mRNA accessibility within mRNPs as a determinant of gene expression.

Gene expression is a complex process requiring many control mechanisms to achieve a desired phenotype. DNA accessibility within chromatin is well established as an important determinant of gene expression. By contrast, while mRNA also associates with a complement of proteins, the exact nature of messenger ribonucleoprotein (mRNP) packaging and its functional relevance is not as clear. Recent reports indicate that exon junction complex (EJC)-mediated mRNP packaging renders exon junction-proximal regions inaccessible for m6A methylation, and that EJCs reside within the inaccessible interior of globular transcription and export (TREX) complex-associated nuclear mRNPs. We propose that 'mRNA accessibility' within mRNPs is an important determinant of gene expression that may modulate the specificity of a broad array of regulatory processes including but not limited to m6A methylation.

Differential m6A, m6Am, and m1A Demethylation Mediated by FTO in the Cell Nucleus and Cytoplasm.

FTO, the first RNA demethylase discovered, mediates the demethylation of internal N6-methyladenosine (m6A) and N6, 2-O-dimethyladenosine (m6Am) at the +1 position from the 5' cap in mRNA. Here we demonstrate that the cellular distribution of FTO is distinct among different cell lines, affecting the access of FTO to different RNA substrates. We find that FTO binds multiple RNA species, including mRNA, snRNA, and tRNA, and can demethylate internal m6A and cap m6Am in mRNA, internal m6A in U6 RNA, internal and cap m6Am in snRNAs, and N1-methyladenosine (m1A) in tRNA. FTO-mediated demethylation has a greater effect on the transcript levels of mRNAs possessing internal m6A than the ones with cap m6Am in the tested cells. We also show that FTO can directly repress translation by catalyzing m1A tRNA demethylation. Collectively, FTO-mediated RNA demethylation occurs to m6A and m6Am in mRNA and snRNA as well as m1A in tRNA.

m6 A RNA methylation: from mechanisms to therapeutic potential.

RNA carries a diverse array of chemical modifications that play important roles in the regulation of gene expression. N6 -methyladenosine (m6 A), installed onto mRNA by the METTL3/METTL14 methyltransferase complex, is the most prevalent mRNA modification. m6 A methylation regulates gene expression by influencing numerous aspects of mRNA metabolism, including pre-mRNA processing, nuclear export, decay, and translation. The importance of m6 A methylation as a mode of post-transcriptional gene expression regulation is evident in the crucial roles m6 A-mediated gene regulation plays in numerous physiological and pathophysiological processes. Here, we review current knowledge on the mechanisms by which m6 A exerts its functions and discuss recent advances that underscore the multifaceted role of m6 A in the regulation of gene expression. We highlight advances in our understanding of the regulation of m6 A deposition on mRNA and its context-dependent effects on mRNA decay and translation, the role of m6 A methylation of non-coding chromosomal-associated RNA species in regulating transcription, and the activities of the RNA demethylase FTO on diverse substrates. We also discuss emerging evidence for the therapeutic potential of targeting m6 A regulators in disease.

Determinants of Histone H3K4 Methylation Patterns.

Various factors differentially recognize trimethylated histone H3 lysine 4 (H3K4me3) near promoters, H3K4me2 just downstream, and promoter-distal H3K4me1 to modulate gene expression. This methylation "gradient" is thought to result from preferential binding of the H3K4 methyltransferase Set1/complex associated with Set1 (COMPASS) to promoter-proximal RNA polymerase II. However, other studies have suggested that location-specific cues allosterically activate Set1. Chromatin immunoprecipitation sequencing (ChIP-seq) experiments show that H3K4 methylation patterns on active genes are not universal or fixed and change in response to both transcription elongation rate and frequency as well as reduced COMPASS activity. Fusing Set1 to RNA polymerase II results in H3K4me2 throughout transcribed regions and similarly extended H3K4me3 on highly transcribed genes. Tethered Set1 still requires histone H2B ubiquitylation for activity. These results show that higher-level methylations reflect not only Set1/COMPASS recruitment but also multiple rounds of transcription. This model provides a simple explanation for non-canonical methylation patterns at some loci or in certain COMPASS mutants.

The Emerging Role of Gut Microbiota in Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is a progressive, degenerative retinal disease that is a leading cause of blindness globally. Although multiple risk factors have been identified regarding disease incidence and progression, including smoking, genetics, and diet, the understanding of AMD pathogenesis remains unclear. As such, primary prevention is lacking, and current treatments have limited efficacy. More recently, the gut microbiome has emerged as an influential player in various ocular pathologies. As mediators of metabolism and immune regulation, perturbations in gut microbiota may impart significant effects distally on the neuroretina and its adjacent tissues, termed the gut-retina axis. In this review, key studies over the past several decades are summarized, both in humans and in animal models, which shed insight on the relationships between the gut microbiome and retinal biology and their implications for AMD. The literature linking gut dysbiosis with AMD is examined, along with preclinical animal models and techniques apt for studying the role of gut microbiota in AMD pathogenesis, which include interactions with systemic inflammation, immune regulation, chorioretinal gene expression, and diet. As understanding of the gut-retina axis continues to advance, so too will the possibility for more accessible and effective prevention and therapy of this vision-threatening condition.

