Large-Scale Comparative Analyses of Tick Genomes Elucidate Their Genetic Diversity and Vector Capacities.

Among arthropod vectors, ticks transmit the most diverse human and animal pathogens, leading to an increasing number of new challenges worldwide. Here we sequenced and assembled high-quality genomes of six ixodid tick species and further resequenced 678 tick specimens to understand three key aspects of ticks: genetic diversity, population structure, and pathogen distribution. We explored the genetic basis common to ticks, including heme and hemoglobin digestion, iron metabolism, and reactive oxygen species, and unveiled for the first time that genetic structure and pathogen composition in different tick species are mainly shaped by ecological and geographic factors. We further identified species-specific determinants associated with different host ranges, life cycles, and distributions. The findings of this study are an invaluable resource for research and control of ticks and tick-borne diseases.

Filaggrin-Associated Atopic Skin, Eye, Airways, and Gut Disease, Modifying the Presentation of X-Linked Reticular Pigmentary Disorder (XLPDR).

BACKGROUND: X-linked reticular pigmentary disorder (XLPDR) is a rare condition characterized by skin hyperpigmentation, ectodermal features, multiorgan inflammation, and recurrent infections. All probands identified to date share the same intronic hemizygous POLA1 hypomorphic variant (NM_001330360.2(POLA1):c.1393-354A > G) on the X chromosome. Previous studies have supported excessive type 1 interferon (IFN) inflammation and natural killer (NK) cell dysfunction in disease pathogenesis. Common null polymorphisms in filaggrin (FLG) gene underlie ichthyosis vulgaris and atopic predisposition. CASE: A 9-year-old boy born to non-consanguineous parents developed eczema with reticular skin hyperpigmentation in early infancy. He suffered recurrent chest infections with chronic cough, clubbing, and asthma, moderate allergic rhinoconjunctivitis with keratitis, multiple food allergies, and vomiting with growth failure. Imaging demonstrated bronchiectasis, while gastroscopy identified chronic eosinophilic gastroduodenitis. Interestingly, growth failure and bronchiectasis improved over time without specific treatment. METHODS: Whole-genome sequencing (WGS) using Illumina short-read sequencing was followed by both manual and orthogonal automated bioinformatic analyses for single-nucleotide variants, small insertions/deletions (indels), and larger copy number variations. NK cell cytotoxic function was assessed using 51Cr release and degranulation assays. The presence of an interferon signature was investigated using a panel of six interferon-stimulated genes (ISGs) by QPCR. RESULTS: WGS identified a de novo hemizygous intronic variant in POLA1 (NM_001330360.2(POLA1):c.1393-354A > G) giving a diagnosis of XLPDR, as well as a heterozygous nonsense FLG variant (NM_002016.2(FLG):c.441del, NP_0020.1:p.(Arg151Glyfs*43)). Compared to healthy controls, the IFN signature was elevated although the degree moderated over time with the improvement in his chest disease. NK cell functional studies showed normal cytotoxicity and degranulation. CONCLUSION: This patient had multiple atopic manifestations affecting eye, skin, chest, and gut, complicating the presentation of XLPDR. This highlights that common FLG polymorphisms should always be considered when assessing genotype-phenotype correlations of other genetic variation in patients with atopic symptoms. Additionally, while the patient exhibited an enhanced IFN signature, he does not have an NK cell defect, suggesting this may not be a constant feature of XLPDR.

An automated ICU agitation monitoring system for video streaming using deep learning classification.

OBJECTIVE: To address the challenge of assessing sedation status in critically ill patients in the intensive care unit (ICU), we aimed to develop a non-contact automatic classifier of agitation using artificial intelligence and deep learning. METHODS: We collected the video recordings of ICU patients and cut them into 30-second (30-s) and 2-second (2-s) segments. All of the segments were annotated with the status of agitation as "Attention" and "Non-attention". After transforming the video segments into movement quantification, we constructed the models of agitation classifiers with Threshold, Random Forest, and LSTM and evaluated their performances. RESULTS: The video recording segmentation yielded 427 30-s and 6405 2-s segments from 61 patients for model construction. The LSTM model achieved remarkable accuracy (ACC 0.92, AUC 0.91), outperforming other methods. CONCLUSION: Our study proposes an advanced monitoring system combining LSTM and image processing to ensure mild patient sedation in ICU care. LSTM proves to be the optimal choice for accurate monitoring. Future efforts should prioritize expanding data collection and enhancing system integration for practical application.

