Differential effect of pre-pregnancy low BMI on fetal macrosomia: a population-based cohort study.

BACKGROUND: The differential effect of pre-pregnancy low BMI on macrosomia has not been fully addressed. Herein, we conducted a city-wide population-based cohort study to illuminate the association between pre-pregnancy low BMI and macrosomia, stratifying by maternal age, parity, and GDM status. METHODS: All pregnant women who paid their first prenatal visit to the hospital in Qingdao during August 1, 2018, to June 30, 2020, were recruited to this study. The interactive effect of maternal age and pre-pregnancy low BMI on macrosomia was evaluated using logistic regression models, followed by strata-specific analyses. RESULTS: A total of 105,768 mother-child pairs were included, and the proportion of fetal macrosomia was 11.66%. The interactive effect of maternal pre-pregnancy BMI and age was statistically significant on macrosomia irrespective of parity (nullipara: Padjusted=0.0265; multipara: Padjusted=0.0356). The protective effect of low BMI on macrosomia was most prominent among nullipara aged 35 years and above (aOR=0.16, 95% CI 0.05-0.49) and multipara aged 25 years and below (aOR=0.17, 95% CI 0.05-0.55). In nullipara without GDM, the risk estimates gradually declined with increasing conception age (20-to-24 years: aOR=0.64, 95% CI 0.51-0.80; 25-to-29 years: aOR=0.43 95% CI 0.36-0.52; 30-to-34 years: aOR=0.40 95% CI 0.29-0.53; and ≥35 years: aOR=0.19, 95% CI 0.06-0.60). A similar pattern could also be observed in nullipara with GDM, where the aOR for low BMI on macrosomia decreased from 0.54 (95% CI 0.32-0.93) in pregnant women aged 25-29 years to 0.30 (95% CI 0.12-0.75) among those aged 30-34 years. However, younger multiparous mothers, especially those aged 25 years and below without GDM (aOR=0.21, 95% CI 0.06-0.68), were more benefited from a lower BMI against the development of macrosomia. CONCLUSIONS: Maternal low BMI is inversely associated with macrosomia irrespective of maternal age and parity. The impact of pre-pregnancy low BMI on macrosomia varied by maternal age and parity. The protective effect of a lower maternal BMI against fetal macrosomia was more prominent in nulliparous mothers aged 35 years and above, whereas multiparous mothers younger than 25 years of age were more benefited.

Joint effect of 25-hydroxyvitamin D and secondhand smoke exposure on hypertension in non-smoking women of childbearing age: NHANES 2007-2014.

BACKGROUND: Vitamin D deficiency (VDD) may increase the risk of hypertension in women of childbearing age, who may be exposed to secondhand smoke (SHS) simultaneously. Till now, few studies have investigated the joint effects of VDD and SHS on hypertension in this population. We evaluated whether exposure to SHS modified the association between VDD and hypertension. METHODS: Data from National Health and Nutrition Examination Surveys (NHANES) 2007-2014 were analyzed. Our research subjects were 2826 nonsmoking and nonpregnant women of childbearing age (20-44 years old). Hypertension was defined based either on systolic blood pressure (SBP) ≥ 130 mmHg and/or diastolic blood pressure (DBP) ≥ 80 mmHg or on now taking prescribed medicine for hypertension. The directed acyclic graphs (DAG) and the back-door criterion were used to select a minimal sufficient adjustment set of variables (MSAs) that would identify the unconfounded effect of 25(OH)D and hypertension. The interactive effect of VDD and SHS on hypertension was evaluated by using logistic regression models, followed by strata-specific analyses. RESULTS: The prevalence of VDD in the hypertension group was significantly higher than that in the non-hypertension group (48.2% vs 41.0%, P = 0.008), as well as the exposure rate of SHS (39.1% vs 33.8%, P = 0.017). VDD was independently associated with nearly 50% increased risk of hypertension [adjusted odds ratio (aOR) = 1.43, 95% confidence interval (CI): 1.01, 2.04], while no significant association was observed between SHS and hypertension. However, SHS showed a significant synergistic effect on VDD with a higher aOR of 1.79 (95% CI: 1.14, 2.80) (Pinteraction = 0.011). This synergistic effect was more obvious when stratified by BMI (in overweight women, aOR, 95% CI =4.74, 1.65-13.60 for interaction vs 2.33, 1.01-5.38 for VDD only) and race (in Non-Hispanic Black women, aOR, 95% CI =5.11, 1.58-16.54 for interaction vs 2.69, 1.10-6.62 for VDD only). CONCLUSION: There exist synergistic effects of SHS and VDD on the prevalence of hypertension in American women of childbearing age, with more significant effects in women who were overweight or Non-Hispanic Black. Further studies are warranted to verify this finding in other populations, and the molecular mechanisms underlying the joint effect of SHS and VDD need to be elucidated.

