An international multidisciplinary consensus on pediatric metabolic dysfunction-associated fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in children and adolescents, particularly those with obesity. NAFLD is considered a hepatic manifestation of the metabolic syndrome due to its close associations with abdominal obesity, insulin resistance, and atherogenic dyslipidemia. Experts have proposed an alternative terminology, metabolic dysfunction-associated fatty liver disease (MAFLD), to better reflect its pathophysiology. This study aimed to develop consensus statements and recommendations for pediatric MAFLD through collaboration among international experts. METHODS: A group of 65 experts from 35 countries and six continents, including pediatricians, hepatologists, and endocrinologists, participated in a consensus development process. The process encompassed various aspects of pediatric MAFLD, including epidemiology, mechanisms, screening, and management. FINDINGS: In round 1, we received 65 surveys from 35 countries and analyzed these results, which informed us that 73.3% of respondents agreed with 20 draft statements while 23.8% agreed somewhat. The mean percentage of agreement or somewhat agreement increased to 80.85% and 15.75%, respectively, in round 2. The final statements covered a wide range of topics related to epidemiology, pathophysiology, and strategies for screening and managing pediatric MAFLD. CONCLUSIONS: The consensus statements and recommendations developed by an international expert panel serve to optimize clinical outcomes and improve the quality of life for children and adolescents with MAFLD. These findings emphasize the need for standardized approaches in diagnosing and treating pediatric MAFLD. FUNDING: This work was funded by the National Natural Science Foundation of China (82070588, 82370577), the National Key R&D Program of China (2023YFA1800801), National High Level Hospital Clinical Research Funding (2022-PUMCH-C-014), the Wuxi Taihu Talent Plan (DJTD202106), and the Medical Key Discipline Program of Wuxi Health Commission (ZDXK2021007).

Sequencing and Analysis of the Complete Mitochondrial Genome of Lentipes ikeae.

We sequenced and analyzed the complete mitochondrial genome of Lentipes ikeae and explored the phylogenetic relationships among Sicydiinae based on mitochondrial genome sequences. The complete mitochondrial genome sequence of L. ikeae was determined using the Illumina HiSeq X Ten sequencing platform, and the gene structural characteristics and base composition were analyzed. Based on the mitochondrial genome sequences of 28 Sicydiinae species published in GenBank and mitochondrial protein-coding genes (PCGs), Acanthogobius flavimanus (Gobionellinae) was selected as an outgroup to construct phylogenetic trees of Sicydiinae using the maximum likelihood and Bayesian inference methods. The mitochondrial genome of L. ikeae (GenBank number: OP764680) has a total length of 16,498 bp and encodes 13 PCGs, 22 transfer RNA genes, two ribosomal RNA genes, and a D-loop (control) region. Gene rearrangement is not observed. The mitochondrial genome of L. ikeae exhibits an AT preference, with AT skew > 0 and GC skew < 0 across the entire genome. The phylogenetic relationships of Sicydiinae based on 13 mitochondrial PCG sequences are Sicydium + (Stiphodon + (Sicyopus + Lentipes)) + Sicyopterus, indicating that Sicydium, Sicyopterus, Lentipes, and Stiphodon are all monophyletic groups.

Safety and effectiveness of nano composite hydrogel stent implantation in the treatment of coronary cardiovascular disease: A preclinical study.

With the improvement of people's quality of life, various cardiovascular diseases are the most common diseases. Therefore, the main site of disease atherosclerosis is blood vessels, so we can see that its flow rate has obvious changes. Through the analysis of coronary heart disease, this paper studies the relationship between coronary artery disease and cardiovascular disease, which is helpful to evaluate the risk of disease, and also provides the best prevention and treatment plan to overcome cardiovascular disease. As the material of artificial cartilage repair, nanocomposite hydrogel has excellent application value and attraction, because nanocomposite hydrogel has a structure similar to the extracellular matrix of natural chondrocytes. The patients in the experimental group were treated with nano composite hydrogel stent implantation. The other group of patients used the traditional way to carry out the comparative experiment. In the perfusion data of each ventricular wall in the coronary angiography and anterior wall perfusion group, the percentage of lateral wall in the normal proportion was the highest, 69.2%, 59.3% in the anterior wall, 39.5% in the inferior wall, and 19.7% in the apical value and interval. The percentage of LAD stenosis in anterior wall perfusion was O. The highest percentage in the lateral wall was 69.2%, and the lowest in the septum and apex was 19.7%. Nanocomposite hydrogel stent implantation can effectively treat coronary heart disease. The research shows that it is safe and effective in application.