Gimap5 promoted RSV degradation through interaction with M6PR.

Respiratory syncytial virus (RSV) is one of the main pathogens of viral pneumonia and bronchiolitis in infants and young children and life-threatening diseases among infants and young children. GTPases of the immune-associated protein family (GIMAP) are new family members of immune-associated GTPases. In recent years, much attention has been paid to the function of the GIMAP family in coping with infection and stress. Gimap5 is a member of the GIMAP family, which may be correlated with anti-infectious immunity. RT-qPCR, Western blot, and indirect immunofluorescence (IFA) were used to detect the expression of Gimap5, M6PR and IGF1R(the major RSV receptor). Transmission electron microscopy (TEM) was used to detect the degradation of RSV in Gimap5-overexpressed or -silent cell lines. Computer virtual screening was used to screen small molecule compounds targeting Gimap5 and the anti-RSV effects were explored through in vivo and in vitro experiments. GIMAP5 and M6PR were significantly downregulated after RSV infection. Gimap5 accelerated RSV degradation in lysosomes by interacting with M6PR, and further prevented RSV invasion by downregulating the expression of RSV surface receptor IGF1R. Three small molecule compounds targeting Gimap5 were confirmed to be the agonists of Gimap5. The three compounds effectively inhibited RSV infection and RSV-induced complications. Gimap5 promotes the degradation of RSV and its receptor through interacting with M6PR. Gimap5 agonists can effectively reduce RSV infection and RSV-induced complication in vivo and in vitro, which provides a new choice for the treatment of RSV.

Catalyzing Benzoxazine Polymerization with Titanium-Containing POSS to Reduce the Curing Temperature and Improve Thermal Stability.

Trisilanolphenyl-polyhedral oligomeric silsesquioxane titanium (Ti-Ph-POSS) was synthesized through the corner-capping reaction, and Ti-Ph-POSS was dispersed in benzoxazine (BZ) to prepare Ti-Ph-POSS/PBZ composite materials. Ti-Ph-POSS could catalyze the ring-opening polymerization (ROP) of BZ and reduce the curing temperature of benzoxazine. In addition, Ti immobilized on the Ti-Ph-POSS cage could form covalent bonds with the N or O atoms on polybenzoxazine, improving the thermal stability of PBZ. The catalytic activity of the Ti-Ph-POSS/BZ mixtures was assessed and identified through 1H nuclear magnetic resonance (1H-NMR) and Fourier-transform infrared (FTIR) analyses, while thermogravimetric analysis (TGA) and dynamic mechanical analysis (DMA) were used to determine the thermal properties of the composite. It was found that PBZ exhibited a higher glass transition temperature (Tg) and better thermal stability when Ti-Ph-POSS was added. The curing behavior of the Ti-Ph-POSS/BZ mixtures showed that the initial (Ti) and peak (Tp) curing temperatures sharply decreased as the content of Ti-Ph-POSS and the heating rate increased. The curing kinetics of these Ti-Ph-POSS/BZ systems were analyzed using the Kissinger method, and the morphology of Ti-Ph-POSS/PBZ was determined via scanning electron microscopy (SEM). It was found that the Ti-Ph-POSS particles were well distributed in the composites. When the content exceeded 2 wt%, several Ti-Ph-POSS particles could not react with benzoxazine and were only dispersed within the PBZ matrix, resulting in aggregation of the Ti-Ph-POSS molecules.

The antiviral efficacies of small-molecule inhibitors against respiratory syncytial virus based on the F protein.