[Correlation analysis between Pirani score and talo-navicular angle,calcaneo-cuboid angle and tibio-calcaneall angle of infant clubfoot under ultrasound].

Objective: To explore the evaluation effect of ultrasonography and Pirani score on tarsal deformity, treatment effect and pseudo-correction of congenital clubfoot in infants and young children, and the correlation between the two methods. Methods: This is a retrospective case series study. The clinical data of 26 children (40 feet) with congenital clubfoot who were evaluated by ultrasonography in the Third Affiliated Hospital of Zhengzhou University from January 2020 to January 2023 were retrospectively collected. There were 16 males and 10 females. The age at the first ultrasound examination was (M(IQR)) 9.0 (18.0) days (range: 1 to 46 days). All patients were treated with Ponseti method by the same physician. The Pirani scores before and after treatment and at the last examination, and the talonavicular angle, calcaneocuboid angle and tibiocalcaneal angle measured by ultrasound were collected, and the treatment and follow-up were recorded. Paired sample t test, repeated measures analysis of variance or Kruskal-Wallis test were used for data comparison, and Spearman correlation analysis was used for correlation analysis. The receiver operating characteristic curve was used to calculate the efficacy of ultrasound in evaluating different Pirani scores. Results: The number of plaster fixation in 26 children was 4.0 (1.0) times (range: 2 to 8 times). The medial talonavicular angle and posterior tibiocalcaneal angle were significantly improved after treatment and at the last follow-up compared with those before treatment, and the differences were statistically significant (all P<0.01). There was no difference in lateral calcaneocuboid angle before and after treatment and at the last follow-up (F=1.971, P>0.05). Pseudo-correction occurred in 2 cases (2 feet) during the treatment, with an incidence of 5%. Correlation analysis showed that there was a moderate positive correlation between talonavicular angle and Pirani midfoot score (r=0.480, P<0.01). There was no correlation between calcaneocuboid angle and Pirani midfoot score (r=0.114, P=0.105). There was a moderate negative correlation between tibial heel angle and Pirani hindfoot score (r=-0.566, P<0.01). The cut-off point of Pirani midfoot score of 1.5 was 38.78°, the sensitivity was 0.90, the specificity was 0.56, and the area under the curve was 0.75. The cut-off value of angle was 27.51 °, the sensitivity was 0.16, the specificity was 0.92, and the area under the curve was 0.44.The cut-off points of Pirani midfoot score of 3.0 were 45.08°and 9.96°, the sensitivity was 0.94 and 0.91, the specificity was 0.37 and 0.42, and the area under the curve was 0.59 and 0.62, respectively. The cut-off values of Pirani hindfoot score of 2.0 and 3.0 were 167.46° and 160.15°, respectively. The sensitivity was 0.75 and 0.67, the specificity was 0.81 and 0.83, and the area under the curve was 0.78 and 0.71, respectively. Conclusion: Ultrasound can complement with Pirani score, visually and dynamically observe the morphology and position changes of talonavicular joint, calcaneocuboid joint and tibiotalocalcaneal joint, monitor the recovery and pseudo-correction of tarsal bones, and better evaluate the therapeutic effect.

[Mechanisms by which Mettl3 regulates pericyte-myofibroblast transdifferentiation through PI3K/AKT signaling pathway].

