[Effects of specimen preservation and transportation on blood paraquat concentration in rats].

Objective: To investigate the effects of duration, temperature and shake on paraquat (PQ) concentration in the blood of PQ-exposed rats during the specinen preservation and transportation. Methods: In March 2021, 60 SD male rats of Specific Pathogen Free class were randomly divided into low-dose group (10 mg/kg PQ) and high-dose group (80 mg/kg PQ). Each group was divided into 5 subgroups (normal temperature group, cold storage group, 37 ℃ storage group, shaking on normal temperature group and shaking on 37 ℃ group), six rats in each subgroup. The rats were given intraperitoneal injection of PQ, 1 h after exposure, the blood samples were obtained by cardiac extraction. After different interventions, the concentrations of PQ were detected and compared before and after the intervention in each subgroup. Results: In the shaking on 37 ℃ group, the results of PQ concentrations in PQ-exposed rats were significantly lower than those before the intervention (P<0.05). In the other subgroups, the results were not significantly different compared with before intervention (P>0.05) . Conclusion: The concentration of PQ in the blood of rats exposed to PQ was decreased by shaking for 4 hours at 37 ℃.

[Research progress of diabetic corneal neuropathy].

Diabetic neuropathy is a common complication of diabetes. Its incidence among diabetic patients is more than 50%, and its ocular manifestations include diabetic retinopathy and diabetic corneal neuropathy. By using confocal microscopy, diabetic neuropathy in the cornea has been found to occur earlier than other parts of the body, which helps for early diagnosis, risk assessment and treatment options for diabetic peripheral neuropathy. The repair and treatment of nerve damage in diabetic corneal neuropathy has been frequently studied. This review focuses on the research progress of diabetic corneal neuropathy in recent years, and discusses the research findings on corneal nerve injury, anatomical and functional changes, and mechanism of injury and repair. (Chin J Ophthalmol, 2021, 57: 630-636).

[Deep learning based lesion detection from anterior segment optical coherence tomography images and its application in the diagnosis of keratoconus].

Objective: To developed an image analysis system of anterior segment optical coherence tomography (AS-OCT) examination results based on deep learning technology, and to evaluate its effect in identifying various types of corneal pathologies and quantified indices. Methods: A total of 4 026 patients (5 617 eyes), including 1 977 males and 2 049 females, aged (45±23) years, were enrolled in Qingdao Eye Hospital from January 2011 to August 2019. The AS-OCT images were used as a training dataset, which were labeled with location information of 16 corneal pathologies (including corneal epithelial defect, corneal epithelial thickening, corneal thinning and so on) by clinical experts, as well as the tissue stratification of the corneal epithelium and stroma. The labeled AS-OCT images were used to train the corneal pathology detection model and corneal stratification model based on deep convolutional neural network algorithm. Then 1 709 AS-OCT images of the affected eyes were collected as a validation dataset. Compared with the artificial labeling results, the accuracy, sensitivity and specificity were evaluated in the corneal pathology detection model, and the overlapping rate (Dice coefficient) between the labeled area of the model and the artificial labeling area was used to evaluate the corneal stratification model. Results: The results of 5 617 training sets showed that there were 1 472 cases of corneal epithelial defect, 2 416 cases of corneal epithelial thickening, 2 001 cases of corneal thinning, 780 cases of corneal lordosis, 2 064 cases of corneal thickening, 358 cases of subepithelial blisters, 486 cases of subepithelial opacity, 1 010 cases of corneal ulcer, 3 635 cases of stromal opacity, 1 060 cases of posterior elastic layer fold, 137 cases of posterior elastic layer detachment, 665 cases of keratic precipitate, 176 cases of corneal perforation, 127 cases of corneal foreign body, 299 cases of after lamellar keratoplasty (LKP) and 234 cases of after penetrating keratoplasty (PKP). Among 1 709 images, 1 596 were manually labeled. The average sensitivity and specificity of the corneal pathology detection model were 96.5% and 96.1% compared with the results of manual labeling. Fifteen samples were missed for detection, and the rate was 0.93%. The average Dice coefficients of the corneal stratification model for the corneal epithelium and stroma were 0.985 and 0.917, respectively. Conclusions: Our artificial intelligence-based diagnosis system with AS-OCT is able to give quantified information and location information of corneal lesions with high accuracy, which can help ophthalmologists improve the efficiency and accuracy of diagnosis. (Chin J Ophthalmol, 2021, 57: 447-453).

