[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.

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.

17ß-estradiol regulates adenosine triphosphate-binding cassette transporters A1 expression via estrogen receptor A to increase macrophage cholesterol efflux.

The liver is the focus of research on the effects of estrogen on cholesterol metabolism. Few studies have investigated the effects of estrogen on macrophages despite the significance of cells in atherosclerosis. The purpose of this study is to examine the effect of estrogen on macrophage cholesterol efflux. Macrophage cholesterol efflux, oil red O staining, RT-qPCR, Western blotting analyses were used to determine cholesterol metabolize and the expressions of adenosine triphosphate (ATP)-binding cassette transporter G1 (ABCG1) and ATP-binding cassette transporter A1 (ABCA1) in J774A.1 cells, and the effect of these treatments was compared to without adding 17ß-estradiol (E2). Gain and loss of estrogen receptor alpha (ERα), liver X receptor α (LXRα) were conducted to study interactions between E2, ERα, LXRα and ABCA. Finally, in mice, we validate the relationship between ERα and ABCA1. E2 increases cholesterol efflux from macrophages and decreases the formation of lipid droplets and positively regulates the expression of ABCA1. This suggests that estrogen receptors (ERs) directly regulate ABCA1 translation. We suppressed ERα, which decreased the mRNA and protein expression of ABCA1. At the mRNA level, E2 treatment could partially counteract these phenomena, but not at the protein level. ABCA1 expression decreased after LXRα was inhibited. This suggests that ABCA1 translation is directly regulated by ERα. In the ovariectomized mouse model of ABCA1 protein expression was significantly reduced in the peritoneal macrophages of the ovariectomy (OVX) group. ABCA1 protein expression was greater in the E2+OVX group than in the OVX group. E2 contributes to the positive regulation of ABCA1 expression and promotes cholesterol efflux in macrophages by binding to ERα. The effect is independent of ABCA1 transcription regulation by LXRα.

[Epidemiological investigation of constipation in urban areas of Hangzhou, China].

Objective: To determine the prevalence and risk factors of constipation in Hangzhou urban areas by analyzing data from a recent epidemiological survey. Methods: From August 2022 to June 2023, a cross-sectional survey was conducted on 43 communities on eight streets in suburbs of Hangzhou, including Wangjiang, Sijiqing, Puyan, Changhe, Ziyang, Xiaoshanchengxiang, Zhuantang, and Banshan. Written questionnaires were filled out face to face by community doctors. The prevalence of constipation was investigated using a combination of the Bristol stool typing method and the Rome IV criteria. The risk factors for constipation were analyzed using multivariate logistic regression analysis. Results: The study cohort comprised 10,479 participants, 5551 of whom were male (53.0%) and 4928 female (47.0%). The overall prevalence of constipation was 10.6% (1107/10,479). The prevalence was 11.0% (613/5551) for male and 10.0% (494/4928) for female participants; this difference is not statistically significant (P>0.05).There were no significant differences in the prevalence of constipation between different categories of body mass index (P>0.05). The prevalence of constipation was highest in individuals aged 70 years and above, accounting for 15.4% (264/1717) of all cases. There were significant differences in the prevalence of constipation between different occupations, marital statuses, and educational levels (P<0.001). Patients with hypertension or diabetes mellitus had a higher prevalence of constipation than those without these conditions, those who had been taking long-term medication had a higher prevalence of constipation than those who did not, parents of children with constipation had a higher prevalence of constipation than those with children who did not have constipation, and there were other significant differences in various variables (P<0.001). Multivariate logistic regression analysis of modifiable factors revealed that eating less fruit (OR=1.284, 95%CI: 1.061-1.553, P=0.010), liking spicy and salty food (OR=1.234, 95%CI: 1.039-1.466, P=0.016), sleeping for too long (OR=1.644, 95%CI: 1.260-2.144, P<0.001), irregular sleep patterns (OR=1.370, 95%CI: 1.127-1.665, P=0.002) and minimal exercise (OR=1.388, 95% CI: 1.168-1.649, P<0.001) were all risk factors for constipation; whereas mix diets (OR=0.709,95%CI:0.608-0.826, P<0.001), meat diets (OR=0.604,95%CI: 0.495-0.736, P<0.001), moderate alcohol consumption (OR=0.659, 95% CI: 0.534-0.812, P<0.001), less or no drinking (OR=0.523, 95% CI: 0.428-0.638, P<0.001), and non-smoking (OR=0.819, 95%CI:0.674-0.995, P<0.001) protected against constipation. We found no association between dietary preferences and the risk of constipation (refined grains: OR=1.147, 95%CI:0.944-1.393, P=0.167; no specific preference: OR=0.935, 95%CI:0.783-1.117, P=0.459). The rate of agreement between self-evaluation of constipation by the respondents and objective criteria was higher for negatives (95.8%) than for positives (38.0%). Conclusion: The prevalence of constipation is relatively high in the urban population of Hangzhou. A good lifestyle and diet can significantly reduce its incidence. There should be more emphasis on preventive education, promotion of prevention of constipation, and advocacy for a healthy lifestyle.

