Multiple myeloma (MM) is a common hematologic malignancy that originates from precursor conditions such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Identifying its risk factors is crucial for early intervention. The etiology of MM is multifactorial, involving race, familial clustering, gender, age, obesity, cytogenetic abnormalities, and environmental exposures. Among these, cytogenetic abnormalities and modifiable factors play pivotal roles in MM pathogenesis and progression. 1) cytogenetic abnormalities. Primary abnormalities [e.g., hyperdiploidy, t(11;14), t(14;16)] emerge at the MGUS stage, while secondary abnormalities [e.g., 1q+, del(17p)] drive disease progression. The accumulation of 1q+ promotes clonal evolution, and del(17p) is associated with significantly reduced survival. 2) modifiable risk factors. Obesity promotes MM via the acetyl-CoA synthetase 2 (ACSS2)-interferon regulatory factor 4 (IRF4) pathway. Vitamin D deficiency weakens immune surveillance. Exposure to herbicides such as Agent Orange and glyphosate increases MGUS incidence. Insufficient UV exposure, by reducing vitamin D synthesis, elevates MM risk. Gut microbiota dysbiosis (enrichment of nitrogen-cycle bacteria and depletion of short-chain fatty acids producers) induces chromosomal instability through the ammonium ion-solute carrier family 12 member 22 (SLC12A2)-NEK2 axis. Therefore, risk-based screening among high-risk populations (e.g., those who are obese, elderly, or chemically exposed), along with early interventions targeting cytogenetic abnormalities [e.g., B cell lymphoma 2 (Bcl-2) inhibitors for t(11;14), ferroptosis inducers for t(4;14)] and modifiable factors (e.g., vitamin D supplementation, gut microbiota modulation), may effectively delay disease progression and improve prognosis.
Humans ; Multiple Myeloma/epidemiology* ; Risk Factors ; Obesity/complications* ; Chromosome Aberrations ; Monoclonal Gammopathy of Undetermined Significance/etiology* ; Gastrointestinal Microbiome ; Vitamin D Deficiency/complications* ; Precancerous Conditions/genetics*

OBJECTIVES: To prepare a stable mouse model of chronic liver fibrosis induced by dietary vitamin A (VA) deficiency combined with CCl₄ injections. METHODS: A total of 126 Balb/c mice were randomized into 3 groups for feeding with a normal VA diet or a VA-deficient diet containing 500 or 200 IU/kg VA. After 4 weeks of feeding, half of the mice in each group were given intraperitoneal injections of 5% CCl₄ (10 mL/kg, twice a week) for 8 weeks. Serum retinol, ALT/AST and liver index of the mice were examined, liver tissue pathologies were observed with HE and Masson staining, and liver fibrosis score and oxidative stress level were evaluated. RESULTS: Four weeks of VA-deficient feeding, especially at 200 IU/kg, significantly lowered serum retinol level of the mice. CCl₄ injections for 8 weeks obviously increased liver index and ALT/AST and caused obvious liver fibrosis in all the mice, but liver pathologies were more severe in the 2 VA-deficient groups; severe liver necrosis with inflammatory cell infiltration was observed in 200 IU/kg VA group, where 2 mice died. After discontinuation of CCl₄, the mice with normal dietary VA showed gradual recovery of the liver index, ALT/AST, liver cord structure and liver fibrosis; the mice with VA deficiency, however, showed no significant improvements in these parameters, and the mice with 200 IU/kg VA still had serious abdominal adhesion, false lobules and massive inflammatory cell infiltration with a fibrosis stage score of 3. The oxidative damage index 8-OHdG was significantly higher in 500 IU/kg VA group than in normal VA group after CCl₄ modeling. CONCLUSIONS Feeding with diet containing 500 IU/kg VA for 4 weeks and 10 mL/kg CCl₄ injections for 8 weeks can result in stable moderate to severe liver fibrosis in mice without spontaneous reversal at 8 weeks of drug withdrawal.
Animals ; Mice ; Mice, Inbred BALB C ; Disease Models, Animal ; Carbon Tetrachloride ; Vitamin A Deficiency/complications* ; Male ; Liver Cirrhosis/etiology* ; Oxidative Stress ; Vitamin A/blood*