Long noncoding RNA LINP1 promoted proliferation and invasion of ovarian cancer via inhibiting KLF6.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long noncoding RNA LINP1 promoted proliferation and invasion of ovarian cancer via inhibiting KLF6, by Y. Li, C.-Z. Hou, Y.-L. Dong, L. Zhu, H. Xu, published in Eur Rev Med Pharmacol Sci 2020; 24 (1): 36-42-DOI: 10.26355/eurrev_202001_19893-PMID: 31957816" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19893.

[Clinical observation of ocular injury caused by chestnut burr].

Objective: To analyze the clinical characteristics and treatment of ocular injury caused by chestnut burr. Methods: Retrospective case series study. Data of 48 patients (48 eyes) with ocular injuries caused by chestnut burrs hospitalized in Qingdao Eye Hospital were collected from January 2013 to March 2019. All patients were followed up for at least 3 months. The time of seeking medical advice, lesion region, and characteristics and treatment methods were analyzed. Results: There were 48 patients, including 33 males and 15 females, aged 19 to 74 years [mean, (56±10) years]. The time of injury was late September (25 cases) and early October (23 cases). The shortest time to visit our hospital was 3 hours after injury, and the longest was 8 months after injury. There were 13 cases (27.1%, 13/48) with corneal and/or scleral foreign bodies. All patients were treated with corneal or scleral foreign body extraction. Twenty-four patients (50.0%, 24/48) developed fungal keratitis. Among them, 18 patients had a corneal ulcer, and the infection involved the superficial or full-thickness corneal layer. Six patients had no corneal ulcer, and the infection involved the deep stroma and corneal endothelial surface. The positive rate of fungal examination by confocal microscopy was 87.5% (21/24). Antifungal drugs (2 cases), corneal debridement (5 cases), conjunctival flap covering (2 cases), corneal stroma injection (1 case), and penetrating keratoplasty(14 cases) were given according to the depth of fungal infection. Most of the pathogens were Alternaria spp. Eleven patients (22.9%, 11/48) with necrotizing scleritis were treated with exploration of the sclera. Three patients had scleral foreign body residues on ultrasound biomicroscopy examination, which were removed by operation. Four patients were found to have fungi at the necrotic site of the sclera. Conclusions: The main types of ocular injuries caused by chestnut burrs are corneal and/or scleral foreign bodies, fungal keratitis, and necrotizing scleritis. Chestnut burr foreign bodies should be removed as soon as possible. In the case of fungal keratitis, a drug or surgical intervention should be carried out as early as possible. Necrotizing scleritis is often induced by long-term foreign body retention. Scleral incision and exploration is an effective form of treatment. (Chin J Ophthalmol, 2020, 56: 370-375).

[A clinical analysis of 1 414 cases of fungal keratitis].