OBJECTIVES: Respiratory syncytial virus (RSV) infection is one of the three most common causes of death in the infants, pre-schoolers, immunocompromised patients and elderly individuals due to many complications and lack of specific treatment. During RSV infection, the fusion protein (F protein) mediates the fusion of the virus envelope with the host cell membrane. Therefore, the F protein is an effective target for viral inhibition. METHODS: We identified potential small-molecule inhibitors against RSV-F protein for the treatment of RSV infection using virtual screening and molecular dynamics (MD) simulations. The CCK8 assay was used to determine the cytotoxicity and quantitative RT-PCR and indirect fluorescence assay (IFA) were used to determine the viral replication and RSV-induced inflammation in vitro. An RSV-infected mouse model was established, and viral replication was assayed using real-time quantitative PCR and IFA. Virus-induced complications were also examined using histopathological analysis, airway resistance and the levels of IL-1ß, IL-6 and TNF-α. RESULTS: The top three potential inhibitors against the RSV-F protein were screened from the FDA-approved drug database. Z65, Z85 and Z74 significantly inhibited viral replication and RSV-induced inflammation. They also significantly alleviated RSV infection and RSV-induced complications in vivo. Z65 and Z85 had no cytotoxicity and better anti-RSV effects than Z74. CONCLUSIONS: Z65 and Z85 may be suitable candidates for the treatment of RSV and serve as the basis for the development of new drugs.

Recommendations for next generation sequencing data reanalysis of unsolved cases with suspected Mendelian disorders: A systematic review and meta-analysis.

PURPOSE: The study aimed to determine the diagnostic yield, optimal timing, and methodology of next generation sequencing data reanalysis in suspected Mendelian disorders. METHODS: We conducted a systematic review and meta-analysis of studies that conducted data reanalysis in patients with suspected Mendelian disorders. Random effects model was used to pool the estimated outcome with subgroup analysis stratified by timing, sequencing methodology, sample size, segregation, use of research validation, and artificial intelligence (AI) variant curation tools. RESULTS: A search of PubMed, Embase, Scopus, and Web of Science between 2007 and 2021 yielded 9327 articles, of which 29 were selected. Significant heterogeneity was noted between studies. Reanalysis had an overall diagnostic yield of 0.10 (95% CI = 0.06-0.13). Literature updates accounted for most new diagnoses. Diagnostic yield was higher after 24 months, although this was not statistically significant. Increased diagnoses were obtained with research validation and data sharing. AI-based tools did not adversely affect reanalysis diagnostic rate. CONCLUSION: Next generation sequencing data reanalysis can improve diagnostic yield. Owing to the heterogeneity of the studies, the optimal time to reanalysis and the impact of AI-based tools could not be determined with confidence. We propose standardized guidelines for future studies to reduce heterogeneity and improve the quality of the conclusions.

Dispersion and utilization of lipid droplets mediates respiratory syncytial virus-induced airway hyperresponsiveness.

BACKGROUND: Respiratory viral infections (RSV) can induce acute asthma attacks, thereby destroying lung function and accelerating the progression of the disease. However, medications in the stable phase of asthma are often not effective for acute attacks induced by viral infections. We aimed to clarify the possible mechanism of viral infection-induced asthma through fatty acid metabolism. METHODS AND RESULTS: The airway resistances, inflammatory injuries, and oxidative stress in the RSV-induced animal models were significantly higher than those in the control group at acute phase (7 days) and chronic phase (28 days). Moreover, the concentrations of the medium- and long-chain fatty acids in lung tissue at (28 days) were significantly increased, including 14:0 (myristic acid), 16:0 (palmitic acid, PA), 18:1 (oleic acid, OA), and 18:2 (linoleic acid, LA) using non-targeted metabonomics. Airway epithelial cells treated with RSV showed the reduced expression of FSP27, RAB8A, and PLIN5, which caused the fusion and growth of lipid droplet (LD), and increased expression of the LD dispersion gene perilipin 2. There was also a decrease in PPARγ expression and an increase in the fatty acid catabolism gene PPARα, causing lipid oxidation, free fatty acid releases, and an upsurge in IL-1, IL-2, IL-4, and IL-6 expression, which could be abrogated by GPR40 inhibitor. Treated mice or epithelial cells with C18 fatty acid exhibited inhibition of epithelial proliferation, increases of inflammation, and oxidative damage. CONCLUSIONS: RSV promoted lipid dispersion and utilization, causing enlarged oxidative injuries and an upsurge in the pro-inflammatory cytokines, leading to the progression of airway hyperresponsiveness (AHR).

