Quality of sleep and related factors during chemotherapy in patients with stage I/II breast cancer.

BACKGROUND: Insomnia causes severe distress in patients with breast cancer who receive chemotherapy. Few studies have focused on using objective methods to assess sleep. This study explored the quality of sleep and related factors in patients with breast cancer during chemotherapy. METHODS: The participants were 16 women with stage I or II breast cancer receiving their third cycle of chemotherapy with cyclophosphamide, epirubicin and fluorouracil, or cyclophosphamide, methotrexate and fluorouracil. The effects of chemotherapy on sleep were assessed on the 8th and 9th days of the third cycle, i.e. the active phase in terms of side effects, and the last 2 days before the start of the fourth cycle for comparison. Instruments used to assess sleep quality and related factors included actigraphy, the Hospital Anxiety and Depression Scale (HADS), the Symptom Distress Scale (SDS), the Fatigue Visual Analogue Scale (FVAS), the Epworth Sleepiness Scale (ESS), and sleep logs. RESULTS: During the active phase, patients showed an anxiety tendency with an average HADS score of 7.8 +/- 3.8. The average FVAS score was 4 +/- 2, indicative of mild fatigue, and SDS score (1.8 +/- 0.3) also indicated mild symptom distress. The number of awakenings each night was 2.2 +/- 1.6 by sleep logs, and the total time spent awake during these episodes was 47.8 +/- 26.1 minutes by Actiwatch. Sleep efficiency measured by Actiwatch in the active phase was 82.1 +/- 9.4% below the normal limit. Daytime sleepiness assessed by ESS showed mild sleepiness (6.0 +/- 3.5) in the active phase. CONCLUSION: The study showed poor sleep quality and daytime sleepiness in patients with breast cancer during the active phase of chemotherapy. Chemotherapy may bring symptom distress to patients and adversely influence sleep quality.     

Pivotal study of iodine-131-labeled chimeric tumor necrosis treatment radioimmunotherapy in patients with advanced lung cancer.

PURPOSE: Tumor necrosis treatment (TNT) uses degenerating tumor cells and necrotic regions of tumors as targets for radioimmunotherapy. Previous studies in animal tumor models and clinical trials have demonstrated that when linked to the therapeutic radionuclide iodine-131, recombinant chimeric TNT antibody ((131)I-chTNT) can deliver therapeutic doses to tumors regardless of the location or type of malignancy. Therapeutic efficacy and toxicity of (131)I-chTNT in advanced lung cancer patients were studied in this pivotal registration trial. PATIENTS AND METHODS: Patients with advanced lung cancer were treated with systemic or intratumoral injection of (131)I-chTNT in eight oncology centers in China. The objective response rate (ORR) was assessed as the primary end point. RESULTS: All 107 patients who were entered onto the study and completed therapy had experienced treatment failure after prior radiotherapy or chemotherapy a mean of three times. The results showed an ORR of 34.6% (complete response, 3.7%; partial response, 30.8%; no change, 55.1%; and progressive disease, 10.3%) in all patients and 33% in 97 non-small-cell lung cancer patients. A biodistribution study demonstrated excellent localization of the radioactivity in tumors in both systemically and intratumorally injected patients. The most obvious adverse side effect was mild and reversible bone marrow suppression. CONCLUSION: Radioimmunotherapy with (131)I-chTNT was well tolerated and can be used systemically or locally to treat refractory tumors of the lung.     

Efficacy and safety of nafamostat mesilate anticoagulation in blood purification treatment of critically ill patients: a systematic review and meta-analysis

BackgroundNafamostat mesilate (NM), a broad-spectrum and potent serine protease inhibitor, can be used as an anticoagulant during extracorporeal circulation, as well as a promising drug effective against coronavirus disease 2019 (COVID-19). We conducted a systematic meta-analysis to evaluate the safety and efficacy of NM administration in critically ill patients who underwent blood purification therapy (BPT).MethodsThe Cochrane Library, Web of Science and PubMed were comprehensively searched from inception to August 20, 2021, for potential studies.ResultsFour randomized controlled trials (RCTs) and seven observational studies with 2723 patients met the inclusion criteria. The meta-analysis demonstrated that conventional therapy (CT) significantly increased hospital mortality compared with NM administration (RR = 1.25, p = 0.0007). In subgroup analyses, the in-hospital mortality of the NM group was significantly lower than that of the anticoagulant-free (NA) group (RR = 1.31, p = 0.002). The CT interventions markedly elevated the risk ratio of bleeding complications by 45% (RR = 1.45, p = 0.010) compared with NM interventions. In another subgroup analysis, NM used exhibited a significantly lower risk of bleeding complications than those of the low-molecular-weight heparin (LMWH) used (RR = 4.58, p = 0.020). The filter lifespan was decreased significantly (MD = −10.59, p < 0.0001) in the NA groups compared with the NM groups. Due to the poor quality of the included RCTs, these results should be interpreted with caution.ConclusionGiven the better survival outcomes, lower risk of bleeding, NM anticoagulation seems to be a safe and efficient approach for BPT patients and could yield a favorable filter lifespan. More multi-center RCTs with large samples are required for further validation of this study.     