The possible role of visceral fat in early pregnancy as a predictor of gestational diabetes mellitus by regulating adipose-derived exosomes miRNA-148 family: protocol for a nested case-control study in a cohort study.

BACKGROUND: Gestational diabetes mellitus (GDM) has become alarming public health concern. It is associated with adverse pregnancy outcomes and increased risk of postpartum type 2 diabetes. Pre-pregnant body mass index (BMI), waist circumference and other anthropometric parameters have been proposed to predict GDM. However, visceral fat thickness can better reflect the distribution of body fat, and may more accurately predict the risk of GDM. Visceral fat thickness may lead to insulin resistance by regulating the adipose-derived exosomes miRNA-148 family, which affect the development of GDM. Evidence from prospective cohort studies on visceral fat thickness as a predictor of GDM and the possible mechanisms is still insufficient. METHODS: In this prospective cohort study, we will recruit 3000 women at first antenatal visit between 4 and 12 weeks of gestation. Baseline socio-demographic factors and visceral fat thickness will be assessed by questionnaire form and the ultrasonic measurement, respectively. At 20 weeks of gestation, 10 ml blood samples will be drawn and we will extract adipose-derived exosomes miRNA on the basis of nested case-control study. GDM will be screened at 24-28 weeks' gestation and the expression of miRNA-148 family between pregnant women with GDM and without GDM will be analyzed. Intermediary analysis will be used to investigate whether visceral fat thickness can predict GDM by regulating adipose-derived exosomes miRNA-148 family. DISCUSSION: We hypothesized that visceral fat thickness may predict GDM by regulating the miRNA-148 family of adipose-derived exosomes. The findings of the study will assist in further clarifying the pathophysiological mechanism of GDM, it will also provide technical support for effective screening of high-risk pregnant women with GDM.

Interaction of sex, age, body mass index and race on hypertension risk in the American population: a cross-sectional study.

BACKGROUND: The joint effects of sex, age, body mass index (BMI) and race on hypertension have not been fully addressed. Herein, we carried out this study aiming to investigate the possible effects of the interaction of sex, age, BMI and race on risk of hypertension. METHODS: By using the data of a sample-adjusted 2656 women and 2515 men in American National Health and Nutrition Examination Survey 2015-16, we analyzed the interaction of sex, age, BMI and race by logistic regression models, followed by strata-specific analyses. Hypertension was defined as a systolic blood pressure ≥130 mmHg/diastolic blood pressure ≥80 mmHg or taking anti-hypertensive medication. RESULTS: A total of 5171 participants were included in analysis, and the prevalence of hypertension was 53.68%. The interactive effect of sex and age, BMI and age, race and age were statistically significant on hypertension. Strata-specific analyses showed that female at 40 years and above were positively associated with hypertension than those at 20-39 years. The associations also persistence in male. The risk estimates for age ≥40 on hypertension were consistently positive across all overweight/obesity and race groups. The effect was most prominent among overweight populations aged 60-80 years and Other Hispanic aged 40 years and above. CONCLUSION: There exists interactive effect of sex and age, BMI and age, race and age on hypertension in American population. The effect of age on hypertension was more prominent in female, overweight populations and Other Hispanic populations. Differences in age, BMI and race should be considered when providing corresponding antihypertensive measures.

