Circulating mid-regional proadrenomedullin is a predictor of mortality in patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: Although there is increasing understanding of the changes in the laboratory parameters of Coronavirus disease 2019 (COVID-19), the correlation between circulating Mid-regional Proadrenomedullin (MR-proADM) and mortality of patients with COVID-19 is not fully understood. In this study, we conducted a systematic review and meta-analysis to evaluate the prognostic value of MR-proADM in patients with COVID-19. METHODS: The PubMed, Embase, Web of Science, Cochrane Library, Wanfang, SinoMed and Chinese National Knowledge Infrastructure (CNKI) databases were searched from 1 January 2020 to 20 March 2022 for relevant literature. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess quality bias, STATA was employed to pool the effect size by a random effects model, and potential publication bias and sensitivity analyses were performed. RESULTS: 14 studies comprising 1822 patients with COVID-19 met the inclusion criteria, there were 1145 (62.8%) males and 677 (31.2%) females, and the mean age was 63.8 ± 16.1 years. The concentration of MR-proADM was compared between the survivors and non-survivors in 9 studies and the difference was significant (P < 0.01), I2 = 46%. The combined sensitivity was 0.86 [0.73-0.92], and the combined specificity was 0.78 [0.68-0.86]. We drew the summary receiver operating characteristic (SROC) curve and calculated the area under curve (AUC) = 0.90 [0.87-0.92]. An increase of 1 nmol/L of MR-proADM was independently associated with a more than threefold increase in mortality (odds ratio (OR) 3.03, 95% confidence interval (CI) 2.26-4.06, I2 = 0.0%, P = 0.633). The predictive value of MR-proADM for mortality was better than many other biomarkers. CONCLUSION: MR-proADM had a very good predictive value for the poor prognosis of COVID-19 patients. Increased levels of MR-proADM were independently associated with mortality in COVID-19 patients and may allow a better risk stratification.

Health Beliefs, Trust in Media Sources, Health Literacy, and Preventive Behaviors among High-Risk Chinese for COVID-19.

The coronavirus disease (COVID-19) broke out in China in January 2020 and has been effectively controlled in April 2020 after China's relentless efforts. People's engagement in disease-related preventive behaviors is crucial in containing such infectious disease. Vulnerable populations often have higher chances of developing severe illness from COVID-19 and the mortality rate is also higher. Thus, at-risk populations for COVID-19 request extra attention. The current study conducted a national online survey among vulnerable populations in China in early February 2020 to examine their engagement in coronavirus-related preventive health behaviors (e.g., frequent handwashing) and the potential determinants including factors from the Health Belief Model, trust in different media sources, and health literacy. The results suggested that the vulnerable populations' engagement in coronavirus-related preventive behaviors were significantly associated with barriers, benefits, self-efficacy, trust in doctors' social media, and trust in TV for COVID-19-related information. Besides, barriers, benefits, self-efficacy, trust in doctors' social media, and trust in TV mediated the effects of health literacy on preventive behaviors. Our findings provided directions for future health promotions and interventions targeting vulnerable populations to enhance their preventive behaviors in China.

Highly enantioselective one-pot sequential synthesis of valerolactones and pyrazolones bearing all-carbon quaternary stereocentres.

Highly enantiopure and bioactive δ-valerolactones and pyrazolones, bearing α-all-carbon quaternary stereocentres, were successfully and sequentially prepared via a one-pot procedure starting from readily available, inexpensive materials, catalysed by a new chiral squaramide under mild reaction conditions. An organocatalytic Michael reaction afforded the valerolactones, while a one-pot Michael-hydrazinolysis-imidization cascade yielded the pyrazolones. This procedure is economically efficient and environmentally benign.

[Infiltration of Th1 and Th17 cells into the L5－S2 spinal cord in CP/CPPS rats and its central sensitization mechanism].

