Incidence and trends of nosocomial infection in a tertiary general hospital in China from 2018 to 2021: a retrospective observational study.

OBJECTIVE: This study aimed to investigate the current status and changing trend of nosocomial infection in a tertiary general hospital in China, to provide a reference for the prevention and control of healthcare-associated/acquired infection (HAI). PATIENTS AND METHODS: A retrospective investigation of the clinical data of HAI patients in Dongying People's Hospital in China from January 1, 2018, to December 31, 2021, was carried out. The incidence of HAI in different units and sites, distribution of pathogenic microorganisms, and antimicrobial use were investigated. RESULTS: The incidence of HAI was 0.93%. It was on the rise from 2018 to 2020 but declined in 2021. The departments with the highest rate of HAI were the Intensive Care Unit (ICU), neurosurgery department, cardiothoracic surgery department, and hematology department. HAI often occurs in the lower respiratory tract, urinary tract, and in blood. The most common pathogenic microorganisms in cases of HAI were Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus. The rate of bacterial culture delivery for therapeutic drugs has increased from year to year. CONCLUSIONS: This study shows that the incidence of HAI in the hospital is generally low. Gram-negative bacteria are still the main source of HAI. The rate of bacterial culture delivery for therapeutic use improved over the years and has gradually been standardized. It is necessary to focus on the management of HAI in the ICU, neurosurgery, cardiothoracic surgery, and hematology departments.

A Canine Surgical Model of Stroke by Minimally Invasive Occlusion of the Proximal Middle Cerebral Artery.

In this study, a model of ischemic stroke by surgical proximal middle cerebral artery (MCA) occlusion was developed on 10 beagle dogs. The advantages of this model are the transtemporal approach and a minimally invasive surgical procedure. Dogs were randomly assigned to two groups: sham-operated (proximal MCA exposure without occlusion) and experimental (permanent proximal MCA occlusion) groups. Different evaluation methods were used to assess the consequences of MCA occlusion in dogs, including neurobehavioral tests, MRI, and immunohistochemical staining. Clear signs of cerebral infarction associated with the region supplied by MCA were confirmed and the model showed good repeatability and consistency. The model can serve as an appropriate large animal model to improve the translation of stroke therapeutics research from the laboratory to the clinical practice.

Chronotype and insomnia may affect the testosterone levels with a sexual difference: a Mendelian randomization.

OBJECTIVE: To evaluate the causal effects of sleep traits (i.e., chronotype, insomnia, and sleep duration) on bioavailable testosterone (BT), sex hormone-binding globulin (SHBG), and total testosterone (TT) levels in women and men. METHODS: We performed Mendelian randomization (MR) using random-effect inverse-variance weighted (IVW) and 7 other MR analyses. Exposure data for sleep traits were obtained from the largest-to-date genome-wide association study (GWAS) from 339,926 to 1,331,010 individuals. Summary data for testosterone levels were obtained from GWAS based on the UK Biobank. RESULTS: For women, our study supported that chronotype was associated with decreased BT (IVW: ß = - 0.042, 95% CI - 0.060, - 0.023, p = 1.17E-05) and TT (IVW: - 0.053, 95% CI - 0.075, - 0.031, p = 2.30E-06). Besides, insomnia can significantly increase BT (IVW: ß = 0.025, 95% CI 0.009, 0.041, p = 0.002). These findings were significant in most sensitivity analyses. For men, statistical significance was found between chronotype and BT (ß = - 0.027, 95% CI - 0.048, - 0.005, p = 0.016), and insomnia and TT (ß = - 0.028, 95% CI - 0.049, 0.007, p = 0.009) in IVW. However, the effect estimates were not broadly consistent with other sensitivity analyses. Our study did not find support for causal effects of sleep duration on testosterone levels in both women and men. CONCLUSION: Our study reveals the sex differences in the effects of sleep traits on testosterone levels. A healthy sleep habit is vital for the maintenance of testosterone homeostasis in women. Further studies are warranted to investigate the associations between sleep traits and testosterone levels in men.

Surgical learning curve in reverse shoulder arthroplasty for proximal humerus fractures.

