Anthocyanins and proanthocyanidins synergistically inhibit the growth of gastric cancer cells in vitro: exploring the potential physiological activity of grape and red wine.

Red wine is rich in anthocyanins and procyanidins which possess multiple health-promoting properties. However, the synergistically anticancer effects of them on gastric cancer cells still undefined. The results showed that combination of malvidin-3-O-(6-O-coumaroyl)-glucoside-5-O-glucoside (M35GC) and procyanidin C1 could effectively inhibited the viability of MKN-28 cells with the lowest IC50 value. Mechanistically, M35GC and procyanidin C1 significantly induced cell apoptosis by reducing the ratio of Bcl-2/Bax, blocked cell cycle in G0/G1 phase by decreasing CDK4 protein and decreased glucose consumption and lactate production during aerobic glycolysis through suppressing the expression of HK2 protein in MKN-28 cells. In conclusion, induction of cell apoptosis and cell cycle arrest, as well as the inhibition of HK2 protein that participates in the glycolytic pathway and the suppression of aerobic glycolysis by M35GC and procyanidin C1 contributed to the anti-cancer effects in gastric cancer.

Advancements and Challenges in the Integration of Indium Arsenide and Van der Waals Heterostructures.

The strategic integration of low-dimensional InAs-based materials and emerging van der Waals systems is advancing in various scientific fields, including electronics, optics, and magnetics. With their unique properties, these InAs-based van der Waals materials and devices promise further miniaturization of semiconductor devices in line with Moore's Law. However, progress in this area lags behind other 2D materials like graphene and boron nitride. Challenges include synthesizing pure crystalline phase InAs nanostructures and single-atomic-layer 2D InAs films, both vital for advanced van der Waals heterostructures. Also, diverse surface state effects on InAs-based van der Waals devices complicate their performance evaluation. This review discusses the experimental advances in the van der Waals epitaxy of InAs-based materials and the working principles of InAs-based van der Waals devices. Theoretical achievements in understanding and guiding the design of InAs-based van der Waals systems are highlighted. Focusing on advancing novel selective area growth and remote epitaxy, exploring multi-functional applications, and incorporating deep learning into first-principles calculations are proposed. These initiatives aim to overcome existing bottlenecks and accelerate transformative advancements in integrating InAs and van der Waals heterostructures.

The complex world of kefir: Structural insights and symbiotic relationships.

Kefir milk, known for its high nutritional value and health benefits, is traditionally produced by fermenting milk with kefir grains. These grains are a complex symbiotic community of lactic acid bacteria, acetic acid bacteria, yeasts, and other microorganisms. However, the intricate coexistence mechanisms within these microbial colonies remain a mystery, posing challenges in predicting their biological and functional traits. This uncertainty often leads to variability in kefir milk's quality and safety. This review delves into the unique structural characteristics of kefir grains, particularly their distinctive hollow structure. We propose hypotheses on their formation, which appears to be influenced by the aggregation behaviors of the community members and their alliances. In kefir milk, a systematic colonization process is driven by metabolite release, orchestrating the spatiotemporal rearrangement of ecological niches. We place special emphasis on the dynamic spatiotemporal changes within the kefir microbial community. Spatially, we observe variations in species morphology and distribution across different locations within the grain structure. Temporally, the review highlights the succession patterns of the microbial community, shedding light on their evolving interactions.Furthermore, we explore the ecological mechanisms underpinning the formation of a stable community composition. The interplay of cooperative and competitive species within these microorganisms ensures a dynamic balance, contributing to the community's richness and stability. In kefir community, competitive species foster diversity and stability, whereas cooperative species bolster mutualistic symbiosis. By deepening our understanding of the behaviors of these complex microbial communities, we can pave the way for future advancements in the development and diversification of starter cultures for food fermentation processes.

Clinical features of ocular damage in systemic lupus erythematosus and risk factors for hydroxychloroquine-related complications.