Objective: To investigate the role and underlying mechanisms of methyltransferase (Mettl) 3 in the process of angiotensin Ⅱ (Ang Ⅱ)-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis. Methods: C57BL/6J mice were used, in cell experiments, mouse renal pericytes were isolated and cultured using magnetic bead sorting. These pericytes were then induced to transdifferentiate into myofibroblasts with 1×106 mmol/L Ang Ⅱ, which was the Ang Ⅱ group, while pericytes cultured in normal conditions served as the control group. Successful transdifferentiation was verified by immunofluorescence staining, Western blotting, and real-time reverse transcription PCR (RT-qPCR) for α-smooth muscle actin (α-SMA). The levels of m6A modifications and related enzymes (Mettl3, Mettl14), Wilms tumor 1-associated protein (WTAP), fat mass and obesity protein (FTO), ALKBH5, YTHDF1, YTHDF2, YTHDC1, YTHDC2, YTHDC3 were assessed by Dot blot, RT-qPCR and Western blot. Mettl3 expression was inhibited in cells using lentivirus-mediated Mettl3-shRNA transfection, creating sh-Mettl3 and Ang Ⅱ+sh-Mettl3 groups, while lentivirus empty vector transfection served as the negative control (Ang Ⅱ+sh-NC group). The impact of Ang Ⅱ on pericyte transdifferentiation was observed, and the expression of downstream phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway proteins, including PI3K, AKT, phosphorylated AKT at serine 473 (p-AKT (S473)), and phosphorylated AKT at threonine 308 (p-AKT (T308)), were examined. PI3K gene transcription was inhibited by co-culturing cells with actinomycin D, and the half-life of PI3K mRNA was calculated by measuring residual PI3K mRNA expression over different co-culture time. The reversibility of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was assessed by adding the AKT activator SC79 to the Ang Ⅱ+sh-Mettl3 group. In animal experiments, mice were divided into these groups: sham group (administered 0.9% sterile saline), Ang Ⅱ group (infused with Ang Ⅱ solution), sh-Mettl3 group (injected with Mettl3 shRNA lentivirus solution), Ang Ⅱ+sh-Mettl3 group (infused with Ang Ⅱ solution and injected with Mettl3 shRNA lentivirus solution), and Ang Ⅱ+sh-Mettl3+SC79 group (administered Ang Ⅱ solution and Mettl3 shRNA lentivirus, with an additional injection of SC79). Each group consisted of six subject mice. Blood pressure was measured using the tail-cuff method before and after surgery, and serum creatinine, urea, and urinary albumin levels were determined 4 weeks post-surgery. Kidney tissues were collected at 28 days and stained using hematoxylin-eosin (HE) and Masson's trichrome to assess the extent of renal fibrosis. Results: Primary renal pericytes were successfully obtained by magnetic bead sorting, and intervened with 1×106 mmol/L Ang Ⅱ for 48 hours to induce pericyte-to-myofibroblast transdifferentiation. Dot blot results indicated higher m6A modification levels in the Ang Ⅱ group compared to the control group (P<0.05). RT-qPCR and Western blot results showed upregulation of Mettl3 mRNA and protein levels in the Ang Ⅱ group compared to the control group (both P<0.05). In the Ang Ⅱ+sh-Mettl3 group, Mettl3 protein expression was lower than that in the Ang Ⅱ group, with reduced expression levels of α-SMA, vimentin, desmin, fibroblast agonist protein (FAPa) and type Ⅰ collagen (all P<0.05). Compared to the control group, PI3K mRNA expression level was elevated in the Ang Ⅱ group, along with increased p-AKT (S473) and p-AKT (T308) expressions. In the Ang Ⅱ+sh-Mettl3 group, PI3K mRNA expression and p-AKT (S473) and p-AKT (T308) levels were decreased (all P<0.05). The half-life of PI3K mRNA was shorter in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ+sh-NC group (2.34 h vs. 3.42 h). The ameliorative effect of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was reversible by SC79. Animal experiments showed higher blood pressure, serum creatinine, urea, and 24-hour urinary protein levels, and a larger fibrosis area in the Ang Ⅱ group compared to the sham group (all P<0.05). The fibrosis area was smaller in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ group (P<0.05), but increased again upon addition of SC79. Conclusion: Mettl3-mediated RNA m6A epigenetic regulation is involved in Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis, potentially by affecting PI3K stability and regulating the PI3K/AKT signaling pathway.

[Study on the risk factors of coal workers' pneumoconiosis and the mechanism of pyroptosis in peripheral blood].