妊娠期亚临床甲状腺功能减退孕妇叶酸利用能力与血清同型半胱氨酸、维生素B12的相关性分析

目的 探究妊娠期亚临床甲状腺功能减退(妊娠期亚甲减)孕妇叶酸(FA)利用能力与血清同型半胱氨酸(Hcy)、维生素B₁₂的相关性。方法 选取100例妊娠期亚甲减孕妇为研究组;另选同期100例甲状腺功能正常孕妇为对照组。检测两组孕妇FA、Hcy、维生素B₁₂以及甲状腺功能,并分析其相关性。结果 两组FA利用能力比较,差异具有统计学意义(P<0.05)。研究组血清Hcy水平高于对照组,维生素B₁₂水平低于对照组,差异具有统计学意义(P<0.05)。两组游离三碘甲状腺原氨酸(FT₃)、游离四碘甲状腺原氨酸(FT₄)水平比较,差异无统计学意义(P>0.05),研究组促甲状腺激素(TSH)水平高于对照组,差异具有统计学意义(P<0.05)。FA利用能力与Hcy呈负相关(r=-0.454),与维生素B₁₂呈正相关(r=0.219);Hcy与维生素B₁₂、FT₃、FT₄呈负相关(r=...     

Vitamin D Enhances Neutrophil Generation and Function in Zebrafish (Danio rerio)

Vitamin D (VD) is a major regulator of calcium metabolism in many living organisms. In addition, VD plays a key role in regulating innate and adaptive immunity in vertebrates. Neutrophils constitute an important part of the first line of defense against invading microbes; however, the potential effect of VD on neutrophils remains elusive. Thus, in this study zebrafish in different developmental stages were utilized to identify the potential role of VD in the basal homeostasis and functions of neutrophils. Our results showed that addition of exogenous VD₃ promoted granulopoiesis in zebrafish larvae. Reciprocally, neutrophil abundance in the intestine of adult zebrafish with a cyp2r1 mutant, lacking the capacity to 25-hydroxylate VD, was reduced. Moreover, VD-mediated granulopoiesis was still observed in gnotobiotic zebrafish larvae, indicating that VD regulates neutrophil generation independent of the microbiota during early development. In contrast, VD was incapable to influence granulopoiesis in adult zebrafish when the commensal bacteria were depleted by antibiotic treatment, suggesting that VD might modulate neutrophil activity via different mechanisms depending on the developmental stage. In addition, we found that VD₃ augmented the expression of il-8 and neutrophil recruitment to the site of caudal fin amputation. Finally, VD₃ treatment significantly decreased bacterial counts and mortality in zebrafish infected with Edwardsiella tarda (E. tarda) in a neutrophil-dependent manner. Combined, these findings demonstrate that VD regulates granulopoiesis and neutrophil function in zebrafish immunity.     

Effects of Iron Supplementation on Testicular Function and Spermatogenesis of Iron-Deficient Rats