[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.

[Enamel developmental defects: environmental factors and clinical management].

Enamel formation is a complex physiological process that depends on the coordinated regulation of multiple mechanisms. This process is quite sensitive to various local and systemic interference factors. Therefore, during the long period from the embryonic stage to adolescence or even adulthood, various interference factors may lead to enamel developmental defects. Among them, early life is the most sensitive stage to environmental factors exposure, while it is also the critical period of enamel development of deciduous and permanent teeth. Environmental factors exposure during this period often leads to varying degrees of enamel development defects. In this review, we generalize the research progress of environmental factors affecting enamel developmental defects, summarize the potential mechanisms of environmental factors leading to enamel developmental defects, and conclude the clinical management strategies based on tertiary prevention. This work hopes to provide a theoretical basis for preventing abnormal teeth development from the critical time window of early life, propose eugenics health consultation and promote children 's oral health management.

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.

[Current status of diagnosis and treatment of chronic lymphocytic leukemia in China: A national multicenter survey research].

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.

[A study on knowledge, attitude, and vaccination behavior of herpes zoster vaccine among urban residents in selected areas of China].

Objective: To understand the knowledge, attitude, and current status of vaccination of herpes zoster vaccination among urban residents aged 25 years and above in China. Methods: In August to October 2022, a convenience sampling method was used to survey residents aged 25 years and above at 36 community centers in 9 cities across China. Questionnaires were used to collect basic information, knowledge, and attitude toward herpes zoster and its vaccination, as well as vaccination status and reasons for non-vaccination among residents. Results: A total of 2 864 urban residents were included in the study. The total score of residents' cognition of herpes zoster and its vaccine was 3.01±2.08, and the total score of their attitude was 18.25±2.76. Factors such as being male (ß=-0.45, P<0.001), older than 40-59 years (ß=-0.34, P=0.023) or ≥60 years (ß=-0.68, P<0.001), married (ß=-0.69, P=0.002) were negatively associated with knowledge score. The educational level of high school or secondary school (ß=0.44, P=0.036), college (ß=0.65, P=0.006), bachelor's degree and above (ß=1.20, P<0.001), annual net household income ≥120 000 Yuan in 2021 (ß=0.42, P=0.020), having urban employee medical insurance (ß=0.62, P=0.030), having public or commercial medical insurance (ß=0.65, P=0.033), and having a history of chickenpox (ß=0.29, P=0.025) were positively associated with knowledge scores. Being male (ß=-0.38, P=0.008) and not remembering a history of chickenpox (ß=-0.49, P=0.012) were negatively associated with attitude scores. Annual net household income in 2021 was between 40 000-80 000 Yuan (ß=0.44, P=0.032) or between 80 000-120 000 Yuan (ß=0.62, P=0.002) or ≥120 000 Yuan (ß=0.93, P<0.001), and a history of herpes zoster (ß=0.59, P=0.004) were positively associated with attitude scores. Of the 2 864 residents surveyed, only 29 (1.01%) had received the herpes zoster vaccine, with a vaccination rate of 1.70% for those aged 50 years and above, with the main reason for non-vaccination being lack of knowledge about the herpes zoster vaccine, followed by the high price. 42.67% of the population said they would consider getting the herpes zoster vaccine in the future. Conclusion: Low knowledge of herpes zoster and its vaccine, positive attitudes towards the preventive effects of herpes zoster and its vaccine, and extremely low vaccination rates among the urban population in China call for multiple measures to strengthen health education and vaccination recommendations for residents, especially for the elderly, low-education and low-income populations.

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.

[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.

[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.

Exon architecture controls mRNA m6A suppression and gene expression.

N6-methyladenosine (m6A) is the most abundant messenger RNA (mRNA) modification and plays crucial roles in diverse physiological processes. Using a massively parallel assay for m6A (MPm6A), we discover that m6A specificity is globally regulated by suppressors that prevent m6A deposition in unmethylated transcriptome regions. We identify exon junction complexes (EJCs) as m6A suppressors that protect exon junction-proximal RNA within coding sequences from methylation and regulate mRNA stability through m6A suppression. EJC suppression of m6A underlies multiple global characteristics of mRNA m6A specificity, with the local range of EJC protection sufficient to suppress m6A deposition in average-length internal exons but not in long internal and terminal exons. EJC-suppressed methylation sites colocalize with EJC-suppressed splice sites, which suggests that exon architecture broadly determines local mRNA accessibility to regulatory complexes.

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.

DPSC-Derived Extracellular Vesicles Promote Rat Jawbone Regeneration.