MiR-34a-5p and miR-452-5p: The Novel Regulators of Pancreatic Endocrine Dysfunction in Diabetic Zucker Rats?

Objective: The pancreatic endocrinal system dominates the regulation of blood glucose levels in vivo, and the dysfunction of pancreatic endocrine ß-cells is a major cause of the occurrence and development of Type 2 diabetes (T2D). Although microRNA (miRNA) have been found to be key regulators of pancreatic ß-cells proliferation, differentiation and apoptosis, the underlying mechanism remains enigmatic. The aim of this study was to identify several novel miRNAs which might be involved in the etiopathogenesis of diabetic ß-cells dysfunction. Methods: The miRNA expression profiles in the pancreas of high-fat diet (HFD) fed Zucker diabetic fatty (ZDF) rats and Zucker lean (ZL) rats feed with normal-fat diet (NFD) were detected by using miRNA microarray chip, and individually verified the most significant factors by quantitative real-time polymerase chain reaction (qRT-PCR) assay. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to predict the target genes related to each of the identified miRNAs and the functions of these target genes in different metabolic signaling pathways. Results: Compared with the ZL rats, a total of 24 differentially expressed miRNAs were detected in ZDF rats. Among which miR-34a-5p and miR-452-5p were the most significantly up-regulated and down-regulated respectively. These miRNAs have not been reported in rats' pancreas before. By GO and KEGG enrichment analyses, we found that miR-34a-5p could negatively regulate pancreatic ß-cell proliferation through the involvement of Wnt signaling pathway. In addition, it was also found to regulate insulin secretion through the insulin signaling pathway to modulate blood glucose levels. At the same time, miR-452-5p was found to positively regulate the activity of the key rate-limiting enzyme branched-chain α-keto acid dehydrogenase-ß (BCKDHB) in the catabolism of branched chain amino acids (BCAA), leading to mitochondrial dysfunction in pancreatic ß-cells. Conclusions: miR-34a-5p and miR-452-5p were identified as the novel regulators of pancreatic endocrine dysfunction. These miRNAs might have the potential to be utilized as the new predictive biomarkers for the diagnosis of the occurrence and development of T2D, as well as the therapeutic targets for T2D treatment.

Effect of Cognitive Function on Balance and Posture Control after Stroke.

Hemiplegic gait is the most common sequela of stroke. Patients with hemiplegic gait are at a risk of falling because of poor balance. The theory of cognitive-motor networks paved the way for a new field of research. However, the mechanism of the relationship of cognition with gait or posture control networks is unclear because of the dynamic characteristics of walking and changing postures. To explore differences in the balance function and fall risk between patients with and without cognitive impairment after stroke, we utilized the Berg balance scale, Timed "Up and Go" test, and 10 m walking test. Patients were divided into two groups: the observation group (16 patients, female 6 and male 10), comprising patients with cognitive impairment after stroke, and the control group (16 patients, female 7 and male 9), comprising patients without cognitive impairment after stroke. We found that patients with cognitive impairment had worse balance function and a higher risk of falls. They needed a longer time to turn around or sit down. Our findings indicated that posture control in turning around and sitting down required more cognitive resources in daily life.

Expression of the intrarenal angiotensin receptor and the role of renin-angiotensin system inhibitors in IgA nephropathy.