Scavenger receptor class B, member 2 (SCARB2) is linked to Gaucher disease and Parkinson's disease. Deficiency in the SCARB2 gene causes progressive myoclonus epilepsy (PME), a rare group of inherited neurodegenerative diseases characterized by myoclonus. We found that Scarb2 deficiency in mice leads to age-dependent dietary lipid malabsorption, accompanied with vitamin E deficiency. Our investigation revealed that Scarb2 deficiency is associated with gut dysbiosis and an altered bile acid pool, leading to hyperactivation of FXR in intestine. Hyperactivation of FXR impairs epithelium renewal and lipid absorption. Patients with SCARB2 mutations have a severe reduction in their vitamin E levels and cannot absorb dietary vitamin E. Finally, inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice. These data indicate that gastrointestinal dysfunction is associated with SCARB2 deficiency-related neurodegeneration, and SCARB2-associated neurodegeneration can be improved by addressing the nutrition deficits and gastrointestinal issues.
Animals ; Mice ; Dysbiosis/metabolism* ; Mice, Knockout ; Humans ; Lysosomal Membrane Proteins/genetics* ; Receptors, Scavenger/genetics* ; Gastrointestinal Microbiome ; Myoclonic Epilepsies, Progressive/genetics* ; Vitamin E Deficiency/complications* ; Neurodegenerative Diseases/genetics* ; Bile Acids and Salts/metabolism* ; Male ; Lipid Metabolism ; Intestinal Mucosa/pathology*

OBJECTIVES: To study the correlation between 25-hydroxyvitamin D [25-(OH)D] and nephroblastoma in children and its value in assessing the prognosis of the disease. METHODS: A total of 50 children with nephroblastoma who were admitted from January 2018 to December 2022 were included as the nephroblastoma group, and according to the postoperative pathological type, they were divided into a good prognosis group with 38 children and a poor prognosis group with 12 children. A total of 50 healthy children who underwent physical examination during the same period of time served as the healthy control group. The above groups were compared in terms of serum creatinine and 25-(OH)D level. A Spearman correlation analysis was used to investigate the correlation between serum 25-(OH)D level and therapeutic effect reaction. A multivariate logistic regression analysis was used to identify the risk factors affecting the prognosis of nephroblastoma in children. RESULTS: The nephroblastoma group had significantly lower levels of serum creatinine and 25-(OH)D than the healthy control group (P<0.05). Compared with the good prognosis group, the poor prognosis group had a significantly larger tumor diameter, a significantly higher proportion of children with stage III-IV tumors, a significantly higher rate of tumor metastasis, and significantly lower serum levels of creatinine and 25-(OH)D (P<0.05). The Spearman correlation analysis showed that serum 25-(OH)D level was negatively correlated with therapeutic effect reaction (r_s=-0.685, P<0.001). The multivariate logistic regression analysis showed that tumor diameter ≥10 cm, stage III-IV tumors, presence of tumor metastasis, and 25-(OH)D <19 ng/mL were closely associated with the poor prognosis of nephroblastoma in children (P<0.05). Serum 25-(OH)D level had an area under the curve of 0.805 (95%CI: 0.706-0.903, P<0.001) in evaluating the prognosis of nephroblastoma in children, with a Youden index of 0.512, a sensitivity of 0.938, and a specificity of 0.575 at the optimal cut-off value of 1.764 ng/mL. CONCLUSIONS There is a significant correlation between 25-(OH)D level and the prognosis of nephroblastoma in children, and 25-(OH)D can be used for prognosis prediction.
Humans ; Child ; Creatinine ; Vitamin D Deficiency/complications* ; Vitamin D ; Calcifediol ; Prognosis ; Wilms Tumor ; Kidney Neoplasms/complications*

OBJECTIVETo evaluate the relationship of vitamin D level with the development of necrotizing enterocolitis (NEC) in preterm infants.

METHODSA total of 429 preterm infants with a gestational age of <36 weeks, who were admitted to the department of neonatology within 2 hours after birth between January and December, 2016, were enrolled in the study. According to whether these infants developed NEC, the 429 subjects were divided into NEC group (n=22) and non-NEC group (n=407). Peripheral venous blood was collected from these preterm infants and their mothers at admission to measure the level of 25-hydroxyvitamin D (25-OHD). The two groups were compared in terms of the serum 25-OHD levels of preterm infants and their mothers. Pearson correlation analysis was used to investigate the correlation between the serum 25-OHD levels of preterm infants and their mothers. The distribution of vitamin D levels in preterm infants was compared between the two groups. The univariate logistic regression analysis was used to determine the risk factors for NEC in preterm infants.