BACKGROUND: Fracture reverse shoulder arthroplasty (fRSA) in geriatric, complex dislocated proximal humerus fractures is becoming the standard treatment next to conservative treatment. fRSA is a multifaceted, reasonably challenging procedure of which functional outcomes and complication rates are likely to depend on the experience of the surgeon. The goal of this study was to determine whether there is a learning curve for fRSA. METHODS: All patients with a dislocated multipart proximal humerus fracture that were treated with an fRSA between 2013 and 2019 in a specialized institution were included. The functional outcomes (Constant Shoulder Score, Oxford Shoulder Score, and range of motion), complications, and operation time of fRSA were assessed with linear regression plots and cumulative summation analysis to establish whether a learning curve was present. RESULTS: In this cohort study, 50 patients were included. They had a mean age of 77.1 years and were treated with an fRSA by one trauma surgeon. Learning curves were distinguished for functional outcomes, complications, and operation time based on learning targets for daily activity and the mean complications and operation time. Results indicated that an optimal treatment is achieved after performing 20 fRSAs. CONCLUSION: The results show that functional outcomes of PHFs treated with an fRSA improve with surgical experience. Also, outcomes are getting less variable after about 20 procedures. Surgeons starting this procedure should be aware of the learning curve and, therefore, should consider guidance from an experienced surgeon to swiftly optimize functional outcomes and prevent unnecessary complications.

Serum Levels of HDL Cholesterol are Associated with Diffuse Axonal Injury in Patients with Traumatic Brain Injury.

BACKGROUND: It is well known that lipids are vital for axonal myelin repair. Diffuse axonal injury (DAI) is characterized by widespread axonal injury. The association between serum lipids and DAI is not well known. The purpose of this study was to investigate the associations of serum lipid profile variables (triglycerides, high- and low-density lipoproteins, and total cholesterol) with DAI detected by magnetic resonance imaging (MRI) and with clinical outcome for patients suffering from traumatic brain injury (TBI). METHODS: This study included 176 patients with a history of TBI who had undergone initial serum lipid measurements within 1 week and brain MRIs within 30 days. Based on MRI findings, patients were divided into negative and positive DAI groups. RESULTS: Of the 176 patients, 70 (39.8%) were assigned to DAI group and 106 (60.2%) patients to non-DAI group. Compared with the non-DAI group, patients with DAI had significantly lower levels of high-density lipoprotein cholesterol (HDL-C) in serum during the first week following TBI. Multivariate analysis identified HDL-C as an independent predictor of DAI. Patients with lower serum HDL-C levels were less likely to regain consciousness within 6 months in TBI patients with DAI lesions identified by MRI. CONCLUSIONS: Plasma levels of HDL-C may be a viable addition to biomarker panels for predicting the presence and prognosis of DAI on subsequent MRI following TBI.

[Research progression and application of Laennec capsule in liver].

The Laennec capsule of liver was first discovered and reported by French doctor Rene Theophile Hyacinthe Laennec in 1802.However, it has not received enough attention for more than 200 years since then. In recent years, with the rapid development of liver surgery represented by laparoscopic technology, and the deepening of the theory of precise liver surgery, the fine anatomical structure of liver Laennec capsule has returned to the vision of liver surgeons.Recent studies have demonstrated the presence of Laennec capsule in liver histology, covering the whole liver surface, and lining the surface of liver parenchyma around the Glisson pedicle and the main hepatic vein along the inflow and outflow channels of the liver. Based on the Laennec capsule approach, it is expected to unify the current approach of Glisson pedicle and the approach of hepatic vein, and provide a new theoretical basis for the liver surgery, and guide us in the standardization of liver surgeries.

The olfactory subgenome and specific odor recognition in forest musk deer.

Olfactory receptors (ORs) are encoded by OR genes. The OR genes in forest musk deer (Moschus berezovskii), which rely on olfaction for reproductive and social communication, are poorly understood. In this study, we analyzed the genome sequence of the forest musk deer to obtain its olfactory subgenome and compared it to other species. A total of 1378 OR-related sequences were detected in the forest musk deer genome including 864 functional genes, 366 pseudogenes and 148 partial genes. These OR genes were classified into Class I and Class II and were further classified into 18 families and 244 subfamilies through sequence identity. Comparative analyses of the OR genes' protein sequences in species from different orders (forest musk deer, human, mouse and dog) showed that 12 clusters were specific to forest musk deer. However, when compared to other Artiodactyl species (i.e. cattle, yak and pig) only two clusters were specific to forest musk deer. The odor identification potential of the OR genes in the forest musk deer was focused mainly on floral, woody, lemon, sweet and fatty odors. We also found that OR genes specific to forest musk deer were involved in the identification of spearmint and caraway. Our work is the first genome-wide analysis of OR genes in forest musk deer. These findings will assist with better understanding the relationship between behavior and olfaction in the forest musk deer and the characteristics of the olfactory subgenome in Artiodactyl mammals.

