Impact of Vitamin D Deficiency on Survival for Patients Received Haploidentical Hematopoietic Stem Cell Transplantation (haplo-HSCT)

Background Beyond its role in bone health, vitamin D is known to have immunomodulatory effects including cell proliferation, differentiation and apoptosis. Delays in immune reconstitution following HSCT increase transplant-related toxicity. Several studies have explored the role of vitamin D deficiency after HSCT with mixed results regarding its impact on survival outcomes. Our aim in this study was to examine the impact of vitamin D deficiency prior to HSCT on transplant outcomes in patients who received a haplo-HSCT. Methods This retrospective study included consecutive patients who underwent haplo-HSCT at our institution between 02/2009 and 01/2021. Primary objectives were to assess progression-free survival (PFS) and overall survival (OS) by vitamin D status at the time of transplant. Vitamin D deficiency was defined as vitamin D levels < 20 nmol/L within 6 months prior to transplant. Survival estimates were calculated using Kaplan-Meier method. Proportional cox hazards analysis was used to adjust for multivariable analysis (MVA). Results Four-hundred and eighty-four patients out of 508 patients had vitamin D checked at baseline and were included in the final analysis. Table 1 summarizes patient, disease, and transplant characteristics for all study patients, and by vitamin D status. Median age for all study patients was 48 (18-72) years, of which 237 (49%) had vitamin D deficiency and 247 (51%) had normal vitamin D level. Overall, the two groups were comparable, except that patients in the vitamin D deficiency group were younger in age. Furthermore, we adjusted for disease subtype heterogeneity by using the validated disease risk index (DRI). With a median follow-up of 35.4 (range, 1.4-132.8) months, the 3-year PFS and OS for all study patients were 44% and 48%, respectively. The respective 3-year PFS and OS for the vitamin D deficiency group were 42% and 47% compared to 46% and 50% for patients with adequate vitamin D (p=0.773 for PFS; p=0.704 for OS). Furthermore, we found no difference in non-relapse mortality at 3 years (each for 30%; p=0.6682). Univariate analysis (UVA) was performed for the following variables: vitamin D, age, gender, KPS, DRI, HCT-CI, and intensity of conditioning regimen. MVA included only the factors with p value<0.1 in in the UVA (plus vitamin D). In UVA for PFS, age ≥55, KPS <90, high/very-high DRI, HXT-CI >3 and reduced intensity conditioning were associated with inferior outcome. Same factors were significantly associated with inferior OS, but the reduced conditioning regimen. In MVA, age ≥55 (HR 1.627, 95% CI: 1.212-2.212; p=0.0013), high/very-high DRI (HR 1.865, 95% CI: 1.427-2.437; p=<0.0001), and HCT-CI >3 (HR 1.314, 95% CI: 1.001-1.726; p=0.0493) were associated with decreased PFS. Patients in the vitamin D deficiency group had a trend towards decreased PFS (HR 1.292, 95% CI: 0.975-1.712; p=0.0746), but this didn't reach statistical significance. In regard to OS, age ≥55 (HR 1.727, 95% CI: 1.278-2,334; p=0.0004), high/very-high DRI (HR 1.855, 95% CI: 1.396-2.467; p=<0.0001), and HCT-CI >3 (HR 1.411, 95% CI: 1.058-1.882; p=0.0191) were again associated with decreased OS, while vitamin D deficiency patients showed a trend for decreased OS (HR 1.312, 95% CI: 0.973-1.77; p=0.0753). Conclusion Our study demonstrates that serum vitamin D levels prior to haplo-HSCT have no significant impact on either progression-free or overall survival, albeit with a trend for worse outcomes in the vitamin D deficient group. Prospective controlled studies are needed to assess the impact of vitamin D deficiency on transplant outcomes, and on the role of vitamin D supplementation to improve the outcomes. Figure 1 Figure 1. Disclosures Qazilbash: Bristol-Myers Squibb: Other: Advisory Board; Oncopeptides: Other: Advisory Board; Angiocrine: Research Funding; Amgen: Research Funding; Biolline: Research Funding; NexImmune: Research Funding; Janssen: Research Funding. Shpall: Navan: Consultancy; Novartis: Honoraria; Axio: Consultancy; Magenta: Honoraria; Takeda: Patents & Royalties; Bayer HealthCare Pharmaceuticals: Honoraria; Adaptimmune: Consultancy; Affimed: Patents & Royalties; Magenta: Consultancy; Novartis: Consultancy.