Ocular damage in systemic lupus erythematosus (SLE) may cause insidious visual impairment, but its clinical features and the risk of hydroxychloroquine (HCQ)-related complications are still controversial. We performed a meta-analysis to evaluate ocular damage in SLE, the correlation between eye and systemic involvement, and the ocular side effects of treatment. The database PubMed, Embase, and Ovid were used for literature from reception to July, 2023, and the calculation was carried out with R. About 48,693 patients from 66 studies were included. The results indicated that ocular damage in SLE was insidious, appearing in 28 % of patients with no complaints. The most common symptoms and manifestations were dry eye (30 %) and keratoconjunctivitis sicca (26 %). Retinopathy was detected in 10 % of patients and was related to antiphospholipid antibodies (25 % versus 8 %). The proportion of retinopathy also significantly increased in patients with lupus nephropathy or neuropsychiatric systemic lupus erythematosus (risk ratio of 2.29 and 1.95, respectively). HCQ was used in 82 % of patients, of which 4 % suffered from ocular toxicity. HCQ-related retinopathy was dose-dependent. Dosage below 5 mg/kg/d was relatively effective and safe for long-term use, while routine examination was recommended.

Effect of anti-Müllerian hormone on early pregnancy loss in hormone replacement therapy-frozen-thawed embryo transfer cycles: An analysis including 6597 pregnant patients undergoing their first in vitro fertilization/intracytoplasmic sperm injection cycle.

OBJECTIVE: To investigate the relationship between anti-Müllerian hormone (AMH) level and early pregnancy loss in patients who underwent their first embryo transfer by hormone replacement therapy-frozen-thawed embryo transfer (HRT-FET) and analyze the threshold effect. METHODS: A retrospective cohort analysis was performed on pregnant women undergoing HRT-FET at the Reproductive Medical Center of Henan Provincial People's Hospital from January 2016 to December 2021. The patients were divided into four groups based on AMH concentration according to the Poseidon criteria: group A (≤1 µg/L), group B (1-≤2 µg/L), group C (2-≤6 µg/L), and group D (>6 µg/L). Univariate analysis, multivariate logistic regression analysis, smooth curve fitting, and threshold effect analysis were applied to investigate the influence of AMH on the outcome of early pregnancy loss in in vitro fertilization/intracytoplasmic sperm injection and HRT-FET cycles. RESULTS: Of the 6597 pregnant women, early pregnancy loss occurred in 893, giving an early pregnancy loss rate of 13.54%. Univariate regression analysis demonstrated that age, female body mass index, AMH, antral follicle count, endometrial thickness at endometrial transformation day, total retrieved oocyte number, number of pregnancies, duration of infertility, type of infertility, and the number of embryos transferred were all factors influencing the early pregnancy loss rate (P < 0.050). Multivariate logistic regression analysis, after adjusting for confounders, further stratified the analysis of patients of different ages. With group A as the control group, the results showed that when age was younger than 35 years, the pregnancy loss rates in groups B, C, and D were lower than that in group A, with statistical significance (P < 0.050); when age was 35 years or older, there was no statistically significant difference in outcome indicators between the groups (P > 0.050). A threshold effect analysis revealed that the AMH threshold was 2.83 µg/L. When the AMH concentration was less than 2.83 µg/L, the early pregnancy loss rate decreased significantly with increasing AMH concentration; the early pregnancy loss rate decreased by 21% for each unit increase in AMH (odds ratio 0.79; 95% confidence interval 0.71-0.88; P < 0.001); when the AMH concentration was 2.83 µg/L or more, there was no statistical difference in the change in early pregnancy loss rate (odds ratio 1.01; 95% confidence interval 0.99-1.03; P = 0.383). CONCLUSION: For pregnant women after their first embryo transfer, there is a curvilinear relationship between the influences of AMH levels on early pregnancy loss rates in patients younger than 35 years. When the AMH level was less than 2.83 µg/L, the early pregnancy loss rate declined significantly with increasing AMH levels.

Effect of short-term moderate intake of ice wine on hepatic glycolipid metabolism in C57BL/6J mice.