Association between new onset type 1 diabetes and real-world antibiotics and neonicotinoids' exposure-related gut microbiota perturbation.

BACKGROUND: The real-world exposure levels of non-therapeutic antibiotics and neonicotinoids in type 1 diabetes (T1D) children and their associations as environmental triggers through gut microbiota shifts remained unknown. We thus investigated the antibiotics and neonicotinoids' exposure levels and their associations with gut microbiota in pediatric T1D. METHODS: Fifty-one newly onset T1D children along with 67 age-matched healthy controls were recruited. Urine concentrations of 28 antibiotics and 12 neonicotinoids were measured by mass spectrometry. Children were grouped according to the kinds of antibiotics' and neonicotinoids' exposures, respectively. The 16S rRNA of fecal gut microbiota was sequenced, and the correlation with urine antibiotics and neonicotinoids' concentrations was analyzed. RESULTS: The overall detection rates of antibiotics were 72.5% and 61.2% among T1D and healthy children, whereas the neonicotinoids detection rates were 70.6% and 52.2% (P = 0.044). Children exposed to one kind of antibiotic or two or more kinds of neonicotinoids had higher risk of T1D, with the odd ratios of 2.579 and 3.911. Furthermore, co-exposure to antibiotics and neonicotinoids was associated with T1D, with the odd ratio of 4.924. Antibiotics or neonicotinoids exposure did not affect overall richness and diversity of gut microbiota. However, children who were exposed to neither antibiotics nor neonicotinoids had higher abundance of Lachnospiraceae than children who were exposed to antibiotics and neonicotinoids alone or together. CONCLUSION: High antibiotics and neonicotinoids exposures were found in T1D children, and they were associated with changes in gut microbiota featured with lower abundance of butyrate-producing genera, which might increase the risk of T1D.

The Value of Endoscopic Ultrasonography in the Endoscopic Resection of Gastrointestinal Stromal Tumors.

OBJECTIVE: This study aimed to explore the clinical value of endoscopic ultrasonography (EUS) in the endoscopic resection of gastrointestinal stromal tumors (GISTs). METHODS: A retrospective study of 92 patients who were confirmed to have GISTs by endoscopic resection after EUS examination was conducted. The preoperative features of the EUS examination, ultrasound diagnosis, endoscopic resection methods, surgical procedures, complications, and complete degree of lesion resection were recorded. And 16 patients who were diagnosed by endoscopy and EUS and confirmed by surgical operation were included and analyzed in the subsequent part of the investigation (gastroscopy and EUS image analysis, EUS image and risk classification). RESULTS: The preoperative diagnosis rate of EUS and postoperative pathological diagnosis of GISTs was 78.7% (85/108), and the presence of a non-homogeneous echo and liquid anechoic zone in GISTs often indicated higher risk (P < 0.05). There was a positive correlation between tumor size and risk (P < 0.05). CONCLUSION: The endoscopic resection of GISTs is feasible and safe. EUS is of great significance for the diagnosis and risk assessment of GISTs and can assist in the endoscopic resection of GISTs.

Association of ß-cell function and insulin resistance with pediatric type 2 diabetes among Chinese children.