207 Satellite Cells Participate in the wnt/ca2+ Pathway Controlled Porcine Myofiber Determination

The type of myofiber is important for porcine meat quality. Meanwhile, the nt/Ca2+ pathway has been showed multiple roles in skeletal muscle formation; however, the distinct mechanism is still unclear. In this study, the weaned piglets and satellite cells were designed into the control group, lysine deficiency group and lysine rescue group to investigate the function of Wnt/Ca2+ pathway in governing skeletal muscle typing. After we confirm the growth of weaned piglets was controlled by lysine, the isobaric tag for relative and absolute quantification (iTRAQ) analysis of skeletal muscle detected that Wnt/Ca2+ pathway was involved in the transition of fast and slow fiber. Then, we found the ratio of type I myofiber in Semimembranous (fast muscle) was significantly increased after lysine deficiency (P < 0.05), and decreased by lysine rescue (P < 0.05). In contrast, the ratio of type I myofiber in Semitendinous muscle (slow muscle) was significantly decreased in the lysine deficiency group, and increased in the lysine rescue group (P < 0.05). Furthermore, the Wnt/Ca2+ pathway was significantly increased in Semimembranous muscle, while decreased in Semitendinous muscle with lysine deficiency, and this phenomenon was inversed after lysine rescue (P < 0.05). Meanwhile, the Wnt/Ca2+ pathway was stronger in satellite cells isolated from Semitendinous muscle (StSCs) than that of Semimembranous satellite cell (SmSCs) (P < 0.05). And we also found the StSCs enter in differentiation is more easily than SmSCs (P < 0.05). Besides, the ratio of type I myofiber originated from StSCs showed greater than StSCs (P < 0.05). In summary, we conclude that satellite cells participate in the Wnt/Ca2+ pathway controlled porcine myofiber determination.

A Study on the Law of Birth and Formation of Yang-Deficiency Constitution Based on the Theory of Five Movement and Six Qi

Objective: To explore the law of birth and yang deficiency constitution based on the theory of five movements and six qi, as well as to provide a new way to better realize the prevention of yang deficiency constitution. Methods: The data of TCM quality table and luck data were collected via questionnaires. According to the data of from the TCM quality table, the respondents were divided into yang deficiency constitution group and non-yang deficiency group. According to the luck data, the distributions of gestational age were compared between the two groups. Results: A total of 175 questionnaires were collected, of which 89 were non-yang deficiency constitution and 86 were yang deficiency constitution. The proportion of Ding year (15.1%) in the yang deficiency group was significantly higher than that in non-yang deficiency group (5.6%), in which the difference was statistically significant (P < 0.05). Conclusion: The possibility of yang deficiency constitution is higher.

Expression of Th17/Treg Cells in Peripheral Blood and Related Cytokines of Patients with Ulcerative Colitis of Different Syndrome Types and Correlation with the Disease