Sex Differences in Sex Hormone Profiles and Prediction of Consciousness Recovery After Severe Traumatic Brain Injury.

Objective: The clinical course of unconsciousness after traumatic brain injury (TBI) is commonly unpredictable and it remains a challenge with limited therapeutic options. The aim of this study was to evaluate the early changes in serum sex hormone levels after severe TBI (sTBI) and the use of these hormones to predict recovery from unconsciousness with regard to sex. Methods: We performed a retrospective study including patients with sTBI. A statistical of analysis of serum sex hormone levels and recovery of consciousness at 6 months was made to identify the effective prognostic indicators. Results: Fifty-five male patients gained recovery of consciousness, and 37 did not. Of the female patients, 22 out of 32 patients regained consciousness. Male patients (n = 92) with sTBI, compared with healthy subjects (n = 60), had significantly lower levels of follicular stimulating hormone (FSH), testosterone and progesterone and higher levels of prolactin. Female patients (n = 32) with sTBI, compared with controls (n = 60), had significantly lower levels of estradiol, progesterone, and testosterone and significantly higher levels of FSH and prolactin. Testosterone significantly predicted consciousness recovery in male patients. Normal or elevated testosterone levels in the serum were associated with a reduced risk of the unconscious state in male patients with sTBI. For women patients with sTBI, sex hormone levels did not contribute to the prediction of consciousness recovery. Conclusion: These findings indicate that TBI differentially affects the levels of sex-steroid hormones in men and women patients. Plasma levels of testosterone could be a good candidate blood marker to predict recovery from unconsciousness after sTBI for male patients.

Influence of Feeding Type and Nosema ceranae Infection on the Gut Microbiota of Apis cerana Workers.

The gut microbiota plays an essential role in the health of bees. To elucidate the effect of feed and Nosema ceranae infection on the gut microbiota of honey bee (Apis cerana), we used 16S rRNA sequencing to survey the gut microbiota of honey bee workers fed with sugar water or beebread and inoculated with or without N. ceranae. The gut microbiota of A. cerana is dominated by Serratia, Snodgrassella, and Lactobacillus genera. The overall gut microbiota diversity was show to be significantly differential by feeding type. N. ceranae infection significantly affects the gut microbiota only in bees fed with sugar water. Higher abundances of Lactobacillus, Gluconacetobacter, and Snodgrassella and lower abundances of Serratia were found in bees fed with beebread than in those fed with sugar water. N. ceranae infection led to a higher abundance of Snodgrassella and a lower abundance of Serratia in sugar-fed bees. Imputed bacterial Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed the significant metagenomics functional differences by feeding and N. ceranae infections. Furthermore, A. cerana workers fed with sugar water showed lower N. ceranae spore loads but higher mortality than those fed with beebread. The cumulative mortality was strongly positive correlated (rho = 0.61) with the changes of overall microbiota dissimilarities by N. ceranae infection. Both feeding types and N. ceranae infection significantly affect the gut microbiota in A. cerana workers. Beebread not only provides better nutrition but also helps establish a more stable gut microbiota and therefore protects bees in response to N. ceranae infection. IMPORTANCE The gut microbiota plays an essential role in the health of bees. Scientific evidence suggests that diet and infection can affect the gut microbiota and modulate the health of the gut; however, the interplay between those two factors and the bee gut microbiota is not well known. In this study, we used a high-throughput sequencing method to monitor the changes of gut microbiota associated with both feeding types and Nosema ceranae infection. Our results showed that the gut microbiota composition and diversity of Asian honey bee were significantly associated with both feeding types and the N. ceranae infection. More interestingly, bees fed with beebread showed higher microbiota stability and lower mortality rates than those fed with sugar water when infected by N. ceranae. Those data suggest that beebread has the potential not only to provide better nutrition but also help to establish a more stable gut microbiota to protect bees against N. ceranae infection.

Modulation of colonic hydrogen sulfide production by diet and mesalazine utilizing a novel gas-profiling technology.

