Oxidation Analysis of l-Cysteine with a Chiral Sensor Based on Quantum Weak Measurement.

l-Cysteine, distinguished by its possession of reactive sulfhydryl groups within its molecular structure, plays a significant role in both biological systems and the pharmaceutical industry. It stands not only as a natural component integral to the constitution of glutathione but also as the principal precursor for the synthesis of l-cystine through an oxidation reaction. This study endeavors to introduce a novel approach to l-cysteine analysis, capitalizing on its optical activity, whereby an optical rotation detection system grounded in the principles of quantum weak measurement is proffered. The optical rotation angle corresponding to the concentration of chiral solutions can be accurately ascertained through spectral analysis. In practical implementation, a chiral sensing system, boasting a sensitivity of 372 nm/rad, was meticulously constructed, leveraging the concept of weak value amplification. Then, the real-time monitoring of chemical reactions involving l-cysteine and dimethyl sulfoxide was performed. Under the specific experimental conditions outlined in this investigation, it was observed that the oxidation process culminated within approximately 12 h. The application of weak measurement-based chiral sensors holds immense potential, providing robust technical support for real-time monitoring in fields such as chiral analysis and the synthesis of chiral pharmaceutical compounds.

Circ-0000953 deficiency exacerbates podocyte injury and autophagy disorder by targeting Mir665-3p-Atg4b in diabetic nephropathy.

Circular RNAs (circRNAs) are special non-coding RNA (ncRNA) molecules that play a significant role in many diseases. However, the biogenesis and regulation of circRNAs in diabetic nephropathy (DN) are largely unknown. Here, we investigated the expression profile of circRNAs in kidney of DN mice through circular RNA sequencing (circRNA-seq). The renal biopsy samples of patients with DN had low circ -0,000,953 expression, which was significantly associated with renal function. Furthermore, loss-of-function and gain-of-function experiments were carried out to prove the role of circ -0,000,953 in DN. Podocyte conditional knockin (cKI) or systemic overexpression of circ -0,000,953 alleviated albuminuria and restored macroautophagy/autophagy in kidney of diabetic mice. However, circ -0,000,953 knockdown exacerbated albuminuria and podocyte injury. Mechanistically, we found circ -0,000,953 directly binds to Mir665-3p-Atg4b to perform its function. Silencing of Mir665-3p or overexpression of Atg4b recovered podocyte autophagy both in vitro and in vivo. To examine the cause of circ -0,000,953 downregulation in DN, bioinformatics prediction found that circ -0,000,953 sequence has a high possibility of containing an m6A methylation site. Additionally, METTL3 was proved to regulate the expression and methylation level of circ -0,000,953 through YTHDF2 (YTH N6-methyladenosine RNA binding protein 2). In conclusion, this study revealed that circ -0,000,953 regulates podocyte autophagy by targeting Mir665-3p-Atg4b in DN. Therefore, circ -0,000,953 is a potential biomarker for prevention and cure of DN.Abbreviation: CCL2/MCP-1: C-C motif chemokine ligand 2; ceRNA: competing endogenous RNA; circRNA: circular RNA; cKI: conditional knockin; cKO: conditional knockout; CRE: creatinine; DM: diabetes mellitus; DN: diabetic nephropathy; ESRD: end-stage renal disease; HG: high glucose; IF: immunofluorescence; MAP1LC3/LC3B: microtubule-associated protein 1 light chain 3 beta; MPC5: mouse podocyte clone 5; MTECs: mouse tubular epithelial cells; MTOR: mechanistic target of rapamycin kinase; NC: normal control; ncRNA: non-coding RNA; NPHS1: nephrosis 1, nephrin; NPHS2: nephrosis 2, podocin; PAS: periodic acid-Schiff; RELA/p65: v-rel reticuloendotheliosis viral oncogene homolog A (avian); SDs: slit diaphragm proteins; Seq: sequencing; STZ: streptozotocin; SV40: SV40-MES13-cells, mouse mesangial cell line; T1D: type 1 diabetes mellitus; T2D: type 2 diabetes mellitus; TEM: transmission electron microscopy; TNF/TNF-α: tumor necrosis factor; VECs: vascular endothelial cells; WT1: WT1 transcription factor; YTHDF2: YTH N6-methyladenosine RNA binding protein 2.