Objective: To discuss clinical features and treatments of fungal keratitis, and to provide statistical data for clinical therapy and increase the therapeutic effects. Methods: This is a retrospective case series study. An analysis was performed by collecting patients' demography features, risk factors, onset time, lab results, clinical features and treatment from 1 414 cases of fungal keratitis from January 2006 to October 2016 in Qingdao Eye Hospital, Shandong Eye Institute. Results: In the 1 414 cases (1 414 patients), 1 174 patients (83.0%) came from different areas in Shandong Province, and the rest mainly from provinces on the north of Yangtze River. The age was 40 to 60 years in 874 cases (61.4%). The onset time was often in autumn and winter. The average duration between the onset and treatment was 1 to 74 days; 942 patients (67.1%) visited our hospital in 8-30 days after the appearance of the symptoms. Corneal trauma was the most common risk factor, especially injury by plants (367 cases, 26.4%). The positive rate of direct microscopic examination of potassium hydroxide wet mounts was 96.4%. The positive rate of confocal microscopy was 89.8%. Fungi were detected in corneal ulcer scrapings and (or) diseased corneal tissues obtained during surgery from 973 patients (68.8%). Most of the fungi were Fusarium (595 cases, 61.1%), followed by Alternaria (184 cases, 18.9%) and Aspergillus (119 cases, 12.2%). There were 603 cases (42.7%) of superficial and middle stromal infiltration, 614 cases (43.4%) of deep stromal infiltration and 197 cases (13.9%) of full-thickness corneal infiltration. Diameters of the corneal ulcer lesion were mostly between 4 and 6 mm (725 cases, 51.6%), followed by<3 mm (372 cases, 26.4%) and>6 mm (302 cases, 22.0%). Hypopyon was combined in 498 cases (35.2%), corneal perforation in 34 cases (2.4%), and endophthalmitis in 58 cases (4.1%). Surgery was performed in 1 198 cases (84.8%), including penetrating keratoplasty in 416 cases (29.4%), lamellar keratoplasty in 199 cases (14.1%), and corneal ulcer debridement in 532 cases (37.6%), with an effective rate of 98.1% (408 cases), 97.0% (193 cases) and 92.8% (494 cases), respectively. Two hundred and fifteen cases (15.2%) were treated with medical therapy alone, of which 147 cases (68.4%) were cured. Fifty-six patients (3.9%) finally lost their eye balls, including 54 cases of evisceration and 2 cases of ophthalmectomy. Conclusions: Fusarium is the main causative agent of fungal keratitis in Shandong Province. Direct microscopic examination of potassium hydroxide wet mounts is a simple, rapid and effective test method. Early diagnosis can be made if the result of corneal ulcer scraping examination is positive. Antifungal drug treatments can be done in early onset time. If the drug efficacy is poor or the patient's condition gets worse, immediate surgery is the key to controlling fungal keratitis. (Chin J Ophthalmol, 2020, 56:286-293).

Long noncoding RNA LINP1 promoted proliferation and invasion of ovarian cancer via inhibiting KLF6.

OBJECTIVE: Ovarian cancer is one of the most ordinary fatal cancers. The role of long noncoding ribonucleic acids (lncRNAs) in tumor progression has caught the attention of numerous researchers. In this work, lncRNA LINP1 was studied to identify how it functioned in the progression of ovarian cancer. PATIENTS AND METHODS: Firstly, quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to measure LINP1 expression in ovarian cancer tissues. Furthermore, to identify the function of LINP1 in ovarian cancer, functional experiments were conducted. Also, by performing qRT-PCR and Western blot assay, the underlying mechanism was explored. RESULTS: In this research, LINP1 expression was remarkably higher in ovarian carcinoma samples compared with adjacent tissues. Moreover, cell proliferation, migration, and invasion were inhibited after LINP1 was silenced in the ovarian cancer cells. Besides, the messenger (mRNA) and the protein of KLF6 were overexpressed after LINP1 was silenced. Furthermore, the KLF6 expression level was negatively related to the LINP1 expression level in ovarian cancer samples. CONCLUSIONS: We discovered a potential oncogene in ovarian cancer and identified that LINP1 enhanced cell metastasis and proliferation via down-regulating KLF6.

[Surgical treatment of keratoglobus: key techniques of bridge-shaped flap penetrating keratoplasty and whole lamellar keratoplasty with corneoscleral limbal].