As the correlation between high fructose intake and metabolism-related diseases (e.g., obesity, fatty liver, and type 2 diabetes) has been increasingly reported, the health benefits of consuming ice wine high in fructose have been called into question. In this study, 6-week-old male C57BL/6J mice were divided into control (pure water), fructose (130 g L-1 fructose solution), alcohol (11% alcohol solution), low-dose (50% diluted ice wine) and high-dose ice wine (100% ice wine) groups to investigate the effects and mechanisms of short-term (4 weeks) ice wine intake on hepatic glycolipid metabolism in mice. The results showed that short-term consumption of ice wine suppressed the elevation of low-density lipoprotein cholesterol content and did not cause hepatic lipid accumulation compared with those of the fructose group. Meanwhile, ice wine had no significant effect on lipogenesis although it inhibited fatty acid oxidation via the PPARα/CPT-1α pathway. Compared with the control group, ice wine interfered with the elevation of fasting glucose and the insulin resistance index in a dose-dependent manner, and led to an increase in plasma uric acid levels, which may further contribute to the disruption of glucolipid metabolism. Overall, short-term moderate intake of ice wine over a 4-week period may not significantly affect hepatic glycolipid metabolism in C57BL/6J mice for the time being.

Association with pre-pregnancy BMI on early pregnancy loss in infertility patients in first HRT-FET cycles: A retrospective cohort study.

OBJECTIVE: To investigate the association between pre-pregnancy body mass index (BMI) and the early pregnancy loss rate in patients in first hormone replacement therapy-frozen-thawed embryo transfer (HRT-FET) cycles and find the threshold. METHODS: A retrospective cohort study was conducted using a total of 14030 HRT-FET cycles at the Reproductive Center from January 2017 to December 2021. The association of pre-pregnancy BMI on early pregnancy loss rate in patients in HRT-FET cycles was assessed by performing univariate analysis, multivariable logistic regression, curve fitting and threshold effect analysis. RESULTS: There were 2076 cycles of early pregnancy loss, and the pregnancy loss rate was 14.80%. After adjusting for confounding factors, the early pregnancy loss rate of the obese group was significantly higher than that of the normal weight group (P < 0.05). The threshold effect analysis showed that as the pre-pregnancy BMI ranged from 21.2 to 25.8 kg/m2, the early pregnancy loss rate came to the plateau phase at the low level. In addition, when the BMI was ≥ 25.8 kg/m2, the early pregnancy loss rate increased by 3% (aOR = 1.03, P = 0.01) with each 1 kg/m2 increment of BMI. CONCLUSION: The early pregnancy loss rate might achieve a low level when the pre-pregnancy BMI was within the range of 21.2- 25.8 kg/m2. The early pregnancy loss rate would increase when pre-pregnancy BMI is more than 25.8 kg/m2. For patients in HRT-FET cycles, adjusting their pre-pregnancy BMI to the optimal level by following a healthy diet and daily exercise may help to reduce the early pregnancy loss.

An analysis of POMC gene methylation and expression in patients with schizophrenia.

Schizophrenia is a chronic mental disorder that affects millions of people and is believed to be caused by both environmental and genetic factors. Despite extensive research, the exact mechanisms underlying schizophrenia are still unclear. Studies have shown that numerous psychiatric disorders are associated with methylation of the POMC gene, which encodes adrenocorticotropic hormone, a critical player in the hypothalamic-pituitary-adrenal axis. However, the association between DNA methylation in POMC patients and schizophrenia remains unclear. In this study, we evaluated three fragments of the POMC promoter region, including 51 CpG sites, in the peripheral blood of schizophrenia patients and healthy controls. The POMC protein level was measured via enzyme-linked immunosorbent assay (ELISA). The schizophrenia group exhibited significantly greater levels of methylation of the POMC gene than those in the control group. The methylation level of the POMC-2 fragment was significantly greater in the patient group than in the control group. There were 17 significantly hypermethylated CpG sites in the patient group. After stratification by sex, POMC methylation levels were found to be significantly greater in male schizophrenia patients than in healthy controls; the methylation levels of POMC-2 fragments were greater in the male patient group; nine CpG sites were significantly hypermethylated in the male patient group; and only one CpG site was significantly hypermethylated in the female patient group. The POMC protein level in patients was significantly lower than that in healthy controls. These findings demonstrate that the DNA methylation of POMC might be associated with the pathophysiology of schizophrenia. Overall, studying the correlation between POMC methylation and schizophrenia may contribute to the diagnosis and evaluation of neuropsychiatric disorders.