OBJECTIVE: To explore the central sensitization mechanism of pain in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: We randomly divided 40 adult male SPF SD rats, aged 3－4 weeks and weighing 250－350 g, into a normal control and a CP/CPPS model group. After modeling, we analyzed the state of infiltration of CD4+T cells into the L5－S2 spinal cord and detected the expression levels of GFAP and CR3 in the spinal cord tissue using flow cytometry, real-time fluorescent quantitative PCR (RT-qPCR) and immunofluorescence staining. RESULTS: Compared with the normal controls, the CP/CPPS model rats showed dramatically increased expression of CD4+T cells in the mononuclear cells of the L5－S2 spinal cord tissue (P < 0.01), mRNA expressions of interferon-γ (IFN-γ) and tumor necrosis factor α (TNF-α) secreted from the Th1 cells, interleukin (IL)-17 and retinoic acid-associated orphan receptor (ROR) γt secreted from the Th17 cells, cytokines IL-6 and IL-1ß, and chemokines CCL2, CCL20 and CXCL10 (P < 0.01), and expressions of the molecular markers of Th1 and Th17 cells IFN-γ and IL-17 and those of astrocytes and microglias GFAP and CR3. CONCLUSIONS: CD4+T cells, specifically Th1 and Th17 cells, infiltrate L5－S2 spinal cord neurons in CP/CPPS model rats. The inflammatory factors secreted from these cells may damage the neuronal cells, affect nervous conduction, promote central sensitization and activate astrocytes and microglias, leading to the development and progression of pain.

Clinical translation of gene medicine.

Gene therapy has recently witnessed accelerated progress as a new therapeutic strategy with the potential to treat a range of inherited and acquired diseases. Billions of dollars have been invested in basic and clinical research on gene medicine, with ongoing clinical trials focused on cancer, monogenic diseases, cardiovascular diseases and other refractory diseases. Advances addressing the inherent challenges of gene therapy, particularly those related to retaining the delivery efficacy and minimizing unwanted immune responses, provide the basis for the widespread clinical application of gene medicine. Several types of genes delivered by viral or non-viral delivery vectors have demonstrated encouraging results in both animals and humans. As augmented by clinical indications, gene medicine techniques have rapidly become a promising alternative to conventional therapeutic strategies because of their better clinical benefit and lower toxicities. Their application in the clinic has been extensive as a result of the approval of many gene therapy drugs in recent years. In this review, we provide a comprehensive overview of the clinical translation of gene medicine, focusing on the key events and latest progress made regarding clinical gene therapy products. We also discuss the gene types and non-viral materials with respect to developing gene therapeutics in clinical trials.

Simulation of Starch Gel Printing and Deformation Process Using COMSOL.

The food industry holds immense promise for 3D printing technology. Current research focuses mainly on optimizing food material composition, molding characteristics, and printing parameters. However, there is a notable lack of comprehensive studies on the shape changes of food products, especially in modeling and simulating deformations. This study addresses this gap by conducting a detailed simulation of the starch gel printing and deformation process using COMSOL Multiphysics 6.2 software. Additive manufacturing (AM) technology is widely acclaimed for its user-friendly operation and cost-effectiveness. The 3D printing process may lead to changes in part dimensions and mechanical properties, attributable to the accumulation of residual stresses. Studies require a significant amount of time and effort to discover the optimal composition of the printed material and the most effective deformed 3D structure. There is a risk of failure, which can lead to wasted resources and research delays. To tackle this issue, this study thoroughly analyzes the physical properties of the gel material through COMSOL Multiphysics 6.2 software, It simulates the heat distribution during the 3D printing process, providing important insights into how materials melt and solidify. Three-part models with varying aspect ratios were meticulously designed to explore shape changes during both the printing process and exposure to an 80 °C environment, employing NMR and rheological characterization. Using the generalized Maxwell model for material simulation in COMSOL Multiphysics, the study predicted stress and deformation of the parts by analyzing solid heat transfer and solid mechanics physical fields. Simulation results showed that among three models utilizing a gel-PET plastic membrane bilayer structure, Model No. 1, with the largest aspect ratio, exhibited the most favorable deformation under an 80 °C baking environment. It displayed uniform bending in the transverse direction without significant excess warpage in the edge direction. In contrast, Models No. 2 and No. 3 showed varying degrees of excess warpage at the edges, with Model No. 3 exhibiting a more pronounced warpage. These findings closely aligned with the actual printing outcomes.

