interactive effect between factors did not have a significant effect on the yield. The optimal extraction conditions for Lishi humic acid (LSHA) were determined to be an extraction time of 4.4 h, NaOH concentration of 0.30 mol/L, and liquid-solid ratio of 21 mL/g, while those for Wuhai humic acid (WHHA) were 3.1 h, 0.21 mol/L, and 12 mL/g, respectively. Under these optimal conditions, the true yield values closely matched the predicted value obtained from the model optimization. Comparative analysis of the HAs revealed similarities in their chemical properties, including the degree of aromaticity, molecular weight, and distribution of functional groups. The aromaticity of WHHA was higher compared to that of LSHA. The higher hydrophilic-hydrophobic index of LSHA contributed to its relatively high biological activity compared to that of WHHA. Both humic acids belong to terrestrial humic acids. The results of the study provide a reference for further application of humic acid.

Glucose Metabolic Abnormality: A Crosstalk between Depression and Alzheimer's Disease.

Depression and Alzheimer's disease (AD) are two prevalent and debilitating conditions that significantly impact millions of people worldwide. Depressive disorders are characterized by persistent feelings of sadness, loss of interest, and impaired cognitive function. AD is a progressive neurodegenerative disorder that is accompanied by cognitive decline, memory loss, and behavioral changes. To date, the pathogenesis of AD and depression has not yet been fully explained. Recent studies have provided insights into the intricate relationship between these two disorders by emphasizing the role of glucose metabolic abnormalities as a potential link. This review explores the bidirectional association between depression and AD, focusing on common pathophysiological mechanisms involving glucose metabolism, such as hypothalamic-pituitary-adrenal (HPA) axis dysregulation, insulin resistance, glucose transporters, and oxidative stress. Understanding the crosstalk between glucose metabolic abnormalities, depression, and AD will open new avenues for therapeutic interventions. Finally, improving glucose metabolism through lifestyle modifications, pharmaceutical interventions or novel therapeutic approaches could provide a promising therapeutic strategy for managing both conditions simultaneously.

Clinical efficacy and immune response of BCL-2 inhibitors combined with hypomethylating agents in the treatment of acute myeloid leukemia.

OBJECTIVE: Acute myeloid leukemia (AML) is a malignant clonal proliferative disease with a high mortality rate. The combination therapy of BCL-2 inhibitor Venetoclax (VEN) and hypomethylating agents (HMAs) has significant anti-leukemia activity. METHODS: We analyzed the efficacy, safety and immune response characteristics of AML patients who were unfit for high-dose chemotherapy and accepted the medication of VEN + HMAs. RESULTS: After VEN + HMAs treatment, 31 newly diagnosed AML patients had the morphologic leukemia-free state rate (MLFS%) of 80.6% (25/31), complete response rate (CR%) of 54.8% (17/31), the minimal residual disease negative rate (MRD-%) of 51.6% (16/31), and the median progression-free survival (PFS) of 14 months. After treatment, the proportion of bone marrow primitive cells, the MRD level, white blood cell (WBC) count, fibrinogen (FIB) level and the proportion of B cells were significantly decreased. The red blood cell (RBC) count, hemoglobin (HGB) level, platelet count (PLT) count, activated partial thromboplastin time (APTT), the proportion of total T cells, CD8 + T cells and the IFN-γ level were significantly increased. After VEN + HMAs treatment, 12 relapsed AML patients had a MLFS% of 50% (6/12), CR% of 33.3% (4/12), MRD-% of 25% (3/12), and a median PFS of 7 months. After treatment, the proportion of bone marrow primitive cells and MRD level were slightly decreased, the proportions of CD8 + T cells and NK cells were significantly increased, the proportion of B cells and IL-10 level were significantly decreased. 12 AML patients who receive microtransplantation (MST) treatment using VEN + HMAs as a pretreatment regimen had a PFS of 20.5 months, which was much greater than VEN + HMAs group alone. Hematological recovery was better in the MST group with significantly increased RBC count, HGB level and PLT count. The most common adverse events were myelosuppression, agranulocytosis, infection and cardiovascular toxicity. No fatal adverse events were reported. CONCLUSION: The combination of BCL-2 inhibitors and HMAs had good efficacy and safety in AML patients who were unfit for high-dose chemotherapy, which may improve the immune microenvironment and enhance anti-leukemia immune response.