Objective. To explore the expression of helper T cells 17 (Th17)/regulatory T cells (Treg) in peripheral blood and related cytokines of patients with different types of ulcerative colitis (UC) and analyze their correlation with the disease. Methods. From January 2018 to December 2019, 53 patients diagnosed with UC in our hospital were selected. According to their medical syndromes, they were divided into the damp-heat internal accumulation group (n = 35) and the spleen-kidney yang deficiency group (n = 18). 21 healthy volunteers were selected as the control group. The Mayo scoring standard was used to determine the severity of the patient’s condition. The expression levels of Th17/Treg cells and related cytokines in peripheral blood were compared between the groups. Pearson correlation was used to analyze the correlation between the ratio of Th17 and Treg cells in the peripheral blood of UC patients and the ratio of TH17/Treg with Mayo score. Results. The peripheral blood Th17 cell ratio and Th17/Treg ratio of the damp-heat internal accumulation and spleen-kidney yang deficiency group were higher than those of the control group; the Treg cell ratio was lower than that of the control group; the peripheral blood Th17 cell ratio and Th17/Treg ratio of the damp-heat internal accumulation group were higher those of the spleen-kidney yang deficiency group; and the proportion of Treg cells was lower than that of the spleen-kidney yang deficiency group ( P < 0.05 ). The expression levels of serum IL-6, IL-17, IL-22, and TNF-α in the damp-heat internal accumulation and spleen-kidney yang deficiency group were higher than those of the control group; IL-10 and TGF-β were lower than those of the control group; the levels of serum IL-6, IL-17, IL-22, and TNF-α in the damp-heat internal accumulation group were higher than those of the spleen-kidney yang deficiency group; and both IL-10 and TGF-β were lower than those of the spleen-kidney yang deficiency group ( P < 0.05 ). The peripheral blood Th17 cell ratio and Th17/Treg ratio in the moderately active period group and severely active period group were higher than those of the lightly active period group; the Treg cell ratio was lower than that of the lightly active period group; the peripheral blood Th17 cell ratio and Th17/Treg ratio in the severely active period group were higher than those in the moderately active period group; and the proportion of Treg cells was lower than that of the moderately active period group. Pearson correlation analysis showed that the proportion of Th17 cells and Th17/Treg in peripheral blood of UC patients were both positively correlated with Mayo score (r = 0.762, r = 0.777, P < 0.001 ). Treg was negatively correlated with Mayo score (r = −0.790, P < 0.001 ). Conclusion. There are differences in the expression of peripheral blood Th17/Treg cells and related cytokines among UC patients with different syndromes, and the damp-heat content is the most significant. The higher the ratio of Th17 cells in peripheral blood and the degree of Th17/Treg imbalance, the lower the ratio of Treg cells, and the more severe the condition of UC patients, which can provide a preliminary quantitative basis for the TCM classification and severity of the diagnosis of UC.

Alteration of the Intestinal Microbial Flora and the Serum IL-17 Level in Patients with Graves’ Disease Complicated with Vitamin D Deficiency

<b><i>Background:</i></b> Intestinal flora is associated with Graves’ disease (GD). This study explored the association of serum 25(OH)D with the diversity of the intestinal flora and serum IL-17 in GD patients. <b><i>Methods:</i></b> Patients newly diagnosed with GD at 2 centers between 2018 and 2021 were consecutively included. According to their 25(OH)D levels, they were divided into the deficiency group, the insufficiency group, and the sufficiency group. Some patients with vitamin D deficiency or insufficiency were randomly selected and were matched with healthy volunteers (normal control [NC]) in terms of sex, age, and case number. The diversity and differential species of the intestinal flora and serum IL-17 levels were compared. <b><i>Results:</i></b> Serum 25(OH)D negatively correlated with serum IL-17, the platelet/lymphocyte ratio, and TSH receptor antibody. The diversity of the intestinal flora decreased in the GD group, with noticeable differences in the composition of the intestinal flora when compared with the NC group. At the phylum level, the GD group exhibited a significantly lower abundance of Firmicutes but a higher abundance of Actinobacteria. At the genus level, the GD group exhibited higher relative abundances of Bifidobacterium, Collinsella, and Pediococcus but lower abundances of Roseburia and Dialister. <b><i>Conclusions:</i></b> The changes in the vitamin D level and the composition of the intestinal flora may partially contribute to the development of GD.