Specific intracellular retention of circSKA3 promotes colorectal cancer metastasis by attenuating ubiquitination and degradation of SLUG.

Our previous study demonstrated that tumor-suppressor circular RNAs (circRNAs) can be specifically secreted outside of colorectal cancer (CRC) cells within exosomes to maintain tumor cell fitness. However, whether tumor-driving circRNAs can be specifically retained in cells to facilitate tumor progression remains unknown. In this study, circRNA-seq showed that circSKA3 was significantly upregulated in CRC tissues but downregulated in serum samples from CRC patients. In addition, circSKA3 promoted CRC progression in vitro and in vivo and was retained in CRC cells via a specific cellmotif element. Interestingly, the cellmotif element was also the site of interaction of circSKA3 with SLUG, which inhibited SLUG ubiquitination degradation and promoted CRC epithelial-mesenchymal transition (EMT). Moreover, FUS was identified as a key circularization regulator of circSKA3 that bound to the key element. Finally, we designed and synthesized specific antisense oligonucleotides (ASOs) targeting circularization and cellmotif elements, which repressed circSKA3 expression, abolished the SLUG-circSKA3 interaction, and further inhibited CRC EMT and metastasis in vitro and in vivo.

AMER1 deficiency promotes the distant metastasis of colorectal cancer by inhibiting SLC7A11- and FTL-mediated ferroptosis.

The crosstalk between ferroptosis and cancer metastasis remains unclear. Here, we identify AMER1 as a key regulator of ferroptosis. AMER1 loss causes resistance to ferroptosis in colorectal cancer (CRC) cells. Interestingly, AMER1-deficient CRC cells preferentially form distant metastases, while AMER1-naive CRC cells mainly invade lymph nodes. Moreover, the ferroptosis inhibitor liproxstatin-1 effectively promotes hematogenous transfer of AMER1-naive cells. Mechanistically, AMER1 binds to SLC7A11 and ferritin light chain (FTL) and recruits ß-TrCP1/2, which degrade SLC7A11 and FTL by ubiquitination. Therefore, AMER1 deficiency increases cellular cystine levels but decreases the pool of labile free iron, thereby enhancing resistance to ferroptosis in CRC cells. Thus, AMER1 deficiency increases the survival of CRC cells in the blood under conditions of high oxidative stress and then promotes hematogenous metastasis of CRC. In conclusion, AMER1 mediates the crosstalk between ferroptosis and cancer metastasis, which provides a window of opportunity for treating metastatic colorectal cancer patients with AMER1 mutations.

Is shared decision-making a determinant of polypharmacy in older patients with chronic disease? A cross-sectional study in Hubei Province, China.

BACKGROUND: Shared decision-making(SDM) is recognized as an important means of managing polypharmacy among older people with chronic diseases. However, no studies have quantitatively measured the effect of SDM on polypharmacy. The objective of this study was to compare the impact of SDM and other factors on polypharmacy in inpatients and community patients. Additionally, the study aimed to compare the impact of different decision types on polypharmacy in community patients. METHODS: This is a population-based multicenter retrospective study conducted in Hubei Province, China. A cluster sampling approach was used to recruit 536 chronic disease inpatients from March to April 2019, and 849 community patients were recruited from April to June 2021. Propensity score weighting was used to control the confounding variables and determine the net effect of SDM on polypharmacy. RESULTS: Among the 536 hospitalized patients, the prevalence of polypharmacy was 56.3%. A high level of SDM was significantly associated with a lower risk of polypharmacy. Patients with chronic illnesses aged 76 years and older and with an annual family income of 24,001-36,000 yuan were associated with a lower likelihood of polypharmacy (p < 0.05). Multimorbidity was often accompanied by the occurrence of multiple medication use. Among 849 community patients, the prevalence of polypharmacy was 21.8%. Among types of decision-making, informed and paternalistic decision-making showed a higher likelihood of polypharmacy compared with shared decision-making (P < 0.05). Male, older patients over 76 years of age, urban residents, annual household income of 12,001-24,000 yuan, and multimorbidity were associated with higher likelihood of polypharmacy (P < 0.05). Patients with an annual household income of 24,001-36,000 yuan, 36,001 yuan or more, and good medication compliance showed a lower likelihood of polypharmacy (P < 0.05). CONCLUSIONS: The prevalence of polypharmacy is high among China's older population with chronic disease who should be paid more atthention by the healthcare providers. Additionaly, encouraging the patients' attendance in SDM, reducing paternalistic and informed decision-making during prescribing, improving patient medication compliance, and increasing the promotion and guidance of rational medication use for patients are essential to reduce polypharmacy in Chinese chronic disease patients.

