Pharmacist-Driven Dosing Services and Pharmaceutical Care Increase Probability of Teicoplanin Target Concentration Attainment and Improve Clinical and Economic Outcomes in Non-Critically Ill Patients.

INTRODUCTION: Pharmacist-driven (PD) dosing and monitoring services have been shown to improve the clinical and economic outcomes in patients treated with different antibiotics, other than teicoplanin. This study investigates the impact of PD dosing and monitoring services on the clinical and economic outcomes of non-critically ill patients receiving teicoplanin treatment. METHODS: A single-center retrospective study was conducted. Patients were divided into the PD group and the non-PD (NPD) group. Primary outcomes included the achievement of target serum concentration, and a composite endpoint of all-cause mortality, intensive care unit (ICU) admission, and sepsis or septic shock development during hospitalization or within 30 days of hospital admission. The cost of teicoplanin, overall medication cost, and total cost during hospital stay were also compared. RESULTS: A total of 163 patients from January to December 2019 were included and assessed. Seventy patients were assigned to the PD group and 93 to the NPD group. The PD group had a higher percentage of patients reaching the target trough concentration (54% versus 16%, p < 0.001). Around 26% of the patients in the PD group and 50% of the patients in the NPD group met the composite endpoint during their hospital stay (p = 0.002). The PD group exhibited a significantly lower incidence of sepsis or septic shock, shorter hospital stays, reduced drug costs, and lower total expenses. CONCLUSIONS: Our study demonstrates that pharmacist-driven teicoplanin therapy can improve the clinical and economic outcomes for non-critically ill patients. TRIAL REGISTRATION: https://www.chictr.org.cn ; identifier, ChiCTR2000033521.

Understanding online health information seeking behavior of older adults: A social cognitive perspective.

Introduction: Online health information seeking has been verified to play a crucial role in improving public health and has received close scholarly attention. However, the seeking behavior of older adults, especially the underlying mechanism through which they are motivated to seek health information online, remains unclear. This study addresses the issue by proposing a theoretical model leveraging social cognitive theory. Methods: IT self-efficacy and IT innovativeness were identified as personal factors and professional support and social support were identified as environmental factors. We conducted a survey that included 347 older people in China and examined the research hypotheses with a structural equation model. Results: IT self-efficacy and IT innovativeness facilitate older adults to seek health information online by increasing their perceived benefit of using the internet. Additionally, professional support and social support enhanced older adults' online seeking behavior by promoting their health awareness. We also found that perceived benefit displayed a stronger impact than health awareness on older adults' behavior related to searching for health information online. Conclusion: This study reveals that IT self-efficacy, IT innovativeness, professional support, and social support will promote older adults to seek health information online by enhancing their health awareness and perceived benefit. The findings of this study provide significant theoretical and practical implications.

The Therapeutic Potential of Antioxidants in Chemotherapy-Induced Peripheral Neuropathy: Evidence from Preclinical and Clinical Studies.

As cancer therapies advance and patient survival improves, there has been growing concern about the long-term adverse effects that patients may experience following treatment, and concerns have been raised about such persistent, progressive, and often irreversible adverse effects. Chemotherapy is a potentially life-extending treatment, and chemotherapy-induced peripheral neuropathy (CIPN) is one of its most common long-term toxicities. At present, strategies for the prevention and treatment of CIPN are still an open problem faced by medicine, and there has been a large amount of previous evidence that oxidative damage is involved in the process of CIPN. In this review, we focus on the lines of defense involving antioxidants that exert the effect of inhibiting CIPN. We also provide an update on the targets and clinical prospects of different antioxidants (melatonin, N-acetylcysteine, vitamins, α-lipoic acid, mineral elements, phytochemicals, nutritional antioxidants, cytoprotectants and synthetic compounds) in the treatment of CIPN with the help of preclinical and clinical studies, emphasizing the great potential of antioxidants as adjuvant strategies to mitigate CIPN.

Safety and efficacy of extracorporeal shock wave lithotripsy vs. flexible ureteroscopy in the treatment of urinary calculi: A systematic review and meta-analysis.