Molecular epidemiological and hematological profile of thalassemia in the Dongguan Region of Guangdong Province, Southern China.

BACKGROUND: Thalassemia is a common inherited hematological disease in tropical and subtropical regions. This study aimed to investigate the mutation spectrum of thalassemia in the Dongguan region of southern China and comprehensively analyze hematologic features of thalassemia carriers with various types of globin mutations. METHODS: A hematological screening including hematological indices such as mean corpuscular volume (MCV), mean corpuscular hemoglobin content (MCH), and mean corpuscular hemoglobin concentration (MCHC) was conducted in 19 442 people from Dongguan region, Guangdong province of China. Then, 4891 suspected thalassemia carriers were further investigated by genetic analysis of combined NGS and gap-PCR. RESULTS: Totally, 2319 (11.9%) cases were diagnosed as carriers of thalassemia, of which 1483 cases (7.6%) were α-thalassemia, 741 cases (3.8%) were ß-thalassemia, and 95 cases (0.5%) were co-inheritance of α- and ß-thalassemia. In α-thalassemia carriers, the phenotypic severity increases with the number of nonfunctional α-globin genes. The patients with -SEA /αWS α genotype have less severe clinical phenotypes than those with other Hb H diseases. As for ß-thalassemia, the MCV and MCH in both ß0 and ß+ carriers are markedly reduced. CONCLUSIONS: This is the first comprehensive molecular epidemiological survey and hematological profiling of thalassemia in Dongguan area. This study will be benefit for genetic counseling in the clinic and may help pediatricians to make a correct diagnosis of different types of thalassemia.

[Expression of long non-coding RNA linc00467 in childhood acute myeloid leukemia and its role in drug resistance].

OBJECTIVE: To study the expression and function of long non-coding RNA linc00467 in childhood acute myeloid leukemia (AML). METHODS: Bone marrow samples were collected from 5 children with AML who were diagnosed from May 2016 to June 2018. Normal bone marrow samples based on bone marrow examination were collected from 3 children as controls. Quantitative real-time PCR was used to measure the expression of linc00467 in the two groups. A lentivirus system was used to achieve overexpression of linc00467 in AML cells (HL-60) (linc00467 overexpression group), and empty vector expressing green fluorescent protein (GFP) was transfected into AML cells to establish a GFP control group. A lentivirus system was used to insert an interfering sequence into AML cells (sh-linc00467 interfering group), and a random sequence was inserted to establish an sh-NC control group. Cell proliferation and resistance to doxorubicin were observed for all groups. RESULTS: Compared with the normal control group, the children with AML had a significant increase in linc00467 (P=0.018). Overexpression and interference with linc00467 expression had no significant effect on cell proliferation. Compared with the GFP control group, the linc00467 overexpression group had a significant increase in the viability of HL-60 cells at the adriamycin concentrations of 0.1, 0.2, 0.3, 0.4, and 0.5 µg/mL (P<0.05). Compared with the sh-NC control group, the sh-linc00467 interfering group had a significant reduction in the viability of HL-60 cells at the adriamycin concentrations of 0.1, 0.2, 0.3, 0.4, and 0.5 µg/mL (P<0.05). Compared with the untreated group, the adriamycin treatment group had a significant increase in the expression of linc00467 in HL-60 cells (P<0.05). CONCLUSIONS: This study reveals the biological function of linc00467 to promote the resistance to adriamycin in AML, which provides a basis for developing new therapeutic drugs for AML.

[Current status of vitamin A deficiency in preschool children in Dongguan, China and the effect of vitamin A on serum ferritin and red blood cell parameters].