Synbiotic Combination between Lactobacillus paracasei VL8 and Mannan-Oligosaccharide Repairs the Intestinal Barrier in the Dextran Sulfate Sodium-Induced Colitis Model by Regulating the Intestinal Stem Cell Niche.

Previously, Lactobacillus paracasei VL8, a lactobacillus strain isolated from the traditional Finnish fermented dairy product Viili, demonstrated immunomodulatory and antibacterial effects. The prebiotic mannan-oligosaccharide (MOS) further promoted its antibacterial activity and growth performance, holding promise for maintaining intestinal health. However, this has not been verified in vivo. In this study, we elucidated the process by which L. paracasei VL8 and its synbiotc combination (SYN) with MOS repair the intestinal barrier function in dextran sodium sulfate (DSS)-induced colitis mice. SYN surpasses VL8 or MOS alone in restoring goblet cells and improving the tight junction structure. Omics analysis on gut microbiota reveals SYN's ability to restore Lactobacillus spp. abundance and promote tryptophan metabolism. SYN intervention also inhibits the DSS-induced hyperactivation of the Wnt/ß-catenin pathway. Tryptophan metabolites from Lactobacillus induce intestinal organoid differentiation. Co-housing experiments confirm microbiota transferability, replicating intestinal barrier repair. In conclusion, our study highlights the potential therapeutic efficacy of the synbiotic combination of Lactobacillus paracasei VL8 and MOS in restoring the damaged intestinal barrier and offers new insights into the complex crosstalk between the gut microbiota and intestinal stem cells.

Inverse association between adult height and diabetes risk in a cohort study of Chinese population.

Recent studies linking adult height to diabetes risk remain controversial and few were from Asia. This study, therefore, aimed to explore the association of adult height with diabetes risk in a Chinese population. This retrospective cohort study was a secondary analysis of data from the DATADRYAD website, involving 211,172 non-diabetic individuals aged ≥ 20 years from the health screening program in China. Cox regression models were employed to evaluate hazard ratios (HRs) with 95% confidence interval (CI) of diabetes related to height. During an average 3.12-year follow-up, 4156 (1.97%) subjects reported developing diabetes. After adjusting for potential confounding factors, an inverse association of height with diabetes risk was observed among men and women [HR per 10 cm (95% CI), 0.78 (0.73-0.83) and 0.76 (0.68-0.86), respectively]. Moreover, subgroup analyses indicated the inverse association was only detected in individuals with aged < 70 years, fasting plasma glucose (FPG) < 6.1 mmol/L, and men with body mass index (BMI) < 28 kg/m2. In brief, height is inversely associated with diabetes risk in Chinese adults. Specifically, this association appears to be more pronounced in individuals with aged < 70 years, FPG < 6.1 mmol/L, and men with BMI < 28 kg/m2.

Analysis of leaf forage value and screening of different populations of Pteroceltis tatarinowii, a rare and endemic species in China.