BACKGROUND: In addition to insulin resistance, impaired insulin secretion has recently been identified as a crucial factor in the pathogenesis of type 2 diabetes mellitus (T2DM). Scarce clinical data exist for pediatric T2DM. AIM: To investigate the association of ß-cell function and insulin resistance with pediatric T2DM in the first Chinese multicenter study. METHODS: This multicenter cross-sectional study included 161 newly diagnosed T2DM children and adolescents between January 2017 and October 2019. Children with normal glycemic levels (n = 1935) were included as healthy control subjects. The homeostasis models (HOMAs) were used to assess the ß-cell function (HOMA2-%B) and insulin resistance (HOMA2-IR) levels. The HOMA index was standardized by sex and age. We performed logistic regression analysis to obtain odds ratios (ORs) for T2DM risk using the standardized HOMA index, adjusted for confounding factors including sex, Tanner stage, T2DM family history, body mass index z-score, and lipid profile. RESULTS: The male-female ratio of newly diagnosed T2DM patients was 1.37:1 (OR = 2.20, P = 0.011), and the mean ages of onset for boys and girls were 12.5 ± 1.9 years and 12.3 ± 1.7 years, respectively. The prevalence of related comorbidities including obesity, elevated blood pressure, and dyslipidemia was 58.2%, 53.2%, and 80.0%, respectively. The T2DM group had lower HOMA2-%B levels (P < 0.001) and higher HOMA2-IR levels (P < 0.001) than the control group. Both the decrease in HOMA2-%B z-score (OR = 8.40, 95%CI: 6.40-11.02, P < 0.001) and the increase in HOMA2-IR z-score (OR = 1.79, 95%CI: 1.60-2.02, P < 0.001) were associated with a higher risk of T2DM, and the decrease in HOMA2-%B z-score always had higher ORs than the increase in HOMA2-IR z-score after adjusting for confounding factors. CONCLUSION: Besides insulin resistance, ß-cell function impairment is also strongly associated with Chinese pediatric T2DM. Gender difference in susceptibility and high comorbidities warrant specific T2DM screening and prevention strategies in Chinese children.

Keratin 18 induces proliferation, migration, and invasion in gastric cancer via the MAPK signalling pathway.

PURPOSE: Keratin 18 (KRT18) is a cytoskeleton protein that plays a key role in multiple cancers. The present study aims to further investigate the roles of KRT18 in gastric cancer (GC) tissues and cells. METHODS: The KRT18 protein expression levels of GC tissues and cells were detected using immunohistochemistry and western blot. The relationship between KRT18 expression levels and the prognosis of GC patients was further analyzed. To explore this relationship, small interfering RNA (siRNA) was used to inhibit the endogenous expression of KRT18 in GC cells. Furthermore, the effects of KRT18 on the proliferation, invasion, migration, and apoptosis of GC cells were analyzed in vitro. In addition, the role of KRT18 in GC-specific processes was investigated. RESULTS: Keratin 18 expression was shown to be up-regulated in GC tissues and associated with poor prognosis. Following KRT18 silencing with siRNA, the proliferation, invasion, and migration ability of GC cells were significantly inhibited, while the apoptotic process was promoted. Furthermore, the activation of the MAPK signalling pathway was identified as the potential mechanism through which KRT18 influenced GC processes. CONCLUSIONS: Keratin 18 plays a cancer-promoting role and might be a potential therapeutic target in the treatment of GC.

High-throughput metabolomic method based on liquid chromatography: high resolution mass spectrometry with chemometrics for metabolic biomarkers and pathway analysis to reveal the protective effects of baicalin on thyroid cancer.

Cell metabonomics focuses on discovering metabolic biomarkers and pathway changes in cells from biological systems to obtain the cell properties and functional information under different conditions. Baicalin possesses various pharmacological activities, and plays a vital role in the oncology research field. However, the detailed mechanism of its action is still unclear. In this work, we employed ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) based non-targeted metabolomics method associated with chemometrics analysis to explore metabolic pathways and biomarkers for investigating the efficacy and pharmacological targets of baicalin against thyroid cancer cells. In addition, morphological observation, parameter calculation of cell proliferation and apoptosis were carried out, which assisted in elucidation of pharmacological activity of baicalin on the human thyroid cancer cells. The results showed that baicalin possesses an intense stimulative apoptosis and inhibits proliferation activity on SW579 human thyroid cancer cells, and partially reversed the cell metabolite abnormalities. A total of nineteen differentiated metabolites in SW579 cells were identified and deemed as potential biomarkers after the baicalin treatment, involving nine metabolic pathways, such as taurine and hypotaurine metabolism, pyrimidine metabolism, fructose and mannose metabolism, steroid hormone biosynthesis and sphingolipid metabolism. High-throughput non-targeted metabolomics provide an insight into specialized mechanism of baicalin against thyroid cancer and contributes to novel drug discovery and thyroid cancer management in clinical practice.