OBJECTIVE: To investigate the current status of vitamin A deficiency in preschool children in Dongguan, China, as well as the effect of vitamin A on serum ferritin, red blood cell, and reticulocyte parameters. METHODS: Cluster sampling was performed from April 2015 to December 2016 to select 2 085 preschool children (3-6 years old) without any disease in Dongguan. Routine blood test, reticulocyte count, serum ferritin measurement, hemoglobin electrophoresis, and vitamin A measurement were performed for all children. The associations of age and sex with vitamin A and serum ferritin concentrations were analyzed. The effect of vitamin A concentration on serum ferritin, red blood cell, and reticulocyte parameters and the effect of reduced iron storage caused by vitamin A deficiency on red blood cell parameters were evaluated. RESULTS: Of the 2 085 children, 140 (6.71%) had reduced iron storage, and 678 (32.52%) had vitamin A deficiency. Among the 678 children with vitamin A deficiency, 647 (95.4%) had subclinical deficiency and 31 (4.6%) had clinical deficiency. There was no significant difference in vitamin A concentration between boys and girls, however girls had a significantly higher serum ferritin concentration than boys (P<0.05). The clinical vitamin A deficiency group had a significantly higher serum ferritin concentration than the subclinical vitamin A deficiency group and the normal group (P<0.05). In cases of vitamin A deficiency, the reduced iron storage group had significant reductions in mean corpuscular volume and mean corpuscular hemoglobin than the normal iron storage group (P<0.05). Compared with the normal vitamin A group, the vitamin A deficiency group had significantly lower hemoglobin concentration, mean corpuscular hemoglobin, red blood cell count, hematocrit, absolute reticulocyte count, reticulocyte percentage, and reticulocyte hemoglobin content, as well as a significantly higher mean corpuscular volume (P<0.05). CONCLUSIONS: Vitamin A deficiency is prevalent in preschool children in Dongguan, China, and it may adversely affect serum ferritin, red blood cell, and reticulocyte parameters.

Competence of Aedes aegypti, Ae. albopictus, and Culex quinquefasciatus Mosquitoes as Zika Virus Vectors, China.

In China, the prevention and control of Zika virus disease has been a public health threat since the first imported case was reported in February 2016. To determine the vector competence of potential vector mosquito species, we experimentally infected Aedes aegypti, Ae. albopictus, and Culex quinquefasciatus mosquitoes and determined infection rates, dissemination rates, and transmission rates. We found the highest vector competence for the imported Zika virus in Ae. aegypti mosquitoes, some susceptibility of Ae. albopictus mosquitoes, but no transmission ability for Cx. quinquefasciatus mosquitoes. Considering that, in China, Ae. albopictus mosquitoes are widely distributed but Ae. aegypti mosquito distribution is limited, Ae. albopictus mosquitoes are a potential primary vector for Zika virus and should be targeted in vector control strategies.

Affection of Comt1 genetype on anxiety and nociceptive sensitivity: an Ego-network analysis approach.

Purpose: The aim of this study was to predict key genes and their relationships for anxiety and nociceptive sensitivity related to Comt1 genetype. Methods: : The raw data of E-GEOD-20160 related to anxiety and nociceptive sensitivity were obtained. Pearson correlation coefficient of interaction in protein­protein interaction was calculated. Topological analysis was processed for protein­ protein interaction network, and genes in this network were ranked based on their degrees. Ego genes were identified, and models were searched and refined. A total of 1000 randomized tests were processed for ego networks. The classification accuracy of each ego network was obtained in this process. Results: The interactions with genes in gene expression profiles were extracted, and protein­protein interaction was constructed. The protein­protein interaction included 4639 genes and 43,837 relationships. Differential co-expression network was constructed, and 74 ego genes were obtained. Thereinto, top five ego genes were ADCY2, GRM8, S1PR3, ADCY6, and ANXA1. After module searching and refinement, a total of 11 candidate modules were obtained, including module 14, module 51, and module 9. In addition, these 11 modules were confirmed to be with significance. Module 14 contained 10 genes, such as HRH3, DRD2, and CXCR3. Similarly, module 51 included six genes, such as HELZ2, NCOA3, and MED30. Conclusions: Ego network analysis was a useful and comprehensive method for biomarkers screening. Several modules such as module 3 and module 36 were important subnetworks. Potential genes in these modules including ADCYs, GNAI1, DRD2, PNOC, CCR2, DRD2, and LPAR1 might be important genes in the research of anxiety and nociceptive sensitivity.