Objective: Introduce the surgical techniques of bridge-shaped flap penetrating keratoplasty and whole lamellar keratoplasty with corneoscleral limbal and the comparison of therapeutic effects on keratoglobus. Methods: Five patients (eight eyes) with keratoglobus from January 2010 to December 2015 were included. Three eyes received bridge-shaped flap penetrating keratoplasty (two eyes with corneal penetrating injury due to trauma, one eye with descemet's membrane detachment) and five eyes received whole lamellar keratoplasty with corneoscleral limbal. Results: The patients (four male, one female) aged 3 to 67 years old. Three younger patients were complicated with blue sclera. The visual acuity of all the patients pre-operation were lower than 0.05. The average visual acuity after whole lamellar keratoplasty (LKP) surgery was 0.2, while the average visual acuity after bridge-shaped flap penetrating keratoplasty (PKP) was 0.5. The corneal epithelium of the three eyes received bridge-shaped flap PKP surgery was completely healed within a week with no recurrence of corneal epithelial defect. Whereas one eye after whole LKP surgery arised persistent corneal epithelial defect and healed after blepharorrhaphy. The corneal epithelial of another eye after whole LKP surgery healed slowly and was completely healed after wearing a bandage lens on corneal for 2 months. The corneal epithelial of the remaining three eyes after whole LKP surgery was completely healed within a week. Two eyes received bridge-shaped flap PKP surgery arised corneal graft rejection 2 months after operation and recovered after anti-rejection treatment. No corneal graft rejection arised in the patients receiving whole LKP surgery. Conclusions: The whole lamellar keratoplasty with corneoscleral limbal could effectively reinforce corneal, avoid corneal penetrating injury caused by minor trauma, and improve visual acuity in keratoglobus whose corneas were gradually thinning and corrected vision cannot be improved. The patients with corneal perforating injury or descemet's membrane detachment could obtain good visual prognosis receiving bridge-shaped flap penetrating keratoplasty. (Chin J Ophthalmol, 2019, 55:916-922).

[Clinical features, treatment distribution and outcomes of Mooren's ulcer].

Objective: To investigate the clinical features, treatment distribution and transition of Mooren's ulcer, and to observe the clinical outcomes and recurrence. Methods: Retrospective series case study. Medical records of 125 patients (154 eyes) with Mooren's ulcer treated between January 1996 and December 2015 at our hospital were retrospectively reviewed. Seventy-eight males and 47 females were include, with age of (47.6±14.3) years (range: 23-82 years) and median disease course of 6 months (range: 1-240 months). Follow-up occurred between 4.5 and 122 months and the ratio of males to females was 1.66∶1. All patients were divided into two groups: group 1996-2005 and group 2006-2015. Chi-square test was used to analyze the difference of treatment distribution between the two groups and recurrence rate relative to different risk factors. Clinical features and treatment outcomes of Mooren's ulcers were observed simultaneously. Results: The lesion of the primary Mooren's ulcer involved nasal, temporal, superior, inferior and all limbus in 48, 41, 13, 23 and 29 eyes, respectively. The numbers of eyes treated with medical therapy, LKP and amniotic membrane grafting were 6, 61 and 1 in group 1996, with recurrence rate of 1/6, 24.59% and 0 respectively. The numbers in group 2006 were 27, 38 and 14 with recurrence rate of 7.41%, 34.21% and 2/14, respectively. The differences of eyes underwent three different therapies were statistical significance between two groups (χ(2)=29.315, P=0.000), but the differences of total recurrence rate were not (χ(2)=0.149, P=0.699). Thirty-four patients (34 eyes) suffered ulcer recurrence, among which 23 eyes (67.65%) had recurrence within 12 months after treatment and 31 eyes (91.12%) were saved. Finally, 150 of 154 eyes (97.40%) were saved and 129 eyes (83.77%) retained vision better than 0.05. Conclusions: Mooren's ulcers were prone to occur in males and in patients older than 35 years. The lesion more often involved interpalpebral limbus. Lamellar keratoplasty was the most frequently used surgical intervention for primary Mooren's ulcer with a recurrence rate of 28.28%. In recent 10 years, the percentage of patients treated with LKP decreased while percentage of medical treatment and amniotic membrane grafting went up obviously, and the total recurrence rate between two groups had no statitical differences. (Chin J Ophthalmol, 2019, 55:127-133).

Circulating microRNA array (miR-182, 200b and 205) for the early diagnosis and poor prognosis predictor of non-small cell lung cancer.