Objective: This study aims to compare the safety and efficacy of extracorporeal shock wave lithotripsy (SWL) and flexible ureteroscopy lithotripsy (f-URS) in treating urinary tract stones. Methods: We systematically searched PubMed, Embase, and Cochrane for literature comparing SWL with f-URS. The primary outcomes we focused on were stone-free rate (SFR) and complications; the secondary outcomes were operation time, hospital stay, retreatment rate, number of sessions, and auxiliary procedures rate. We used ReviewManager version 5.4.1 and STATA version 14.2 for meta-analysis. Results: Seventeen studies with a total of 2,265 patients were included in the meta-analysis, including 1,038 patients in the SWL group and 1,227 patients in the f-URS group. The meta-analysis indicated that patients in the f-URS group had higher SFR than those in the SWL group [odds ratio (OR): 2.00, 95% confidence interval (CI): 1.29-3.12, p = 0.002]. In addition, we found no significant difference in complications (OR: 1.08, 95% CI: 0.85-1.37) between the two treatments. Also, we found that the retreatment rate and the auxiliary procedure rate in the f-URS group were significantly lower than those in the SWL group (OR: 0.08, 95% CI: 0.02-0.24, p < 0.00001; OR: 0.30, 95% CI: 0.11-0.83, p = 0.02). Moreover, the number of sessions in the f-URS group was significantly lower than that in the SWL group [mean difference (MD): -1.96, 95% CI: -1.55 to -0.33, p = 0.003]. However, the operation time and hospital stay in the f-URS group were significantly longer than those in the SWL group (MD: 11.24, 95% CI: 3.51-18.56, p = 0.004; MD: 1.14, 95% CI: 0.85-1.42, p < 0.00001). Conclusion: For 1-2-cm urinary stones, f-URS can achieve a higher SFR than SWL while having a lower retreatment rate, number of sessions, and auxiliary procedure rate. For urinary stones <1 cm, there was no significant difference in SFR between SWL and f-URS groups. The SWL group has a shorter operative time and hospital stay than the f-URS group.

Genome Editing in Zebrafish by ScCas9 Recognizing NNG PAM.

The CRISPR/Cas9 system has been widely used for gene editing in zebrafish. However, the required NGG protospacer adjacent motif (PAM) of Streptococcus pyogenes Cas9 (SpCas9) notably restricts the editable range of the zebrafish genome. Recently, Cas9 from S. canis (ScCas9), which has a more relaxed 5'-NNG-3' PAM, was reported to have activities in human cells and plants. However, the editing ability of ScCas9 has not been tested in zebrafish. Here we characterized and optimized the activity of ScCas9 in zebrafish. Delivered as a ribonucleoprotein complex, ScCas9 can induce mutations in zebrafish. Using the synthetic modified crRNA:tracrRNA duplex instead of in vitro-transcribed single guide RNA, the low activity at some loci were dramatically improved in zebrafish. As far as we know, our work is the first report on the evaluation of ScCas9 in animals. Our work optimized ScCas9 as a new nuclease for targeting relaxed NNG PAMs for zebrafish genome editing, which will further improve genome editing in zebrafish.

Influence of SLCO1B1 521T>C, UGT2B7 802C>T and IMPDH1 -106G>A Genetic Polymorphisms on Mycophenolic Acid Levels and Adverse Reactions in Chinese Autoimmune Disease Patients.

INTRODUCTION: Mycophenolate mofetil (MMF), a new type of immunosuppressant, has emerged as a frontline agent for treating autoimmune diseases. Mycophenolic acid (MPA) is an active metabolite of MMF. MPA exposure varies greatly among individuals, which may lead to adverse drug reactions such as gastrointestinal side effects, infection, and leukopenia. Genetic factors play an important role in the variation of MPA levels and its side effects. Although many published studies have focused on MMF use in patients after organ transplant, studies that examine the use of MMF in patients with autoimmune diseases are still lacking. METHODS: This study will not only explore the genetic factors affecting MPA levels and adverse reactions but also investigate the relationships between UGT1A9 -118(dT)9/10, UGT1A9 - 1818T>C, UGT2B7 802C>T, SLCO1B1 521T>C, SLCO1B3 334T>G, IMPDH1 -106G>A and MPA trough concentration (MPA C0), along with adverse reactions among Chinese patients with autoimmune diseases. A total of 120 patients with autoimmune diseases were recruited. The MPA trough concentration was detected using the enzyme multiplied immunoassay technique (EMIT). Genotyping was performed using a real-time polymerase chain reaction (PCR) system and validated allelic discrimination assays. Clinical data were collected for the determination of side effects. RESULTS: SLCO1B1 521T>C demonstrated a significant association with MPA C0/d (p=0.003), in which patients with the CC type showed a higher MPA C0/d than patients with the TT type (p=0.001) or the CT type (p=0.000). No significant differences were found in MPA C0/d among the other SNPs. IMPDH1 -106G>A was found to be significantly related to infections (p=0.006). Subgroup analysis revealed that UGT2B7 802C>T was significantly related to Pneumocystis carinii pneumonia infection (p=0.036), while SLCO1B1 521T>C was associated with anemia (p=0.029). CONCLUSION: For Chinese autoimmune disease patients, SLCO1B1 521T>C was correlated with MPA C0/d and anemia. IMPDH1 -106G>A was significantly related to infections. UGT2B7 802C>T was significantly related to Pneumocystis carinii pneumonia infection.