Choroidal and Retinal Thickness in Patients with Vitamin C Deficiency

Purpose: to investigate the effects of vitamin C on central retinal thickness and choroidal thickness.Methods: A total of 72 patients diagnosed with vitamin C deficiency and 1:1 age- and gender-matched 72 healthy individuals with normal serum vitamin C were included in this study. Demographic characteristics of the individuals were collected. All patients underwent a comprehensive ophthalmic examination. Subfoveal choroidal thickness and retinal thickness were measured using a swept-source optical coherence tomography (SS-OCT). Results: The average retinal thickness was 268.96 ± 14.01um in the vitamin C deficiency group and 276.69 ± 13.28um in the control group. The average choroidal thickness was 195.06 ± 66.35um in the in the vitamin C deficiency group and 238.53 ± 56.20um in the control group. There was a significant decrease in both average choroidal thickness and retinal thickness in vitamin C deficiency group compared with normal individuals (p < 0.001, and = 0.003 respectively).Conclusion: The central retinal and choroidal thickness were thinner in vitamin C deficiency group compared with normal individuals. These findings suggested that vitamin C deficiency might play an important role in retinal and choroidal diseases.

The Choice of Dry Eye Therapy Depending on Ocular Surface Condition

Purpose: to develop approaches to differentiated substitution therapy in patients with dry eye (DE) of mild and moderate severity.Patients and methods. We examined 86 DE patients (22–45 years old; 38 men, 48 women). Group-1 included 54 patients (54 eyes) with mild DE under conditions of combined lipid-mucose-deficiency, group-2 32 patients (32 eyes) with moderate DE against the background of combined lipid-aqua-mucose-deficiency. Conducted: DE symptoms registration (OSDI scale); Norn and Shirmer-1 tests; OCT meniscometry; assessment of the Bijsterveld xerosis index and ‘lid-vipers’ symptom identification; Norn’s compression test. To assessment the therapy effectiveness, patients in both groups were divided into subgroups. Patients of subgroup 1.1 (18 eyes) carried out ‘fat-water’ type emulsion instillations, subgroup 1.2 (18 eyes) — 0.15 % sodium hyaluronate instillation (Hylabak®), subgroup 1.3 (18 eyes) — 3.0 % trehalose (Thealoz®) — 1–2 drops, 4 times a day. All persons included in group-1 were additionally recommended to apply 5.0 % dexpanthenol gel at night. Patients of subgroup 2.1 (16 eyes) received 0.15 % sodium hyaluronate instillation (Hylabak®), patients of subgroup 2.2 (16 eyes) 0.15 % sodium hyaluronate (Hylabak®) and 3.0 % trehalose (Thealoz®) instillation — 4 times a day. All patients included in group-2 were additionally recommended to apply ointment with vitamin A at night. The main criterion for the therapy effectiveness was the tear film brake up time (TBUT, s) two months after the start treatment. Statistical processing included: calculation the mean and its standard deviation (M ± s); assessment of the significance of differences (Wilcoxon’s t-test, KruskalWallis test, Mann-Whitney U-test).Results. In group-1 patients the following TBUT dynamics was recorded: in subgroup 1.1 — from 5.4 ± 0.5 to 6.2 ± 0.6 s (p < 0.05); in subgroup 1.2 — from 5.2 ± 0.4 to 6.6 ± 0.6 s (p < 0.05); in subgroup 1.3 — from 5.3 ± 0.5 to 7.1 ± 0.7 s (p < 0.05). The most pronounced TBUT increase was noted in subgroup 1.3 (trehalose instillation). In group-2, the increase in TBUT was: in subgroup 2.1 — from 3.5 ± 0.3 to 4.7 ± 0.3 s (p < 0.05); in subgroup 2.2 — from 3.4 ± 0.2 to 5.2 ± 0.4 s (p < 0.05). A significantly more pronounced TBUT increase was noted in subgroup 2.2 (sodium hyaluronate and trehalose instillation).Conclusion. In our opinion, differentiated approaches to DE replacement therapy may be included: for mild DE in conditions of lipid-mucose-deficiency — instillation of bioprotector based on 3.0 % trehalose (Thealose®); in case of moderate DE against the background of lipid-aqua-mucose-deficiency — 0.15 % sodium hyaluronate (Hylabak®) instillation in combination with a bioprotector based on 3.0 % trehalose (Thealoz®).