Repair and functional reconstruction of large jawbone defects remain one of the challenges in the field of head and neck surgery. The recent progress in tissue engineering technologies and stem cell biology has significantly promoted the development of regenerative reconstruction of jawbone defects. The multiple trophic activities of extracellular vesicles (EVs) produced by mesenchymal stem cells (MSCs) may play a critical role in their therapeutic effects. Accumulating evidence has shown the promise of dental pulp stem cells (DPSCs) in bone regeneration, but less is known about the regenerative effects of DPSC-EVs on jawbone defects. The purpose of this study is to explore the osteogenic effects of DPSC-EVs on jawbone marrow-derived MSCs (JB-MSCs) in vitro and their osteoinductive effects in a mandibular bone defect model in rats. Our results showed that JB-MSCs could efficiently uptake DPSC-EVs, which in turn significantly promoted the expression of osteogenic genes, such as runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), and osteocalcin (OCN), as well as the osteogenic differentiation capability of JB-MSCs. Meanwhile, we found that the pro-osteogenic effect in vitro induced by DPSC-EVs was comparable to that induced by BMP-2 (bone morphogenetic protein 2), currently the only Food and Drug Administration-approved osteoinductive growth factor. In vivo, animals that were locally treated with DPSC-EVs laden with a commercially available collagen membrane exhibited a relatively fast wound closure and increased new bone density at the mandible defects. Our results provide evidence for the osteogenic and osteoinductive effects of DPSC-EVs on jawbone regeneration. Due to the accessibility, rapid proliferation, and osteogenic propensity of DPSCs, DPSC-EVs may represent a safe cell-free therapeutic approach for craniofacial bone regeneration.

Relations of Variety and Quantity of Dietary Proteins Intake from Different Sources with Mortality Risk: A Nationwide Population-Based Cohort.

OBJECTIVES: The relations of variety and quantity of dietary proteins intake from different sources with mortality risk were still controversial. We aimed to examine the associations of variety and quantity of different sourced proteins with all-cause mortality risk in adults and older adults. MATERIALS AND METHODS: 17,310 participants (mean age was 44.0 [SD: 15.9] years and 51.0% were females) with utilizable data from the China Health and Nutrition Survey were included. Dietary intake was collected using three consecutive 24-h dietary recalls combined with a household food inventory. The variety score of protein sources was defined as the number of proteins consumed at the appropriate level, accounting for both types and quantity of proteins. The primary outcome was all-cause mortality. RESULTS: Over a median follow-up of 9.0 years, 1324 (7.6%) death cases were reported. There were reversed J-shaped relationships of percentages energy from total protein, and protein from legume with all-cause mortality; U-shaped relationships of proteins from unprocessed red meat, processed red meat, poultry and whole grain with all-cause mortality; L-shaped relationships of proteins from egg and fish with all-cause mortality; and a reversed L-shaped relationship of protein from refined grain with all-cause mortality (all P values for nonlinearity < 0.001). Moreover, there was a significant inverse association between the variety score of protein sources with overall mortality risk (per score increment, HR, 0.69; 95%CI, 0.66-0.72). CONCLUSIONS: Greater variety of proteins with appropriate quantity from different food sources was associated with significantly lower risk of mortality in Chinese adults and older adults.

Dietary Iron Intake and New-Onset Hypertension: A Nationwide Cohort Study from China.

OBJECTIVES: The relationship of dietary iron intake with the risk of hypertension remains uncertain. We aimed to investigate the prospective association between dietary iron intake and new-onset hypertension among Chinese adults. DESIGN: A nationwide cohort study. SETTING: Using data from seven rounds of the China Health and Nutrition Survey (CHNS) from 1997 to 2015. PARTICIPANTS: A total of 12,245 participants without hypertension at baseline were included in this study. EXPOSURES: Dietary intake was measured by three consecutive 24-h dietary recalls combined with a household weighing inventory. MEASUREMENTS: The study outcome was new-onset hypertension, defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg or diagnosed by physician or currently under antihypertensive treatment during the follow-up. RESULTS: During a median follow-up of 6.1 years, 4,304 (35.1%) participants developed hypertension. Overall, there was a U-shaped association between dietary total iron intake and new-onset hypertension (P for nonlinearity <0.001), with the lowest risk observed at 18.2-<22.1 mg/day (quintile 2-3). Similarly, a U-shaped association between dietary nonheme iron intake and new-onset hypertension was found (P for nonlinearity <0.001), with the lowest risk at 17.4-<21.3 mg/day (quintile 2-3). However, the association between dietary heme iron intake and new-onset hypertension followed a L-shape (P for nonlinearity <0.001), and a significantly lower risk of new-onset hypertension was found in participants with quintile 2-5 of dietary heme iron intake (adjusted HR, 0.75; 95% CI: 0.68, 0.82), compared with those in quintile 1 (<0.25 mg/day). CONCLUSIONS: The association between dietary iron and new-onset hypertension was nonlinear in Chinese adults, following a U-shape for total or nonheme iron intake, and a L-shape for heme iron intake.

[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.

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.