A longitudinal study of trajectories of change in benefit finding among family caregivers of patients with lung cancer / 中国实用护理杂志

Objective:To explore the change trajectory and influencing factors of benefit finding of family caregivers of patients with lung cancer, so as to provide reference for formulating individualized intervention strategies.Methods:This study was a cross-sectional survey. From September 2021 to October 2022, 232 family caregivers of patients with lung cancer from General Hospital of PLA Central Theater Command and Tianyou Hospital affiliated to Wuhan University of Science and Technology were collected by convenience sampling method. The level of benefit finding of family caregivers was investigated at 1 month, 3 months and 6 month, after the patients were diagnosed. Growth Mixture Model was applied to identify distinct trajectory categories. Multinomial Logistic regressions were performed to analyze predictors of trajectory categories.Results:The overall level of benefit finding of family caregivers of lung cancer patients showed an upward trend over time ( F=83.06, P<0.01), from 1 month (47.02 ± 14.79) to 6 months (58.13 ± 13.18). Three categories of benefit finding trajectories were identified, named as "the high level-decline group" 12 cases, "the moderate level-stability group" 67 cases, and "the low level-elevation group" 153 cases. Univariate analysis showed that age and education level of family caregivers, average income per person in patient family, type of medical payment, whether the tumor was metastasized, the treatment method of the patient, whether they lived with the patient, and whether they had co-caregivers were related to the category of benefit finding trajectory ( χ2 values were 6.71-15.05, all P<0.05). Multivariate Logistic regression analysis showed that age and education level of family caregivers, average income per person in patient family, treatment method of the patient and whether they lived with the patients were the main influencing factors of benefit finding trajectory categories(all P<0.05). Conclusions:The benefit finding of family caregivers of lung cancer patients showed different trajectories with the time of diagnosis, and the overall level shows an upward trend. More than half of the family caregivers belong to the low level-elevation group. Medical staff should give family caregivers stage and specific nursing intervention according to the change trajectory of benefit finding and its influencing factors.

Study on the mechanism of luteolin reversing multidrug resistance in leukemia K562/ADR cells / 天津医药

Objective To investigate the mechanism of luteolin's(Lut)reversal effect on multidrug resistance of chronic myeloid leukemia K562/ADR cells.Methods CCK-8 assay was used to detect drug resistance in K562 and K562/ADR cells 24 hours after treatment with different doses of adriamycin(ADR).CCK-8 assay was used to assess the cytotoxicity and sensitizing effect of Lut on ADR after K562/ADR cells were treated with Lut alone or in combination with ADR for 24 hours.K562/ADR cells in logarithmic growth phase were separated into three group:0μmol/L Lut,2μmol/L and 4μmol/L Lut groups.ADR accumulation in cells was measured using flow cytometry.Nuclear factor erythroid-2-related factor 2(Nrf2),multidrug resistance associated protein 1(MRP1),P-glycoprotein(P-gp)and glutathione-S-transferase-PI(GST-pi)mRNA and protein expressions were identified using RT-PCR and Western blot assay.Glutathione(GSH)kit was used to detect intracellular GSH content.Results Compared with K562 cells,K562/ADR cell line was significantly resistant to ADR,and the drug resistance was 53.69 times.K562/ADR cell proliferation was decreased to variable degrees by different doses of Lut when compared to the 0μmol/L Lut group(P＜0.05).The proliferation inhibition rates of K562/ADR cells treated with 2 and 4μmol/L Lut were less than 10%,indicating that the concentration of Lut was non-toxic.Compared with the 0 μmol/L Lut group,the 2 μmol/L Lut group and the 4 μmol/L Lut group showed significantly increased ADR growth inhibition rate on K562/ADR and increased accumulation of ADR in cells,improved the reversal resistance fold,and decreased GSH content in cells.MRP1,P-gp,GST-pi and Nrf2 mRNA and protein expression were reduced in cells(P＜0.05).The effect of 4 mol/L Lut was greater than that of 2 mol/L Lut.Conclusion Lut may decrease K562/ADR cell proliferation and reverse ADR medication resistance.The mechanism could be connected to the downregulation of Nrf2,MRP1,P-gp and GST-pi expression,which leads to an increase in ADR accumulation in K562/ADR cells.