Objective: To explore the risk factors of coal workers' pneumoconiosis, reveal the molecular mechanism of pyroptosis in peripheral blood of coal workers' pneumoconiosis patients, and provide new strategies and potential diagnostic biomarkers for the treatment of the disease. Methods: From January 1, 2020 to December 31, 2022, workers with suspected occupational diseases who were diagnosed with coal workers' pneumoconiosis in the Third People's Hospital of Xinjiang Uygur Autonomous Region were included in the study, including 77 patients with coal workers' pneumoconiosis stage Ⅰ, 10 patients with stage Ⅱ, 6 patients with stage Ⅲ, and 49 workers with dust-free lung disease as the control group. General information of the subjects was collected, blood samples were collected for routine blood and blood biochemical results, and plasma levels of interleukin (IL) -1ß and IL-18 were measured. Combined with the results of clinical examination, multi-factor ordered logistic regression analysis was carried out to evaluate the influencing factors of coal workers' pneumoconiosis. At the same time, the expression of pyroptosis related proteins in blood cells was detected to reveal the molecular mechanism of coal workers' pneumoconiosis. Results: All 142 subjects were male, with an average age of (51.65±6.31) years old and an average working age of (15.94±9.38) years. There were significant differences in smoking age (F=4.95, P=0.003) and lunch break distribution (H=8.84, P=0.031) among all groups. The hemoglobin content of stage Ⅰ patients was higher than that of stage Ⅱ patients, and the neutrophil percentage of stage Ⅲ patients was higher than that of the other 3 groups (P<0.05). The levels of total bilirubin and indirect bilirubin in stage Ⅰ patients were higher than those in control group, while the erythrocyte sedimentation rate in stage Ⅱ patients was higher than that in the other 3 groups (P<0.05). The levels of IL-18 and IL-1ß in stage Ⅲ of coal workers' pneumoconiosis were higher than those in the other 3 groups (P<0.05). Multiple logistic regression analysis showed that smoking age (OR=1.03, 95%CI: 1.00-1.06) and IL-1ß level (OR=4.61, 95%CI: 1.59-13.32) were independent risk factors for coal workers' pneumoconiosis (P<0.05). Compared with the control group, the expression levels of nucleotide-binding of oligomeric domain-like receptor protein 3 (NLRP3), Caspase-1, GSDMD, Caspase-4 and other proteins in stage Ⅲ of coal workers' pneumoconiosis were significantly increased (P<0.05) . Conclusion: Smoking age is a risk factor for coal workers' pneumoconiosis, IL-1ß may be a potential biomarker for the diagnosis of coal workers' pneumoconiosis, and pyroptosis may play a role in the development of peripheral inflammation of coal workers' pneumoconiosis.

Durvalumab with or without tremelimumab versus the EXTREME regimen as first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck: KESTREL, a randomized, open-label, phase III study.

BACKGROUND: Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have a poor prognosis. The phase III KESTREL study evaluated the efficacy of durvalumab [programmed death-ligand 1 (PD-L1) antibody] with or without tremelimumab [cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody], versus the EXTREME regimen in patients with R/M HNSCC. PATIENTS AND METHODS: Patients with HNSCC who had not received prior systemic treatment for R/M disease were randomized (2 : 1 : 1) to receive durvalumab 1500 mg every 4 weeks (Q4W) plus tremelimumab 75 mg Q4W (up to four doses), durvalumab monotherapy 1500 mg Q4W, or the EXTREME regimen (platinum, 5-fluorouracil, and cetuximab) until disease progression. Durvalumab efficacy, with or without tremelimumab, versus the EXTREME regimen in patients with PD-L1-high tumors and in all randomized patients was assessed. Safety was also assessed. RESULTS: Durvalumab and durvalumab plus tremelimumab were not superior to EXTREME for overall survival (OS) in patients with PD-L1-high expression [median, 10.9 and 11.2 versus 10.9 months, respectively; hazard ratio (HR) = 0.96; 95% confidence interval (CI) 0.69-1.32; P = 0.787 and HR = 1.05; 95% CI 0.80-1.39, respectively]. Durvalumab and durvalumab plus tremelimumab prolonged duration of response versus EXTREME (49.3% and 48.1% versus 9.8% of patients remaining in response at 12 months), correlating with long-term OS for responding patients; however, median progression-free survival was longer with EXTREME (2.8 and 2.8 versus 5.4 months). Exploratory analyses suggested that subsequent immunotherapy use by 24.3% of patients in the EXTREME regimen arm contributed to the similar OS outcomes between arms. Grade 3/4 treatment-related adverse events (TRAEs) for durvalumab, durvalumab plus tremelimumab, and EXTREME were 8.9%, 19.1%, and 53.1%, respectively. CONCLUSIONS: In patients with PD-L1-high expression, OS was comparable between durvalumab and the EXTREME regimen. Durvalumab alone, and with tremelimumab, demonstrated durable responses and reduced TRAEs versus the EXTREME regimen in R/M HNSCC.

Ultrasound-guided core-needle biopsy for peripheral pulmonary lesions: a systematic review and meta-analysis.

AIM: To evaluate the diagnostic value and safety of ultrasound-guided core-needle biopsy for peripheral pulmonary lesions (PPLs). MATERIALS AND METHODS: PubMed, EMBASE, and the Cochrane Library for relevant were searched for studies published up to June 2022. The diagnostic accuracy of US-guided percutaneous transthoracic needle biopsy (PTNB) for the diagnosis of PPLs was evaluated using pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive and negative likelihood ratios (PLR and NLR), and the area under the summary receiver operating characteristic curves value (SROC). RESULTS: The search included 12 original studies (3,830 procedures). For US-guided PTNB, the pooled sensitivity and specificity for the diagnosis of PPLs were 0.93 (95% confidence interval [CI]: 0.91-0.94) and 0.99 (95% CI: 0.96-1.00), respectively. The pooled estimates of the PLR, NLR, and DOR were 134.88 (95% CI: 24.88-731.74), 0.07 (95% CI: 0.06-0.09), and 1,814.95 (95% CI: 333.62-9,873.76), respectively. The area under the SROC curve was 0.95 (95% CI: 0.93-0.97). The overall complication rate was 3.6% (136 of 3,830), including self-limited haemoptysis and asymptomatic pneumothorax, and only six cases of pneumothorax requiring chest tube drainage and one case of severe bleeding were reported. CONCLUSIONS: US-guided core-needle biopsy is an excellent diagnostic tool for PPLs, with high accuracy and excellent technical performance and safety.