Transfer learning on T1-weighted images for brain age estimation.

Due to both the hidden nature and the irreversibility of Alzheimers disease (AD), it has become the killer of the elderly and is thus the focus of much attention in the medical field. Radiologists compare the predicted brain age with the ground truth in order to provide a preliminary analysis of AD, which helps doctors diagnose AD as early in its development as possible. In this paper, a transfer learning-based method of predicting brain age using MR images and dataset of a public brain was proposed. In order to get the best transfer results, we froze different layers and only fine-tuned the remaining layers. We used three planes of brain MR images together to predict age for the first time and experiment results showed that the proposed method performs better than the state-of-the-art method under mean absolute error metric by 0.6 years. In addition, to explore the relationship between brain MR images of different planes and predicted age accuracy, we used three different planes of brain MR images to predict age respectively for the first time and found that sagittal plane MR images outperformed two other planes in age estimation. Finally, our research identified, the effective regions that contribute to brain age estimation for cognitively normal individuals and for AD patients with deep learning. For AD patients, the effective region is mainly concentrated in the frontal lobe of the brain, verifying the relevant medical conclusions about AD.

Castleman disease in the hepatic-gastric space: A case report.

BACKGROUND: Castleman disease, also known as giant lymph node hyperplasia, was first reported in 1956. It is a rare benign proliferative pathological change of the lymph nodes. CASE SUMMARY: The patient, a 33-year-old woman, had epigastric distension for half a year. Examinations were performed in a local hospital. Computed tomography scan showed round soft tissue nodules, about 5.45 cm in diameter, in the hepatic-gastric space. Endoscopic ultrasound and endoscopic ultrasound guided fine needle aspiration was performed on the patient. Rapid on-site evaluation, hematoxylin eosin staining and histopathology of the puncture smear was performed. According to the Diff-Quik staining and hematoxylin eosin staining results of preoperative endoscopic ultrasound guided fine needle aspiration puncture smears as well as the immunohistochemistry results, Castleman disease was highly suspected. A sufficient preoperative evaluation was made, and a precise surgical plan was developed. Postoperative pathology confirmed Castleman disease. CONCLUSION: Endoscopic ultrasound guided fine needle aspiration can extract internal tissues of the tumor for histological and cytological examinations and provide accurate diagnosis as much as possible. Therefore, a sufficient preoperative evaluation can be made, and a precise surgical plan can be developed.

Relationship between self-reported residential indoor remodeling and semen quality: a case-control study.

The present study examined the association between residential indoor remodeling and poor semen quality. Sperm donors aged 18-45 years old were recruited in Shanghai, China. Semen specimens were collected and analyzed. An in-person interview was conducted to obtain information on the history of indoor remodeling and potential confounders. A total of 70 participants with abnormal semen quality (case group) and 68 controls were examined. A total of 20 subjects reported indoor remodeling in the recent 24 months, and among them 17 subjects reported indoor remodeling in the recent 12 months. Compared with participants with no history of indoor remodeling, participants with a history of indoor remodeling in the recent 24 months were more than three times as likely to have poor sperm quality (adjusted odds ratio = 3.8, 95% confidence interval: 1.3-12.0) after controlling for potential confounders. The association was strengthened when the analysis was restricted to those who had indoor remodeling in the recent 12 months. Our findings provide preliminary evidence that indoor remodeling has an adverse effect on semen quality.

Rapid separation, identification and analysis of Astragalus membranaceus Fisch using liquid chromatography-tandem mass spectrometry.