RESULTSThe serum 25-OHD levels of preterm infants and their mothers in the NEC group were significantly lower than in the non-NEC group (P<0.001). In both groups, the serum 25-OHD levels of mothers and preterm infants were positively correlated with each other (P<0.001). The distribution of vitamin D levels (normal vitamin D level, low vitamin D level, vitamin D deficiency, and severe vitamin D deficiency) was significantly different between the NEC and non-NEC groups (P<0.001). The univariate logistic regression analysis showed that gestational age, birth weight, 25-OHD levels of preterm infants and their mothers, the duration of mechanical ventilation, the duration of oxygen inhalation, and the length of hospital stay were associated with the development of NEC (P<0.05).

CONCLUSIONSThe serum 25-OHD levels of preterm infants and their mothers may be related to the development of NEC in preterm infants, suggesting that vitamin D supplementation during pregnancy is important for preventing the development of NEC in preterm infants.

Enterocolitis, Necrotizing ; etiology ; Female ; Humans ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases ; etiology ; Logistic Models ; Male ; Vitamin D ; analogs & derivatives ; blood ; Vitamin D Deficiency ; complications

The relationship between vitamin D deficiency and idiopathic central precocious puberty (ICPP) has been recently documented. In this study, 280 girls diagnosed with ICPP and 188 normal puberty control girls of similar ages were enrolled and retrospectively studied. The ICPP group had significantly lower serum 25-hydroxyvitamin D (25[OH]D) levels than the control group. Furthermore, a nonlinear relationship was found between serum 25[OH]D and ICPP, and a cut-off point for serum 25[OH]D was found at 31.8 ng/ml for ICPP with and without adjusting the different confounding factors. Girls with serum 25[OH]D ≥ 31.8 ng/ml had a lower odds ratio (unadjusted: OR 0.36, 95% CI 0.15 to 0.83, P < 0.05; height and weight adjusted: OR 0.44, 95% CI 0.18 to 1.08, P = 0.072; BMI adjusted: OR 0.36, 95% CI 0.16 to 0.84, P < 0.05). The ICPP subjects with 25[OH]D deficiency had a higher body mass index (BMI) than the subjects from the two other subgroups. Correlation analysis showed that vitamin D level is correlated with BMI and some metabolic parameters in the ICPP group. Our study suggested that vitamin D status may be associated with ICPP risk and may have a threshold effect on ICPP.
Body Mass Index ; Child ; China ; Female ; Humans ; Linear Models ; Logistic Models ; Multivariate Analysis ; Puberty, Precocious ; blood ; complications ; Retrospective Studies ; Vitamin D ; analogs & derivatives ; blood ; Vitamin D Deficiency ; epidemiology

OBJECTIVETo examine serum 25-hydroxyvitamin D levels in children with tic disorders (TD) and to explore the relationship between vitamin D level and TD.

METHODSOne hundred and thirty-two children who were diagnosed with TD between November 2016 and May 2017 were enrolled as the TD group, including 8 cases of Tourette syndrome, 32 cases of chronic TD, and 92 cases of transient TD. One hundred and forty-four healthy children served as the control group. Peripheral venous blood samples were collected from each child. Serum levels of 25-hydroxyvitamin D were measured using HPLC-MS/MS. The categories of vitamin D status based on serum 25-hydroxyvitamin D level included: normal (>30 ng/mL), insufficiency (10-30 ng/mL) and deficiency (<10 ng/mL).

RESULTSMean serum level of 25-hydroxyvitamin D in the TD group was significantly lower than that in the control group (P<0.01). The rate of vitamin D insufficiency or deficiency in the TD group was significantly higher than in the control group (P<0.01). Mean serum level of 25-hydroxyvitamin D in the transient tic group was higher than in the TS group (P<0.05).

CONCLUSIONSVitamin D insufficiency or deficiency might be associated with the development of TD, and the level of serum 25-hydroxyvitamin D might be related to the classification of TD.