OBJECTIVE: Non-small cell lung cancer (NSCLC) is the most common cause for cancer-related mortality worldwide. Currently, early detection of NSCLC is one of the main available strategies for improving its prognosis. Due to the lack of non-invasive and convenient tools, early diagnosis of NSCLC remains poor. Recently, it has been reported that circulating microRNAs (miRNAs) can be stably detected in serum. Meanwhile, they play a powerful role as biomarkers in various tumors. Therefore, the aim of this study was to detect the expression levels of serum miR-182, 200b and 205 in NSCLC patients, and to investigate their diagnostic and prognostic values. PATIENTS AND METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was carried out to measure the expressions of miR-182, 200b and 205 in NSCLC tissues and normal controls. Receiver-operating characteristic (ROC) curve analysis was performed to assess the potential value of serum miRNAs for NSCLC diagnosis. Meanwhile, transwell assays were performed to observe the functional effects of miRNAs on the invasion and migration of NSCLC cells. RESULTS: Compared with normal controls, serum levels of miR-182 and 205 in NSCLC patients were significantly upregulated, whereas miR-200b was remarkably downregulated. ROC analysis indicated that miRNA array (miR-182, 200b and 205) was useful biomarkers for early diagnosis of NSCLC. In addition, transwell assays demonstrated that miR-182 promoted the invasion and migration of NSCLC cells. CONCLUSIONS: Our findings revealed that serum miR-182, 200b and 205 might serve as promising biomarkers for early detection and treatment of NSCLC.

[The Rice OsDUF810 Family: OsDUF810.7 May be Involved in the Tolerance to Salt and Drought].

With the advance of sequencing technology, the number of sequenced plant genomes has been rapidly increasing. However, understanding of the gene function in these sequenced genomes lags far behind; as a result, many coding plant sequences in public databases are annotated as proteins with domains of unknown function (DUF). Function of a protein family DUF810 in rice is not known. In this study, we analysed seven members of OsDU810 (OsDUF810.1-OsDUF810.7) family with three distinct motifs in rice Nipponbare. By phylogenetic analysis, OsDUF810 proteins fall into three major groups (I, II, III). Expression patterns of the seven corresponding OsDUF810 protein-encoding genes in 15 different rice tissues vary. Under drought, salt, cold and heat stress conditions and ABA treatment, the expression of OsDUF810.7 significantly increases. Overexpression of this protein in E. coli lead to a significant enhancement of catalase (CAT) and peroxidase (POD) activities, and improved bacterial resistance to salt and drought.

Development of indicators for evaluating the appropriate use of triazoles for invasive fungal disease: A Delphi panel survey.

WHAT IS KNOWN AND OBJECTIVES: Triazoles including fluconazole, itraconazole, voriconazole and posaconazole are now widely used, whereas in some countries, they are reportedly used in inappropriate way frequently; thus, it is clearly a matter of urgency to regulate the use of triazole drugs. Several studies have made good attempts to evaluate antifungal use, but they did not cover the entire medication process. This study aimed to establish indicators for the appropriate use of triazoles for invasive fungal disease, so as to produce a reference for evaluating and standardizing the rational application of triazole antifungals. METHODS: A comprehensive analysis and literature review were conducted to construct an evaluation system for indications, therapeutic timing, duration of drug usage, drug dosage, administration method, drug interactions, medication in specific populations and pharmaceutical care. A Delphi questionnaire was designed based on the preliminary evaluation of an indicator system that comprised eight primary indicators, 29 secondary indicators and 54 tertiary indicators. A Delphi panel survey was completed by 28 and 26 experts in the first and second rounds, respectively, via e-mail. Agreement was considered to be reached when the median score was in the top tertile (4 or 5), and 80% of panel scores were in the top tertile. The experts mainly comprised physicians and clinical pharmacists from different regions. Based on expert opinions, the evaluation indicator system was modified and the final version was established. RESULTS: The response rate was high in the first and second rounds, at 100% and 93%, respectively, as was the dependability coefficient (0.83). The expert opinions resulted in four secondary indicators and nine tertiary indicators being deleted, and 10 tertiary indicators being modified. After the two rounds of the Delphi survey, the final established system of indicators comprised eight primary indicators, 25 secondary indicators and 45 tertiary indicators. WHAT IS NEW AND CONCLUSIONS: Contrasted with previous studies that have only focused on a subset of indicators, this research establishes comprehensive indicators for evaluating the use of triazoles for invasive fungal disease and which cover most of the medication process: indications, therapeutic timing, duration of drug usage, drug dosage, administration method, drug interactions, medication in specific populations and pharmaceutical care. The indicators can reflect the characteristic of triazoles throughout the process of clinical administration for an invasive fungal disease, and it will be helpful as references when hospital administrators are regulating the use of antifungals.