[Value of radiomics models based on MRI diffusion weighted imaging and apparent diffusion coefficient in differentiating benign and malignant thyroid nodules].

Objective: To investigate the value of radiomics models based on magnetic resonance imaging (MRI) diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps in distinguishing benign and malignant thyroid nodules. Methods: A cross-sectional study. Clinical data of 148 thyroid nodules (50 benign, 98 malignant) from 140 patients who underwent thyroid MRI examination in Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences between January 2019 and December 2022 were retrospectively analyzed. The nodules were used as the study units, and a leave-one-out method was used to randomly divide the nodules into a training set and a test set at a 7∶3 ratio. Region of interest was segmented and radiomics features were extracted from the DWI and ADC images. In the training set, feature selection was performed using inter-observer agreement analysis, U-test, least absolute shrinkage and selection operator algorithm, and correlation analysis. Four classifiers, including support vector machine (SVM), random forest (RF), k-nearest neighbors (KNN) and logistic regression (LR) were used to build models with the selected features, including the DWI models, ADC models, and combined models. The models were independently tested in the test set. The performance of the radiomics models in distinguishing benign and malignant thyroid nodules was evaluated using the receiver operating characteristic (ROC) curve, with pathological results as the gold standard. Results: Of the 140 patients, there were 40 males and 100 females, with a mean age of (38.4±12.2) years. After feature selection, 11 DWI features and 11 ADC features were used to build the models. In the training set, the AUC values of the combined models were higher than those of the corresponding DWI and ADC models. In the test set, the SVM combined model showed the best predictive performance, with an AUC of 0.873 (95%CI:0.740-0.954), accuracy of 75.6%, sensitivity of 46.7%, specificity of 90.0%, positive predictive value (PPV) of 70.0% and negative predictive value (NPV) of 77.1%, while the RF combined model had an AUC of 0.836 (95%CI:0.695-0.929), accuracy of 77.8%, sensitivity of 40.0%, specificity of 96.7%, PPV of 85.7% and NPV of 76.3%, the KNN combined model had an AUC of 0.832 (95%CI:0.691-0.927), accuracy of 77.8%, sensitivity of 33.3%, specificity of 100%, PPV of 100% and NPV of 75.0%, the LR combined model had an AUC of 0.813 (95%CI:0.669-0.914), accuracy of 77.8%, sensitivity of 60.0%, specificity of 86.7%, PPV of 69.2% and NPV of 81.3%. Conclusions: Radiomics models based on DWI and ADC image features can effectively distinguish benign and malignant thyroid nodules. The SVM combined model had the best prediction performance.

[Effect of hemoperfusion on protein energy wasting and long-term prognosis in patients on maintenance hemodialysis].

Objective: To explore the effect of hemoperfusion (HP) combined with hemodialysis (HD) (HD+HP) on protein energy wasting (PEW) and long-term prognosis in patients on maintenance HD (MHD). Methods: A prospective multicenter cohort study was conducted. Adult MHD patients who completed PEW assessment and underwent regular dialysis between July 2015 and July 2021 at 23 hemodialysis centers in Guizhou Province were selected. Demographic characteristics, physical indicators, laboratory indicators, 3-day diet diary and HP treatment data of the subjects were collected. The patients were divided into different groups according to the presence or absence of HP, the frequency of HP treatment and the type of cartridge, and then relevant indicators were compared. Multivariate logistic regression model and Cox proportional regression model were used to analyze the influence of HP treatment on PEW risk in MHD patients. Meanwhile, Kaplan-Meier method was used to plot the survival curve. Results: A total of 4 623 MHD patients (2 789 males and 1 834 females) aged (53.7±15.9) years were included in the study, with a median dialysis age of 64.3 (44.3, 92.3) months. There were 3 429 (74.2%) MHD patients treated with HD+HP, and 1 194 patients (25.8%) were not treated with HP. According to the 2008 diagnostic criteria of the International Society for Renal Nutrition and Metabolism (ISRNM), the incidence of PEW was 26.0% (1 204/4 623). Multivariate logistic regression analysis showed that female (OR=2.48, 95%CI: 1.55-3.95, P<0.001), diabetes (OR=1.75, 95%CI: 1.08-2.83, P=0.024) and high-sensitivity C-reactive protein (hs-CRP) (OR=1.02, 95%CI: 1.01-1.03, P=0.003) were risk factors for PEW, while treatment with HD+HP (OR=0.51, 95%CI: 0.31-0.87, P=0.012) and elevated triglyceride levels (OR=0.62, 95%CI: 0.48-0.80, P<0.001) were protective factors. Cox hazard ratio regression showed that among different HP treatment frequencies and cartridge types, 2 times/month (HR=0.40, 95%CI: 0.17-0.95, P=0.037), 3 times/month (HR=0.44, 95%CI: 0.23-0.85, P=0.014), 4 times/month (HR=0.54, 95%CI: 0.34-0.85, P=0.008), HA130 (HR=0.57, 95%CI: 0.36-0.89, P=0.014) and HA230 (HR=0.30, 95%CI: 0.15-0.63, P=0.001) had protective effects on the occurrence of PEW in MHD patients. The all-cause mortality rate was 11.3% (521/4 623) at 33 (24, 48) months of follow-up. Kaplan-Meier analysis showed that patients undergoing 4 times/month HP treatment (χ2=36.78, P<0.001) and using HA230 (χ2=9.46, P=0.002) had the highest survival rate. Conclusion: Treatment with HD+HP is a protective factor for PEW in patients with MHD, and 4 times/month HP treatment or HA230 significantly reduces the risk of PEW and all-cause mortality in patients with MHD.

