Prevalence and contributing factors of anemia in patients with gynecological cancer: a retrospective cohort study.

This retrospective cohort study aimed to determine the prevalence of anemia among patients with gynecological cancer prior to any treatment and to identify contributing factors associated with anemia in this group. We retrospectively analyzed data from female patients aged 18 and above, diagnosed with various forms of gynecological cancer at The Affiliated Hospital of Southwest Medical University between February 2016 and March 2021. Anemia was assessed based on the most recent CBC results before any cancer treatment. Eligibility was based on a definitive histopathological diagnosis. Key variables included demographic details, clinical characteristics, and blood counts, focusing on hemoglobin levels. Statistical analysis was conducted using logistic regression models, and anemia was defined as hemoglobin levels below 12 g/dL for women, according to WHO criteria. Of the 320 participants, a significant prevalence of anemia was found. Correlations between anemia and factors like age, educational level, and biological markers (iron, folic acid, and vitamin B12 levels) were identified. In our study, we found that the prevalence of anemia among patients with gynecological cancer prior to any treatment was 59.06%, indicating a significant health concern within this population. The study highlights a significant prevalence of anemia in patients with gynecological cancer, emphasizing the need for regular hemoglobin screening and individualized management. These findings suggest the importance of considering various characteristics and clinical variables in anemia management among this patient group. Further studies are needed to explore the long-term effects of these factors on patient outcomes and to develop targeted interventions.

WDR61 ablation triggers R-loop accumulation and suppresses breast cancer progression.

Although, superkiller complex protein 8 (SKI8), previously known as WDR61 has been identified and mapped in breast tumor, little is currently known about its function. This study aims to elucidate the role of WDR61 in breast tumor development and its potential as a therapeutic target. Here, we show that tamoxifen-induced knockout of Wdr61 reduces the risk of breast tumors, resulting in smaller tumor size and weight, and improved overall survival. Furthermore, we show that knockdown of WDR61 compromises the proliferation of breast tumor cells with reduced colony-forming capacity. Further investigations demonstrate that the protective effect of WDR61 loss on breast tumor development is due to genomic instability. Mechanistic studies reveal that WDR61 interacts with the R-loop, and loss of WDR61 leads to R-loops accumulation in breast tumor cells, causing DNA damage and subsequent inhibition of cell proliferation. In summary, this study highlights the critical dependence of breast tumors on WDR61, which suppresses R-loop and counteracts endogenous DNA damage in tumor cells.

CK2-HTATSF1-TOPBP1 signaling axis modulates tumor chemotherapy response.

Homologous recombination (HR) plays a key role in maintaining genomic stability, and the efficiency of the HR system is closely associated with tumor response to chemotherapy. Our previous work reported that CK2 kinase phosphorylates HTATSF1 Ser748 (pS748) to facilitate HTATSF1 interaction with TOPBP1, which in turn, promotes RAD51 recruitment and HR repair. However, the clinical implication of the CK2-HTATSF1-TOPBP1 pathway in tumorigenesis and chemotherapeutic response remains to be elucidated. Here, we report that the CK2-HTATSF1-TOPBP1 axis is generally hyperactivated in multiple malignancies and renders breast tumors less responsive to chemotherapy. In contrast, deletion mutations of each gene in this axis, which also occur in breast and lung tumor samples, predict higher HR deficiency (HRD) scores, and tumor cells bearing a loss-of-function mutation of HTATSF1 are vulnerable to PARP inhibitors (PARPis) or platinum drugs. Taken together, our study suggests that the integrity of the CK2-HTATSF1-TOPBP1 axis is closely linked to tumorigenesis, and serves as an indicator of tumor HR status and modulates chemotherapy response.

The in vitro mechanism of Vaspinregulates the proliferation and steroidogenesis of rat lutein cells.