[Influence factors of dislocation after bipolar prosthetic replacement].

OBJECTIVE: To discuss the influence factors of dislocation after bipolar prosthetic replacement. METHODS: A total of 374 patients who received bipolar prosthetic replacement in our hospital from October 2001 to October 2015 were retrospectively studied. The clinic data of patients with dislocation after operation was summarized to analyze the causes. RESULTS: Dislocation happened in 12 patients among all the 374 patients.10 cases received manual relocation, 2 cases open relocation. Most of the 12 patients were accompanied with neurological and psychiatric disorders, such as Alzheimer's disease, Parkinson's disease, sequelae of cerebral infarction, etc. Some factors like improper body position caused by these complications were the main influence factors of dislocation. CONCLUSION: Accompanied with neurological and psychiatric disorders is the important influence factor of dislocation after bipolar prosthetic replacement.

Cyclin D1 G870A gene polymorphism and risk of leukemia and hepatocellular carcinoma: a meta-analysis.

Cyclin D1 (CCND1) is a key protein involved in cell-cycle regulation, and the CCND1 G870A polymorphism is associated with many types of malignancy. Studies examining the associations between this G870A polymorphism and susceptibility to leukemia and hepatocellular carcinoma (HCC) have shown inconsistent results. Therefore, we conducted a meta-analysis to clarify these associations. A search of the PubMed database yielded 7 relevant articles: 3 pertaining to leukemia and 4 to HCC. The odds ratios (ORs) from individual studies were pooled using a fixed or random-effect model. A significant association was observed between the CCND1 G870A variant and leukemia under the allele contrast model [P = 0.003, OR = 1.49, 95% confidence interval (CI) = 1.15-1.95], the homozygote contrast model (P = 0.003, OR = 2.30, 95%CI = 1.34-3.96), and the recessive model (P = 0.002, OR = 2.03, 95%CI = 1.29-3.21). A significant association was observed between this variant and HCC under the recessive model (P = 0.0006, OR = 1.62, 95%CI = 1.23-2.14), the dominant model (P = 0.002, OR = 1.59, 95%CI = 1.19-2.14), the homozygote contrast model (P < 0.0001, OR = 2.06, 95%CI = 1.45-2.94), and the allele contrast model (P < 0.0001, OR = 1.43, 95%CI = 1.20-1.69). Our findings suggest that heritable CCND1 status may influence the risk of developing leukemia and HCC, and that more attention should be given to carriers of these susceptibility genes.

Trends and correlation of antibacterial usage and bacterial resistance: time series analysis for antibacterial stewardship in a Chinese teaching hospital (2009-2013).