Excessive hydrogen sulfide (H2S) production from gut microbial metabolism may have clinically important relevance in the pathogenesis of gut disorders, including ulcerative colitis. However, little is known regarding factors that alter its production. Using a newly-designed in vitro gas-profiling technology, the study aimed to verify real-time H2S measurement reproducibility and thereafter, assess its production following exposure to dietary factors and 5-aminosalicylate acid (5-ASA). Measurements of H2S, carbon dioxide, hydrogen and methane measurements were compared between gas-profiling systems. Homogenized slurries were prepared from freshly-passed healthy human feces. Fifty ml slurries were aliquoted into separate fermentation chambers and substrates added including 1 g highly fermentable fructo-oligosaccharides (FOS) or resistant starch Hi-Maize (RS), or minimally fermentable psyllium or sterculia, 1 g cysteine, 0.9 g sodium sulfate or 1.2 mL of 1 M 5-ASA alone or in combinations. H2S release was sampled every 5 mins over 4-h and expressed relative to unspiked controls. RS suppressed H2S production by a mean 89.0 (SEM 4.8)% and FOS by 82.2 (6.2)% compared to <35 (17)% by psyllium and sterculia (p<0.001, two-way ANOVA). Cysteine stimulated H2S production by 1557 (532)%. The addition of FOS to slurries containing cysteine significantly suppressed H2S by 90 (2)% over the addition of 5-ASA (0.3 (2)%, p<0.001). Sulfate and 5-ASA had minimal overall effects. In conclusion, the H2S-profiling technology is a reproducible tool. Production of H2S is greatly enhanced by sulfur-amino acids but not inorganic sulfate, and is effectively suppressed by readily fermentable fibers. These findings inform potential designs of dietary therapies to reduce H2S production in vivo.

In vivo functional dissection of a context-dependent role for Hif1α in pancreatic tumorigenesis.

Hypoxia-inducible factor 1α (Hif1α) is a key regulator of cellular adaptation and survival under hypoxic conditions. In pancreatic ductal adenocarcinoma (PDAC), it has been recently shown that genetic ablation of Hif1α accelerates tumour development by promoting tumour-supportive inflammation in mice, questioning its role as the key downstream target of many oncogenic signals of PDAC. Likely, Hif1α has a context-dependent role in pancreatic tumorigenesis. To further analyse this, murine PDAC cell lines with reduced Hif1α expression were generated using shRNA transfection. Cells were transplanted into wild-type mice through orthotopic or portal vein injection in order to test the in vivo function of Hif1α in two major tumour-associated biological scenarios: primary tumour growth and remote colonization/metastasis. Although Hif1α protects PDAC cells from stress-induced cell deaths in both scenarios-in line with the general function Hif1α-its depletion leads to different oncogenic consequences. Hif1α depletion results in rapid tumour growth with marked hypoxia-induced cell death, which potentially leads to a persistent tumour-sustaining inflammatory response. However, it simultaneously reduces tumour colonization and hepatic metastases by increasing the susceptibility to anoikis induced by anchorage-independent conditions. Taken together, the role of Hif1α in pancreatic tumorigenesis is context-dependent. Clinical trials of Hif1α inhibitors need to take this into account, targeting the appropriate scenario, for example palliative vs adjuvant therapy.

[Current status and influence factors of ACEI/ARB application in elderly coronary heart disease outpatients complicated with diabetes mellitus in China].