OBJECTIVE: Stable luteal cell function is an important prerequisite for reproductive ability and embryonic development. However, luteal insufficiency seriously harms couples who have the desire to have a pregnancy, and the most important thing is that there is no complete solution. In addition, Vaspin has been shown to have regulatory effects on luteal cells, but the complex mechanisms involved have not been fully elucidated. Therefore, this study aimed to explore the effect of Vaspin on rat luteal cells and its mechanism. METHODS: Granulosa lutein cells separated from the ovary of female rats were incubated for 24h with gradient concentrations of Vaspin, and granulosa lutein cells incubated with 0.5% bovine serum albumin were used as controls. The proliferation, apoptosis, angiogenesis, progesterone (P4) and estradiol (E2) were detected by CCK-8, Anneixn-FITC/PI staining, angiogenesis experiment and ELISA. Western blot was applied to observe the expression levels of proteins related to cell proliferation, apoptosis, angiogenesis and MEK/MAPK signaling pathway. RESULTS: Compared with the Control group, Vaspin could significantly up-regulate the proliferation of granulosa lutein cells and reduce the apoptosis. Moreover, Vaspin promoted the angiogenesis of granulosa lutein cells and the production of P4 and E2 in a concentration-dependent manner. Furthermore, Vaspin up-regulated the CyclinD1, CyclinB1, Bcl2, VEGFA and FGF-2 expression in granulosa lutein cells, and down-regulated the level of Bax. Also, Vaspin increased the p-MEK1 and p-p38 levels. CONCLUSION: Vaspin can up-regulate the proliferation and steroidogenesis of rat luteal cells and reduce apoptosis, which may be related to the influence of MEK/MAPK activity.

Mechanism for Fe(III) to decrease cadmium uptake of wheat plant: Rhizosphere passivation, competitive absorption and physiological regulation.

The presence of dissolved Fe(III) and Fe(III)-containing minerals has been found to alleviate cadmium (Cd) accumulation in wheat plants grown in Cd-contaminated soils, but the specific mechanism remains elusive. In this work, hydroponic experiments were conducted to dissect the mechanism for dissolved Fe(III) (0-2000 µmol L-1) to decrease Cd uptake of wheat plants and study the influence of Fe(III) concentration and Cd(II) pollution level (0-20 µmol L-1) on the Cd uptake process. The results indicated that dissolved Fe(III) significantly decreased Cd uptake through rhizosphere passivation, competitive absorption, and physiological regulation. The formation of poorly crystalline Fe(III) oxides facilitated the adsorption and immobilization of Cd(II) on the rhizoplane (over 80.4 %). In wheat rhizosphere, the content of CaCl2-extractable Cd decreased by 52.7 % when Fe(III) concentration was controlled at 2000 µmol L-1, and the presence of Fe(III) may reduce the formation of Cd(II)-organic acid complexes (including malic acid and succinic acid secreted by wheat roots), which could be attributed to competitive reactions. Down-regulation of Cd uptake genes (TaNramp5-a and TaNramp5-b) and transport genes (TaHMA3-a, TaHMA3-b and TaHMA2), along with up-regulation of the Cd efflux gene TaPDR8-4A7A, contributed much to the reduction of Cd accumulation in wheat plants in the presence of Fe(III). The inhibitory effect of Fe(III) on Cd uptake and transport in wheat plants declined with increasing Cd(II) concentration, particularly at 20 µmol L-1. This work provides important implications for remediating Cd-contaminated farmland soil and ensuring the safe production of wheat by using dissolved Fe(III) and Fe(III)-containing minerals.

Systematic profiling of Taxol resistance and sensitivity to tubulin missence mutations at molecular and cellular levels.