The effect of statins on microalbuminuria, proteinuria, progression of kidney function, and all-cause mortality in patients with non-end stage chronic kidney disease: A meta-analysis.

Conclusive evidence regarding the effect of statins on non-end stage chronic kidney disease (CKD) has not been reported previously. This meta-analysis evaluated the association between statins and microalbuminuria, proteinuria, progression, and all-cause mortality in patients with non-end stage CKD. Databases (e.g., PubMed, Embase and the Cochrane Library) were searched for randomized controlled trials (RCTs) with data on statins, microalbuminuria, proteinuria, renal health endpoints, and all-cause mortality patients with non-end stage CKD to perform this meta-analysis. The mean difference (MD) of the urine albumin excretion ratios (UAER), 24-h urine protein excretion, and risk ratios (RR) of all-cause mortality and renal health endpoints were calculated, and the results are presented with 95% confidence intervals (CI). A total of 23 RCTs with 39,419 participants were selected. The analysis demonstrated that statins statistically reduced UAER to 26.73 µg/min [95%CI (-51.04, -2.43), Z=2.16, P<0.05], 24-h urine protein excretion to 682.68 mg [95%CI (-886.72, -478.63), Z=6.56, P<0.01] and decreased all-cause mortality [RR=0.78, 95%CI (0.72, 0.84), Z=6.08, P<0.01]. However, the analysis results did not indicate that statins reduced the events of renal health endpoints [RR=0.96, 95%CI (0.91,1.01), Z=1.40, P>0.05]. In summary, our study indicates that statins statistically reduced microalbuminuria, proteinuria, and clinical deaths, but statins did not effectively slow the clinical progression of non-end stage CKD.

Analysis of essential amino acid residues for catalytic activity of cis-epoxysuccinate hydrolase from Bordetella sp. BK-52.

cis-Epoxysuccinate hydrolase (CESH) from Bordetella sp. BK-52, an epoxide hydrolase (EH), catalyzes the stereospecific hydrolysis of cis-epoxysuccinate to D(-)-tartrate. The enzyme, which shows no homology to other reported EHs, belongs to the DUF849 superfamily of prokaryotic proteins, which have unknown function. Metal composition analysis revealed that the CESH is a Zn(2+)-dependent enzyme with an approximately 1:1 molar ratio of zinc to enzyme. The results of an (18)O-labeling study suggest that the enzyme catalyzes epoxide hydrolysis by means of a one-step mechanism. We evaluated the relationship between the structure and function of the enzyme by means of sequence alignment, modeling, substrate binding, and reaction kinetics studies. The CESH has a canonical (ß/α)8 TIM barrel fold, and we used site-directed mutagenesis to identify eight residues (H47, H49, R51, T82, Y138, N140, W164, and D251) as being localized to the active site or highly conserved. On the basis of these results and theoretical considerations, we identified H47 and H49 as zinc-binding ligands, and we propose that a zinc atom and R51, T82, Y138, N140, W164, and D251 are the catalytic residues and participate in substrate binding. In summary, the structure and catalytic mechanism of the CESH from Bordetella sp. BK-52 differ from those of classic EHs, which have an α/ß hydrolase fold, act via a two-step catalytic mechanism, and do not require cofactors, prosthetic groups, or metal ions.

Magnetically separable Co0.6Fe2.4O4/MIL-101-NH2 adsorbent for Congo red efficient removal.