Molecular characterization and transcriptional regulation between PPAR and CPT1 in freshwater bivalve Hyriopsis cumingii.

Peroxisome proliferator activated receptors (PPARs) exert their roles in lipid metabolism and adaptive immunity by transactivating carnitine palmitoyltransferase 1 (CPT1). However, it remains unclear whether the PPAR-CPT1 signaling pathway exists in mollusks that only carry out innate immunity. This study cloned and characterized PPAR and CPT1 genes from Hyriopsis cumingii for the first time, designated as HcPPARs and HcCPT1s, respectively. The bioinformatics analysis revealed conservative molecular characteristics of these genes across species. Real-time quantitative PCR results indicated that higher expression levels of HcPPARs and HcCPT1s in the blood, mantle, and intestine suggested their potential involvement in lipid metabolism and innate immunity of mollusks. Treatments with agonists and inhibitors demonstrated a correlation in the expression of HcPPARs and HcCPT1s. Dual luciferase reporter assay identified regions with high transcriptional activities on promoters of HcCPT1s and potential binding sites for HcPPARs through prediction and mutation sites. These results suggested that the PPAR-CPT1 signaling might exist in H. cumingii. This research provides a necessary foundation for exploring the role of the PPAR-CPT1 signaling in innate immunity, and offers new theoretical evidence for the molecular regulatory mechanism of mollusks and the treatment of metabolic disorders and inflammatory diseases.

Lung ultrasound score for prediction of bronchopulmonary dysplasia in newborns: A meta-analysis.

BACKGROUND: Bronchopulmonary dysplasia (BPD) ranks among preterm infants' most common and severe respiratory diseases. Lung ultrasound scores (LUS) play a vital role in predicting early BPD and guiding treatment and intervention strategies for affected patients. OBJECTIVE: Performed a meta-analysis to assess the diagnostic LUS for newborns with BPD. METHODS: Online electronic databases such as MEDLINE, CINAHL, the Cochrane Library, and Web of Science were used to retrieve relevant research until May 2023. A total of 117 literatures were collected, and ten eligible articles were selected for meta-analysis. RESULTS: Meta-analysis was performed on 10 studies (1274 neonates). LUS at 7 days after birth (7 days of life, DOL 7) showed good diagnostic accuracy for any type of BPD, moderate and severe BPD. DOL 7 was more accurate in predicting all types of BPD (AUC = 0.87, sensitivity = 0.75, specificity = 0.83) than moderate and severe BPD (AUC = 0.80, sensitivity = 0.69, specificity = 0.79). There was no statistical significance between DOL 7 and DOL 14 in their accuracy for predicting all types of BPD (difference in AUC = 0.04, p= 0.068). There was no notable distinction between DOL 7 and DOL 14 in their accuracy for predicting moderate and severe BPD (difference in AUC =-0.04, p= 0.104). CONCLUSIONS: The diagnostic efficacy of LUS on DOL 7 in predicting the occurrence of all types of BDP and moderate-severe BPD is determined. This will facilitate rapid and accurate detection and timely treatment, thereby reducing the risk of neonatal mortality and sequelae.

Tyrosine phosphorylation and palmitoylation of TRPV2 ion channel tune microglial beta-amyloid peptide phagocytosis.