Taxol (paclitaxel) is the first approved microtubule-stabilizing agent (MSA) by binding stoichiometrically to tubulin, which is considered to be one of the most significant advances in first-line chemotherapy against diverse tumors. However, a large number of residue missence mutations harboring in the tubulin have been observed to cause acquired drug resistance, largely limiting the clinical application of Taxol and its analogs in chemotherapy. A systematic investigation of the intermolecular interactions between the Taxol and various tubulin mutants would help to establish a comprehensive picture of drug response to tubulin mutations in clinical treatment of cancer, and to design new MSA agents with high potency and selectivity to overcome drug resistance. In this study, we described an integration of in silico analysis and in vitro assay (iSiV) to profile Taxol against a panel of 149 clinically observed, cancer-associated missence mutations in ß-tubulin at molecular and cellular levels, aiming to a systematic understanding of molecular mechanism and biological implication underlying drug resistance and sensitivity conferring from tubulin mutations. It is revealed that the Taxol-resistant mutations can be classified into three types: (I) nonbonded interaction broken due to mutation, (II) steric hindrance caused by mutation, and (III) conformational change upon mutation. In addition, we identified three new Taxol-resistant mutations (C239Y, T274I, and R320P) that can largely reduce the binding affinity of Taxol to tubulin at molecular level, in which the T274I and R320P were observed to considerably impair the antitumor activity of Taxol at cellular level. Moreover, a novel drug-susceptible mutation (M363T) was also identified, which improves Taxol affinity by 2.6-fold and decreases Taxol antitumor EC50 values from 29.4 to 18.7 µM.

Are children with IgA nephropathy different from adult patients?

BACKGROUND: Previously, several studies have indicated that pediatric IgA nephropathy (IgAN) might be different from adult IgAN, and treatment strategies might be also different between pediatric IgAN and adult IgAN. METHODS: We analyzed two prospective cohorts established by pediatric and adult nephrologists, respectively. A comprehensive analysis was performed investigating the difference in clinical and pathological characteristics, treatment, and prognosis between children and adults with IgAN. RESULTS: A total of 1015 children and 1911 adults with IgAN were eligible for analysis. More frequent gross hematuria (88% vs. 20%, p < 0.0001) and higher proteinuria (1.8 vs. 1.3 g/d, p < 0.0001) were seen in children compared to adults. In comparison, the estimated glomerular filtration rate (eGFR) was lower in adults (80.4 vs. 163 ml/min/1.73 m2, p < 0.0001). Hypertension was more prevalent in adult patients. Pathologically, a higher proportion of M1 was revealed (62% vs. 39%, p < 0.0001) in children than in adults. S1 (62% vs. 28%, p < 0.0001) and T1-2 (34% vs. 8%, p < 0.0001) were more frequent in adults. Adjusted by proteinuria, eGFR, and hypertension, children were more likely to be treated with glucocorticoids than adults (87% vs. 45%, p < 0.0001). After propensity score matching, in IgAN with proteinuria > 1 g/d, children treated with steroids were 1.87 (95% CI 1.16-3.02, p = 0.01) times more likely to reach complete remission of proteinuria compared with adults treated with steroids. CONCLUSIONS: Children present significantly differently from adults with IgAN in clinical and pathological manifestations and disease progression. Steroid response might be better in children.

Reducing target binding affinity improves the therapeutic index of anti-MET antibody-drug conjugate in tumor bearing animals.

Many oncology antibody-drug conjugates (ADCs) have failed to demonstrate efficacy in clinic because of dose-limiting toxicity caused by uptake into healthy tissues. We developed an approach that harnesses ADC affinity to broaden the therapeutic index (TI) using two anti-mesenchymal-epithelial transition factor (MET) monoclonal antibodies (mAbs) with high affinity (HAV) or low affinity (LAV) conjugated to monomethyl auristatin E (MMAE). The estimated TI for LAV-ADC was at least 3 times greater than the HAV-ADC. The LAV- and HAV-ADCs showed similar levels of anti-tumor activity in the xenograft model, while the 111In-DTPA studies showed similar amounts of the ADCs in HT29 tumors. Although the LAV-ADC has ~2-fold slower blood clearance than the HAV-ADC, higher liver toxicity was observed with HAV-ADC. While the SPECT/CT 111In- and 124I- DTPA findings showed HAV-ADC has higher accumulation and rapid clearance in normal tissues, intravital microscopy (IVM) studies confirmed HAV mAb accumulates within hepatic sinusoidal endothelial cells while the LAV mAb does not. These results demonstrated that lowering the MET binding affinity provides a larger TI for MET-ADC. Decreasing the affinity of the ADC reduces the target mediated drug disposition (TMDD) to MET expressed in normal tissues while maintaining uptake/delivery to the tumor. This approach can be applied to multiple ADCs to improve the clinical outcomes.