Luteolin induces ferroptosis in adriamycin resistant K562/ADR cells through Nrf2/HO-1 signaling pathway / 肿瘤

Objective:To investigate the effect of luteolin(Lut)on the proliferation and ferroptosis of human adriamycin(ADR)resistant chronic myeloid leukemia(CML)K562/ADR cells and the underlying molecular mechanism. Methods:K562 and K562/ADR cells were treated with different concentrations of ADR.The sensitivity of K562 and K562/ADR cells to ADR was evaluated by CCK-8 assay;the effect of different concentrations of Lut on the proliferation of K562/ADR cells was assessed by CCK-8 assay,and the half inhibitory concentration(IC50)was calculated for subsequent experiments;the morphological changes of the cells were observed by an inverted microscope;CCK-8 assay was used to examine the sensitizing effect of Lut on ADR;FCM assay was used to study the effect of Lut on the apoptosis of K562/ADR cells;fluorescence probe DCFH-DA,Fe2+colorimetric assay and glutathione(GSH)kit were used to detect the content of reactive oxygen species(ROS),Fe2+and GSH in K562/ADR cells,respectively;Western blotting was used to examine the expression levels of glutathione peroxidase 4(GPX4),nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)in K562/ADR cells;the effects of Lut on the proliferation of K562/ADR cells,ROS content,GSH content,Fe2+content and GPX4 expression were studied after treatment with ferroptosis inhibitor Ferrostatin-1(Fer-1). Results:Compared with control group(cells treated with 0 μmol/L Lut),Lut significantly inhibited the proliferation of K562/ADR cells(P＜0.001),improved the chemosensitivity of K562/ADR cells to ADR(P＜0.05),increased apoptosis rate(P＜0.001)and ROS level(P＜0.05)of K562/ADR cells,reduced the GSH level(P＜0.001),and increase Fe2+content(P＜0.01).Compared with control group(cells treated with 0 μmol/L Lut),the protein expressions of GPX4,Nrf2 and HO-1 decreased with the increase of Lut concentration(P＜0.05).Compared with the Lut treatment alone,the inhibitory effect on the proliferation of K562/ADR cells induced by Lut was partially restored by Fer-1 intervention(P＜0.05),and intracellular ROS level was decreased(P＜0.001),GSH level was increased(P＜0.001),Fe2+content was decreased(P＜0.001)and the expression of GPX4 was increased(P＜0.01)in K562/ADR cells. Conclusion:Lut can inhibit the proliferation of K562/ADR cells through ferroptosis pathway,improve the chemosensitivity to ADR,and the potential mechanism may be related to the Nrf2/HO-1 signaling pathway,which provides experimental basis for the treatment of leukemia by ferroptosis.

Andrographolide protects against atrial fibrillation by alleviating oxidative stress injury and promoting impaired mitochondrial bioenergetics / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia seen in clinical settings, which has been associated with substantial rates of mortality and morbidity. However, clinically available drugs have limited efficacy and adverse effects. We aimed to investigate the mechanisms of action of andrographolide (Andr) with respect to AF. We used network pharmacology approaches to investigate the possible therapeutic effect of Andr. To define the role of Andr in AF, HL-1 cells were pro-treated with Andr for 1 h before rapid electronic stimulation (RES) and rabbits were pro-treated for 1 d before rapid atrial pacing (RAP). Apoptosis, myofibril degradation, oxidative stress, and inflammation were determined. RNA sequencing (RNA-seq) was performed to investigate the relevant mechanism. Andr treatment attenuated RAP-induced atrial electrophysiological changes, inflammation, oxidative damage, and apoptosis both in vivo and in vitro. RNA-seq indicated that oxidative phosphorylation played an important role. Transmission electron microscopy and adenosine triphosphate (ATP) content assay respectively validated the morphological and functional changes in mitochondria. The translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus and the molecular docking suggested that Andr might exert a therapeutic effect by influencing the Keap1-Nrf2 complex. In conclusions, this study revealed that Andr is a potential preventive therapeutic drug toward AF via activating the translocation of Nrf2 to the nucleus and the upregulation of heme oxygenase-1 (HO-1) to promote mitochondrial bioenergetics.