The development of effective and practical adsorbents for eliminating pollutants still remains a significant challenge. Herein, we synthesized a novel magnetically separable composite, Co0.6Fe2.4O4/MIL-101-NH2, through the in-situ growth of MIL-101-NH2 on magnetic nanoparticles, designed specifically for the removal of Congo red (CR) from aqueous solutions. MIL-101-NH2 possessed high BET surface area (240.485 m2•g-1) and facile magnetic separation function and can be swiftly separated (within 30 s) through an external magnetic field post-adsorption. The investigation systematically explored the influence of crucial parameters, including adsorbent dosage, pH, adsorption duration, temperature, and the presence of interfering ions, on CR adsorption performance. Findings indicate that CR adsorption adheres to the pseudo-second-order (PSO) kinetic model and the Langmuir isotherm model. Thermodynamic analysis reveals the spontaneity, endothermic nature, and orderly progression of the adsorption process. Remarkably, the adsorbent with 0.1 g•L-1 boasts an impressive maximum adsorption capacity of 1756.19 mg•g-1 for CR at 298.15 K, establishing its competitive advantage. The reuse of the adsorbent over 5 cycles remains 78% of the initial adsorption. The CR adsorption mechanisms were elucidated, emphasizing the roles of π-π interactions, electrostatic forces, hydrogen bonding, and metal coordination. Comparison with other dyes, such as methylene blue (MB) and methyl orange (MO), and exploration of adsorption performance in binary dye systems, demonstrates the superior capacity and selectivity of this adsorbent for CR. In conclusion, our magnetically separable metal-organic framework (MOF)based composite presents a versatile and effective solution for CR removal, with promising applications in water treatment and environmental remediation.

Integrated transcriptomic and metabolomic analyses reveal potential regulatory pathways regulating bone metabolism pre- and postsexual maturity in hens.

At the onset of sexual maturity, the increasing circulating estrogen stimulates the formation of medullary bone, which provides available calcium for eggshell formation. The bone loss of laying hens is caused by the continuous dynamic changes of structure bone leading to bone fragility and susceptibility. The degree of medullary bone mineralization in sexual maturity is positively correlated with bone quality in the late laying stage. This study aimed to explore the molecular regulation mechanism of bone metabolism pre- and postsexual maturity in hens based on the joint analysis of transcriptome and metabolome. A total of 50 Hy-line Sonia pullets with comparable body weight at 13 wk were selected. Eight pullets were killed at 15 wk (juvenile hens, JH) and 19 wk (laying hens, LH), and LHs were killed within 3 h after oviposition. Differentially expressed genes and metabolites in tibia were analyzed based on transcriptome and metabolome, and then combined to construct the relevant metabolisms and hub genes. In the LH hens, plasma levels of estrogen and tartrate-resistant acid phosphatase were significantly elevated by 1.7 and 1.3 times. In addition, the midpoint diameter, bone mineral density and bone mineral content of the tibia and femur were higher at 19 wk of age. A total of 580 differentially expressed genes were found between the JH and LH group in the tibia, including 280 up-regulated, and 300 down-regulated genes in the LH group. Gene set enrichment analysis (GSEA) showed that the intracellular biosynthesis and secretion of matrix vesicles were significantly enrichment in the LH hens. A total of 21 differential metabolites were identified between JH and LH group. Estradiol valerate positively correlated with L-theanine, tryptophan betaine, dopamine, and perindopril. Joint analysis showed that the top 20 hub genes were enriched in cholesterol biosynthesis and phospholipid metabolism, which played a key regulatory role in bone metabolism during pre- and postsexual maturity. These results provide a theoretical foundation for maintaining efficient egg production and reducing bone health problems in laying hens.

Genetic variability of PRNP in Chinese indigenous goats.