Alzheimer's disease (AD) is the leading form of dementia, characterized by the accumulation and aggregation of amyloid in brain. Transient receptor potential vanilloid 2 (TRPV2) is an ion channel involved in diverse physiopathological processes, including microglial phagocytosis. Previous studies suggested that cannabidiol (CBD), an activator of TRPV2, improves microglial amyloid-ß (Aß) phagocytosis by TRPV2 modulation. However, the molecular mechanism of TRPV2 in microglial Aß phagocytosis remains unknown. In this study, we aimed to investigate the involvement of TRPV2 channel in microglial Aß phagocytosis and the underlying mechanisms. Utilizing human datasets, mouse primary neuron and microglia cultures, and AD model mice, to evaluate TRPV2 expression and microglial Aß phagocytosis in both in vivo and in vitro. TRPV2 was expressed in cortex, hippocampus, and microglia.Cannabidiol (CBD) could activate and sensitize TRPV2 channel. Short-term CBD (1 week) injection intraperitoneally (i.p.) reduced the expression of neuroinflammation and microglial phagocytic receptors, but long-term CBD (3 week) administration (i.p.) induced neuroinflammation and suppressed the expression of microglial phagocytic receptors in APP/PS1 mice. Furthermore, the hyper-sensitivity of TRPV2 channel was mediated by tyrosine phosphorylation at the molecular sites Tyr(338), Tyr(466), and Tyr(520) by protein tyrosine kinase JAK1, and these sites mutation reduced the microglial Aß phagocytosis partially dependence on its localization. While TRPV2 was palmitoylated at Cys 277 site and blocking TRPV2 palmitoylation improved microglial Aß phagocytosis. Moreover, it was demonstrated that TRPV2 palmitoylation was dynamically regulated by ZDHHC21. Overall, our findings elucidated the intricate interplay between TRPV2 channel regulated by tyrosine phosphorylation/dephosphorylation and cysteine palmitoylation/depalmitoylation, which had divergent effects on microglial Aß phagocytosis. These findings provide valuable insights into the underlying mechanisms linking microglial phagocytosis and TRPV2 sensitivity, and offer potential therapeutic strategies for managing AD.

Untargeted metabolomics analysis of the urinary metabolic signature of acute and chronic gout.

BACKGROUND: Gout is a common kind of inflammatory arthritis with metabolic disorders. However, the detailed pathogenesis of gout is complex and not fully clear. We investigated the urine metabolic profiling of gout patients by ultra-performance liquid chromatograph quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). METHOD: Urine metabolites were extracted from 26 acute gout patients, 31 chronic gout patients, and 32 healthy controls. Metabolite extracts were analyzed by UPLC-Q-TOF-MS for untargeted metabolomics. The peak area of creatinine was used to correct the content variations of urine samples for the semi-quantitative analysis. The value of variable importance in the projection (VIP) was obtained through the orthogonal partial least squares-discrimination analysis (OPLS-DA), and several differential metabolites were screened out. RESULTS: The potential metabolic markers of gout in different stages were found based on the t-test. Finally, 18 different metabolites were identified through Human Metabolome Database (HMDB) and Targeted-MS/MS. The receiver operating characteristic (ROC) curve results revealed that all the screened biomarkers exerted high accuracy and diagnostic value. Pathway analysis indicated that the significantly different metabolites were mainly involved in purine metabolism and amino acid metabolism. CONCLUSION: The identified potential biomarkers are mainly involved in purine metabolism and amino acid metabolism, which leads us to further explore the pathogenesis of gout. This will lead us to further explore the pathogenesis of gout and provide the basis and ideas for the prevention and treatment of gout.

Exogenous metabolite application is a potential strategy for expanding the use of direct rice seeding with the aim of reducing seeding costs.