To fully exploit the economic value of the Chinese endemic species Pteroceltis tatarinowii and provide new resources for forage production, the forage nutritional value of P. tatarinowii leaves from different populations was analyzed and evaluated. The results were as follows: 1) There were significant differences in the forage nutrient indices of leaves from different populations. The crude protein content was 10.77%-18.65%, with an average of 14.58%, and the SDJN population had the highest crude protein content. The average crude fat, crude fiber content was 7.62%; the average neutral detergent fiber content was 25.33%; and the average acid detergent fiber contents were 6.79%, 7.62%, 25.33%, and 17.52%, respectively. The average phosphorus and calcium content in the leaves was 0.785 g·kg-1 and 58.01 g·kg-1, respectively. The tannin content was much lower than the antifeedant standard, at an average of 4.97 g·kg-1. The average total amounts of hydrolyzed and free amino acids in the leaves were 108.20 mg·g-1 and 47.87 mg·g-1, respectively. Thus, P. tatarinowii leaves have high crude protein, crude fat, and calcium contents, and low fiber, tannin contents, and are protein-rich. These results provide evidence that this species can be developed into an excellent woody forage tree. 2) There were significant differences in the forage quality evaluation indices among the populations. The forage indices of NDP, ADP, DMI, DDM, and RFV of 21 populations all met the super standard of the American Grass and Grassland Association (AFGC) for hay, two crude protein indices met the grade 1 standard, and 12 crude protein indices met the grade 2 standard. Four high-protein and high-RFV forage populations (SDJN, SDZZ, SXLQ, and AHXX) were selected. 3) The results of the correlation analysis showed that there was no significant correlation between the forage characteristics of P. tatarinowii leaves and latitude and longitude, indicating no significant geographical variation. However, the forage characteristics were strongly correlated with elevation, average annual temperature, and annual precipitation. Thus, high elevation, low temperatures, and rainy weather can improve the forage value of the leaves. P. tatarinowii can be planted to provide leaf forage in cold and wet areas at a specific elevation. Moreover, the forage value of P. tatarinowii leaves can be further improved by increasing nitrogen fertilizer and reducing K and Ca fertilizers during cultivation. 4) Cluster analysis revealed obvious regionalism. Taking the Yangtze River Basin as the limit, cluster analysis divided the species into four population groups: the Yangtze River Basin and northern, southwestern, and eastern coastal populations.

Methylation, Hydroxylation, Glycosylation and Acylation Affect the Transport of Wine Anthocyanins in Caco-2 Cells.

Anthocyanins are substances with multiple physiological activities widely present in red wine, but the influence of structure (methylation, hydroxylation, acylation, glycosylation) on the transport remains ill-defined. In the present study, Caco-2 monolayers were used as an in vitro model of the absorptive intestinal epithelium to transport different types of anthocyanin samples. Results showed that both methylation and acetylation promote the level of transport. Monoglycoside standard exhibited higher transport amount and rate compared to diglycoside standard while the transport level of the monoglycoside mixture was unexpectedly lower than that of the diglycoside mixture. Caco-2 monolayers appeared to be more capable of transporting the single standard than the mixed standard. Meanwhile, the transport of anthocyanins in Caco-2 cell model showed time- and concentration-dependent trends. Anthocyanin treatment had a greater effect on sodium-dependent glucose transporter 1 (SGLT1) mRNA expression than glucose transporter 2 (GLUT2), and significantly down-regulated the protein expression of SGLT1. Although the low bioavailability of anthocyanins requires much more research, further evidence of the role of structure is provided.

Network exploration of gene signatures underlying low birth weight induced metabolic alterations.