Ultrasound-Triggered Piezocatalysis for Selectively Controlled NO Gas and Chemodrug Release to Enhance Drug Penetration in Pancreatic Cancer.

Nitric oxide (NO) is drawing widespread attention in treating pancreatic ductal adenocarcinoma (PDAC) as a safe and therapeutically efficient technique through modulating the dense fibrotic stroma in the tumor microenvironment to enhance drug penetration. Considerable NO nanogenerators and NO releasing molecules have been developed to shield the systemic toxicity caused by free diffusion of NO gas. However, on-demand controlled release of NO and chemotherapy drugs at tumor sites remains a problem limited by the complex and dynamic tumor microenvironment. Herein, we present an ultrasound-responsive nanoprodrug of CPT-t-R-PEG2000@BaTiO3 (CRB) which encapsulates piezoelectric nanomaterials barium titanate nanoparticle (BaTiO3) with amphiphilic prodrug molecules that consisted of thioketal bond (t) linked chemotherapy drug camptothecin (CPT) and NO-donor l-arginine (R). Based on ultrasound-triggered piezocatalysis, BaTiO3 can continuously generate ROS in the hypoxic tumor environment, which induces a cascade of reaction processes to break the thioketal bond to release CPT and oxidize R to release NO, simultaneously delivering CPT and NO to the tumor site. It is revealed that CRB shows a uniform size distribution, prolonged blood circulation time, and excellent tumor targeting ability. Moreover, controlled release of CPT and NO were observed both in vitro and in vivo under the stimulation of ultrasound, which is beneficial to the depletion of dense stroma and subsequently enhanced delivery and efficacy of CPT. Taken together, CRB significantly increased the antitumor efficacy against highly malignant Panc02 tumors in mice through inhibiting chemoresistance, representing a feasible approach for targeted therapies against Panc02 and other PDAC.

In situ synthesized nanozyme for photoacoustic-imaging-guided photothermal therapy and tumor hypoxia relief.

Nanozymes have attracted extensive research interest due to their ideal enzymatic catalytic performance; however, uncontrollable activities and nonspecific accumulation limit their further clinical application. To overcome these obstacles, we proposed in situ synthesized nanozyme, and realized the concept through an intelligent nanosystem (ISSzyme) based on Prussian blue (PB) precursor. PB nanozyme was synthesized at the tumor sites through the interaction of ISSzyme with glutathione, which was demonstrated by comparing with conventional PB nanozyme. ISSzyme is capable of tumor-specific photoacoustic imaging (PAI) and photothermal therapy (PTT), reducing the false-positive signals of PAI and the treatment side effects of PTT. ISSzyme has catalase-like activities, resulting in tumor hypoxia relief and metastasis inhibition. More importantly, the in situ synthesized PB nanozyme has the favorable property of minimal liver accumulation. Considering the above advantages, ISSzyme is expected to shed light on the design of the next-generation artificial enzymes, with many new biomedical applications.

Dual-targeting nanozyme for tumor activatable photo-chemodynamic theranostics.