The purpose of this investigation was to describe the effect of antibacterial stewardship and evaluate the trends and correlation of antibacterial resistance and usage from 2009 to 2013 in a tertiary-care teaching hospital in northwest China. Antibacterial usage was expressed as defined daily doses per 100 patients per day (DDDs/100 PDs). Hospital-wide population-level data and time series analysis were used to evaluate the trends and determine associations between antibacterial exposure and acquisition of resistance. Yearly consumption of overall antibacterials significantly decreased from 66.54 to 28.08 DDDs/100 PDs (ß = -10.504, p < 0.01). The resistant rates of the five most frequently isolated species (including Escherichia coli, Acinetobacter baumannii, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae) significantly decreased or remained stable, and none of them showed a statistically significant upward trend. The medical quality indicators got better or remained stable. Autoregressive integrated moving average (ARIMA) models demonstrated that the monthly resistance rate of P. aeruginosa to imipenem was strongly correlated with antipseudomonal carbapenems usage (ß = 34.94, p < 0.001), as did the correlation of P. aeruginosa to meropenem with antipseudomonal third-generation cephalosporins usage (ß = 32.76, p < 0.01) and K. pneumoniae to amikacin with aminoglycosides usage (ß = 22.01, p < 0.001). The decreased antibacterial use paralleled the improved bacterial resistance without deteriorating medical quality indicators during antimicrobial stewardship. It also suggests that optimum antibiotic use is necessary to alleviate the threat posed by resistant microorganisms at the hospital level.

Effects of CYP3A4 polymorphisms on the plasma concentration of voriconazole.

Voriconazole is frequently utilized for the prevention and treatment of invasive fungal infections (IFIs), and is extensively metabolized by the cytochrome P450 (CYP) system. The impact of activity of the genes encoding CYP3A4, CYP3A5, and CYP2C9 on the pharmacokinetics of voriconazole cannot be ignored because, second to CYP2C19, they are the most important enzymes involved in voriconazole metabolism. The influence of genetic polymorphisms in CYP3A4, CYP3A5, and CYP2C9 on the plasma concentrations of voriconazole was evaluated in the present study. The study cohort comprised 158 patients with IFIs in whom 22 single-nucleotide polymorphisms (SNPs) in CYP3A4, CYP3A5, and CYP2C9 were genotyped using the Sequenom MassARRAY RS1000 system, and voriconazole plasma concentrations were measured by high-performance liquid chromatography (HPLC). 40, 91, and 27 patients presented with low (<1 mg/L), normal (1-4 mg/L), and high (>4 mg/L) plasma voriconazole concentrations, respectively. Correlation analysis between polymorphisms and the plasma voriconazole concentration revealed an association between the presence of the rs4646437 T allele and a higher plasma voriconazole concentration [p = 0.033, odds ratio (OR) = 2.832, 95% confidence interval (CI) = 1.086-7.384]. This study has identified a new SNP related to the metabolism of voriconazole, potentially providing novel insight into the influence of CYP3A4 on the pharmacokinetics of this antifungal agent.

Role of monochromatic light on development of cecal tonsil in young broilers.

Previously, the different monochromatic lights have been demonstrated to affect splenocyte proliferation and melatonin (MEL) secretion in broilers. The present study was designed to evaluate the effects of different monochromatic lights on the development and immune function of broiler cecal tonsils, and to disclose the mechanisms underlying these phenomena. A total of 185 broilers (P0) including intact, sham-operated, and pinealectomized groups were exposed to blue light (BL), green light (GL), red light (RL), and white light (WL) by a light-emitting diode system for 14 days. Compared with RL groups, the GL in the intact and sham-operated groups showed larger follicle areas (66.70%), higher percentages of proliferating cell nuclear antigen (PCNA)-positive cells (33.33%), increased numbers of IgA(+) cells (48.60%), and increased antioxidase activity (33.33%-61.37%), whereas, the density of iNOS and MDA content in GL were lower (43.63%-54.43%) than that of RL. In contrast, after pinealectomy, the area of follicles, the percentage of PCNA-positive cells, the number of IgA(+) cells, and the antioxidase activity decreased in the different light treatments, but the density of iNOS and MDA content increased substantially. There was no significant difference in these parameters between broilers exposed to GL and other lights (P = 0.085-1.000). The results suggested that the enhanced effects of GL on the development and immune function of cecal tonsils in young broilers were mediated by elevated antioxidative status via up-regulation of MEL.

Association between methylenetetrahydrofolate reductase polymorphisms and the relapse of acute lymphoblastic leukemia: a meta-analysis.