BACKGROUND: This study explored underlying gene signatures of low birth weight (LBW) by analyzing differentially expressed genes (DEGs) between LBW and normal birth weight (NBW) subjects. METHODS: Subjects with different birth weight was collected from GEO database. P < .05 and | logFC | ≥ 1.0 were used for screening DEGs. David (2021 Update) was used to perform GO annotation and KEGG signaling pathway enrichment analysis. The protein-protein interaction network of DEGs was constructed using the STRING database, in which hub genes were mined through Cytoscape software. RESULTS: A total of 326 DEGs were identified, including 287 up-regulated genes and 39 down-regulated genes. The GO biological processes enriched by DEGs mainly involved epidermal growth, keratinization and intermediate fibrous tissue. The DEGs were significantly enriched in intracellular insoluble membranes, desmosomes and extracellular space. Their molecular functions mainly focused on structural molecular activity, structural components of epidermis and structural components of cytoskeleton. PI3K/AKT signaling pathway and tight junction were highlighted as critical pathways enriched by DEGs. Ten hub genes which included KRT14, EGF, DSP, DSG1, KRT16, KRT6A, EPCAM, SPRR1B, PKP1, and PPL were identified from the constructed protein-protein interaction network. CONCLUSION: A total of 326 DEGs and 10 hub genes were identified as candidates for metabolic disorders in LBW individuals. Our results indicated PI3K/AKT signaling pathway as an intrauterine adaptive mechanism for LBW individuals. We observed activated PI3K/AKT pathway in LBW individuals, which would promote growth and development at the early stage of life, but adversely introduce extra metabolic stress and thereby potentially induce metabolic disorders in adulthood.

Exploration of hub genes involved in PCOS using biological informatics methods.

BACKGROUND: The aim of this study was to find underlying genes and their interaction mechanism crucial to the polycystic ovarian syndrome (PCOS) by analyzing differentially expressed genes (DEGs) between PCOS and non-PCOS subjects. METHODS: Gene expression data of PCOS and non-PCOS subjects were collected from gene expression omnibus (GEO) database. GEO2R were used to calculating P value and logFC. The screening threshold of DEGs was P < .05 and | FC | ≥ 1.2. GO annotation and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment analysis was performed by using DAVID (2021 Update). The protein-protein interaction (PPI) network of DEGs was constructed by using the STRING database, and the hub genes were recognized through Hubba plugin of Cytoscape software. RESULTS: PCOS and non-PCOS subjects shared a total of 174 DGEs, including 14 upregulated and 160 downregulated genes. The GO biological processes enriched by DEGs mainly involved actin cytoskeleton organization, positive regulation of NF-κB signaling pathway, and positive regulation of canonical Wnt signaling pathway. The DEGs were significantly enriched in cytoplasm, nucleus and cytosol. Their molecular functions mainly focused on protein binding, calmodulin binding and glycerol-3-phosphate dehydrogenase activity. The PI3K/Akt signaling pathway and glycosaminoglycan biosynthesis were highlighted as critical pathways enriched by DEGs. 10 hub genes were screened from the constructed PPI network, of which EGF, FN1 and TLR4 were mainly enriched in the PI3K/Akt signaling pathway. CONCLUSION: In this study, a total of 174 DEGs and 10 hub genes were identified as new candidate targets for insulin resistance (IR) in PCOS individuals, which may provide a new direction for developing novel treatment strategies for PCOS.

Comparative Analysis of the Metabolome and Transcriptome between the Green and Yellow-Green Regions of Variegated Leaves in a Mutant Variety of the Tree Species Pteroceltis tatarinowii.

In nature, many different factors cause plants to develop variegated leaves. To explore the mechanism of variegated leaf formation in Pteroceltis tatarinowii, a mutant variety ('Jinyuyuan'), which was induced by ethylmethylsulfone, was selected, and its morphological structure, physiology, biochemistry, transcription and metabolism were analysed. According to differences in colour values, the colours were divided into two regions: a green region and a yellow-green region. The chlorophyll content of the two regions was significantly different. Moreover, the yellow-green regions of the leaves were significantly thinner than the green regions. The chloroplast ultrastructure in the yellow-green region revealed small chloroplasts, large vacuoles, small starch grains, obviously increased numbers of osmophilic grains, loose lamellae of the inner capsule and thin lamellae. Moreover, the yellow-green region was accompanied by oxidative stress, and the activity of the oxidative phosphorylation pathway related to oxidative activity in the transcriptome showed an upward trend. Vitamin B6 and proline contents also increased, indicating that the antioxidant activity of cells in the yellow-green region increased. Transcriptomic and metabolomic analysis showed that the differentially expressed genes (DEGs) related to chlorophyll synthesis and metabolism led to a decrease in the photosynthesis and then a decrease in the assimilation ability and contents of sucrose, starch and other assimilates. Amino acid synthesis and metabolism, lipid synthesis and the activity of metabolic pathways were obviously downregulated, and the contents of differentially accumulated metabolites associated with amino acids and lipids were also reduced. At the same time, 31 out of 32 DEGs involved in the flavonoid synthesis pathway were downregulated, which affected leaf colour. We hypothesized that the variegated leaves of P. tatarinowii 'Jinyuyuan' are caused by transcriptional and post-transcriptional regulation. Mutations in pigment and flavonoid synthesis pathway genes and transcription factor genes directly affect both pigment and flavonoid synthesis and degradation rate, which in turn affect carbon assimilation, carbon fixation, related protein synthesis and enzyme activity, lipid synthesis and degradation and the activity of other metabolic pathways, eventually leading to the formation of different colour regions.