NNT-AS1 enhances bladder cancer cell growth by targeting miR-1301-3p/PODXL axis and activating Wnt pathway.

As a tumor involved in the urinary system, bladder cancer (BC) seriously threatens human health. Emerging as crucial biomarkers, long noncoding RNAs (lncRNAs) play an important role in the regulation of many cancers. lncRNA NNT-AS1 has been studied in a series of cancers, whereas its role and potential molecular mechanism was poorly understood in BC. Here, we found that NNT-AS1 was upregulated in BC cells. Functionally, the silencing of NNT-AS1 inhibited cell proliferation, migration, invasion, and endothelial-mesenchymal transition. Furthermore, the apoptosis of BC cells was induced upon NNT-AS1 knockdown. Later, miR-1301-3p, the downstream gene of NNT-AS1, was found at a low level in BC cells. In addition, we found that miR-1301-3p targeted to PODXL. PODXL expression downregulated in NNT-AS1-silenced cells was restored by miR-1301-3p inhibition. Importantly, NNT-AS1 was discovered to activate Wnt pathway, and the treatment of LiCl recovered the repressive role of NNT-AS1 silencing in BC cell growth. Through restoration assays, we observed that PODXL overexpressing countervailed NNT-AS1 depletion-mediated suppression on BC cell growth and Wnt pathway. These data suggested that NNT-AS1 enhances BC cell growth and activates Wnt pathway by targeting miR-1301-3p/PODXL axis.

Precise A•T to G•C base editing in the zebrafish genome.

BACKGROUND: Base editors are a class of genome editing tools with the ability to efficiently induce point mutations in genomic DNA, without inducing double-strand breaks or relying on homology-direct repair as in other such technologies. Recently, adenine base editors (ABEs) have been developed to mediate the conversion of A•T to G•C in genomic DNA of human cells, mice, and plants. Here, we investigated the activity and efficiency of several adenine base editors in zebrafish and showed that base editing can be used to create new models of pathogenic diseases caused by point mutations. RESULTS: The original ABE7.10 exhibits almost no activity in zebrafish. After codon optimization, we found that a zABE7.10 variant could induce targeted conversion of adenine to guanine in zebrafish at multiple tested genomic loci, and all the target sites showed a high rate of germline targeting efficiency. Furthermore, using this system, we established a zebrafish model of 5q-Syndrome that contained a new point mutation in rps14. The further modification of zABE7.10 by a bipartite nuclear localization signals (bpNLS) resulted in 1.96-fold average improvement in ABE-mediated editing efficiency at four sites. CONCLUSIONS: Collectively, this system, designated as zABE7.10, provides a strategy to perform A•T to G•C base editing in zebrafish and enhances its capacity to model human diseases.

Ethanol extract of Ilex hainanensis Merr. exhibits anti-melanoma activity by induction of G1/S cell-cycle arrest and apoptosis.

OBJECTIVE: To evaluate anti-melanoma effect of ethanol extract of Ilex hainanensis Merr. (IME) and elucidate its underlying mechanism. METHODS: Thirty-six tumor-bearing mice were randomized into 6 groups (n=6) as follows: model group, IME 25, 50, 100, and 200 mg/kg groups and dacarbazine (DTIC) 70 mg/kg group. The mice in the IME treatment groups were intragastrically administered with IME 25, 50, 100 or 200 mg/kg per day, respectively. The mice in the DTIC group were intraperitoneally injected with DTIC 70 mg/kg every 2 days. The drug administration was lasting for 14 days. The cell viability was evaluated by 3-(4,5-dime-thylthylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Flow cytometry was employed to detect cell cycle and apoptosis. The gene and protein expressions of nuclear factor κB-p65 (NF-κB-p65), Bcl-2, B-cell lymphomaextra large (Bcl-xL) and Bax were detected by quantitative real-time polymerase chain reaction and Western blot analyses. Caspases-3, -8, and -9 activities were detected using the colorimetric method. In addition, a B16-F10 melanoma xenograft mouse model was used to evaluate the anti-cancer activity of IME in vivo. Furthermore, a survival experiment of tumor-bearing mice was also performed to evaluate the possible toxicity of IME. RESULTS: IME significantly inhibited the proliferation of B16-F10 cells (P<0.01). Flow cytometric analysis showed that IME induced G1/S cell cycle arrest and apoptosis (both P<0.01). IME inhibited activation of NF-κB, decreased the gene and protein expressions of Bcl-2, Bcl-xL, and increased the gene and protein expressions of Bax (all P<0.01). In addition, IME induced the activation of Caspases-3, -8, and -9 in B16-F10 cells. The study in vivo showed that IME significantly reduced tumor volume (P<0.01), and the inhibitory rate came up to 68.62%. IME also induced large areas of necrosis and intra-tumoral apoptosis that correlated with a reduction in tumor volume. Survival experiment showed that treatment with IME for 14 days significantly prolonged survival time and 20% of mice in the IME 200 mg/kg group were still alive until the 50th day. Notably, IME showed no apparent side-effects during the treatment period. CONCLUSION: IME exhibited significant anti-melanoma activity in vitro and in vivo, suggesting that IME might be a promising effective candidate with lower toxic for malignant melanoma therapy.