[Analysis on health status and influencing factors of 1353 mercury workers in Xinjiang].

Objective: To investigate the health status of workers exposed to occupational mercury, and to provide the theoretical basis for formulating reasonable health monitoring and targeted protection measures. Methods: In November 2021, 1353 mercury-exposed workers who underwent occupational health examination in a hospital in Xinjiang Uygur Autonomous Region from 2018 to 2021 were collected as research subjects. By analyzing their blood pressure, electrocardiogram, blood routine, liver function and urine ß2-microglobulin and urinary mercury in different gender, age, length of service, industry and enterprise scale, and the health status. And the influencing factors of urinary mercury were evaluated. Results: Among 1353 workers exposed to mercury, there were 1002 males (74.1%), the average age was (37.2±9.8) years old, and the length of service was 3.1 (2.0, 8.0) years. The abnormal rates of physical examination, blood pressure, electrocardiogram, blood routine, liver function, urinary ß2-microglobulin and urinary mercury were 73.9% (1000/1353), 12.3% (166/1353), 30.2% (408/1353), 59.9% (810/1353), 32.5% (440/1353), 15.2% (205/1353) and 2.2% (30/1353), respectively. The abnormal rates of blood pressure, blood routine, liver function, urinary ß2-microglobulin and urinary mercury in male workers were higher than those in female workers (P<0.05). The abnormal rates of workers' blood pressure and physical examination results increased with the increase of age and length of service, while the abnormal rate of electrocardiogram results were opposite (P<0.05). There were statistically significant differences in the abnormal rates of blood pressure, blood routine, urinary ß2-microglobulin and physical examination results among workers of different enterprises and different industries (P<0.05). Multivariate logistic regression analysis showed that the workers with age ≥30 years old, microminiature enterprises, abnormal physical examination results and urinary ß2-microglobulin were the susceptible population with abnormal urinary mercury (P<0.05) . Conclusion: The occupational health status of mercury workers in Xinjiang Uygur Autonomous Region is not optimistic, and the health monitoring of microminiature enterprises and older workers should be improved to effectively protect the physical and mental health of workers.

Management of endothelial disease without keratoplasty.

PURPOSE OF REVIEW: Currently, the most widely used treatment for endothelial disease is endothelial replacement via endothelial keratoplasty. Increasingly selective techniques have allowed for increased safety and faster visual recovery. However, alternative treatment options that are lower in cost, require less surgical expertise, and rely less on tissue availability are needed. This review discusses established and emerging therapies for endothelial disease without keratoplasty. RECENT FINDINGS: Regenerative therapies that have been successful include Descemet stripping only and Descemet membrane transplants. Rho-kinase inhibitors promote cell proliferation, adhesion, and migration and appear to have a role in these treatments and possibly in the prevention of endothelial disease. Cell-based therapies and the development of an artificial endothelial implant have also demonstrated promising results. SUMMARY: There are numerous emerging treatments for endothelial disease that have proven successful. Advances in our understanding of disease pathogenesis on a cellular level will continue to expand possibilities for therapeutics.

Comparison of bacterial communities on the surface of concrete breakwater structures and ambient bacterioplankton.