Light-Activated Nanodiamond-Based Drug Delivery Systems for Spatiotemporal Release of Antisense Oligonucleotides.

Nanodiamonds (NDs) are considered promising delivery platforms, but inaccurate and uncontrolled release of drugs at target sites is the biggest challenge of NDs in precision medicine. This study presents the development of phototriggerable ND-based drug delivery systems, utilizing ortho-nitrobenzyl (o-NB) molecules as photocleavable linkers between drugs and nanocarriers. UV irradiation specifically cleaved o-NB molecules and then was followed by releasing antisense oligonucleotides from ND-based carriers in both buffer and cellular environments. This ND system carried cell nonpermeable therapeutic agents for bypassing lysosomal trapping and degradation. The presence of fluorescent nitrogen-vacancy centers also allowed NDs to serve as biological probes for tracing in cells. We successfully demonstrated phototriggered release of antisense oligonucleotides from ND-based nanocarriers, reactivating their antisense functions. This highlights the potential of NDs, photocleavable linkers, and light stimuli to create advanced drug delivery systems for controlled drug release in disease therapy, opening possibilities for targeted and personalized treatments.

Moyamoya syndrome may result from psoriasis: Four case reports.

BACKGROUND: Moyamoya syndrome (MMS) is a group of diseases that involves more than one underlying disease and is accompanied by moyamoya vascular phenomena. Psoriasis is a chronic immune skin disease closely linked to high blood pressure and heart disease. However, psoriasis-related MMS has not been reported. CASE SUMMARY: We collected data on patients with stroke due to MMS between January 2017 and December 2019 and identified four cases of psoriasis. Case histories, imaging, and hematological data were collected. The average age of the initial stroke onset was 58.25 ± 11.52 years; three cases of hemorrhagic and one case of ischemic stroke were included. The average duration from psoriasis confirmation to the initial MMS-mediated stroke onset was 17 ± 3.56 years. All MMS-related stenoses involved the bilateral cerebral arteries: Suzuki grade III in one case, grade IV in two cases, and grade V in one case. Abnormally elevated plasma interleukin-6 levels were observed in four patients. Two patients had abnormally elevated immunoglobulin E levels, and two had thrombocytosis. All four patients received medication instead of surgery. With an average follow-up time of 2 years, two causing transient ischemic attacks occurred in two patients, and no hemorrhagic events occurred. CONCLUSION: Psoriasis may be a potential risk factor for MMS. Patients with psoriasis should be screened for MMS when they present with neurological symptoms.

Risk factors for severe bronchopulmonary dysplasia in a Chinese cohort of very preterm infants.

OBJECTIVES: To examine the risk factors for severe bronchopulmonary dysplasia (BPD) in a cohort of very preterm infants (VPIs) in China, as BPD is common among VPIs and associated with a high mortality rate. METHODS: In this multicenter retrospective study, medical records from infants with BPD born at gestation age (GA) of <32 weeks with birth weight (BW) of <1,500 grams (g) in 7 regions of China were included. The cohort was stratified into different BPD severity groups based on their fraction of inspired oxygen requirement at a modified GA of 36 weeks or post discharge. Risk factors were identified using logistic regression analysis. RESULTS: A significant inverse correlation was revealed between BPD severity and both GA and BW (p<0.001). Independent risk factors for severe BPD (sBPD) were identified as invasive mechanical ventilation (≥7d), multiple blood transfusion (≥3), nosocomial infection (NI), hemodynamically significant patent ductus arteriosus (hsPDA), delayed initiation of enteral nutrition, and longer time to achieve total caloric intake of 110 kcal/kg. Conversely, administration of antenatal steroids was associated with reduced risk of sBPD. CONCLUSION: Our study not only reaffirmed the established risk factors of low GA and BW for sBPD in VPIs, but also identified additional, potentially modifiable risk factors. Further research is warranted to explore whether intervention in these modifiable factors might reduce the risk of sBPD.Clinical Trial Reg. No.: ChiCTR1900023418.