Congenital adrenal hyperplasia with homozygous and heterozygous mutations: a rare family case report.

BACKGROUND: Congenital adrenal hyperplasia (CAH), characterized by defective adrenal steroidogenesis, is transmitted in an autosomal recessive manner. Mutations in the steroid 21-hydroxylase gene CYP21A2 causing steroid 21-hydroxylase deficiency account for most cases of CAH. The c.145l-1452delGGinsC gene mutation is rare, and only one case has been reported, but the form of gene mutation is different from this case, resulting in different clinical phenotype. The most common pathogenic genotype of CAH is a homozygous or compound heterozygous mutation, but CAH patients homozygous for the p.I173N mutation and heterozygous for the c.1451-1452delGGinsC mutation have not been reported previously. We report herein a familial case of CAH, in which both siblings carry the rare homozygous p.I173N mutation and heterozygous c.1451-1452delGGinsC mutation. CASE PRESENTATION: The proband showed amenorrhea, infertility, polycystic ovaries, and increased levels of androgen, rather than the typical clinical manifestations of CAH such as an adrenal crisis or masculine vulva, so was misdiagnosed with polycystic ovary syndrome for many years. Following a correct diagnosis of CAH, she was given glucocorticoid treatment, her menstruation became more regular, and she became pregnant and delivered a healthy baby girl. CONCLUSIONS: The genotypes may be p.I173N homozygous or p.I173N/c.1451-1452delGGinsC heterozygous, both mutations could be pathogenic. This complex combination of mutations has not been reported or studied before. Through the report and analysis of this genotype, the content of CAH gene bank is enriched and the misdiagnosis rate of CAH is reduced.

Investigation of hub genes involved in Turner syndrome using biological informatics methods.

BACKGROUND: This study aimed to explore candidate genes and their potential interaction mechanism critical to the pathophysiology of Turner syndrome by using the Gene Expression Omnibus database. METHODS: GSE58435 data set was obtained by querying the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened using R and subsequently annotated by Gene Ontology. Functional enrichment analysis was performed based on the Kyoto Encyclopedia of Genes and Genomes database for annotation, visualization, and integrated discovery. A protein-protein interaction network of different genes was constructed based on the STRING database, in which hub genes were explored through Cytoscape software. The expression of the hub genes was verified by analyzing the gene expression in the GSE46687 data set. RESULTS: A total of 733 differential genes were identified. These differentially expressed genes were significantly enriched in nucleoplasm and nucleus. Their molecular function was concentrated on DNA binding and transcription, coronary artery, and adipose tissue development. According to the annotation of Kyoto Encyclopedia of Genes and Genomes, the identified DEGs were mainly enriched in inflammatory mediator regulation of TRP channels, osteoclast differentiation. A total of 10 hub genes (HIST1H2BA, TRIM71, HIST1H2BB, HIST1H4D, TNF, TP53BP1, CDCA8, EGF, HMG20B, and BCL9) were identified from the constructed protein-protein interaction network. These genes were discovered to be highly expressed in osteoclasts, ovaries, digestive tract, blood, and lymphatic tissues through the online application of human protein atlas. CONCLUSION: In this study, 733 DEGs and 10 hub genes were identified. They would be new candidate targets in Turner syndrome.