Breakwater structures made of concrete are used widely around the world, and the bacteria living on these surfaces can cause the concrete to deteriorate. In this study, we collected bacterial biofilms from concrete breakwater structures located along the coast of an island, a mainland coast, and a freshwater riverbank as well as planktonic water samples from each site, and we analysed their bacterial community structures using Illumina sequencing. At the phylum level, Proteobacteria and Actinobacteria dominated planktonic samples, whereas Cyanobacteria, Proteobacteria and Bacteroidetes dominated the biofilm samples. High Cyanobacteria abundance was found in all biofilm samples. Bacterial communities significantly varied between planktonic and biofilm samples and between biofilm samples from seawater and freshwater. Only a small number of bacterial operational taxonomic units were shared by planktonic and biofilm samples from each sampling site. The permanganate index in ambient water had a more significant impact on biofilm bacterial communities than on planktonic samples. Additionally, ammonia nitrogen and total nitrogen contents were positively correlated and salinity was negatively correlated with bacterial beta diversity in biofilm samples.

[Molecular characterization of Staphylococcus aureus ST6 and ST7 isolates from food-borne illness outbreaks].

Objective: To analyze the Staphylococcal enterotoxins, Staphylococcal enterotoxin genes, drug resistance and molecular typing of 41 Staphylococcus aureus isolates from 2 food-borne illness outbreaks on 21 August and 27 September 2020 in Guangzhou. Methods: A total of 41 Staphylococcus aureus isolates from 2 outbreaks were analyzed by multilocus sequence typing (MLST) and spa typing. The Staphylococcal enterotoxins typing and the Staphylococcal enterotoxin genes of the isolates were analyzed by ELISA and PCR, respectively. The antimicrobial susceptibility of the isolates was performed by disc diffusion. 21 Staphylococcus aureus isolates were characterized using whole genome sequencing (WGS). Based on the whole genome single nucleotide polymorphism (SNP), the phylogenetic tree was constructed by Snippy. Results: 41 Staphylococcus aureus isolates were divided into 2 types by MLST and spa typing: ST6-t701 and ST7-t091. 2 ST7-t091 isolates were identified as methicillin-resistant Staphylococcus aureus (MRSA). 25 ST7-t091 isolates and 14 ST6-t701 isolates were methicillin-sensitive Staphylococcus aureus (MSSA), and were resistant to 7 and 6 antibiotics, respectively. All isolates were positive for sea by PCR. WGS revealed all 21 isolates carried scn, sak, sea, hla, hld, hlgA, hlgB, hlgC, lukD virulence genes. The results showed the isolates contained an immune evasion cluster type D which located in bacteriophage ϕSa3. The SNP phylogenetic tree showed 2 MRSA ST7-t091 were constituted a separate clade from the 12 MSSA ST7-t091 isolates and 7 ST6-t701 isolates showed high similarity to each other. Conclusion: Base on the results of phylogenetic analysis, the 2 food-borne illness outbreaks occurred on 21 August and 27 September 2020 are caused by the combination of the MRSA ST7-t091 strain and the MSSA ST7-t091 strain, and the MSSA ST6-t701 strain, respectively. All isolates have high level of antibiotic resistance and carry high virulent genes.

[Relationship between simple renal cyst and adverse events in patients receiving thoracic endovascular aortic repair for Stanford B aortic dissection].

Objective: To explore the prognostic value of simple renal cyst (SRC) for adverse events in patients receiving thoracic endovascular aortic repair (TEVAR) for Stanford B aortic dissection (TBAD). Methods: This study is a retrospective cohort study. Consecutive patients receiving TEVAR for TBAD between January 2010 and December 2015 were enrolled in this study. The patients were divided into SRC group and non-SRC group. With sex and age ±2 years old as matching factors, SRC group and non-SRC group were matched by 1∶1. Collect and compare the differences of clinical data between the two groups. Adverse events were recorded through outpatient, telephone follow-up and in-hospital review. After adjusting for confounding factors, multivariate Cox regression was used to analyze the risk factors of aortic adverse events. Kaplan-Meier method was used to analyze the survival curve of SRC group and non-SRC group. Results: A total of 692 consecutive patients were recruited. Patients were divided into SRC group (n=235) and non-SRC group (n=457). After 1∶1 matching, there were 229 cases in SRC group and no SRC group respectively. The age of SRC group was (62.3±10.4) years old, 209 cases were male (91.3%), and the age of no SRC group was (62.0±10.2) years old, 209 cases were male (91.3%). Cox regression analysis showed that, after adjusting for confounding factors, comorbid SRC (HR=1.991, 95%CI: 1.090-3.673, P=0.025), TEVAR in the acute phase (HR=13.635, 95%CI: 5.969-31.147, P=0.001), general anesthesia (HR=2.012, 95%CI: 1.066-3.799, P=0.031) are independent factors of aortic-adverse events after TEVAR for TBAD. Kaplan-Meier analysis showed that the cumulative survival rate of SRC group was significantly lower than non-SRC group (log-rank P=0.031, 0.005). Conclusion: SRC is an independent predictor of aortic-related adverse events in patients following TEVAR for TBAD.