The Therapeutic Potential of Four Main Compounds of Zanthoxylum nitidum (Roxb.) DC: A Comprehensive Study on Biological Processes, Anti-Inflammatory Effects, and Myocardial Toxicity.

Zanthoxylum nitidum (Roxb.) DC. (Z. nitidum) is a traditional Chinese medicinal plant that is indigenous to the southern regions of China. Previous research has provided evidence of the significant anti-inflammatory, antibacterial, and anticancer properties exhibited by Z. nitidum. The potential therapeutic effects and cardiac toxicity of Z. nitidum remain uncertain. The aim of this research was to investigate the potential therapeutic properties of the four main compounds of Z. nitidum in cardiovascular diseases, their impact on the electrical activity of cardiomyocytes, and the underlying mechanism of their anti-inflammatory effects. We selected the four compounds from Z. nitidum with a high concentration and specific biological activity: nitidine chloride (NC), chelerythrine chloride (CHE), magnoflorine chloride (MAG), and hesperidin (HE). A proteomic analysis was conducted on the myocardial tissues of beagle dogs following the administration of NC to investigate the role of NC in vivo and the associated biological processes. A bioinformatic analysis was used to predict the in vivo biological processes that MAG, CHE, and HE were involved in. Molecular docking was used to simulate the binding between compounds and their targets. The effect of the compounds on ion channels in cardiomyocytes was evaluated through a patch clamp experiment. Organ-on-a-chip (OOC) technology was developed to mimic the physiological conditions of the heart in vivo. Proteomic and bioinformatic analyses demonstrated that the four compounds of Z. nitidum are extensively involved in various cardiovascular-related biological pathways. The findings from the patch clamp experiments indicate that NC, CHE, MAG, and HE elicit a distinct activation or inhibition of the IK1 and ICa-L in cardiomyocytes. Finally, the anti-inflammatory effects of the compounds on cardiomyocytes were verified using OOC technology. NC, CHE, MAG, and HE demonstrate anti-inflammatory effects through their specific interactions with prostaglandin-endoperoxide synthase 2 (PTGS2) and significantly influence ion channels in cardiomyocytes. Our study provides a foundation for utilizing NC, CHE, MAG, and HE in the treatment of cardiovascular diseases.

Novel Isoalantolactone-Based Derivatives as Potent NLRP3 Inflammasome Inhibitors: Design, Synthesis, and Biological Characterization.

The NLRP3 inflammasome has been recognized as a promising therapeutic target in drug discovery for inflammatory diseases. Our initial research identified a natural sesquiterpene isoalantolactone (IAL) as the active scaffold targeting NLRP3 inflammasome. To improve its activity and metabolic stability, a total of 64 IAL derivatives were designed and synthesized. Among them, compound 49 emerged as the optimal lead, displaying the most potent inhibitory efficacy on nigericin-induced IL-1ß release in THP-1 cells, with an IC50 value of 0.29 µM, approximately 27-fold more potent than that of IAL (IC50: 7.86 µM), and exhibiting higher metabolic stability. Importantly, 49 remarkably improved DSS-induced ulcerative colitis in vivo. Mechanistically, we demonstrated that 49 covalently bound to cysteine 279 in the NACHT domain of NLRP3, thereby inhibiting the assembly and activation of NLRP3 inflammasome. These results provided compelling evidence to further advance the development of more potent NLRP3 inhibitors based on this scaffold.