The critical role of the intrarenal renin-angiotensin system (RAS) in the development of kidney disease has been well demonstrated in animal and cell-culture experiments, but evidence from human kidney tissues is lacking. In this study, we screened 438 patients with IgA nephropathy (IgAN) and analyzed their clinical characteristics. Renal biopsy revealed the expression of angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), and MAS receptor (MASR) in the tissues of 260 patients not treated with RAS inhibitors, 32 patients treated with angiotensin-converting enzyme inhibitors (ACEIs), and 89 patients treated with angiotensin receptor blockers (ARBs). The correlations in expression among these three receptors and the results of Oxford typing were analyzed, together with the ability of ACEIs and ARBs to reduce proteinuria and the effects of ARBs on AT1R and AT2R expression. The results showed significantly higher AT1R, AT2R, and MASR expression in the M1 group (mesangial score > 0.5) than in the M0 group (mesangial score < 0.5), significantly higher AT1R expression in the S1 group (presence of segmental glomerulosclerosis) than in the S0 group (absence of segmental glomerulosclerosis); AT1R expression in the C2 group (crescent formation > 25%) was significantly higher than in the C0 (crescent formation = 0) and C1 (crescent formation < 25%) groups. Patients treated with an ARB for < 6 months had significantly lower urinary protein levels than those taking these drugs for > 6 months. These findings imply that overexpression of AT1R on the mesangial cells of IgAN patients is associated with mesangial cell proliferation, glomerular segmental sclerosis, and crescent formation. In addition, long-term administration of ARB may decrease the efficacy of these medications in terms of reducing proteinuria.

A functional Au array SERS chip for the fast inspection of pesticides in conjunction with surface extraction and coordination transferring.

The fast inspection of the pesticide residues on fruits and vegetables requires the development of facile, sensitive and accurate methods. Surface enhanced Raman scattering (SERS) is a promising way to provide a fast inspection method, which requires significant improvements in the reproducibility and feasibility. In the present work, an SERS method was developed for the fast inspection of pesticides on fruit peels in conjunction with surface extraction and coordination transferring. In this new method, the residual pesticides were directly extracted from fruit peels with an appropriate extraction solution and then quantitatively transferred onto an organic solvent-compatible Au array SERS chip through the strong chemical interactions between the heteroatoms in the pesticides and the gold surface. The functional SERS chip was fabricated by the interfacial assembly of an Au array on a membrane, which produced dense and uniformly distributed SERS hot spots and enabled compatibility with random curvature surfaces and handheld Raman spectrometers. As a proof of concept, sulfur atoms containing thiram on apples were detected at a concentration as low as 5 ng cm-2 with good reproducibility (relative standard deviation lower than 10%). The strong interactions between the sulfur atoms and gold surface during the coordination transferring process were confirmed by the enhanced vibrations of the specified bands occurring in both the Raman and IR spectra. This surface extraction-coordination transferring-based method holds wide applicability for heteroatom-containing pesticides, as demonstrated by the detection of various S- and P-containing pesticides.

Transcriptome and metabolome analyses of Coilia nasus in response to Anisakidae parasite infection.

Parasites from the family Anisakidae are capable of infecting a range of marine fish species worldwide. Coilia nasus, which usually feeds and overwinters in coastal waters and spawns in freshwater, is highly susceptible to infection by Anisakidae. In this study, we used scanning electron microscopes to show that C. nasus infected by Anisakidae exhibited damage and fibrosis of the liver tissue. To better understand host immune reaction and metabolic changes to Anisakidae infection, we used a combination of transcriptomic and metabolomic method to characterize the key genes and metabolites, and the signaling pathway regulation of C. nasus infected by Anisakidae. We generated 62,604 unigenes from liver tissue and identified 391 compounds from serum. Of these, Anisakidae infection resulted in significant up-regulation of 545 genes and 28 metabolites, and significant down-regulation of 416 genes and 37 metabolites. Seventy-four of the 961 differentially expressed genes were linked to immune response, and 1, 2-Diacylglycerol, an important immune-related metabolite, was significantly up-regulated after infection. Our results show activation of antigen processing and presentation, initiation of the T cell receptor signaling pathway, disruption of the TCA cycle, and changes to the amino acid and Glycerolipid metabolisms, which indicate perturbations to the host immune system and metabolism following infection. This is the first study describing the immune responses and metabolic changes in C. nasus to Anisakidae infection, and thus improves our understanding of the interaction mechanisms between C. nasus and Anisakidae. Our findings will be useful for future research on the population ecology of C. nasus.