The Association Between Vitamin D and Type 2 Diabetes Mellitus Complicated with Non-Alcoholic Fatty Liver Disease: An Observational Cross-Sectional Study.

OBJECTIVE: To investigate the association between vitamin D deficiency and NAFLD risk in patients with type 2 diabetes mellitus (T2DM). METHODS: Overall, 434 patients with T2DM admitted to Hebei General Hospital from January 2019 to December 2019 were selected as the study subjects. According to abdominal ultrasound findings, patients were divided into the NAFLD group and the non-NAFLD group. Participants were divided into two study groups according to the 25-hydroxyvitamin D [25(OH)D] level. 25(OH)D deficiency was defined if 25(OH)D vitamin levels were <20 ng/mL. Chi-square test and one-way analysis of variance were used to compare groups. The relationship between 25(OH)D and NAFLD risk was analyzed using correlation and regression analyses. Furthermore, subgroup analyses were performed to verify the robustness of the results. RESULTS: The 25(OH)D level in patients with T2DM complicated by NAFLD was significantly lower than in patients with T2DM only. Vitamin D deficiency was highly prevalent among T2DM patients with NAFLD. This study suggested that vitamin D deficiency was an independent factor for developing NAFLD in patients with T2DM. T2DM patients with vitamin D deficiency had 2.045 times higher risk of developing NAFLD than those without vitamin D deficiency. Vitamin D deficiency was associated with high NAFLD preference in T2DM patients with BMI >23kg/m2, but not those with BMI ≤23kg/m2. The significant correlation between vitamin D deficiency and NAFLD was found in participants with BMI >23kg/m2, age ≤65 years, without hypertension, TG <1.7mmol/l, HDL ≥1 mmol/l in men, ≥1.3 mmol/l in women, HBA1C ≤7%, or females. CONCLUSION: This study suggests that T2DM people with BMI >23kg/m2 were more susceptible to NAFLD by vitamin D deficiency and that it is necessary to maintain optimal serum vitamin D levels in this population.

Clinical Features, Diagnosis, Management and Prognosis of Primary Intraocular Lymphoma.

PURPOSE: To evaluate the clinical features, diagnostic techniques, various treatment strategies and prognosis of primary intraocular lymphoma (PIOL). METHODS: The databases PubMed, EMBASE, and Ovid were searched from inception to March 2021 to identify relevant studies. Statistical analyses were performed with R version 3.3.1. RESULTS: 87 studies involving 1484 patients (aged from 14 to 90 years old) were finally included. The pooling results indicated PIOL patients were female, elderly, binocular and B cell type dominated. About 19% have central nervous system (CNS) involvement at the first visit. During follow-up, the incidence of CNS involvement, death rate, 2-year and 5-year survival rate, 1-year and 2-year progression-free survival, and recurrence rate were 58%, 33%, 82%, 70%, 88%, 70%, 44%, respectively. The most common recurrent site was CNS. The delayed diagnosis rate was 85%, the misdiagnosed rate was 64%. The diagnostic technique with the highest positive rate was IL10:IL6>1 of aqueous (98%). The most common symptoms, signs, FFA and OCT features were blurring of vision (72%), vitreous inflammatory opacity (92%), FA/FAF reversal (91%) and hyper-reflective foci in posterior vitreous (53%), respectively. The prognosis of PIOL patients without CNS involvement was obviously better than those with CNS involvement. Overall, intravitreal injection of chemotherapy drug plus systemic chemotherapy (IV+CT) could achieve satisfactory prognosis, the combination of local radiotherapy (RT) could further decrease the recurrent and death rate. CONCLUSION: PIOL patients with CNS involvement had significantly worse prognosis. The aqueous humor examination should be regarded as first-line and routine diagnostic technique. IV+CT could achieve satisfactory prognosis, the combination of RT was also beneficial.