Child ; Child, Preschool ; Female ; Humans ; Male ; Tandem Mass Spectrometry ; Tic Disorders ; blood ; etiology ; Vitamin D ; analogs & derivatives ; blood ; Vitamin D Deficiency ; complications ; epidemiology

OBJECTIVETo investigate the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels at birth and respiratory distress syndrome (RDS) in preterm infants.

METHODSThis retrospective study recruited preterm infants with gestational age of below 34 weeks who were born between January 2014 and December 2016. These preterm infants were divided into two groups: RDS (n=72) and control (n=40). Clinical data of the two groups were collected, including gestational age, birth weight, gender, delivery mode, Apgar scores at 1 minute and 5 minutes, incidence of maternal gestational diabetes mellitus, and use of prenatal steroid hormone. Peripheral blood samples were collected and 25(OH)D levels were measured by chemiluminescence immunoassay. The association between serum 25(OH)D levels at birth and RDS was analyzed by multivariate logistic regression.

RESULTSApgar scores at 1 minute and 5 minutes and serum 25(OH)D levels in the RDS group were significantly lower than those in the control group (P<0.05), while the rates of neonatal asphyxia and vitamin D deficiency were significantly higher than those in the control group (P<0.05). Multivariate logistic regression analysis showed that neonatal asphyxia (OR=2.633, 95%CI: 1.139-6.085) and vitamin D deficiency (OR=4.064, 95%CI: 1.625-10.165) were risk factors for RDS in preterm infants.

CONCLUSIONSVitamin D deficiency might be associated with increased risk of RDS in preterm infants. Reasonable vitamin D supplementation during pregnancy might reduce the incidence of RDS in preterm infants.

Dietary Supplements ; Female ; Humans ; Infant, Newborn ; Infant, Premature ; Male ; Respiratory Distress Syndrome, Newborn ; blood ; etiology ; Vitamin D ; analogs & derivatives ; blood ; Vitamin D Deficiency ; complications

OBJECTIVETo assess the association between serum 25-hydroxyvitamin D [25(OH)D] levels at birth and bronchopulmonary dysplasia (BPD) in preterm infants.

METHODSThis study recruited preterm infants with gestational age of below 34 weeks who were born between January 2014 and December 2016. These preterm infants were classified into two groups: BPD and control. The association between serum 25(OH)D levels at birth and BPD was analyzed.

RESULTSSerum 25(OH)D levels in the BPD group was significantly lower than those in the control group [(37±17 nmol/L vs 47±20 nmol/L; P<0.05), and the rate of vitamin D deficiency was significantly higher than those in the control group (90.2% vs 74.0%; P<0.05). The level of serum 25(OH)D was negatively correlated with the incidence of BPD (r=-0.201, P=0.001).

CONCLUSIONSVitamin D deficiency at birth may be associated with BPD in preterm infants, but need to be further studied by multivariate analysis.

Bronchopulmonary Dysplasia ; blood ; etiology ; Female ; Humans ; Infant, Newborn ; Infant, Premature ; blood ; Male ; Vitamin D ; analogs & derivatives ; blood ; Vitamin D Deficiency ; complications

Vitamin D is an important secosteroid hormone in skeletal and non-skeletal systems. Vitamin D has relevance to muscle and immune function, hypertension, diabetes mellitus, cancer, and pregnancy because vitamin D receptors (VDR) are present in many non-skeletal tissues. Vitamin D acts on target tissues via the binding of its active form to VDR. As vitamin D affects not only bone metabolism but also glucose metabolism, vitamin D deficiency may affect the development of gestational diabetes mellitus and fetal growth. Although vitamin D deficiency is prevalent during pregnancy, there are conflicting reports on the effect of vitamin D deficiency on pregnancy complications, such as fetal growth restriction and gestational diabetes. This article reviews published papers on the effects of vitamin D on gestational diabetes and fetal growth.
Diabetes Mellitus ; Diabetes, Gestational* ; Female ; Fetal Development ; Glucose ; Hypertension ; Metabolism ; Pregnancy ; Pregnancy Complications ; Receptors, Calcitriol ; Vitamin D Deficiency ; Vitamin D* ; Vitamins*