A meta-analysis: neoadjuvant chemotherapy versus primary surgery in ovarian carcinoma FIGO stageIII and IV.

BACKGROUND: The purpose of the current study is to analyze the existing data comparing neoadjuvant chemotherapy with primary debulking surgery (PDS) in patients with advanced ovarian carcinoma. METHODS: Patients with stage IIIC and IV ovarian cancer were identified from articles in Medline, PubMed, Cochrane Library, and EMBASE database (1989 to February 2013). Two authors independently extracted the data. To assess the risk of bias of included literatures, Cochrane Collaboration's risk of bias tool was used. Meta-analysis on literatures was conducted by using RevMan 5.2 software. RESULTS: Two high-quality randomized controlled trials (RCTs) met the inclusion criteria. These multicenter trials randomized 1,220 women with stage IIIc/IV ovarian cancer to NACT or PDS followed by chemotherapy. There were no significant differences between the study groups with regard to overall survival (OS) (1,120 women; HR 0.98; 95% CI 0.85 to 1.14) or progression-free survival (PFS) (1,120 women; HR 1.03; 95% CI 0.91 to 1.16). CONCLUSION: There was no statistical difference in median OS and PFS between the two treatment groups. With regard to selecting who will benefit from NACT, treatment should be tailored to the patient and should take into account respectability, age, histology, stage, and performance status.

Molecular characterization, expression and function analysis of Epinephelus coioides PKC-ɑ response to Singapore grouper iridovirus (SGIV) infection.

Protein kinase C (PKC) constitutes the main signal transduction pathway, and participates in the signal pathway of cell proliferation and movement in mammals. In this study, PKC-ɑ was obtained from Epinephelus coioides, an important marine fish cultivated in the coastal areas of southern China and Southeast Asia. The full length cDNA of PKC-ɑ was 3362 bp in length containing a 23 bp 5'UTR, a 1719 bp 3'UTR, and a 1620 bp open reading frame encoding 539 amino acids. It contains three conservative domains including protein kinase C conserved region 2 (C2), Serine/Threonine protein kinases, catalytic domain (S_TKc) and ser/thr-type protein kinases (S_TK_X). Its mRNA can be detected in all 11 tissues examined of E. coioides, and the expression was significantly upregulated response to Singapore grouper iridovirus (SGIV) infection, one of the important pathogens of marine fish. Upregulated E. coioides PKC-ɑ significantly inhibited the activation of nuclear factor kappa-B (NF-κB) and activator protein-1 (AP-1), and SGIV-induced cell apoptosis. The results indicated that the PKC-ɑ may play an important role in pathogenic stimulation.

Comparing the effectiveness of continuous subcutaneous insulin infusion with multiple daily insulin injection for patients with type 1 diabetes mellitus evaluated by retrospective continuous glucose monitoring: A real-world data analysis.

Objective: Regarding the effects and practical application of insulin pumps on patients with type 1 diabetes mellitus (T1DM), the real-world evidence is limited especially concerning the incidence of hypoglycemia. This study aimed to compare the efficacy of continuous subcutaneous insulin infusion (CSII) therapy with multiple daily injection (MDI) therapy on glycemic metrics evaluated by retrospective continuous glucose monitoring (CGM) in Chinese patients with T1DM. Methods: In total, 362 T1DM Chinese patients from the outpatient department of the Second Xiangya Hospital, Central South University, who underwent intensive insulin therapy and used a retrospective CGM system were included in this retrospective cross-sectional study. Comprehensive analysis of clinical and biological features and retrospective CGM derived-metrics was performed on the 362 enrolled T1DM patients who underwent CSII (n = 61) or MDI (n = 301) therapy (defined as 4 or more insulin injections per day). Results: Our findings demonstrated that patients who underwent CSII therapy, compared with those who received MDI therapy, had lower levels of hemoglobin A1c (HbA1c) and fasting blood glucose; moreover, CSII therapy was associated with better glycemic outcomes in terms of increasing time in range (TIR), decreasing time above range (TAR), and achieving CGM-associated targets of TIR ≥70% and TAR <25%. However, patients who underwent CSII therapy did not experience decreasing time below range (TBR), achieving CGM-associated targets of TBR <4%, and reduction of the risk of hypoglycemia as evidenced by comparing TBR and low blood glucose index (LBGI) between the two treatment regimens. The parameters of glycemic variability, such as standard deviation of glucose (SD), mean amplitude glycemic excursion (MAGE), and large amplitude glycemic excursion (LAGE) in T1DM patients who underwent CSII therapy outperformed. Conclusion: Our results provided further evidence that CSII therapy is safe and effective for management of Chinese T1DM patients, which was confirmed by a lower HbA1c level and better CGM-derived metrics but no demonstration of improvment in the risk of hypoglycemia. To achieve more satisfactory glycemic outcomes through the utilization of CSII therapy for Chinese T1DM patients, a strong physician-patient relationship is essential.