Experimental research on the therapeutic effect of MMR vaccine to juvenile-onset recurrent respiratory papillomatosis.

OBJECTIVE: To evaluate the efficacy of MMR vaccine in the treatment of juvenile-onset recurrent respiratory papillomatosis as adjuvant therapy by experimental research. METHODS: Thirty-one children with RRP were enrolled and assigned randomly to intervention group or control group. Fifteen subjects in intervention group were treated with local application MMR vaccine on the lesion after surgery; sixteen subjects in the control group were treated with surgical excision alone. The quantity of virus of positive specimens was measured by fluorescence quantitative polymerase chain reaction. RESULTS: After treatment with MMR vaccine, viral load of intervention group was (9.56 ± 11.03) × 108  copies/ml, that of control group was (22.01 ± 17.78) × 108 copies/ml, and there was significant difference between the two groups (P = 0.040). CONCLUSIONS: Local application MMR vaccine as adjuvant therapy can reduce HPV viral load significantly. It is suggested that the MMR vaccine may inhibit replication of HPV DNA, but the curative effect needs further confirmation.

Cyclophilin A is the potential receptor of the Mycoplasma genitalium adhesion protein.

The Mycoplasma genitalium adhesion protein (MgPa), the most important outer membrane protein of M. genitalium, plays a vital role in the adhesion to and invasion of host cells by M. genitalium. Identification of MgPa receptors will help elucidate the pathogenic mechanism of M. genitalium. However, the receptor protein of MgPa has not been reported to date. In this study, an MgPa-binding protein with a molecular weight of approximately 17 kDa was screened from SV-HUC-1 cell membrane proteins by a modified virus overlay protein binding assay (VOPBA). Liquid chromatography-mass spectrometry (LC-MS) was used to analyze the protein components of the 17-kDa protein. The results demonstrated that the MgPa-binding protein was most likely Cyclophilin A (CyPA). The binding activity and distribution of CyPA in SV-HUC-1 cells were detected using indirect ELISA, western blotting, far-western blotting and indirect immunofluorescence. We found that recombinant MgPa (rMgPa) could bind with CyPA from SV-HUC-1 cell membrane proteins and to recombinant CyPA, which indicated that CyPA was predominant component of the 17-kDa protein band and can interact with rMgPa. In addition, an indirect immunofluorescence assay showed that CyPA was partially distributed on the membrane surfaces of SV-HUC-1 cells and could partially inhibit the adhesion of rMgPa and M. genitalium to SV-HUC-1 cells. Co-localization assays further indicated that rMgPa and M. genitalium can interact with CyPA. These results suggested that the CyPA located on SV-HUC-1 cell membranes may be the potential receptor of MgPa, which could provide an experimental basis for elucidating the function of MgPa and the possible pathogenic mechanism of M. genitalium.

Three polypeptides screened from phage display random peptide library may be the receptor polypeptide of Mycoplasma genitalium adhesion protein.

Mycoplasma genitalium adhesion protein (MgPa) is a major adhesin of M. genitalium, a human pathogen associated with a series of genitourinary tract diseases. MgPa plays a very important role in M. genitalium adhering to the host cells. However, the exact receptor peptides or proteins of MgPa are still poorly understood so far. Three polypeptides (V-H-W-D-F-R-Q-W-W-Q-P-S), (D-W-S-S-W-V -Y-R-D-P-Q-T) and (H-Y-I-D-F-R-W) were previously screened from a phage display random peptide library using recombinant MgPa (rMgPa) as a target molecule. In this study, three polypeptides were artificially synthesized and investigated as to whether they are potential receptors of MgPa. We found that rMgPa specifically bound to three synthesized polypeptides as determined via an indirect enzyme-linked immunosorbent assay (ELISA). Moreover, three polypeptides were further identified by indirect immunofluorescence microscopy (IFM). We confirmed that rMgPa and M. genitalium can adhere to SV-HUC-1 cells in vitro and that anti-rMgPa antibody and three synthesized polypeptides can partially inhibit the adherence of rMgPa and M. genitalium to SV-HUC-1 cells. In summary, these three polypeptides may be the essential receptor peptides of MgPa, and may aid in enhancing the understanding of biological function of MgPa and the possible pathogenic mechanism of M. genitalium.