A rapid, sensitive and selective liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) method has been developed for the rapid separation and structural identification of constituents in Astragali Radix (AR) The analysis was conducted on an ACQUITY HPLC chromatographic instrument and a mass spectrometer using positive electrospray ionization. Using a fast HPLC system with an ACQUITY HPLC BEH C18 column, the total analysis time for this complex herb was less than 30 min. The method used a column with 1.7 µm particle packing, which allowed a higher speed of analysis, peak capacity, greater resolution and increased sensitivity. With various fragmentor voltage levels in MS, accurate mass measurements (less than 5 ppm error) for molecular ions and characteristic fragment ions represented reliable identification criteria for these compounds. The constituents of AR were identified or tentatively characterized based on their retention times, mass fragmentation behavior, MS-MS fragment ions, literature reports and the establishment of an in-house molecular formula database. With this method, a total of 22 compounds of AR were tentatively identified based on MS data and comparison with available databases. In conclusion, fast HPLC with MS is a highly useful and efficient technique to separate and identify constituents in complex matrices of herbal medicines.

[Levels of blood pressure and blood glucose in elderly patients with hypertension and diabetes: association with carotid atherosclerosis].

OBJECTIVE: To explore the association between blood pressure and blood glucose levels and carotid atherosclerosis in elderly patients with essential hypertension and type 2 diabetes mellitus (T2DM). METHODS: A total of 670 patients aged 60 years or over with hypertension and T2DM were recruited and categorized by their systolic blood pressure (SBP): tight control, < 130 mm Hg, usual control, 130 - 139 mm Hg, or uncontrolled, ≥ 140 mm Hg; and by their HbA1c level: tight control < 6.5%, usual control 6.5% - 7.5%, or uncontrolled, ≥ 7.5% respectively. Carotid ultrasonography was performed in all subjects for the evaluations of intima-media thickness (IMT) and plaque. RESULTS: Multiple linear regression analyses revealed that IMT was positively correlated with SBP (ß = 0.215, P = 0.002) and HbA1c (ß = 0.149, P = 0.031), whereas IMT was negatively correlated with high-density lipoprotein cholesterol (ß = -0.196, P = 0.002). According to the multivariate logistic regression analysis, SBP ≥ 140 mm Hg (OR = 1.473, 95%CI 1.044 - 2.078 P = 0.027), HbA1c ≥ 7.5% (OR = 1.445, 95%CI 1.031 - 2.027, P = 0.033) and total cholesterol (OR = 1.014, 95%CI 1.004 - 1.024, P = 0.019) were significant risk factors for carotid artery atherosclerotic plaques whereas high-density lipoprotein cholesterol (OR = 0.895, 95%CI 0.805 - 0.994, P = 0.012) was a protective factor for carotid artery atherosclerotic plaques in elderly patients with hypertension and T2DM. CONCLUSION: There is a significant correlation between the levels of blood pressure, blood glucose and carotid atherosclerosis in elderly patients.

[Reference values of semen parameters for normal fertile men in Shanghai].

OBJECTIVE: To analyze the distribution characteristics of the main semen parameters of healthy semen donors and normal fertile men in Shanghai, compare the semen quality between the two groups, and investigate the normal reference values of the semen parameters of the fertile population in Shanghai. METHODS: We obtained semen samples from 100 healthy donors and 41 fertile men, performed semen analyses according to the WHO (2010) guidelines, and determined the semen volume, sperm concentration, sperm progressive motility, total sperm count and total progressively motile sperm count. We analyzed the distribution of the semen parameters of the normal fertile men, and obtained the lower limits of their normal reference values. RESULTS: There were no statistically significant differences in the main semen parameters between the healthy donors and normal fertile men (P < 0.05). The lower reference limits for the semen parameters of normal fertile men in Shanghai (P < 0.05) were as follows: sperm concentration > or = 27.3 x 10(6)/ml, sperm progressive motility > or = 8.1%, semen volume > or = 0.82 ml, total sperm count > or = 44.73 x 10(6) per ejaculate, and total progressively motile sperm count > or = 24.68 x 10(6) per ejaculate. CONCLUSION: For the evaluation of male fecundity, total sperm count and total progressively motile sperm count may be two better predictors than others.

Long-term follow-up and humanistic care for patients with hypophyseal tumor.