Recent advances in lentiviral vectors for gene therapy.

Lentiviral vectors (LVs), derived from human immunodeficiency virus, are powerful tools for modifying the genes of eukaryotic cells such as hematopoietic stem cells and neural cells. With the extensive and in-depth studies on this gene therapy vehicle over the past two decades, LVs have been widely used in both research and clinical trials. For instance, third-generation and self-inactive LVs have been used to introduce a gene with therapeutic potential into the host genome and achieve targeted delivery into specific tissue. When LVs are employed in leukemia, the transduced T cells recognize and kill the tumor B cells; in ß-thalassemia, the transduced CD34+ cells express normal ß-globin; in adenosine deaminase-deficient severe combined immunodeficiency, the autologous CD34+ cells express adenosine deaminase and realize immune reconstitution. Overall, LVs can perform significant roles in the treatment of primary immunodeficiency diseases, hemoglobinopathies, B cell leukemia, and neurodegenerative diseases. In this review, we discuss the recent developments and therapeutic applications of LVs. The safe and efficient LVs show great promise as a tool for human gene therapy.

Multifunctional Mitochondria-Targeting Nanosystems for Enhanced Anticancer Efficacy.

Mitochondria, a kind of subcellular organelle, play crucial roles in cancer cells as an energy source and as a generator of reactive substrates, which concern the generation, proliferation, drug resistance, and other functions of cancer. Therefore, precise delivery of anticancer agents to mitochondria can be a novel strategy for enhanced cancer treatment. Mitochondria have a four-layer structure with a high negative potential, which thereby prevents many molecules from reaching the mitochondria. Luckily, the advances in nanosystems have provided enormous hope to overcome this challenge. These nanosystems include liposomes, nanoparticles, and nanomicelles. Here, we summarize the very latest developments in mitochondria-targeting nanomedicines in cancer treatment as well as focus on designing multifunctional mitochondria-targeting nanosystems based on the latest nanotechnology.

Neuroprotection of Chikusetsu saponin V on transient focal cerebral ischemia/reperfusion and the underlying mechanism.

BACKGROUND: Oxidative stress and frequently unwanted alterations in mitochondrial structure and function are key aspects of the pathological cascade in transient focal cerebral ischemia. Chikusetsu saponin V (CHS V), a major component of saponins from Panax japonicas, can attenuate H2O2-induced oxidative stress in SH-SY5Y cells. PURPOSE: The aim of the present study was to investigate the neuroprotective effects and the possible underlying mechanism of CHS V on transient focal cerebral ischemia/reperfusion. METHODS: Mice with middle cerebral artery occlusion (MCAO) and cultured cortical neurons exposed to oxygen glucose deprivation (OGD) were used as in vivo and in vitro models of cerebral ischemia, respectively. The neurobehavioral scores, infarction volumes, H&E staining and some antioxidant levels in the brain were evaluated. The occurrence of neuronal death was estimated. Total and mitochondrial reactive oxygen species (ROS) levels, as well as mitochondrial potential were measured using flow cytometry analysis. Mitochondrial structure and respiratory activity were also examined. Protein levels were investigated by western blotting and immunohistochemistry. RESULTS: CHS V effectively attenuated cerebral ischemia/reperfusion (CI/R) injury, including improving neurological deficits, shrinking infarct volume and reducing the number of apoptotic cells. Furthermore, CHS V treatment remarkably increased antioxidant levels and reduced ROS levels and mitochondrial damage by enhancing the expression and deacetylation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) by activating AMPK and SIRT-1, respectively. CONCLUSION: Our data demonstrated that CHS V prevented CI/R injury by suppressing oxidative stress and mitochondrial damage through the modulation of PGC-1α with AMPK and SIRT-1.