Polymorphism of the prion protein gene (PRNP) is usually associated with scrapie susceptibility or resistance. To determine the variability of PRNP in Chinese indigenous goat breeds, we isolated genomic DNA from goat blood and amplified and sequenced the coding region of the gene. We identified 10 polymorphic sites that gave rise to 28 haplotypes. Clear frequency differences were found between northern and southern breeds and confirmed by genetic distance analysis, except for the Tangshan dairy goat. Phylogeographic analysis supported the idea that northern and southern breeds might be considered separate clusters, except for the Tangshan dairy goat. The finding of significant differences in allele distribution in northern and southern goats, especially if involved in modulating resistance/susceptibility, needs to be carefully considered for the feasibility of selection plans for resistance to scrapie.

Choriocarcinoma masquerading as lumbar spinal tumor: Case report and literature review.

RATIONALE: Choriocarcinoma is a highly invasive gestational trophoblastic neoplasm, usually metastasis to lung and brain, but occurrence of choriocarcinoma following spontaneous abortion presenting as a vertebral tumor is extremely rare, to the best of our knowledge. Because of the poor diagnosis and high malignancy, the low progression-free survival follows up. PATIENT CONCERNS: We here are reporting a case of choriocarcinoma that presented with vertebral tumor induced paralysis of limbs and incontinence of urine. DIAGNOSIS: Combined with the childbearing history, high ß-human chorionic gonadotrophinin levels, and imaging examination, a clinical diagnosis was made exactly. Till the pathological results after the operation of lumbar spinal canal tumorectomy, the diagnosis was exactly clear. INTERVENTIONS: After performing the laminectomy, the fierce bleeding follows up, just did the temporary limited decompression. Because of the vertebral artery embolization, lumbar spinal canal tumorectomy, spinal canal and root canal decompression, subdural decompression and hematoma removal were performed. OUTCOMES: After performing the operation and chemotherapy timely and positively, the patient lost consciousness and died due to the pulmonary embolism at last. LESSONS: This is the first case report describing choriocarcinoma with metastases to the spine amongst Chinese population as well. Early metastasis is one of the marked tendencies of choriocarcinoma, but spine metastasis and the related spinal oppressional symptoms were found instead of vaginal bleeding in this case, which is indeed rare.

Case Report: A de novo NLRP3 variant resulting in autoinflammatory disease in a Chinese newborn.

Background: Cryopyrin-associated periodic syndromes (CAPS) have been considered autoinflammatory diseases resulting from NLRP3 gene mutations. In recent years, these conditions have been redefined as NLRP3-associated autoinflammatory diseases (NLRP3-AID). Our previous study highlighted a case of a Chinese individual carrying the de novo NLRP3 mutation. Results: A female child carrying a de novo variant (c.1718T>G, p. L573W) in the NLRP3 gene was presented in this work. The patient manifested various symptoms, including recurrent fever, a rash resembling urticaria, arthritis, physical growth retardation, a notable prominence of the forehead, and a flat nose bridge. Additionally, inflammatory markers, like WBC count, PLT count, CRP, ESR, and IL-6 showed elevated levels. Additionally, we observed interstitial pulmonary disease in the patient, which is not frequently mentioned in previous studies. Notably, the proband did not present with any ocular, auditory, or neurological symptoms. After 12 weeks of subcutaneous canakinumab injection, there was a clear improvement in the patient's clinical manifestations and inflammatory markers. Conclusion: Our study contributes to broadening the clinical spectrum of established pathogenic variants of NLRP3 gene, which are related to NLRP3-AID.

Raised SPINK1 levels play a role in angiogenesis and the transendothelial migration of ALL cells.