Objective: To investigate the current status and influence factors of ACEI/ARB application in elderly coronary heart disease outpatients complicated with diabetes mellitus in 21 provinces of China. Methods: In this multicenter, non-intervention and cross-sectional survey, the elderly coronary heart disease patients aged 60 years or over were recruited from 165 hospitals in 21 provinces across China from April to July 2011. Current status and influence factors of ACEI/ARB application among 1 789 cases with diabetes mellitus were investigated in the survey. Results: Totally, 1 069 patients used ACEI/ARB drugs (59.8%); proportion of ACEI (544 cases, 30.4%) drugs were the same as ARB drugs (533 cases, 29.8%) in terms of usage of drug types, and combination of the two drugs were taken by 28 cases (1.6%) at the same time. ACEI/ARB usage decreased with the increasing of age, and the rate of drug usage in male patients was slightly higher than that in female, however there was no statistical difference (both P>0.05); the rate of usage of ACEI/ARB drugs gradually decreased with increasing of coronary heart disease or diabetes duration (P<0.05); the rates of usage of ACEI/ARB drugs in hypertension, dyslipidemia, myocardial infarction, renal insufficiency patients and patients received revascularization therapy were significantly higher (all P<0.05). Multivariable logistic regression analysis showed that hypertension (OR=3.016, 95%CI: 1.376-4.887), dyslipidemia (OR=1.489, 95%CI: 1.114-2.031), revascularization (OR=2.291, 95%CI: 1.276-3.277), myocardial infarction (OR=2.561, 95%CI: 1.571-4.545), renal insufficiency (OR=1.337, 95%CI: 1.145-2.013), and insulin treatment (OR=1.584, 95%CI: 1.084-2.511) were positively correlated with ACEI/ARB usage (P<0.05); and coronary heart disease duration was negatively correlated with ACEI/ARB drugs usage (duration 5-10 years: OR=0.621, 95%CI: 0.416-0.823; duration >10 years, OR=0.664, 95%CI: 0.471-0.840). Conclusions: The rate of usage of ACEI/ARB drugs in elderly coronary heart disease outpatients complicated with diabetes mellitus is still low, however, patients with hypertension, dyslipidemia, myocardial infarction, renal insufficiency and patients received revascularization therapy and insulin treatment are more likely to use ACEI/ARB drugs.

[Effects of body mass index on blood pressure control rate in elderly coronary heart disease outpatients with hypertension].

Objective: To explore the influences of body mass index (BMI) on blood pressure control rate in elderly coronary heart disease (CHD) outpatients with hypertension. Methods: In this multicenter, non-intervention and cross-sectional survey, the elderly coronary heart disease patients with hypertension aged 60 years or over were recruited from 165 hospitals in 21 provinces or cities across China from April to July 2011, and 5 140 cases of elderly CHD patients with hypertension were finally included into the study. The cases were divided into low BMI group (n=130 cases), normal body mass index (BMI) group (n=1 390 cases), overweight (n=2 418 cases), obesity group (n=662 cases) according to the different levels of BMI. Clinical data and blood pressure control rate were compared among the groups, and relationships of different BMI levels with blood pressure control rate were analyzed by the binary classification unconditioned Logistic regression equation. Results: There was a statistically significant difference in blood pressure control rate of general population, men and women patients among low BMI group, normal BMI group, overweight and obesity group (χ2=66.346, 58.995, 26.044, respectively, P<0.001), blood pressure failure rate in obesity group (73.7%) was higher than that in overweight group (65.8%) and normal BMI group (57.5%) (P<0.05), and overweight group was also higher than normal BMI group (P<0.05); blood pressure failure rate in obesity men was higher than that in normal BMI and low BMI group (P<0.05), overweight group was higher than normal BMI group (P<0.05); blood pressure failure rate in obesity women was higher than that in normal BMI and low BMI group (P<0.05). There was a statistically significant difference in blood pressure control rate of different age groups (60-70, 71-80, >80 years old) among low BMI group, normal BMI group, overweight and obesity group (χ2=37.729, 20.007, 15.538, respectively, P<0.001). Blood pressure failure rate in obesity patients with 60-70 years old was higher than that in overweight and normal BMI group (P<0.05), blood pressure failure rates in obesity and overweight patients with 71-80 and > 80 years old were also higher than those in normal BMI group (P<0.05). Multivariable Logistic regression equation showed that overweight in overall population (OR=1.313, 95%CI 1.170-1.731, P<0.05), obesity (OR=2.295, 95%CI 2.295-1.496, P<0.05) were independent risk factors for blood pressure failure rate, in addition, obesity was also risk factor for blood pressure failure rate in men and women patients. Conclusions: Increased BMI has an adverse effect on blood pressure control rate in elderly CHD outpatients with hypertension, and may be the independent risk for blood pressure failure rate in those patients. Much more attention should be given to control BMI level so as to increase the blood pressure success rate and improve the patients' prognosis.

Application of molecular imaging combined with genetic screening in diagnosing MELAS, diabetes and recurrent pancreatitis.