Rice is a staple food for over half of the global population, necessitates efficient and cost-effective production methods to ensure food security. However, direct seeding of rice often encounters challenges due to adverse environmental conditions, resulting in increased seeding costs. In this study, we analyzed the germination and physiological data of sixty-six rice varieties under cold and submergence conditions. Our results demonstrate that selecting rice varieties with superior germination capacity in these adverse conditions can improve germination rates by 39.43%. Transcriptomic and metabolomic analyses of two contrasting varieties revealed potential regulatory mechanisms involving hormonal pathways and the glycerophospholipid metabolism pathway. Furthermore, we found that the exogenous application of specific metabolites provides a cost-effective seed enhancement strategy for varieties with poor germination capacity. These findings suggest that combining suitable variety selection with seed enhancement treatments can significantly reduce seeding costs in rice production. This research offers valuable insights for developing resilient rice varieties and cost-effective seeding strategies, potentially contributing to improved rice cultivation practices and enhanced global food security.

Effect of long-acting PEGylated growth hormone for catch-up growth in children with idiopathic short stature: a 2-year real-world retrospective cohort study.

Several evidence gaps exist regarding the use of long-acting polyethylene glycol recombinant human growth hormone (PEG-rhGH) in children with idiopathic short stature (ISS), particularly studies conducted in real-world settings, with long-term follow-up, involving varied dosing regimens, and in comparison with daily rhGH. The study aimed to evaluate the effectiveness, safety, and adherence of once-weekly PEG-rhGH for catch-up growth in children with prepubertal ISS compared to daily rhGH. A real-world retrospective cohort study was conducted in prepubertal children with ISS in China. Children who voluntarily received once-weekly PEG-rhGH or daily rhGH were included and were followed up for 2 years. Ninety-five children were included, 47 received PEG-rhGH 0.2-0.3 mg/kg weekly and 48 received daily rhGH. Outcome measures included effectiveness in catch-up growth, adverse events, and treatment adherence. Height velocity increased significantly in both groups during rhGH therapy. In children who received PEG-rhGH treatment, height velocity was 10.59 ± 1.37 cm/year and 8.75 ± 0.86 cm/year in the first and second year, respectively, which were significantly more than those who received daily rhGH (9.80 ± 1.05 cm/year, P = 0.002, and 8.03 ± 0.89 cm/year, P < 0.001). The height standard deviation score improved at the end of the second year for all children (P < 0.001). However, children who received PEG-rhGH showed more excellent improvement than those with daily rhGH (1.65 ± 0.38 vs. 1.50 ± 0.36, P = 0.001). In children who received PEG-rhGH, lower missed doses were observed than those with daily rhGH (0.75 ± 1.06 vs. 4.4 ± 2.0, P < 0.001). No serious adverse events were observed. CONCLUSION: PEG-rhGH demonstrated superior effectiveness and adherence compared to daily rhGH in the treatment of children with ISS. The safety profiles were similar between the two treatments. WHAT IS KNOWN: • Recombinant human growth hormone (rhGH) has been used to increase adult height in children with idiopathic short stature (ISS), and its safety profile is comparable to other indications for growth hormone treatment. • The use of long-acting rhGH in children with ISS is still an area of uncertainty. WHAT IS NEW: • This 2-year real-world study provides new evidence that PEGylated rhGH (PEG-rhGH) is more effective than daily rhGH in promoting catch-up growth in children with ISS. • PEG-rhGH also demonstrated superior treatment adherence compared to daily rhGH in children with ISS. • The safety profiles of PEG-rhGH and daily rhGH were found to be similar.

Efficacy and challenges of anti-PD1 in MSI-H mCRC: a case report on concurrent infections and ir-AIHA.

Anti-programmed cell death protein 1 (PD-1) therapy has demonstrated notable efficacy in treating patients with deficient mismatch repair/high microsatellite instability (dMMR/MSI-H) metastatic colorectal cancer (mCRC). However, its clinical application is fraught with challenges and can lead to significant immune-related adverse events (ir-AEs). In this report, we present a complicated case of an mCRC patient with MSI-H and mutations in ß2M and LRP1B proteins, complicated by concurrent bacteremia and liver fluke infection, who received first-line anti-PD1 therapy. The patient exhibited a positive response to anti-PD1 treatment, even in the presence of concomitant antibiotic and anti-parasitic interventions. Additionally, the patient experienced immunotherapy-related autoimmune hemolytic anemia (ir-AIHA), a rare hematological ir-AE, which was effectively treated later on. Immunotherapy represents a pivotal and highly effective approach to tumor treatment. Baseline assessment of the MMR and MSI status is a crucial step before initiating immunotherapy, and regular ongoing assessments during the treatment course can facilitate early recognition of any secondary complications, enabling prompt intervention and ensuring optimal therapeutic outcomes. Overall, a multidisciplinary diagnostic and therapeutic algorithm can help maximize the therapeutic benefits of immunotherapy.