Tumor phototheranostics holds a great promise on account of its high spatiotemporal resolution, tumor-specificity, and noninvasiveness. However, physical limitation of light penetration and "always on" properties of conventional photothermal-conversion agents usually cause difficulty in accurate diagnosis and completely elimination of tumor. Meanwhile, nanozymes mediated Fenton reactions can well utilize the tumor microenvironment (TME) to generate hydroxyl radicals for chemodynamic therapy (CDT), but limited by the concentration of H2O2 in TME and the delivery efficiency of nanozymes. To overcome these problems, a dual-targeting nanozyme (FTRNPs) is developed for tumor-specific in situ theranostics, based upon the assembling of ultrasmall Fe3O4 nanoparticles, 3,3',5,5'-tetrameth-ylbenzidine (TMB) and the RGD peptide. The FTRNPs after H2O2 treatment exhibits superior photothermal stability and high photothermal conversion efficiency (η = 50.9%). FTRNPs shows extraordinary accumulation and retention in the tumor site by biological/physical dual-targeting, which is 3.54-fold higher than that without active targeting. Cascade-dual-response to TME for nanozymes mediated Fenton reactions and TMB oxidation further improves the accuracy of both photoacoustic imaging and photothermal therapy (PTT). The tumor inhibition rate of photo-chemodynamic therapy is ~ 97.76%, which is ~ 4-fold higher than that of PTT or CDT only. Thus, the combination of CDT and PTT to construct "turn on" nanoplatform is of great significance to overcome their respective limitations. Considering its optimized "all-in-one" performance, this new nanoplatform is expected to provide an advanced theranostic strategy for the future treatment of cancers.

Simvastatin Attenuated Tumor Growth in Different Pancreatic Tumor Animal Models.

Newly diagnosed pancreatic cancer increases year by year, while the prognosis of pancreatic cancer has not been very good. Statin drugs were found to have protective effects against a variety of cancers, but their association with pancreatic cancer remains to be clarified. This study used different pancreatic cancer cell lines and in different animal models to confirm the relationship between simvastatin and pancreatic cancer. Flow cytometry and luciferase-based bioluminescent images were used to investigate the cell cycle and tumor growth changes under simvastatin treatment. Simvastatin decreased the MIA PaCa-2 cells, PANC-1 cells, and BxPC-3 cell viability significantly and may arrest the cell cycle in the G0 phase. During in vivo study, subcutaneously implanted simvastatin pre-treated pancreatic cancer cells and intraperitoneally treated simvastatin continuously demonstrated a slower tumor growth rate and decreased the tumor/body weight ratio significantly. In intravenous implant models, implanted simvastatin-pre-treated BxPC-3 cells and cells treated along with simvastatin significantly decreased the tumor growth curve. Implanting the simvastatin-pre-treated pancreatic cells in the subcutaneous model showed better growth inhibition than the intravenous model. These results suggest simvastatin treatment may relate to different signaling pathways in local growth and metastasis. Pancreatic cancer cells presented different growth patterns in different animal-induced models, which could be important for clinical reference when it comes to the relationship of long-term statin use and pancreatic cancer.

Optical biosensor based on weak value amplification for the high sensitivity detection of Pertuzumab in combination with Trastuzumab binding to the extracellular domain of HER2.

A real-time optical phase sensing scheme based on weak value amplification was proposed to monitor the especially binding process of Pertuzumab combined with Trastuzumab on HER2 positive cells. From the wavelength shift of output spectrum, the phase difference between measuring and referential path related to the concentration of Pertuzumab as well as Trastuzumab could be calculated. With this approach, the limit of detection (LOD) of 5.54 × 10-13 M for Pertuzumab assay was achieved. Besides, the kinetics signal of Pertuzumab in combination with Trastuzumab binding to HER2 was detected in real time. Experimental results demonstrated that both Trastuzumab and Pertuzumab can be captured by HER2, but the former was significantly superior to the latter in terms of the target number. Additionally, the binding speed was analyzed and demonstrated to be closely correlated with the initial concentration of the targeting agents.