Analgesic effects of different acupuncture therapies on postherpetic neuralgia:a Bayes-ian network meta-analysis / 中国药理学与毒理学杂志

OBJECTIVE To assess the effi-cacy and safety of acupuncture-related treat-ments for postherpetic neuralgia(PHN),identify the most effective acupuncture and related treat-ments.METHODS PubMed,Cochrane Central Register of Controlled Trials,Embase,Web of Science,and four Chinese databases,a clinical research registration platform,and grey literature were searched.We evaluated the risk of bias and quality in the included studies and per-formed a Bayesian multiple network meta-analy-sis.RESULTS We included 29 randomized con-trolled trials comprising 1973 patients,of which approximately 17.24%showed a high risk of bi-as.According to the Jadad scale,2,16,and 11 studies were high,medium,and low quality,respectively.The pairwise meta-analysis results revealed that the efficacy of all acupuncture-related treatments for pain relief related to PHN showed the difference was statistically significant com-pared with that of antiepileptics.The network meta-analysis results showed that pricking and cupping plus antiepileptics were the most effec-tive,followed by electroacupuncture(EA)plus antiepileptics for pain relief in patients with PHN.EA plus antiepileptics ranked the best regarding reduced Pittsburgh Sleep Quality Index and Self-Rating Depression Scale scores in patients with PHN.No results were found regarding total response rate or quality of life among this study.Acupuncture-related treatments showed a lower incidence of adverse events than that of antiepi-leptics-related treatments.CONCLUSION Acu-puncture-related therapies may be potential treat-ment options for PHN and are relatively safe.Pricking and cupping plus antiepileptics are the most effective techniques for pain relief.EA plus antiepileptics is the best approach for improving insomnia and depression symptoms of PHN.

Efficacy of acupuncture on acute tonsillitis:a systematic review and meta-analysis / 中国药理学与毒理学杂志

OBJECTIVE To systematically assess the efficacy and safety of acupuncture in treating acute tonsillitis,providing a reference for clinical decision-making.METHODS We searched PubMed,CENTRAL,Embase,Web of Science,China National Knowledge Infrastruc-ture,China Biomedical,clinical research registra-tion platforms,grey literature,and the reference lists of the selected studies from inception to Oct.30,2022.The risk of bias assessment used Rev-Man.Meta-analysis was performed using STATA with Hedges' g value.In addition,we performed subgroup analysis,meta-regression,and publica-tion bias detection with Harbord's and Egger's tests.RESULTS We included 19 randomized controlled trials comprising 1701 patients,of which 1 study was assessed high risk of bias.The primary outcome,the response rate,revealed that acupuncture was more effective than antibi-otics.The secondary outcomes showed that the difference in the reduction of the VAS scores,sore throat time,and white blood cell counts was statistically significant with acupuncture compared to antibiotics.However,the difference in modulat-ing neutrophil percentage and C-reactive protein was not statistically significant.Besides,acupunc-ture treatments showed a lower incidence of adverse events than antibiotics.CONCLUSION Acupuncture therapy on acute tonsillitis is safe,and the response rate is superior to antibiotics.For alleviating sore throat symptoms,shortening sore throat time,and improving immune inflam-mation index,acupuncture has positive signi fi cance.Nevertheless,because of the limitations of this study,our conclusions should be inter-preted with caution.Future efforts still need more high-quality trials to improve the methodology and reporting quality.