AIM: We report molecular imaging combined with gene diagnosis in a family with 7 members who carried an A3243G mutation in mitochondrial tRNA and p.Thr 137 Met in cationic trypsinogen (PRSS1) gene presented with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), diabetes, and recurrent pancreatitis. MATERIAL AND METHODS: DNA sequencing was used to detect and validate mitochondrial DNA and PRSS1. We also verified that mitochondrial heterozygous mutations and c.410 C>T mutation causing p.Thr 137 Met could be detected in oral epithelial cells or in urine sediment cells. In addition, molecular imaging was carried out in the affected family members. RESULTS: In this pedigree, MELAS syndrome accompanied by pancreatitis was an important clinical feature, followed by diabetes. Heteroplasmy of the mtDNA A3243G and c.410 C>T mutation of PRSS1 was found in all tissue samples of these patients, but no mutations were found in 520 normal control and normal individuals of the family. However, based on molecular imaging observations, patients with relatively higher lactate/pyruvate levels had more typical and more severe symptoms, particularly those of pancreatic disease (diabetes or pancreatitis). CONCLUSIONS: MELAS syndrome may be associated with pancreatitis. For the diagnosis, it is more reasonable to perform molecular imaging combined with gene diagnosis.

Residues of carbosulfan and its metabolites carbofuran and 3-hydroxy carbofuran in rice field ecosystem in China.

The fate of carbosulfan (seed treatment dry powder) was studied in rice field ecosystem, and a simple and reliable analytical method was developed for determination of carbosulfan, carbofuran, and 3-hydroxyl carbofuran in brown rice, rice straw, paddy water, and soil. The target compounds were extracted using acetonitrile or dichloromethane, cleaned up on acidic alumina or florisil solid phase extraction (SPE) cartridge, and analyzed by gas chromatography. The average recoveries of carbosulfan, carbofuran and 3-hydroxy carbofuran in brown rice, rice straw, paddy water, and soil ranged from 72.71% to 105.07%, with relative standard deviations of 2.00-8.80%. The limits of quantitation (LOQs) of carbosulfan, carbofuran and 3-hydroxy carbofuran in the samples (brown rice, rice straw, paddy water and soil) were 0.011, 0.0091, 0.014, 0.010 mg kg(-1), 0.016, 0.019, 0.025, 0.013 mg kg(-1), and 0.031, 0.039, 0.035, 0.036 mg kg(-1), respectively. The trials results showed that the half-lives of carbosulfan, carbofuran and 3-hydroxy carbofuran in rice straw were 4.0, 2.6 days, 3.9, 6.0 days, and 5.8, 7.0 days in Zhejiang and Hunan, respectively. Carbosulfan, carbofuran and 3-hydroxy carbofuran were detected in soils. Carbosulfan and 3-hydroxy carbofuran were almost undetectable in paddy water. Carbofuran was detected in paddy water. The final residues of carbosulfan, carbofuran and 3-hydroxy carbofuran in brown rice were lower than 0.05 mg kg(-1), which were lower than 0.5 mg kg(-1) (MRL of carbosulfan) or 0.1 mg kg(-1) (MRL of carbofuran). Therefore, a dosage of 420 g active ingredient per 100 kg seed was recommended, which could be considered as safe to human beings and animals. These would contribute to provide the scientific basis of using this insecticide.

Oxidative stress-induced overexpression of miR-25: the mechanism underlying the degeneration of melanocytes in vitiligo.

Oxidative stress has a critical role in the pathogenesis of vitiligo. However, the specific molecular mechanism involved in oxidative stress-induced melanocyte death is not well characterized. Given the powerful role of microRNAs (miRNAs) in the regulation of cell survival as well as the fact that the generation of miRNAs can be affected by oxidative stress, we hypothesized that miRNAs may participate in vitiligo pathogenesis by modulating the expression of vital genes in melanocytes. In the present study, we initially found that miR-25 was increased in both serum and lesion samples from vitiligo patients, and its serum level was correlated with the activity of vitiligo. Moreover, restoration of miR-25 promoted the H2O2-induced melanocyte destruction and led to the dysfunction of melanocytes. Further experiments proved that MITF, a master regulator in melanocyte survival and function, accounted for the miR-25-caused damaging impact on melanocytes. Notably, other than the direct role on melanocytes, we observed that miR-25 inhibited the production and secretion of SCF and bFGF from keratinocytes, thus impairing their paracrine protective effect on the survival of melanocytes under oxidative stress. At last, we verified that oxidative stress could induce the overexpression of miR-25 in both melanocytes and keratinocytes possibly by demethylating the promoter region of miR-25. Taken together, our study demonstrates that oxidative stress-induced overexpression of miR-25 in vitiligo has a crucial role in promoting the degeneration of melanocytes by not only suppressing MITF in melanocytes but also impairing the paracrine protective effect of keratinocytes. Therefore, it is worthy to investigate the possibility of miR-25 as a potential drug target for anti-oxidative therapy in vitiligo.