A novel pentacyclic triterpenoid, Ilexgenin A, shows reduction of atherosclerosis in apolipoprotein E deficient mice.

Ilexgenin A (IA), a novel pentacyclic triterpenoid, is a compound extracted from leaves of Ilex hainanensis Merr. In this study, we explored the efficacy of IA on atherosclerosis and its underlying mechanism. We determined that treatment with IA attenuated atherosclerosis in high-fat diet-induced apolipoprotein E deficient mice via a series of effects involving regulation of lipid parameters, decrease of atherosclerosis-related indexes, inhibition of inflammatory cytokines secretion and pathological changes of main organs. Furthermore, the underlying mechanism of IA was investigated on oxidized low-density lipoprotein (Ox-LDL)-induced THP-1 cells. We showed that pre-treatment with IA decreased active inflammation cytokines involving interleukin-6 (IL-6), IL-1 and tumor necrosis factor-α (TNF-α) expression in a concentration-dependent manner. In addition, we confirmed that IA inhibited the phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), IKKα phosphorylation and NF-κB activity induced by Ox-LDL. Overall, these findings define IA as a novel drug candidate for anti-atherosclerotic therapy.

[Interaction Between Occupational Vanadium Exposure and hsp70-hom on Neurobehavioral Function].

OBJECTIVE: In determine the effect of heat shock protein 70-hom gene (hsp70-hom) polymorphism on the neurobehavioral function of workers exposed to vanadium. METHODS: Workers from the vanadium products and chemical industry were recruited by cluster sampling. Demographic data and exposure information were collected using a questionnaire. Neurobehavioral function was assessed by Neurobehavioral Core Test Battery. The hsp70-hom genotype was detected by restricted fragment length polymorphism-polymerase chain reaction (RFLP-PCR). A neurobehavioral index (NBI) was formulated through principal component analysis. RESULTS: Workers with a T/C genotype had worse performance in average reaction time, visual retention, digital span (backward), Santa Ana aiming (non-habitual hand), pursuit aiming (right points, total points), digit symbol and NBI score than others (P < 0.05). The relative risk of abnormal NBI score of the workers with a T/C genotype was 1.748 fold of those with a T/T genotype. The relative risk of abnormal.NBI score of the workers exposed to vanadium was 3.048 fold of controls (P < 0.05). But after adjustment with age and education, only vanadium exposure appeared with a significant effect on NBI score. When gene polymorphism and vanadium exposure coexisted, the effect of vanadium on neurobehavioral function was attenuated, but the influence of T/C genotype increased Codds ratio (OR = 4.577, P < 0.05). After adjustment with age and education, the OR of T/C genotype further increased to 7.777 (P < 0.05). Vanadium exposure and T/C genotype had.a bio-interaction effect on NBI score Crelative excess risk due to interaction (RERI) = 4.12, attributable proportion (AP) = 0.7, synergy index (S) = 6.45]. After adjustment with age and education, the RERI became 2.49 and the AP became 0.75, but no coefficient of interaction was produced. CONCLUSION: Priorities of occupational protection should be given to vanadium-exposed workers with a hsp70-hom T/C genotype and low education level.

[Oxidative Stress Level of Vanadium-exposed Workers].

OBJECTIVE: To determine the oxidative stress level in peripheral blood of vanadium-exposed workers, as an indication of population health effect of vanadium on human neurobehavioral system. METHODS: 86 vanadium-exposed workers and 65 non-exposed workers were recruited by cluster sampling. A questionnaire was administered to collect demographic and occupational exposure information. Serum activity of superoxide dismutase (SOD), inducible nitric oxide synthase (iNOS) and malonaldehyde (MDA) contents were detected by kit assay. The differences in oxidative stress level between vanadium-exposed and non-exposed workers were compared. RESULTS: Vanadium-exposed workers had higher levels of MDA contents than the controls. The total superoxide dismutase(T-SOD) activity in vanadium-exposed workers was significantly lower than that in the controls, which was associated with lowered levels of manganese superoxide dismutase (Mn-SOD) activity. No changes in serum levels of cupro-zinc superoxide dismutase (CuZn-SOD) was found in vanadium-exposed workers. No difference in iNOS activity was found between vanadium-exposed workers and controls. CONCLUSION: Vanadium exposure increases free radical production in serum and reduces antioxidant capacity. But the relationship between vanadium exposure and iNOS damage remains uncertain.