Pure drug nano-assemblies: A facile carrier-free nanoplatform for efficient cancer therapy

Nanoparticulate drug delivery systems (Nano-DDSs) have emerged as possible solution to the obstacles of anticancer drug delivery. However, the clinical outcomes and translation are restricted by several drawbacks, such as low drug loading, premature drug leakage and carrier-related toxicity. Recently, pure drug nano-assemblies (PDNAs), fabricated by the self-assembly or co-assembly of pure drug molecules, have attracted considerable attention. Their facile and reproducible preparation technique helps to remove the bottleneck of nanomedicines including quality control, scale-up production and clinical translation. Acting as both carriers and cargos, the carrier-free PDNAs have an ultra-high or even 100% drug loading. In addition, combination therapies based on PDNAs could possibly address the most intractable problems in cancer treatment, such as tumor metastasis and drug resistance. In the present review, the latest development of PDNAs for cancer treatment is overviewed. First, PDNAs are classified according to the composition of drug molecules, and the assembly mechanisms are discussed. Furthermore, the co-delivery of PDNAs for combination therapies is summarized, with special focus on the improvement of therapeutic outcomes. Finally, future prospects and challenges of PDNAs for efficient cancer therapy are spotlighted.

Posterior circulation ischemic stroke: emergency diagnosis errors and improvement strategies / 国际脑血管病杂志

Posterior circulation ischemic stroke (PCIS) is caused by the infarction of the blood supply area of vertebrobasilar artery system, accounting for about 20% of all ischemic strokes. The clinical manifestations of PCIS are different and usually lack specificity. The commonly used pre-hospital stroke scale can not fully reflect signs and symptoms of PCIS, and even imaging examination is not easy to detect PCIS. As a result, it is difficult to correctly identify PCIS in the early stage in emergency settings, and the rates of misdiagnosis and missed diagnosis are significantly higher than those of the anterior circulation ischemic stroke. Early and correct identification of PCIS is of great significance to improve the prognosis of patients. By summarizing the relevant literature at home and abroad, this article discusses the diagnostic error factors of PCIS in emergency room from different angles, and summarizes the strategies and methods to improve the speed and accuracy of PCIS recognition and early management.

Screening strategy on precision prevention strategies for three types of malignant tumors / 上海预防医学

Malignant tumors can be classified into three categories， rapidly progressing tumors， slowly progressing tumors， and "indolent" tumors. Rapidly progressing tumors （such as liver cancer， pancreatic cancer， and cholangiocarcinoma） have acute onset， shorter time duration from onset to death， and poorer treatment effects， which warrants primary prevention. Slowly progressing tumors （such as lung cancer， colorectal cancer， breast cancer， and gastric cancer） have slow onset， clear precancerous lesions， longer time duration from onset to death， and better therapeutic effects， which is accordingly suitable for secondary prevention. “Indolent” tumors （such as prostate and thyroid cancer） do not affect the life expectancy and are suitable for tertiary prevention. Early screening of “indolent” tumors may lead to overtreatment. Furthermore， early screening of rapidly progressing tumors is difficult to identify early cancers， which results in low cost-effectiveness. In contrast， for slowly progressing tumors suitable for secondary prevention， early screening may have cost-effectiveness， though there might be over-diagnosis. It is crucial to adopt appropriate prevention and treatment strategies for diverse types of tumors. Currently， large-scale cohort studies and randomized controlled clinical trials with complete follow-up may accurately evaluate the effect of cancer prevention strategies. This review discusses the significance of screening in precision prevention of tumors based on the characteristics of tumor progression and patients’ prognosis.

Research progress of ferroptosis in the treatment of leukemia / 国际肿瘤学杂志

Leukemia is a group of hematologic malignancie. Ferroptosis is a novel of cell death caused by iron-dependent lipid peroxidation accumulation, which participates in the occurrence and development of leukemia. Activation of different regulatory sites in the ferroptosis pathway can promote the death of leukemia cells. Therefore, it can provide a new direction for the treatment of leukemia by inducing ferroptosis of cells.