Association Between Genetic Polymorphisms of Metabolic Enzymes and Azathioprine-Induced Myelosuppression in 1,419 Chinese Patients: A Retrospective Study.

The aim of this study was to investigate the correlation between genetic polymorphisms of azathioprine-metabolizing enzymes and adverse reactions of myelosuppression. To this end, a retrospective analysis was performed on 1,419 Chinese patients involving 40 different diseases and 3 genes: ITPA (94C>A), TPMT*3 (T>C), and NUDT15 (415C>T). Strict inclusion and exclusion criteria were established to collect the relative cases, and the correlation between azathioprine and myelosuppression was evaluated by adverse drug reaction criteria. The mutation rates of the three genes were 29.32, 3.73, and 21.92% and grades I to IV myelosuppression occurred in 54 (9.28%) of the 582 patients who took azathioprine. The highest proportion of myelosuppression was observed in 5 of the 6 (83.33%) patients carrying the NUDT15 (415C>T) TT genotype and 12 of the 102 (11.76%) patients carrying the NUDT15 (415C>T) CT genotype. Only the NUDT15 (415C>T) polymorphism was found to be associated with the adverse effects of azathioprine-induced myelosuppression (odds ratio [OR], 51.818; 95% CI, 5.280-508.556; p = 0.001), which suggested that the NUDT15 (415C>T) polymorphism could be an influencing factor of azathioprine-induced myelosuppression in the Chinese population. Epistatic interactions between ITPA (94C>A) and NUDT15 (415C>T) affect the occurrence of myelosuppression. Thus, it is recommended that the genotype of NUDT15 (415C>T) and ITPA (94C>A) be checked before administration, and azathioprine should be avoided in patients carrying a homozygous NUDT15 (415C>T) mutation. This study is the first to investigate the association between genetic polymorphisms of these three azathioprine-metabolizing enzymes and myelosuppression in a large number of cases with a diverse range of diseases.

Validating the Chinese geriatric trigger tool and analyzing adverse drug event associated risk factors in elderly Chinese patients: A retrospective review.

OBJECTIVE: The aim was to evaluate the performance of the initial Chinese geriatric trigger tool to detect adverse drug events (ADEs) in Chinese older patients, to attempt to shorten this list for improving the efficiency of the trigger tool, and to study the incidence and characteristics of ADEs in this population. METHODS: A sample of 25 cases was randomly selected per half a month from eligible patients who aged 60 years and older, hospitalized more than 24 hours, and discharged or died between January 1, 2015 and December 31, 2017 in West China hospital. A two-stage retrospective chart review of the included inpatients were conducted. ADEs were detected using a list of 42 triggers previously selected by an expert panel by means of a Delphi method. The number of triggers identified and ADEs detected were recorded and the positive predictive value (PPV) of each trigger was calculated to select the most efficient triggers. Several variables were recorded, including age, sex, number of diseases, length of hospital stay and so on, to analyze the risk factor of ADEs. RESULTS: Among 1800 patients, 1646 positive triggers and 296 ADEs were detected in 234 (13.00%) patients. Older patients who were younger, had more medications, longer stays or more admission, and did not experience surgical operation more likely experienced ADEs. Triggers with PPV less than 5% were eliminated, which resulted in the upgraded version of Chinese geriatric trigger tool of 20 triggers with a PPV of 28.50%. This upgraded tool accounted for 99.66% of all ADEs detected. CONCLUSIONS: The upgraded version of Chinese geriatric trigger tool was an efficient tool for identifying ADEs in Chinese older patients. Future, the trigger tool could be incorporated into routine screen systems to provide real-time identification of ADEs, thereby enabling timely clinical interventions.