Revolutionizing breast cancer treatment: Harnessing the related mechanisms and drugs for regulated cell death (Review).

Breast cancer arises from the malignant transformation of mammary epithelial cells under the influence of various carcinogenic factors, leading to a gradual increase in its prevalence. This disease has become the leading cause of mortality among female malignancies, posing a significant threat to the health of women. The timely identification of breast cancer remains challenging, often resulting in diagnosis at the advanced stages of the disease. Conventional therapeutic approaches, such as surgical excision, chemotherapy and radiotherapy, exhibit limited efficacy in controlling the progression and metastasis of the disease. Regulated cell death (RCD), a process essential for physiological tissue cell renewal, occurs within the body independently of external influences. In the context of cancer, research on RCD primarily focuses on cuproptosis, ferroptosis and pyroptosis. Mounting evidence suggests a marked association between these specific forms of RCD, and the onset and progression of breast cancer. For example, a cuproptosis vector can effectively bind copper ions to induce cuproptosis in breast cancer cells, thereby hindering their proliferation. Additionally, the expression of ferroptosis­related genes can enhance the sensitivity of breast cancer cells to chemotherapy. Likewise, pyroptosis­related proteins not only participate in pyroptosis, but also regulate the tumor microenvironment, ultimately leading to the death of breast cancer cells. The present review discusses the unique regulatory mechanisms of cuproptosis, ferroptosis and pyroptosis in breast cancer, and the mechanisms through which they are affected by conventional cancer drugs. Furthermore, it provides a comprehensive overview of the significance of these forms of RCD in modulating the efficacy of chemotherapy and highlights their shared characteristics. This knowledge may provide novel avenues for both clinical interventions and fundamental research in the context of breast cancer.

Pulmonary succinate receptor 1 elevation in high-fat diet mice exacerbates lipopolysaccharides-induced acute lung injury via sensing succinate.

BACKGROUND: Individuals with obesity have higher level of circulating succinate, which acts as a signaling factor that initiates inflammation. It is obscure whether succinate and succinate receptor 1 (SUCNR1) are involved in the process of obesity aggravating acute lung injury (ALI). METHODS: The lung tissue and blood samples from patients with obesity who underwent lung wedgectomy or segmental resection were collected. Six-week-old male C57BL/6J mice were fed a high-fat diet for 12 weeks to induce obesity and lipopolysaccharides (LPS) were injected intratracheally (100 µg, 1 mg/ml) for 24 h to establish an ALI model. The pulmonary SUCNR1 expression and succinate level were measured. Exogenous succinate was supplemented to assess whether succinate exacerbated the LPS-induced lung injury. We next examined the cellular localization of pulmonary SUCNR1. Furthermore, the role of the succinate-SUCNR1 pathway in LPS-induced inflammatory responses in MH-s macrophages and obese mice was investigated. RESULT: The pulmonary SUCNR1 expression and serum succinate level were significantly increased in patients with obesity and in HFD mice. Exogenous succinate supplementation significantly increased the severity of ALI and inflammatory response. SUCNR1 was mainly expressed on lung macrophages. In LPS-stimulated MH-s cells, knockdown of SUCNR1 expression significantly inhibited pro-inflammatory cytokines' expression, the increase of hypoxia-inducible factor-1α (HIF-1α) expression, inhibitory κB-α (IκB-α) phosphorylation, p65 phosphorylation and p65 translocation to nucleus. In obese mice, SUCNR1 inhibition significantly alleviated LPS-induced lung injury and decreased the HIF-1α expression and IκB-α phosphorylation. CONCLUSION: The high expression of pulmonary SUCNR1 and serum succinate accumulation at least partly participate in the process of obesity aggravating LPS-induced lung injury.