The number of new cases of hypophyseal tumor increases along with the advances in neuroimaging technology in recent years. The common treatment models include surgical treatment, radiotherapy, and medical therapies. This article discusses the application of long-term follow-up in non-operative hypophyseal tumor patients and its influence on the prognosis. Meanwhile, since the medical mode has switched from biomedical model to biopsychosocial medical model, management of hypophyseal tumor should not be limited in its biological aspect, but also from the perspective of psychology by providing more humanistic care to meet the patients'psychological needs.

Glycemic and blood pressure control in older patients with hypertension and diabetes: association with carotid atherosclerosis.

BACKGROUND: Numerous studies have confirmed the effectiveness of slowing the progression of atherosclerosis by blood pressure (Bp) control in patients with hypertension and several studies also showed the efficacy of intensive glycemic control in decreasing progression of carotid intima-media thickness (CIMT) in patients with type 1 and type 2 diabetes. However, few studies have compared the relative importance of glycemic vs. Bp control in patients with diabetes and hypertension. We aimed to investigate the association between Bp and glycemic control and subclinical carotid atherosclerosis in older patients with hypertension and type 2 diabetes. METHODS: In a cross-sectional study, B-mode high-resolution ultrasonography of the carotid artery was performed in 670 subjects (508 males and 162 females) aged 60 years or over who had self-reported hypertension and diabetes but no history of coronary heart disease or stroke. Subjects were categorized by their systolic blood pressure: tight control, < 130 mmHg; usual control, 130-139 mmHg; or uncontrolled, ≥ 140 mmHg, and by their hemoglobin A1c (HbA1c) level: tight control, < 6.5%; usual control, 6.5%-7.5%; or uncontrolled, ≥ 7.5%, respectively. RESULTS: The mean CIMT was 8.20 ± 0.11 mm, and carotid plaque was found in 52.5% (352/670) subjects. Overall, 62.1% of the subjects had subclinical carotid atherosclerosis, defined as having either carotid plaque or elevated CIMT (≥ 1.1 mm). The mean CIMT was significantly different between Bp control categories (7.60 ± 0.09 mm, 7.90 ± 0.08 mm, and 8.60 ± 0.12 mm, respectively, P = 0.03) but not between glycemic control categories (8.20 ± 0.10 mm, 8.1 ± 0.08 mm, and 8.40 ± 0.14 mm, respectively, P = 0.13) using ANCOVA analysis. Multivariable logistic regression adjusting for potential confounding factors showed that usual or uncontrolled Bp control were associated with having carotid plaque (OR = 1.08 and OR = 1.42, respectively), or elevated CIMT [Odd ratio (OR) = 1.17, 95% confidence interval (CI) 1.04-2.24, and OR = 1.54, 95% CI 1.36-2.96, respectively compared to tight Bp control; but did not show glycemic control as independent predictor of either having carotid plaque or elevated CIMT. CONCLUSIONS: In older patients with hypertension and diabetes, blood pressure control, but not glycemic control is associated with subclinical carotid atherosclerosis.

[Integration and expression of polyphosphate kinase gene in Pseudomonas putida].

In order to construct high accumulating-phosphate microorganism, the ppk gene from E. coli was inserted to the broad-host-range plasmid pBBR1MCS-2 to form plasmid pBBR1MCS-2-ppk. The complete ppk gene with promoter and terminator sequences from pBBR1MCS-2-ppk was then cloned and inserted to suicide plasmid pUTmini-Tn5 to form plasmid pUTmini-Tn5-ppk, which was transformed into Pseudomonas putida KT2440 by triparental conjugation. Finally, ppk gene was integrated into the chromosomal DNA of KT2440. The results of RT-PCR showed that the selected genetically engineered bacterium KT2440-PPK expressed ppk efficiently, while KT2440 as control expressed weakly. The results of artificial wastewater treatment showed after 1h inoculation, the concentration of poly-phosphate in KT2440-PPK came to the maximum approximately 3.05 mg/g, which was 15 times higher than that in KT2440 at the same experimental condition. And KT2440-PPK can remove more than 90% phosphate in artificial wastewater.