Cost-effectiveness analysis of ramucirumab treatment for patients with hepatocellular carcinoma who progressed on sorafenib with α-fetoprotein concentrations of at least 400 ng/ml.

Objective: This study aimed to compare the cost-effectiveness of ramucirumab versus placebo for patients with hepatocellular carcinoma who progressed on sorafenib with α-fetoprotein concentrations (AFP) of at least 400 ng/ml in the United States.Methods: A Markov model was constructed to assess the cost-effectiveness of ramucirumab. Health outcomes were measured as quality-adjusted life years (QALYs). With TreeAge software, the disease process was modeled as three health states: progression-free survival (PFS), progressive disease (PD), and death. Costs were extracted from the REACH-2 trial, and utility was derived from published literature. Incremental cost-effectiveness ratios (ICERs) were calculated to compare ramucirumab with placebo. Probabilistic sensitivity analyses were developed to examine the robustness of the results.Results: In the base case analysis, ramucirumab therapy had a cost of $55,508.41 and generated 0.54 QALYs, while placebo therapy had a cost of $761.09 and generated 0.47 QALYs, leading to an additional $54,747.32 in costs and 0.07 QALYs. The ICER was $782,104.57 per QALY, which was much higher than the willingness-to-pay threshold of $100,000 per QALY. According to sensitivity analyses, the utility of PD in the two groups was the dominant parameter influencing the ICER.Conclusion: Although ramucirumab was associated with prolonged survival for patients with advanced hepatocellular carcinoma who progressed on sorafenib treatment with an AFP of at least 400 ng/ml, it is not a cost-effective treatment from a United States payer perspective.

Current RNA-based Therapeutics in Clinical Trials.

Long-term research on various types of RNAs has led to further understanding of diverse mechanisms, which eventually resulted in the rapid development of RNA-based therapeutics as powerful tools in clinical disease treatment. Some of the developing RNA drugs obey the antisense mechanisms including antisense oligonucleotides, small interfering RNAs, microRNAs, small activating RNAs, and ribozymes. These types of RNAs could be utilized to inhibit/activate gene expression or change splicing to provide functional proteins. In the meantime, some others based on different mechanisms like modified messenger RNAs could replace the dysfunctional endogenous genes to manage some genetic diseases, and aptamers with special three-dimensional structures could bind to specific targets in a high-affinity manner. In addition, the recent most popular CRISPR-Cas technology, consisting of a crucial single guide RNA, could edit DNA directly to generate therapeutic effects. The desired results from recent clinical trials indicated the great potential of RNA-based drugs in the treatment of various diseases, but further studies on improving delivery materials and RNA modifications are required for the novel RNA-based drugs to translate to the clinic. This review focused on the advances and clinical studies of current RNA-based therapeutics, analyzed their challenges and prospects.

Applications of Genome Editing Technology in Animal Disease Modeling and Gene Therapy.

Genome editing technology is a technique for targeted genetic modifications, enabling the knockout and addition of specific DNA fragments. This technology has been widely used in various types of biomedical research, clinics and agriculture. In terms of disease research, constructing appropriate animal models is necessary. Combining reproductive technology with genome editing, many animal disease models have been generated for basic and clinical research. In addition, precisely targeted modifications allow genome editing to flourish in the field of gene therapy. Many mutations refractory to traditional gene therapy could be permanently corrected at the DNA level. Thus, genome editing is undoubtedly a promising technology for gene therapy. In this review, we mainly introduce the applications of genome editing in constructing animal disease models and gene therapies, as well as its future prospects and challenges.

Development of a trigger tool for the detection of adverse drug events in Chinese geriatric inpatients using the Delphi method.