Prevalence of hepatitis A viral RNA and antibodies among Chinese blood donors.

Like other developing countries, China was reported to have a relatively high seroprevalence of anti-hepatitis A antibodies (anti-HAV). However, no studies have evaluated the prevalence of anti-HAV and HAV RNA among voluntary blood donors with or without elevated serum alanine transaminase (ALT) levels. Anti-HAV antibodies were detected using an enzyme-linked immunosorbent assay, and reverse transcription quantitative polymerase chain reaction was carried out for detection of HAV RNA. In the current study, we analyzed a total of 450 serum samples with elevated ALT levels (≥40 U/L) and 278 serum samples with non-elevated ALT levels. Seroprevalence rates of anti-HAV were 51.6% in donors with elevated ALT and 41.4% in donors with non-elevated ALT; however, none of the samples was positive for HAV RNA. The results of our study showed lower seroprevalence rates of anti-HAV in blood donors (irrespective of ALT levels) than those in published data on Chinese populations. Although donors with elevated ALT had statistically higher prevalence rates of anti- HAV than did those with non-elevated ALT, none of the serum samples had detectable levels of the active virus. In conclusion, our results demonstrate that the transmission of hepatitis A by blood transfusion will occur rarely.

MiR-204 regulates HMGA2 expression and inhibits cell proliferation in human thyroid cancer.

BACKGROUND: Analysis using publicly available algorithms has found that high mobility group AT-hook 2 (HMGA2), a key transcriptional regulatory factor, is a potential target of microRNA-204 (miR-204). Some studies have shown that both miR-204 and HMGA2 are associated with cancer development. OBJECTIVE: We examined the possible relationship between miR-204 and HMGA2 in the development of thyroid cancer. METHODS: We assessed miR-204 expression in thyroid cancer specimens and cell lines using real-time polymerase chain reaction (PCR). Luciferase reporter assay was used to confirm the target associations. The effect of miR-204 on cell proliferation was confirmed with tetrazolium and colony formation assays. Gene and protein expression were examined using real-time PCR and western blotting, respectively. RESULTS: MiR-204 was downregulated in the thyroid cancer specimens and cell lines, and targeted the 3^\prime untranslated region of HMGA2 directly. MiR-204 overexpression decreased cyclin D1 and Ki67 expression and increased P21 expression, which subsequently inhibited thyroid cancer cell proliferation. CONCLUSIONS: Our findings suggest that miR-204 plays a protective role by inhibiting thyroid cancer cell proliferation, and may identify new targets for anti-cancer treatment.

miR-196a-2 rs11614913 polymorphism is associated with vitiligo by affecting heterodimeric molecular complexes of Tyr and Tyrp1.

Tyrosinase and tyrosinase-related protein 1 (Tyr-Tyrp1) complex plays a critical role in the synthesis of melanin intermediates, which involves the production of reactive oxygen species (ROS) and contributes to the development of vitiligo. Based on our previous observation that rs11614913 single nucleotide polymorphism (SNP) in miR-196a-2 could affect the risk of vitiligo by influencing Tyrp1, we hypothesized that the same SNP could also regulate the level of Tyr in vitiligo. The aim of this study was to evaluate the potential association between rs11614913 SNP in miR-196a-2 and serum Tyr level in vitiligo and the regulatory role of miR-196a-2 in the expression of Tyr in melanocytes. The serum Tyr level was detected in 116 patients with vitiligo and 116 controls by ELISA plate assay. The expression level of Tyrp1 and Tyr in PIG1(normal melanocyte cell lines) cells was analyzed by western blotting. The ROS level and apoptosis rate in PIG1 cells transfected with si-Tyr or control siRNA were tested by flow cytometry. The results show that the individuals with TT+TC genotypes in miR-196a-2 and higher Tyr level in serum had an increased risk of vitiligo compared with those who had the CC genotype and lower Tyr level (P < 0.001). Furthermore, the rs11614913 C allele in miR-196a-2 enhanced its inhibitory regulation on the expression of Tyr, the down-regulation of which in melanocytes successfully reduced the intracellular ROS levels and the apoptosis rate. In conclusion, our findings suggest that miR-196a-2 polymorphisms can regulate the Tyr levels, which influences the susceptibility of vitiligo.