Highly Expressed Z-DNA Binding Protein 1 in Esophageal Cancer Promotes Tumor Growth.

BACKGROUND: Esophageal cancer (ESCA) is a common malignant tumor of the digestive tract, and its poor prognosis is mainly attributed to the occurrence of invasion and metastasis. Z-DNA binding protein 1 (ZBP1), as a mRNA regulatory factor, plays an important role in the occurrence and development of various tumors. However, the role of ZBP1 in ESCA is not yet understood. AIMS: This study aims to explore the expression of ZBP1 in ESCA and its role in the development of ESCA. METHODS: Using bioinformatics analysis and immunohistochemistry staining, we detected the expression of ZBP1 in ESCA and normal tissues. The potential mechanism of ZBP1 in ESCA was analyzed from the aspects of genetic mutations, protein interaction networks, and pathway enrichment. We performed functional experiments in vitro to elucidate the effect of ZBP1 on ESCA cells. RESULTS: ZBP1 was found to be significantly upregulated in ESCA compared to adjacent noncancerous tissues, and its expression is closely related to gender, age, and lymph node metastasis. In ESCA, the genetic variation rate of ZBP1 is 8%, and its expression is positively correlated with immune cell infiltration. The ZBP1 co-expressed gene is mainly involved in processes such as lymph node proliferation and intercellular adhesion. In vitro experiments have confirmed that downregulation of ZBP1 significantly inhibited the proliferation, migration, and invasion of ESCA cells. CONCLUSION: This research proves that downregulation of ZBP1 can inhibit the progression of ESCA. This finding indicates that ZBP1 may be a novel biomarker to improve the diagnosis and treatment of ESCA.

Study on the cut-off point and the influencing factors of distress in newly diagnosed breast cancer patients.

Objective: Our aim is to investigate the cut-off point of distress and the influencing factors associated with distress in patients with newly diagnosed breast cancer. Methods: A cross-sectional survey of distress was conducted in 167 patients with newly diagnosed breast cancer admitted to the Department of General Surgery of a tertiary care hospital from July 2020 to March 2022. Patients completed the Hospital Anxiety and Depression Scale (HADS) and the Distress Thermometer (DT) questionnaire within 3 days of admission. The HADS ≥15 was used as the gold standard, and the cut-off point of the DT measure was analyzed using the Receiver Operating Characteristic (ROC) curve. The cut-off point obtained by ROC curve analysis was used to analyze the influencing factors of distress in breast cancer patients by univariate and multivariate regression analysis. Results: A total of 167 patients completed the survey, with an average HADS score of 8.43 ± 5.84 and a total HADS score of ≥15 in 37 (22.16%) patients, the mean DT score was 2.96 ± 1.85. ROC curve analysis showed an area under the curve of 0.885, with a maximum Jorden index (0.723) at a DT score of 4, the sensitivity was 100.0% and specificity was 72.3%. There were 73 (43.71%) patients with DT score ≥ 4. Regression analysis showed that insurance/financial problems, dealing with partner problems, tension, bathing/dressing problems, pain, and sleep problems were independent risk factors for l distress in newly diagnosed breast cancer patients. Conclusion: A DT score 4 is the cut-off point for distress in patients with newly diagnosed breast cancer. In clinical practice, target intervention should be carried out according to the risk factors of distress of patients.

Comparative analysis of hemoglobin, potassium, sodium, and glucose in arterial blood gas and venous blood of patients with COPD.