Background The global trigger tool is a method of retrospective medical record review that identifies possible harm in hospitalized patients using "triggers". Elderly patients with multiple co-morbid illnesses are especially vulnerable to adverse drug events (ADEs) that have high prevalence rates. Objective The purpose of this study was to develop an appropriate trigger tool to detect ADEs in Chinese geriatric inpatients by combining a literature review with the Delphi method. Setting Chinese geriatric inpatients. Methods Two steps were used to develop the trigger tool. First, we conducted a comprehensive literature review for existing ADE triggers (adult or elderly) to form the initial triggers for the Delphi process. Second, a group of clinical experts, including physicians, clinical pharmacists and nurses, was established to score candidate triggers for utility according to the usefulness and feasibility of implementing triggers in clinical practice. Main outcome measures The frequency of the full mark, arithmetic mean and coefficient of variation of each trigger. Results An initial set of 51 triggers was selected by literature review for evaluation. The group of experts was composed of 18 clinical experts: 13 physicians, 4 clinical pharmacists, and 1 nurse. Based on the two-phase Delphi process, 42 triggers in five categories (laboratory index, plasma concentration, antidotes, clinical symptoms and intervention) were retained. Conclusion The 42-trigger tool was developed to identify ADEs in Chinese geriatric inpatients. A pilot study that tests the list of triggers to identify ADEs in Chinese geriatric inpatients is the next step for establishing a specific trigger tool for Chinese geriatric inpatients.

Stress-responsive genes (hsp70 and mt) and genotoxicity elicited by roxarsone exposure in Carassius auratus.

In this study, comet assay (single-cell gel electrophoresis), real-time quantitative PCR (qPCR) and proteomics approach were used to comprehensively assess toxicity elicited by roxarsone exposure in C. auratus at 50, 150 and 300 µg/L for 7, 14 and 21 days. Results of comet assay showed that DNA were seriously damaged under the pressure of roxarsone, especially the concentration of 50 µg/L that always maintained a sustained and increased damage effect to fish liver cell during the 21 days experiment. The expressions of biomarker genes showed that hsp70 gene expressions raised significantly and the group of 50 µg/L also showed a continued increased response effect, whereas mt gene was only slightly increased. Results of proteomics for the concentration of 300 µg/L found that thirty six significantly changed proteins were identified by MALDI-TOF/TOF-MS. They are involved in many important processes including energy producing, cytoskeleton stabilization, substance metabolism and stress response. Among these metabolites, carbohydrate metabolism (mainly occurred during day 1-14) and cytoskeleton proteins (mainly occurred during day 14-21) were the most identified proteins. These results revealed that the low levels of 50 µg/L probably led to a continuous damage than the higher groups during the experiment time. Furthermore, proteomics results might implied that though cell system expected to mobilize almost all the functional proteins to quickly establish a new homeostasis together when facing the roxarsone at first, but in the end the destroyed cell cytoskeleton structure might burst the bubble.

Non-viral and viral delivery systems for CRISPR-Cas9 technology in the biomedical field.

The clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR-Cas9) system provides a novel genome editing technology that can precisely target a genomic site to disrupt or repair a specific gene. Some CRISPR-Cas9 systems from different bacteria or artificial variants have been discovered or constructed by biologists, and Cas9 nucleases and single guide RNAs (sgRNA) are the major components of the CRISPR-Cas9 system. These Cas9 systems have been extensively applied for identifying therapeutic targets, identifying gene functions, generating animal models, and developing gene therapies. Moreover, CRISPR-Cas9 systems have been used to partially or completely alleviate disease symptoms by mutating or correcting related genes. However, the efficient transfer of CRISPR-Cas9 system into cells and target organs remains a challenge that affects the robust and precise genome editing activity. The current review focuses on delivery systems for Cas9 mRNA, Cas9 protein, or vectors encoding the Cas9 gene and corresponding sgRNA. Non-viral delivery of Cas9 appears to help Cas9 maintain its on-target effect and reduce off-target effects, and viral vectors for sgRNA and donor template can improve the efficacy of genome editing and homology-directed repair. Safe, efficient, and producible delivery systems will promote the application of CRISPR-Cas9 technology in human gene therapy.