The present study was designed to assess whether raised Serine protease inhibitor Kazal type 1 (SPINK1) expressions modulates angiogenesis. Human umbilical vein endothelial cells (HUVECs) exposed to SPINK1 were noted to exhibit raised expressions of interleukin-8 (IL-8) as well as VCAM-1 and ICAM-1 cell adhesion molecules in a dose-dependent manner. In co-culture system of HUVECs and Acute lymphoblastic leukemia (ALL) cells, SPINK1 exposure also resulted in enhanced endothelial cell motility and ALL cells trans-endothelial migration. High concentrations of SPINK1 caused in vitro cellular reorganization into tubes in Matrigel-cultured HUVECs and induced in vivo vascularization and brain infiltration of NOD/SCID ALL model mice. The further transcriptomic analysis indicated that SPINK1 treatment altered several biological processes of endothelial cells and led to activation of the MAPK pathway. This study is the first to determine the neovascularization effects of raised SPINK1.

The Application Value of Syndecan-2 Gene Methylation for Colorectal Cancer Diagnosis: A Clinical Study and Meta-Analyses.

Objective: Syndecan-2 (SDC2) methylation has been previously reported as a sensitive biomarker for the early detection of colorectal cancer (CRC). Droplet digital PCR (ddPCR) is the latest development of PCR technology. It can accurately detect and quantify the target sequence of nucleic acid. ddPCR is widely used in research and clinical diagnosis. In the present study, we aimed to develop a ddPCR method to detect SDC2 gene methylation and evaluate the diagnostic value of SDC2 gene methylation. Methods: First, a ddPCR method was developed to measure SDC2 methylation in stool samples collected from 51 cases of normal, 23 cases of adenoma, and 86 cases of CRC. Subsequently, a meta-analysis of existing studies was conducted to judge the diagnostic value of SDC2 gene methylation in CRC. PUBMED, EMBASE, Web of Science, and Scopus databases were searched for relative studies. Meta-analysis was performed using Meta Disc 1.4 and STATA 15.0 software. Results: The ddPCR showed that the linearity, sensitivity, and specificity for the detection of SDC2 gene methylation could be down to 0.1% methylation level and 5 ng of methylated DNA input. In 109 cases of CRC, 107 cases could be detected, and the sensitivity was 98.17%. The median value of the percentage of methylated reference (PMR) in colorectal adenoma and CRC patients was significantly higher compared with the normal individuals (p < 0.001). In addition, we found that the PMR value was associated with the clinical staging of CRC. The difference of PMR in stage II and stage IIIA was statistically significant (p < 0.05). Moreover, the meta-analysis showed that 11 out of 87 studies were identified to report the feasibility of SDC2 gene methylation as a method to diagnose early CRC. The pooled sensitivity and specificity of SDC2 gene methylation test for CRC were 0.80 [95% CI (0.68-0.88)] and 0.93 [95% CI (0.91-0.94)], respectively. The pooled diagnostic odds ratio (DOR) and area under curve (AUC) were 52.46 [95% CI (30.43-90.45)] and 0.94 [95% CI (0.92, 0.96)], respectively. Conclusions: The ddPCR method was more sensitive and convenient to detect SDC2 gene methylation, and the pooled analysis showed that methylated SDC2 was a valuable biomarker for the non-invasive detection of CRC.

Salivary Fusobacterium nucleatum serves as a potential biomarker for colorectal cancer.

Fusobacterium nucleatum (Fn) is primarily colonized in the oral cavity. Recently, Fn has been closely associated with the tumorigenesis of colorectal cancer (CRC). Here, we showed that the relative level of Fn DNA was increased in the saliva of the CRC group compared with the normal colonoscopy, hyperplastic polyp, and adenoma groups. Receiver operating characteristic curve analysis illustrated that Fn DNA was superior to carcinoembryonic antigen and carbohydrate antigen 19-9 in CRC diagnosis. Moreover, levels of Fn DNA were associated with the overall survival and disease-free survival of CRC patients, which was an independent factor for prognostic prediction. Transcriptome sequencing identified 1,287 differentially expressed mRNAs in tumor tissues between CRC patients with high-Fn and low-Fn infection. Kyoto encyclopedia of genes and genomes analysis showed that ECM-receptor interaction and focal adhesion were the top two significant pathways. Overall, salivary Fn DNA may be a noninvasive diagnostic and prognostic biomarker for CRC patients.