Planktonic and sediment bacterial communities in an integrated mariculture system.

An integrated multi-trophic aquaculture (IMTA) system, with one fish cage model surrounded by an island and shellfish rafts, was used in the current study. Planktonic and sediment bacterial communities in the IMTA system were monitored over four seasons in 2019. In both plankton and sediment samples, the most dominant phyla were Proteobacteria and Bacteroidota. Sediment bacterial samples were more similar and had higher levels of biodiversity than planktonic bacterial samples. Obvious seasonal variations were found in plankton samples, but not in sediment samples. No obvious inter-site variations in planktonic and sediment bacteria (fish cages, shellfish rafts and control sites) were found and the results suggested that no obvious impact of feeding operations in fish culture cage model on bacterial communities in the IMTA system was observed in this study. Based on the sequence data, some faecal indicator bacteria and potentially pathogenic bacterial species were detected. According to the results, the bacterial water quality in the IMTA system was acceptable. PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) analysis revealed that the primary difference in potential functional roles of planktonic and sediment bacteria was amino acid transport and metabolism, which was active in different seasons.

Characterisation of the complete mitochondrial genome, genetic diversity and maternal origin of Huainan Partridge chicken.

1. The objectives of the present study were to investigate the complete mitochondrial genome, genetic diversity and maternal origin of Huainan Partridge chicken (HPC).2. One complete mitochondrial genome and 37 complete D-loop regions of HPC were sequenced. Moreover, 400 mitochondrial genome D-loop sequences of Chinese native chicken were downloaded from the National Centre for Biotechnology Information database.3. The complete HPC genome was 16,785 bp in size, including 22 tRNA genes, two rRNA genes, 13 protein-coding genes and one non-coding control region. The haplotype diversity and nucleotide diversity of HPC were 0.964, and 0.00615, respectively. Twenty-three variable sites defining 22 haplotypes were identified, and the 22 haplotypes were distributed into three haplogroups (A, B, and C).4. In conclusion, HPC has a typical vertebrate mitochondrial genome, relatively high haplotype diversity, relatively low nucleotide diversity, and potentially three maternal lineages. HPC showed considerable genetic information exchange with Southwest Chinese chicken populations and had not admixed with European commercial breeds in the course of domestication.

[Lengths of the fixed loop and the adjustable loop in the coarse bone tunnel were compared to influence the widening of the femoral bone tunnel and the function of the knee joint].

OBJECTIVE: To evaluate the effects of two different femoral cortical suspension devices (fixation loop and adjustable loop) on tunnel widening and knee function in patients following anterior cruciate ligament reconstruction for 12 months. METHODS: A total of 60 patients who had undergone anterior cruciate ligament reconstruction were included in this study. According to the length of the loop(n)[n= total length of loop-(total length of femoral tunnel-total length of coarse tunnel)] in the rough bone tunnel, the patients were divided into A (adjustable loop was 0 mm in the coarse bone tunnel), B (fixation loop was greater than 0 mm and less than or equal to 10 mm in the coarse bone tunnel) and C (fixation loop was greater than 10 mm in the coarse bone tunnel) groups, of which 11 cases were in group A, 27 cases in group B and 22 cases in group C. In the three-dimensional reconstruction of the knee joint with multi-slice spiral CT, the widening of the bone tunnel in the three groups was compared. At the same time, IKDC, Lysholm and Tegner scores of the patients in the three groups were compared. RESULTS: There were differences in the widening degree of the femoral canal among groups A, B and C, and the median difference of the widening degree of the femoral tunnel 12 months and immediately after the surgery was A < B < C. The difference of femoral canal widening in group A was significantly different from that in groups B and C (P < 0.05).According to the linear regression the relationship between the difference of the width of the femoral canal and the change of the length (n) of the loop in the coarse canal, it was found that there was a linear relationship between the value of n and the difference of the width of the bone canal. With the increase of the value of n, the difference of the width of the bone canal gradually became larger. The median difference of the width of the middle and superior tunnel was negative, while the median difference of the width of the middle and inferior tunnel was positive. During the follow-up, we found that there were no statistical differences in IKDC, Lysholm and Tegner scores among the three groups one year after surgery (P > 0.05). CONCLUSION: Twelve months after surgery, compared with group B (fixed loop group) and group C (fixed loop group), group A (adjustable loop group) had less bone tunnel widening.In groups A, B and C, as the length of the loop in coarse bone tunnel gradually increased, the width of bone tunnel became more significant. At the end of 12 months follow-up after anterior cruciate ligament reconstruction, the medial and inferior femoral tunnel was significantly wider than immediately after surgery, and the medial and superior femoral tunnel had gradually begun to undergo tendon-bone healing. There was no significant difference in knee function scores among groups A, B, and C in the follow-up 12 months after surgery.