ENO2 Promotes Colorectal Cancer Metastasis by Interacting with the LncRNA CYTOR and Activating YAP1-Induced EMT.

The glycolytic enzyme enolase 2 (ENO2) is dysregulated in many types of cancer. However, the roles and detailed molecular mechanism of ENO2 in colorectal cancer (CRC) metastasis remain unclear. Here, we performed a comprehensive analysis of ENO2 expression in 184 local CRC samples and samples from the TCGA and GEO databases and found that ENO2 upregulation in CRC samples was negatively associated with prognosis. By knocking down and overexpressing ENO2, we found that ENO2 promoted CRC cell migration and invasion, which is dependent on its interaction with the long noncoding RNA (lncRNA) CYTOR, but did not depend on glycolysis regulation. Furthermore, CYTOR mediated ENO2 binding to large tumor suppressor 1 (LATS1) and competitively inhibited the phosphorylation of Yes-associated protein 1 (YAP1), which ultimately triggered epithelial-mesenchymal transition (EMT). Collectively, these findings highlight the molecular mechanism of the ENO2-CYTOR interaction, and ENO2 could be considered a potential therapeutic target for CRC.

Long Noncoding RNA MIR4435-2HG Suppresses Colorectal Cancer Initiation and Progression By Reprogramming Neutrophils.

MIR4435-2HG, also known as LINC00978, has previously been described as an oncogenic long noncoding RNA (lncRNA). However, we show here that Mir4435-2hg depletion promoted colorectal tumorigenesis and progression in in vivo models of colitis-associated colorectal cancer, spontaneous intestinal adenomatous polyposis, and subcutaneous tumors. Alteration of MIR4435-2HG in colorectal cancer cells did not change the potential for cell proliferation, migration, or invasion in vitro. RNAscope assays showed that most MIR4435-2HG was located in the tumor stroma, which caused high expression of MIR4435-2HG in colorectal cancer tumor tissue. Transcriptome analysis of colorectal cancer tissues from wild-type and Mir4435-2hg-deficient mice revealed Mir4435-2hg as a tumor suppressor gene that regulated the immune microenvironment. Loss of Mir4435-2hg led to a decline in neutrophils and elevation of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC). In tissue-specific Mir4435-2hg knockout mice, we confirmed that Mir4435-2hg depletion in neutrophils, but not in intestinal epithelial cells, promoted colorectal cancer progression. Mechanistically, Mir4435-2hg depletion enhanced the immunosuppressive ability of PMN-MDSCs by disturbing their fatty acid metabolism. These findings suggest that MIR4435-2HG is a tumor-suppressing lncRNA whose deficiency could increase tumor-infiltrating PMN-MDSCs and enhance the immunosuppressive potential of PMN-MDSCs to promote colorectal cancer development. This provides a theoretical basis for further illustrating the pathogenesis of colorectal cancer and a potential antitumor immunotherapy target.

Charge Reversal Polypyrrole Nanocomplex-Mediated Gene Delivery and Photothermal Therapy for Effectively Treating Papillary Thyroid Cancer and Inhibiting Lymphatic Metastasis.

As a traditional treatment for papillary thyroid cancer (PTC), surgical resection of diseased tissues often brings lots of inconveniences to patients, and the tumor recurrence and metastasis are difficult to avoid. Herein, we developed a gene and photothermal combined therapy nanosystem based on a polypyrrole (Ppy)-poly(ethylene imine)-siILK nanocomplex (PPRILK) to achieve minimally invasive ablation and lymphatic metastasis inhibition in PTC simultaneously. In this system, gelatin-stabilized Ppy mainly acted as a photothermal- and photoacoustic (PA)-responsive nanomaterial and contributed to its well-behaved photosensitivity in the near-infrared region. Moreover, gelatin-stabilized Ppy possessed a charge reversal function, facilitating the tight conjunction of siILK gene at physiological pH (7.35-7.45) and its automatic release into acidic lysosomes (pH 4.0-5.5); the proton sponge effect generated during this process further facilitated the escape of siILK from lysosomes to the cytoplasm and played its role in inhibiting PTC proliferation and lymphatic metastasis. With the guidance of fluorescence and PA bimodal imaging, gene delivery and Ppy location in tumor regions could be clearly observed. As a result, tumors were completely eradicated by photothermal therapy, and the recurrences and metastases were obviously restrained by siILK.