The study aims to assess the accuracy of the arterial blood gas (ABG) analysis in measuring hemoglobin, potassium, sodium, and glucose concentrations in comparison to standard venous blood analysis among patients diagnosed with chronic obstructive pulmonary disease (COPD). From January to March 2023, results of ABG analysis and simultaneous venous blood sampling among patients with COPD were retrospectively compared, without any intervention being applied between the two methods. The differences in hemoglobin, potassium, sodium, and glucose concentrations were assessed using a statistical software program (R software). There were significant differences in the mean concentrations of hemoglobin (p < 0.001), potassium (p < 0.001), and sodium (p = 0.001) between the results from ABG and standard venous blood analysis. However, the magnitude of the difference was within the total error allowance (TEa) of the United States of Clinical Laboratory Improvement Amendments (US-CLIA). As for the innovatively studied glucose concentrations, a statistically significant difference between the results obtained from ABG (7.8 ± 3.00) mmol·L-1 and venous blood (6.72 ± 2.44) mmol·L-1 was noted (p < 0.001), with the difference exceeding the TEa of US-CLIA. A linear relationship between venous blood glucose and ABG was obtained: venous blood glucose (mmol·L-1) = - 0.487 + 0.923 × ABG glucose (mmol·L-1), with R2 of 0.882. The hemoglobin, potassium, and sodium concentrations in ABG were reliable for guiding treatment in managing COPD emergencies. However, the ABG analysis of glucose was significantly higher as compared to venous blood glucose, and there was a positive correlation between the two methods. Thus, a linear regression equation in this study combined with ABG analysis could be helpful in quickly estimating venous blood glucose during COPD emergency treatment before the standard venous blood glucose was available from the medical laboratory.

Histidine re-sensitizes pediatric acute lymphoblastic leukemia to 6-mercaptopurine through tetrahydrofolate consumption and SIRT5-mediated desuccinylation.

Despite progressive improvements in the survival rate of pediatric B-cell lineage acute lymphoblastic leukemia (B-ALL), chemoresistance-induced disease progression and recurrence still occur with poor prognosis, thus highlighting the urgent need to eradicate drug resistance in B-ALL. The 6-mercaptopurine (6-MP) is the backbone of ALL combination chemotherapy, and resistance to it is crucially related to relapse. The present study couples chemoresistance in pediatric B-ALL with histidine metabolism deficiency. Evidence was provided that histidine supplementation significantly shifts the 6-MP dose-response in 6-MP-resistant B-ALL. It is revealed that increased tetrahydrofolate consumption via histidine catabolism partially explains the re-sensitization ability of histidine. More importantly, this work provides fresh insights into that desuccinylation mediated by SIRT5 is an indispensable and synergistic requirement for histidine combination therapy against 6-MP resistance, which is undisclosed previously and demonstrates a rational strategy to ameliorate chemoresistance and protect pediatric patients with B-ALL from disease progression or relapse.

Curcumin relieves oxaliplatin-induced neuropathic pain via reducing inflammation and activating antioxidant response.

Oxaliplatin (OXA) has shown high effectiveness in the treatment of cancers, but its anticancer clinical effects often induce neurotoxicity leading to neuropathic pain. Oxidative damage and NLRP3 inflammasome play important roles in neuropathic pain development. Here, neuropathic pain mouse model was constructed by continuous intraperitoneal injection of OXA. OXA administration induced mechanical pain, spontaneous pain, thermal hyperalgesia and motor disability in mice. The spinal cord tissues of OXA mice exhibited the suppressed antioxidative response, the activated NLRP3 inflammasome mediated inflammatory responses, and the increased GSK-3ß activity. Next, we injected curcumin (CUR) intraperitoneally in OXA mice for seven consecutive days. CUR-treated mice showed increased mechanical pain thresholds, reduced number of spontaneous flinches, increased paw withdrawal latency, and restored latency to fall. While in the spinal cord, CUR treatment inhibited the NLRP3 inflammasome mediated inflammatory response, increased Nrf2/GPX4-mediated antioxidant responses, and decreased mitochondrial oxidative generation. Additionally, CUR combined with GSK-3ß through four covalent bonds and reduced GSK-3ß activity. In conclusion, our findings suggest that CUR treatment inhibits GSK-3ß activation, increases Nrf2 mediated antioxidant responses, inhibits oxidative damage and inflammatory reaction, and alleviates OXA-induced neuropathic pain.