Relationship between serum vitamin D3 concentration and anaemia in patients with chronic kidney disease in China

Objective In the present study, we aimed to investigate the relationship between serum vitamin D3 concentration and anaemia in patients with chronic kidney disease (CKD) in China, to assist understanding of the effects of vitamin D treatment in such patients. Methods A total of 225 patients with CKD were enrolled and a range of laboratory parameters were measured. The participants were allocated to three groups, according to their serum 25-hydroxyvitamin D3 concentration: a severe deficiency group, a deficiency group, and a sufficiency group. The prevalences of anaemia in the three groups were assessed, and the factors associated with anaemia in patients with CKD were analysed using logistic regression. Results The prevalences of anaemia were 79.5% in the severe deficiency group, 63.5% in the deficiency group, and 48.0% in the sufficiency group. The prevalence of anaemia gradually increased with the severity of vitamin D3 deficiency. The prevalences of anaemia in participants with stages 1 to 5 CKD were 21.1%, 30.4%, 39.5%, 78.7%, and 94.6%, respectively. Conclusion Vitamin D3 deficiency may increase the risk of anaemia in patients with CKD.

Incidence and risk factors of micronutrient deficiency in patients with IBD and intestinal Behçet’s disease: folate, vitamin B12, 25-OH-vitamin D, and ferritin

Background Patients with inflammatory bowel disease (IBD) and intestinal Behçet’s disease (BD) are vulnerable to micronutrient deficiencies due to diarrhea-related gastrointestinal loss and poor dietary intake caused by disease-related anorexia. However, few studies have investigated the incidence and risk factors for micronutrient deficiency. Methods We retrospectively analyzed 205 patients with IBD who underwent micronutrient examination, including folate, vitamin B12, 25-OH-vitamin D, and/or ferritin level quantification, with follow-up blood tests conducted 6 months later. Results Eighty patients (39.0%), who were deficient in any of the four micronutrients, were classified as the deficiency group, and the remaining 125 (61.0%) were classified as the non-deficient group. Compared to those in the non-deficiency group, patients in the deficiency group were much younger, had more Crohn's disease (CD) patients, more patients with a history of bowel operation, and significantly less 5-amino salicylic acid usage. Multivariate analysis revealed that CD and bowel operation were significant independent factors associated with micronutrient deficiency. Conclusions The incidence of micronutrient deficiency was high (39.0%). Factors including CD, bowel operation, and younger ages were found to be associated with higher risks of deficiency. Therefore, patients with IBD, especially young patients with CD who have undergone bowel resection surgery, need more attention paid to micronutrition.

Smell Regions in Patients with Vitamin D Deficiency: An MRI Evaluation

Objectives We investigated the effects of vitamin D deficiency in the peripheral and central smell regions by magnetic resonance imaging (MRI). Methods This retrospective study included 29 patients (12 males, 17 females) with 25-dihydroxy vitamin D3 [25(OH)2D3] deficiency (group 1) and 34 subjects without 25(OH)2D3 deficiency (14 males, 20 females) (group 2). Using cranial MRIs, the peripheral (olfactory bulb [OB] volume and olfactory sulcus [OS] depth) and central (insular gyrus and corpus amygdala) smell regions were evaluated. Results The OB volume and OS depth values of the 25(OH)2D3 deficiency group were significantly lower than those of the control group (p < 0.05). For the central smell regions, the insular gyrus and corpus amygdala areas of the 25(OH)2D3 deficiency group were nonsignificantly lower than those in the control group (p > 0.05). There were positive correlations between OB volumes, OS depths, and insular gyrus and corpus amygdala areas bilaterally in the 25(OH)2D3 deficiency group separately and in all subjects (groups 1 and 2) (p < 0.05). In the 25(OH)2D3 deficiency group, as the 25(OH)2D3 values became lower, the insular gyrus area values decreased bilaterally (p < 0.05). In females, the corpus amygdala area values were lower than in males (p < 0.05). Conclusion Since vitamin D3 deficiency affected the peripheral and central smell regions negatively, we recommend evaluating patients' vitamin D levels as a health policy to prevent vitamin D3 deficiency-related cranial smell region problems. Moreover, sunlight exposure is very important to increase vitamin D levels, and the public should be informed about this topic.