Tumor-suppressive circRHOBTB3 is excreted out of cells via exosome to sustain colorectal cancer cell fitness.

BACKGROUND & AIMS: To clarify the biological roles, circularization process and secretion pathway of circRHOBTB3 in colorectal cancer (CRC) progression. METHODS: We performed a comprehensive analysis of circRNA levels in serum exosomes from multiple types of cancer patients in public databases and verified the higher level of circRHOBTB3 in CRC sera versus healthy donors by RT-qPCR. Then, the function of circRHOBTB3 in CRC was investigated in vitro and in vivo. RNA-seq and RNA pull-down assays together with mass spectrometry identified the downstream signals and the binding proteins of circRHOBTB3. Finally, Antisense oligonucleotides (ASOs) were designed to target circularization and secretion elements of circRHOBTB3 for CRC therapy. RESULTS: circRHOBTB3 levels were increased in the sera but was downregulated in tissue samples in CRC, and the downregulation was associated with poor prognosis. Furthermore, circRHOBTB3 acts a tumor-suppressive circRNA by repressing metabolic pathways, intracellular ROS production in CRC. Several key elements were discovered to regulate circRHOBTB3 circularization and exosomal secretion. Moreover, SNF8 was identified that sorts circRHOBTB3 into exosomes. Interestingly, we found that CRC cells could actively secrete more circRHOBTB3 than normal cells. According to the sequence of regulatory elements for circularization and exosomal secretion, we designed and synthesized ASOs, which increased circRHOBTB3 expression and blocked circRHOBTB3 exosomal secretion. More importantly, ASOs could inhibit CRC growth and metastasis in vitro and in vivo. CONCLUSIONS: circRHOBTB3 plays a tumor-suppressive role in CRC and has to be excreted out of cells to sustain cancer cell fitness. ASOs targeting regulatory elements for circularization and exosomal secretion will become a novel antitumor strategy.

Correlation between preoperative psychological personality traits of glioma patients and psychological distress in their primary caregivers.

OBJECTIVE: To explore the relationship between preoperative psychological personality traits of glioma patients and preoperative psychological distress of their primary caregivers. METHODS: A retrospective analysis was conducted on 85 glioma patients (tumor group) who were admitted to our hospital from February 2016 to December 2018 and 85 primary caregivers. Forty-one healthy volunteers were used as controls. RESULTS: The scores of 9 scales of the Minnesota Multiphasic Personality Inventory (MMPI) increased significantly in the tumor group compared to the healthy controls (P < 0.05), including L (lie): [(56.0 ± 11.5 vs. 50.0 ± 10.0)], F (fake): [(53.0 ± 10.6 vs. 41.7 ± 8.8)], Hs (hypochondriasis): [(55.6 ± 11.2 vs. 44.2 ± 8.3)], D (depressive personality): [(49.2 ± 9.6 vs. 42.2 ± 10.3)], Mf (masculinity-femininity): [(49.9 ± 9.4 vs. 42.8 ± 14.0)], Pt (psychasthenia): [(51.5 ± 10.0 vs. 40.9 ± 11.5)], Sc (schizophrenia): [(51.2 ± 10.6 vs. 40.2 ± 10.6)], Ma (hypomania): [(51.8 ± 9.1 vs. 47.7 ± 9.4)] and Si (social introversion): [(46.6 ± 8.7 vs. 36.7 ± 13.0)]. However, the K (defensive responses) scale score in the tumor group decreased significantly (52.1 ± 13.9 vs. 58.8 ± 12.1, P = 0.009). The F (fake): [(rs=0.253, P=0.019 / rs=0.215, P=0.048)], Hs (hypochondriasis): [(rs=0.310, P=0.004 / rs=0.345, P=0.001)], Pt (psychasthenia): [(rs=0.299, P=0.006 / rs=0.258, P=0.017)], and Sc (schizophrenia): [(rs=0.325,P=0.002/rs=0.322, P=0.003)] of preoperative glioma patients were positively correlated with their preoperative psychological distress (depression/anxiety); the D (depressive personality): [(rs=0.229, P=0.035)] of preoperative glioma patients was positively correlated with the preoperative depression symptoms of their primary caregivers, and the Hy (hysteria): [(rs=0.233, P=0.002)] and Pd (psychopathic deviate): [(rs=0.215, P=0.006)] of preoperative glioma patients were positively correlated with the preoperative anxiety symptoms of their primary caregivers. CONCLUSIONS: The preoperative psychological personality traits of glioma patients were positively correlated with preoperative symptoms of depression and anxiety in primary caregivers.