Relapse is a threat in patients treated for acute lymphoblastic leukemia (ALL). Methylenetetrahydrofolate reductase (MTHFR) activity may affect the sensitivity of patients to folate-based chemotherapeutic drugs, thus influencing the relapse risk. Two polymorphisms of the gene encoding MTHFR, C677T and A1298C, alter MTHFR enzyme activity and may be associated with ALL relapse. The aim of this meta-analysis was to clarify the correlation between the C677T and A1298C polymorphisms and ALL relapse. To this end, data were collected from studies of the association between these two polymorphisms and ALL relapse. Analysis of the data revealed a serious contradiction among the results. A recessive model demonstrated that the ALL relapse risk was significantly increased in carriers of the 677 TT genotype, especially for pediatric ALL, but was unaffected by the A1298C polymorphism. These findings confirm that the MTHFR C677T polymorphism could be considered as a good marker of the pediatric ALL relapse risk.

Therapeutic drug monitoring and receiver operating characteristic curve prediction may reduce the development of linezolid-associated thrombocytopenia in critically ill patients.

To investigate the risk factors associated with the development of thrombocytopenia, and define the thresholds of efficacy and safety in critically ill patients who received linezolid therapy. A retrospective study was performed in critically ill patients treated with linezolid. Risk factors associated with thrombocytopenia were identified via medical records and trough levels (C(min)) measured during linezolid treatment. By establishing a logistic model, the risks were predicted by the receiver operating characteristic (ROC) curve and the thresholds of efficacy and safety were identified in the patients. Logistic analysis showed that, weight (OR = 0.906; 95% CI, 0.839-0.978; P = 0.011), baseline platelet count (OR = 0.989; 95% CI, 0.977-1.000; P = 0.049), C(min) (OR = 1.545; 95% CI, 1.203-1.983; P = 0.001), and APACHE II score (OR = 1.130; 95% CI, 1.003-1.273; P = 0.044) were significant factors for linezolid-associated thrombocytopenia. The area under the ROC curve of the combined predictor was larger based on the above factors. When the Youden index was the maximum, the best optimal cut-off point was 205.6 on the ROC curve; when C(min) ≥ 2 mg/L, the probability of bacterial eradication was more than 80%; when C(min) ≥ 6.3 mg/L, the probability of thrombocytopenia was more than 50 %. In clinical practice, when the calculating results of the combined predictor ≤205.6, the risk of the development of thrombocytopenia may be higher. Furthermore, maintenance of C(min) between 2 and 6.3 mg/L over time may be helpful in retaining appropriate efficacy and reducing the associated thrombocytopenia.

Expression of vesicular glutamate transporters in peripheral vestibular structures and vestibular nuclear complex of rat.

Glutamate transmission from vestibular end organs to central vestibular nuclear complex (VNC) plays important role in transferring sensory information about head position and movements. Three isoforms of vesicular glutamate transporters (VGLUTs) have been considered so far the most specific markers for glutamatergic neurons/cells. In this study, VGLUT1 and VGLUT2 were immunohistochemically localized to axon terminals in VNC and somata of vestibular primary afferents in association with their central and peripheral axon endings, and VGLUT1 and VGLUT3 were co-localized to hair cells of otolith maculae and cristae ampullaris. VGLUT1 and VGLUT2 defined three subsets of Scarpa's neurons (vestibular ganglionic neurons): those co-expressing VGLUT1 and VGLUT2 or expressing only VGLUT2, and those expressing neither. In addition, many neurons located in all vestibular subnuclei were observed to contain hybridized signals for VGLUT2 mRNA and a few VNC neurons, mostly scattered in medial vestibular nucleus (MVe), displayed VGLUT1 mRNA labelling. Following unilateral ganglionectomy, asymmetries of VGLUT1-immunoreactivity (ir) and VGLUT2-ir occurred between two VNCs, indicating that the VNC terminals containing VGLUT1 and/or VGLUT2 are partly of peripheral origin. The present data indicate that the constituent cells/neurons along the vestibular pathway selectively apply VGLUT isoforms to transport glutamate into synaptic vesicles for glutamate transmission.