SOS! Hydrogen Sulfide Enhances the Flavonoid Early Warning System in Rice Plants to Cope with Thiocyanate Pollution.

The presence of thiocyanate (SCN-) in irrigation water has adverse effects on both plant growth and crop output. Hydrogen sulfide (H2S) is an important gaseous signaling molecule that can alleviate SCN- stress. Flavonoids are secondary compounds produced by plants and are ubiquitous in the plant kingdom. They play important roles in several physiological and biochemical processes. To investigate the effect of exogenous H2S on the growth of early rice plants under SCN- stress, we carried out a hydroponic experiment focusing on the interaction of exogenous H2S with flavonoids. In this study, a hydroponic experiment was performed to investigate the behavior of SCN- when subjected to varying effective doses (EC20: 24.0 mg/L; EC50: 96.0 mg/L; and EC75: 300.0 mg/L). The findings indicated that the relative growth rate (RGR) of the plants treated with H2S + SCN- was greater than that of the plants treated with SCN- alone. Higher amounts of flavonoids were detected in the shoots than in the roots, with more variability in the shoots. The early warning level results showed that most of the flavonoids were present at levels I and II, while quercetin was present at level IV. Genetic expression variation factor (GEVF) analyses revealed an increase in the quantity of "promoter genes" with increasing SCN- concentration in both rice tissues. Furthermore, administering external H2S while exposing rice tissues to SCN- resulted in a considerable decrease in the levels of reactive oxygen species. This study provides novel insights into the regulation of flavonoid levels in rice plants by exogenous H2S, facilitating enhanced resistance to SCN- stress and promoting sustainable agriculture.

Prognostic significance of CRLF2 in patients with acute lymphoblastic leukemia: a meta-analysis and systematic review.

The association between cytokine receptor-like factor 2 (CRLF2) and clinical outcomes in acute lymphoblastic leukemia (ALL) has been a topic of ongoing debate, with divergent findings. This article intended to investigate the influence of CRLF2 alterations on ALL prognosis. Following the PRISMA 2020 guidelines, this meta-analysis was conducted. Hazard ratio (HR) values and confidence intervals (CIs) were the primary statistical measures used. Data heterogeneity was judged using the chi-square test and I2 statistic. Publication bias was appraised with funnel plots, Begg's test, and Egger's test. 16 studies with 6771 patients were finally screened out. CRLF2 over-expression (CRLF2 OE) was associated with poorer event-free survival (EFS) (HR = 1.70, 95% CI = 1.18-2.44, P = 0.004) and relapse-free survival (RFS) (HR = 1.70, 95% CI = 1.28-2.24, P = 0.000) in pediatric ALL. Patients with CRLF2-deregulation (CRLF2-d), also known as CRLF2 rearrangement, exhibited shorter overall survival (OS) (HR = 2.22, 95% CI = 1.49-3.32, P = 0.000), EFS (HR = 1.93, 95% CI = 1.43-2.60, P = 0.000), and RFS (HR = 2.2, 95% CI = 1.53-3.18, P = 0.000) compared to those without CRLF2-d. Subgroup analysis of multivariate HRs and corresponding CIs indicated that childhood with CRLF2 OE had a shorter RFS (HR = 1.70, 95% CI = 1.28-2.24, P = 0.006), and CRLF2-d was identified as an independent prognostic biomarker for OS (HR = 2.22, 95% CI = 1.49-3.32, P = 0.000), EFS (HR = 1.95, 95% CI = 1.44-2.64, P = 0.000), and RFS (HR = 2.2, 95% CI = 1.53-3.18, P = 0.000) in pediatric ALL patients. Both CRLF2 OE and CRLF2-d are associated with poor prognosis in ALL patients.