Caregiver burden and influencing factors among family caregivers of patients with glioma: A cross-sectional survey.

OBJECTIVE: The main responsibility of caring for patients with glioma is assumed by family caregivers who experience a considerable burden during the care process. This study aimed to investigate the level of caregiver burden and explore its associated factors among family caregivers of patients with glioma. METHODS: We conducted a cross-sectional study among 131 family caregivers of glioma patients from October 2017 to November 2019. We used the following measurement tools: a demographic questionnaire, the Zarit Burden interview (ZBI), the Hamilton anxiety and depression scale, and the family APGAR index. We used multiple linear regression analysis to determine the factors related to caregiver burden. RESULTS: The ZBI score for the family caregivers of glioma patients was 31.29 (SD = 13.54), and most caregivers (71.7%) reported moderate and severe caregiver burdens. Caregivers' daily sleep time and anxiety symptoms and patients' depressive symptoms independently predicted caregiver burden. CONCLUSIONS: Family caregivers of glioma patients experienced a moderate burden. Personalised psychological intervention and sleep health guidance for patients and caregivers should be considered to reduce family caregiver burden and enhance the quality of life and mental health of both patients and their caregivers.

Predictors of Polypharmacy Among Elderly Patients in China: The Role of Decision Involvement, Depression, and Taking Chinese Medicine Behavior.

Introduction: The prevalence of polypharmacy is gradually increasing in geriatrics, which may contribute to adverse effects, such as potential drug-drug and drug-disease interactions. These side effects remain an important challenge in patient safety, which has a significant impact on mortality and incidence rate. Aims: Therefore, this study aims to understand the epidemiology of polypharmacy and identify factors that have an impact on the management of potentially inappropriate prescribing. Methods: This study is a cross-sectional study, analyzing the prescription data from 720 hospitalized patients aged 50+ with a random cluster sampling method. We used inverse probability treatment weighting (IPTW) method to group and match polypharmacy and non-polypharmacy patients, and logistic regression was conducted to explore the factors associated with polypharmacy. Results: The prevalence of polypharmacy accounted for 50.14% among the old patients in this study. Female patients (67.34%) have more polypharmacy than male patients, and key predictors associated with polypharmacy in the logistic regression model included the following: domicile (AOR = 0.63, 95% CI 0.42-0.95), annual income (AOR = 0.38, 95% CI 0.20-0.70), the number of chronic diseases (AOR = 3.68, 95% CI 2.69-5.06), taking Chinese medicine (AOR = 1.70, 95% CI 1.22-2.36), decision involvement (AOR = 1.49 95% CI 1.10-2.03), and depression (AOR = 1.42, 95% CI 1.03-1.96). Conclusion: Polypharmacy is common among the participants with chronic diseases in Hubei province, China. The study emphasizes that gerontology practitioners should be prudent in applying clinical guidelines to provide personalized, comprehensive assessment of decision making of prescriptions, especially in socioeconomically deprived areas.