Vancomycin-induced acute kidney injury in elderly Chinese patients: a single-centre cross-sectional study.

AIMS: The objective of the present study was to investigate the current situation concerning, and risk factors for, vancomycin (VAN)-induced acute kidney injury (VI-AKI) in elderly Chinese patients, to assess outcomes and risk factors in patients who have developed VI-AKI, in order to provide suggestions for improving the prevention and treatment of this condition in these patients. METHOD: We retrospectively identified elderly older inpatients who had received four or more doses of VAN treatment. We compared patients with VI-AKI with those who received VAN treatment and had not developed AKI (NO-AKI). We defined VI-AKI as developing AKI during VAN therapy or within 3 days after withdrawal of VAN. RESULTS: A total of 647 out of 862 elderly inpatients were included in the study. Among those excluded, in 89.3% of cases (192/215) this was because of lack of data on serum creatinine (SCr). Among included patients, 32.5% (210/647) of patients received therapeutic drug monitoring (TDM) during VAN therapy. In 66.9% of cases (424/634), there was insufficient TDM, and in 3.9% (25/634) this was appropriate. A total of 102 patients had confirmed VI-AKI, with an incidence of 15.8% (102/647). Multiple logistic regression analysis revealed that hyperuricaemia [odds ratio (OR) = 3.045; P = 0.000)], mechanical ventilation (OR = 1.906; P = 0.022) and concomitant vasopressor therapy (OR = 1.919; P = 0.027) were independent risk factors for VI-AKI; higher serum albumin (OR = 0.885; P = 0.000) was determined to be an independent protective factor for VI-AKI. CONCLUSIONS: For the elderly Chinese patients treated with VAN, there was insufficient monitoring of SCr, too little use of VAN TDM, and lower rate of patients whose VAN though serum concentrations were not obtained at the correct time. We recommend that hospital managers increase investment in clinical pharmacists, to strengthen professional management. Patients with concomitant hyperuricaemia and on mechanical ventilation and vasopressor therapy should be paid more attention, and a higher serum albumin was determined to be an independent protective factor for VI-AKI.

Effects of adding Rheum officinale to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on renal function in patients with chronic renal failure: A meta-analysis of randomized controlled trials
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OBJECTIVE: Rheum officinale is a traditional medicinal herb used widely in China to treat chronic renal failure, but the proof of evidence-based medicine is poor. This meta-analysis aims to assess the benefits of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) supplemented with Rheum officinale for delaying the progression of chronic renal failure. MATERIALS AND METHODS: The MEDLINE, EMBASE, Cochrane Library, SinoMed, Chinese National Knowledge Infrastructure, Wanfang, and VIP databases were searched to identify studies published before September 2016 that investigated the effects of ACEI/ARB plus the Chinese patented medicine Rheum (CPM-Rheum) compared to ACEI/ARB alone in lowering serum creatinine (SCr) and blood urea nitrogen (BUN) levels in chronic renal failure patients. Review Manager 5.3 was used to perform the meta-analysis. Fixed- and random-effects models were used to analyze the data. RESULTS: The meta-analysis included nine clinical trials. Comparisons of patients before and after treatment with ACEI/ARB plus CPM-Rheum or ACEI/ARB alone revealed that ACEI/ARB plus CPM-Rheum resulted in significantly greater reductions in SCr (short-term: weighted mean difference (WMD): 17.26, 95% confidence interval (CI): 7.28 - 27.24; long-term: WMD: 63.71, 95% CI: 51.01 - 76.41) and BUN (short-term: WMD: 1.70, 95% CI: 1.27 - 2.12; long-term: WMD: 3.98, 95% CI: 3.14 - 4.82) than ACEI/ARB alone. CONCLUSION: In patients with chronic renal failure, the addition of CPM-Rheum to ACEI/ARB significantly lowered both SCr and BUN, particularly after long-term administration. Thus, the combination of ACEI/ARB and CPM-Rheum may improve the treatment of patients with impaired renal function.
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