Trophoblast fusion in fetal growth restriction is inhibited by CTGF in a cell-cycle-dependent manner.

Fetal growth restriction (FGR) is a relatively common complication of pregnancy, and insufficient syncytialization in the placenta may play an important role in the pathogenesis of FGR. However, the mechanism of impaired formation of the syncytiotrophoblast layer in FGR patients requires further exploration. In the present study, we demonstrated that the level of syncytialization was decreased in FGR patient placentas, while the expression of connective tissue growth factor (CTGF) was significantly upregulated. CTGF was found to inhibit trophoblast fusion via regulating cell cycle progress of BeWo cells. Furthermore, we found that CTGF negatively regulates cell cycle arrest in a p21-dependent manner as overexpression of p21 could rescue the impaired syncytialization induced by CTGF-overexpression. Besides, we also identified that CTGF inhibits the expression of p21 through ITGB4/PI3K/AKT signaling pathway. Our study provided a new insight for elucidating the pathogenic mechanism of FGR and a novel idea for the clinical therapy of FGR.

[Preparation Method and Quality Evaluation of Novel Frozen Human Platelets].

OBJECTIVE: To optimize the technical parameters related to the preparation of novel frozen human platelets and formulate corresponding protocol for its preparation. METHODS: Novel frozen human platelets were prepared with O-type bagged platelet-rich plasma (PRP), the key technical parameters (DMSO addition, incubation time, centrifugation conditions, etc.) of the preparation process were optimized, and the quality of the frozen platelets was evaluated by routine blood tests, apoptosis rate, platelet activation rate and surface protein expression level. RESULTS: In the preparation protocol of novel frozen human platelets, the operation of centrifugation to remove supernatant was adjusted to before the procedure of platelets freezing, and the effect of centrifugation on platelets was minimal when the centrifugation condition was 800×g for 8 min. In addition, platelets incubated with DMSO for 30 min before centrifugation exhibited better quality after freezing and thawing. The indexes of novel frozen human platelets prepared with this protocol remained stable after long-term cryopreservation. CONCLUSION: The preparation technique of novel frozen human platelets was established and the protocol was formulated. It was also confirmed that the quality of frozen platelets could be improved by incubating platelets with DMSO for 30 min and then centrifuging them at 800×g for 8 min in the preparation of novel frozen human platelets.

Effects of psychological support intervention on patients with nasopharyngeal carcinoma undergoing radiotherapy.

Objective: To find out the effects of psychological support intervention on patients with nasopharyngeal carcinoma undergoing radiotherapy. Methods: This was a retrospective study. Sixty six patients with nasopharyngeal carcinoma who received radiotherapy in the Affiliated Hospital of Hebei University from March 2021 to March 2022 were included and randomly divided into the observation group and the control group, with 33 cases in each group. Patients in the control group were given conventional care measures, while those in the observation group were given psychological support intervention on top of conventional care measures. The nursing effects between the two groups were compared. Results: After the intervention, the psychological resilience score of the observation group was significantly higher than that of the control group, with a statistically significant difference (P<0.05). The psychological resilience scores after the intervention were significantly higher in the observation group than before the intervention, and those in the control group were higher than before the intervention, with a statistically significant difference(P<0.05). The overall health score of quality of life in the observation group was significantly higher than that in the control group after the intervention, with a statistically significant difference(P<0.05). Moreover, the skin reaction in the observation group after radiotherapy was significantly better than that of the control group (P<0.01). Conclusion: Psychological support intervention is an effective means to treat patients with nasopharyngeal carcinoma, which results in various benefits such as improving patients' mental resilience and quality of life and reducing the incidence of adverse reactions after radiotherapy.