The Cell Protective Effect of Adenine on Hypoxia-Reoxygenation Injury through PPAR Delta Activation.

Ischemia followed by blood supply reperfusion in cardiomyocytes leads to an overproduction of free radicals and a rapid decrease of adenosine triphosphate concentration. The cardioprotective effect of a potential drug, adenine, was evaluated using H9c2 rat cardiomyoblasts. After hypoxia-reoxygenation (HR) treatment consisting of hypoxia for 21 h followed by reoxygenation for 6 h, it was revealed that pretreatment with 200 µM adenine for 2 h effectively prevented HR-induced cell death. Adenine also significantly decreased the production of reactive oxygen species and reduced cell apoptosis after HR injury. The antioxidant effect of adenine was also revealed in this study. Adenine pretreatment significantly reduced the expression of activating transcription factor 4 (ATF4) and glucose-regulated protein 78 (GRP78) proteins, and protein disulfide isomerase induced a protective effect on mitochondria after HR stimulation. Intracellular adenosine monophosphate-activated protein kinase, peroxisome proliferator-activated receptor delta (PPARδ), and perilipin levels were increased by adenine after HR stimulation. Adenine had a protective effect in HR-damaged H9c2 cells. It may be used in multiple preventive medicines in the future.

What Factors Hindered the Access to Essential Anticancer Medicine in Public Hospitals for the Local Population in Hubei Province, China.

Background: Cancer poses a serious threat to one's health, which caused significant economic burden on the family and society. Poor availability and affordability resulted in some essential medicines failing to meet the basic health needs of this group of patients. The objective of this study was to evaluate the availability, prices and affordability of 32 anticancer essential medicines in Hubei Province, China. Methods: Data on the availability and price related information of 32 essential anticancer medicines in the capital and five other cities of Hubei Province were collected. A total of 28 hospitals were sampled, which included 13 tertiary hospitals and 15 secondary hospitals. We used the standard methods developed by the World Health Organization and Health Action International to compare the differences in drug price, availability and affordability between secondary hospitals and tertiary hospitals. Results: Overall, the availability of medicine was higher in tertiary hospitals. The average availability of originator brand (OBs) was 13.70% (tertiary hospitals) VS 6.67% (secondary hospitals), and lowest-priced generic (LPGs) was 62.83% (tertiary hospitals) VS 42.92% (secondary hospitals). The MPR value of most sampled medicines in secondary hospitals were less than 1. In contrast, the MPR of Cytarabine (17.15), Oxaliplatin (12.73) were significantly higher than the international reference price. The top three OBs' total expenses for 30-days treatment were Irinotecan, Oxaliplatin, Bicalutamide. Further, their affordability was relative low, as the costs for one course using these medicines were much higher than 20% of the minimum family monthly income. Conclusion: Though the "Zero Mark-Up" and "Centralized procurement policy of anti-tumor drugs" policies have been implemented in China, the availability issue yet to be addressed. High price and low affordability were the major barriers to the access of essential anticancer medicines. Measures should be taken to provide sufficient, available and affordable medicines to patients in need.

Effect of Corrosion Temperature on the Corrosion of Q235 Steel and 16Mn Steel in Sodium Aluminate Solutions.

This study investigates the effect of corrosion temperature on the corrosion of Q235 steel and 16Mn steel in the sodium aluminate solution using the weight loss method and electrochemical method. The results indicate that the corrosion rates of two steels show an increasing trend with the temperature and that of Q235 steel increases more than that of 16Mn steel at higher temperatures. The corrosion products have changed from four forms at 25 °C to two forms at 65 and 110 °C, namely, the octahedral particles and the bulk particles formed by the flocculent aggregation. The corrosion products are composed of FeS, FeS2, Fe2O3, Fe3O4, NaFeO2, and Al2O3. The I corr of the two steels increases with temperature, while R p gradually decreases. The two steels are controlled by the charge transfer at 25 and 65 °C and the charge transfer and the ion diffusion at 95 °C, indicating that the temperature changes the kinetics of the corrosion process.