Iron deficiency is the most common micronutrient deficiency in the world. Previous studies have shown that iron deficiency increases oxidative stress and decreases antioxidant enzymes, and studies of male infertility indicated that oxidative stress may affect male reproductive functions. The aim of this study was to investigate the effects of iron supplementation on spermatogenesis and testicular functions in iron-deficient rats. Three-week-old male Sprague Dawley (SD) rats were randomly divided into two groups: an iron-adequate control (AI group, 35 ppm FeSO₄) and an iron-deficient group (ID group, <5 ppm FeSO₄). After three weeks, the iron-deficient group was divided into an original iron-deficient group and five iron-supplemented groups, the latter fed diets containing different doses of FeSO₄ (6, 12, 18, 24, and 35 ppm). After five weeks, blood and testis tissue were analyzed. We presented as median (interquartile range, IQR) for continuous measurements and compared their differences using the Kruskal–Wallis test followed by the Mann–Whitney U test among groups. The results showed that as compared with the AI group, the ID group had significantly lower serum testosterone and poorer spermatogenesis (The medians (QR) were 187.4 (185.6–190.8) of AI group vs. 87.5 (85.7–90.4) of ID group in serum testosterone, p < 0.05; 9.3 (8.8–10.6) of AI group vs. 4.9 (3.4–5.4) of ID group in mean testicular biopsy score (MTBS], p < 0.05); iron supplementation reversed the impairment of testis tissue. In the testosterone biosynthesis pathway, iron supplementation improved the lowered protein expressions of hydroxysteroid dehydrogenases caused by iron deficiency. Additionally, decreased activities of glutathione peroxidase and catalase, and increased cleaved-caspase 8 and caspase 3 expression, were found in the iron-deficient rats. The iron-supplemented rats that received > 12 ppm FeSO₄ exhibited improvements in antioxidant levels. In conclusion, iron supplementation can abrogate testis dysfunction due to iron deficiency through regulation of the testicular antioxidant capacity.     

耳穴压豆法治疗失眠症的护理研究

目的:探讨耳穴压豆法治疗失眠症的效果及方法。方法:将我院失眠症患者60例采用耳穴压豆法实施护理,追踪随访临床效果。结果:治疗后患者入睡时间小于30分钟人数明显多于治疗前,比较差异具有统计学意义(P<0.05)。治疗后患者睡眠时间大于6h人数明显多于治疗前,比较差异具有统计学意义(P<0.05)。本组总有效率达98.33%。结论:耳穴压豆法治疗失眠症的效果明确,值得应用。     

7,7'-Dimethoxyagastisflavone-induced apoptotic or autophagic cell death in different cancer cells

7,7'-Dimethoxyagastisflavone (DMGF), a biflavonoid isolated from the needles of Taxus × media cv. Hicksii, was evaluated for its antiproliferative and antineoplastic effects in three human cancer cell lines. Interestingly, DMGF caused cell death via different pathways in different cancer cells. DMGF induced apoptosis, activated caspase-3 activity and changed the mitochondrial membrane potential in HT-29 human colon cancer cells. However, the apoptotic pathway is not the major pathway involved in DMGF-induced cell death in A549 human lung cancer cells and HepG2 human hepatoma cells. Treatment with 3-MA, an inhibitor of autophagy, significantly decreased DMGF-induced cell death in HepG2 and A549 cells, but did not affect DMGF-induced cell death in HT-29 cells. Following DMGF treatment, the HepG2 cells increased expression of LC3B-II, a marker used to monitor autophagy in cells. Thus, DMGF induced apoptotic cell death in HT-29 cells, triggered both apoptotic and autophagic death in A549 cells and induced autophagic cell death in HepG2 cells.     

“Pincer movement”: Reversing cisplatin resistance based on simultaneous glutathione depletion and glutathione S-transferases inhibition by redox-responsive degradable organosilica hybrid nanoparticles

The therapeutic efficacy of cisplatin has been restricted by drug resistance of cancers. Intracellular glutathione (GSH) detoxification of cisplatin under the catalysis of glutathione S-transferases (GST) plays important roles in the development of cisplatin resistance. Herein, a strategy of “pincer movement” based on simultaneous GSH depletion and GST inhibition is proposed to enhance cisplatin-based chemotherapy. Specifically, a redox-responsive nanomedicine based on disulfide-bridged degradable organosilica hybrid nanoparticles is developed and loaded with cisplatin and ethacrynic acid (EA), a GST inhibitor. Responding to high level of intracellular GSH, the hybrid nanoparticles can be gradually degraded due to the break of disulfide bonds, which further promotes drug release. Meanwhile, the disulfide-mediated GSH depletion and EA-induced GST inhibition cooperatively prevent cellular detoxification of cisplatin and reverse drug resistance. Moreover, the nanomedicine is integrated into microneedles for intralesional drug delivery against cisplatin-resistant melanoma. The in vivo results show that the nanomedicine-loaded microneedles can achieve significant GSH depletion, GST inhibition, and consequent tumor growth suppression. Overall, this research provides a promising strategy for the construction of new-type nanomedicines to overcome cisplatin resistance, which extends the biomedical application of organosilica hybrid nanomaterials and enables more efficient chemotherapy against drug-resistant cancers.KEY WORDS: Cancer therapy, Cisplatin, Drug resistance, Glutathione depletion, Glutathione S-transferases, Disulfide bonds, Organosilica hybrid nanoparticles, Ethacrynic acid