Combination of BCL-2 inhibitors and immunotherapy: a promising therapeutic strategy for hematological malignancies.

The rapid development of high-throughput sequencing in recent years has facilitated great progress in the molecular-targeted therapy of hematological malignancies, including leukemia, lymphoma, and multiple myeloma. BCL-2 inhibitors are among the most important molecular-targeted agents. Immunotherapy for hematologic malignancy has rapidly increased in popularity in recent years and has been proven to improve the overall survival rate. However, few clinical studies have investigated combination therapy with BCL-2 inhibitors and immunotherapies, such as immune molecule-targeted drugs or immune cell adoptive therapy. In this review, we discuss the drug discovery process, current clinical application status, and resistance and tolerance issues associated with BCL-2 inhibitors. We emphasize their important role in regulating the immune system and propose that the combination of BCL-2 inhibitors with immunotherapy may be one of the most promising treatment methods for hematologic malignancies.

OTUB1 regulates ferroptosis to inhibit myoblast differentiation into myotubes by deubiquitinating P62.

As the largest organ in the human body, skeletal muscle is essential for breathing support, movement initiation, and maintenance homeostasis. It has been shown that programmed cell death (PCD), which includes autophagy, apoptosis, and necrosis, is essential for the development of skeletal muscle. A novel form of PCD called ferroptosis is still poorly understood in relation to skeletal muscle. In this study, we observed that the activation of ferroptosis significantly impeded the differentiation of C2C12 myoblasts into myotubes and concurrently suppressed the expression of OTUB1, a crucial deubiquitinating enzyme. OTUB1-silenced C2C12 mouse myoblasts were used to investigate the function of OTUB1 in ferroptosis. The results show that OTUB1 knockdown in vitro significantly increased C2C12 ferroptosis and inhibited myogenesis. Interestingly, the induction of ferroptosis resulting from OTUB1 knockdown was concomitant with the activation of autophagy. Furthermore, OTUB1 interacted with the P62 protein and stabilized its expression by deubiquitinating it, thereby inhibiting autophagy-dependent ferroptosis and promoting myogenesis. All of these findings demonstrate the critical role that OTUB1 plays in controlling ferroptosis, and we suggest that focusing on the OTUB1-P62 axis may be a useful tactic in the treatment and prevention of disorders involving the skeletal muscle.

Fabrication of sea urchin shaped polyaniline-modified magnetic microporous organic network for efficient extraction of non-steroidal anti-inflammatory drugs from animal-derived food samples.

In this work, a novel polyaniline-modified magnetic microporous organic network (MMON-PANI) composite was fabricated for effective magnetic solid phase extraction (MSPE) of five typical nonsteroidal anti-inflammatory drugs (NSAIDs) from animal-derived food samples before high performance liquid chromatography (HPLC) detection. The core-shell sea urchin shaped MMON-PANI integrates the merits of Fe3O4, MON, and PANI, exhibiting large specific surface area, rapid magnetic responsiveness, good stability, and multiple binding sites to NSAIDs. Convenient and effective extraction of trace NSAIDs from chicken, beef and pork samples is realized on MMON-PANI via the synergetic π-π, hydrogen bonding, hydrophobic, and electrostatic interactions. Under optimal conditions, the MMON-PANI-MSPE-HPLC-UV method exhibits wide linear ranges (0.2-1000 µg L-1), low limits of detection (0.07-1.7 µg L-1), good precisions (intraday and inter-day RSDs < 5.4 %, n = 3), large enrichment factors (98.6-99.9), and less adsorbent consumption (3 mg). The extraction mechanism and selectivity of MMON-PANI are also evaluated in detail. This work proves the incorporation of PANI onto MMON is an efficient way to promote NSAIDs enrichment and provides a new strategy to synthesize multifunctional MON-based composites in sample pretreatment.