Plant-based diets, mediating biomarkers, and mortality risk among adults with diabetes or prediabetes.

Background: A healthy eating pattern characterized by a higher intake of healthy plant foods has been associated with a lower risk of premature mortality, but whether this applies to individuals with varying glycemic status remains unclear. Methods: This study included 4621 participants with diabetes and 8061 participants with prediabetes from the US National Health and Nutrition Examination Survey (2007-2016). Using the dietary data assessed by two 24 h dietary recalls, a healthful plant-based diet index (hPDI) and an unhealthful plant-based diet index (uPDI) were created based on 15 food groups and were assessed for their relationships with mortality risk. Results: Over a median follow-up of 7.2 years, there were 1021 deaths in diabetes and 896 deaths in prediabetes. A higher hPDI (highest vs. lowest quartile) was associated with a 41% (HR = 0.59, 95% CI: 0.49-0.72; P-trend < 0.001) lower risk of all-cause mortality in diabetes and a 31% (HR = 0.69, 95% CI: 0.55-0.85; P-trend < 0.001) lower risk in prediabetes. A higher uPDI was associated with an 88% (HR = 1.88, 95% CI: 1.55-2.28; P-trend < 0.001) higher risk of mortality in diabetes and a 63% (HR = 1.63, 95% CI: 1.33-1.99; P-trend < 0.001) higher risk in prediabetes. Mediation analysis suggested that C-reactive protein and γ-glutamine transaminase explained 6.0% to 10.9% of the relationships between hPDI or uPDI and all-cause mortality among participants with diabetes. Conclusions: For adults with diabetes as well as those with prediabetes, adhering to a plant-based diet rich in healthier plant foods is associated with a lower mortality risk, whereas a diet that incorporates less healthy plant foods is associated with a higher mortality risk.

Association of phthalate exposure with all-cause mortality across renal function status: The U.S. National Health and Nutrition Examination Survey, 2005-2018.

BACKGROUND: Wide phthalate exposure has been associated with both declines in renal function and an elevated risk of mortality. Whether phthalate-associated risk of premature mortality differs by renal function status remains unclear. METHODS: This study included 9605 adults from the U.S. National Health and Nutrition Examination Survey. Urinary concentrations of 11 phthalate metabolites were assessed using high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. According to estimated glomerular filtration rate (eGFR), participants were grouped as having normal or modestly declined renal functions, or chronic kidney disease (CKD). Multivariable Cox regression models estimated all-cause mortality associated with phthalate exposure, overall and by renal function status. RESULTS: Overall, Mono-n-butyl phthalate (MnBP), Mono-benzyl phthalate (MBzP), Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and Mono-(2-ethyl-5-carbox-ypentyl) phthalate (MECPP) were associated with an elevated risk of mortality (P-trend across tertile <0.05). Moreover, significant interactions were observed between eGFR and MEHHP, MEOHP, MECPP, DEHP in the whole population (P for interactions <0.05). After stratification by renal function, total Di (2-ethylhexyl) phthalate (DEHP) was additionally found to be associated with mortality risk in the CKD group (HR = 1.12; 95% CI: 1.01, 1.25). Co-exposure to the 11 phthalate metabolites was associated with a higher risk of all-cause mortality in the CKD (HR = 1.47; 95% CI: 1.18, 1.84) and modestly declined renal function group (HR = 1.25; 95% CI: 1.09, 1.44). CONCLUSIONS: The associations between phthalate exposure and risk of all-cause mortality were primarily observed in CKD patients, reinforcing the need for monitoring phthalate exposure in this patient population.

Efficacy and safety profile of phosphodiesterase 4 inhibitor in the treatment of psoriasis: A systematic review and meta-analysis of randomized controlled trials.

Background: Systemic therapy is an important treatment for psoriasis. Phosphodiesterase 4 (PDE4) inhibitors are new candidates for psoriasis therapy. Objectives: To evaluate the efficacy and safety of PDE4 inhibitors in psoriasis. Method: Randomized clinical trials with PDE4 inhibitors vs placebos in patients with psoriasis were identified from MEDLINE, Embase, Cochrane Controlled Register of Trials, ClinicalTrials.gov, from inception to July 14, 2022. The study was registered in PROSPERO (CRD42022345700). Results: 18 studies were identified, 9 of which included moderate-to-severe plaque psoriasis, 2 mild-to-moderate plaque psoriasis, and 7 psoriatic arthritis. A total of 6036 patients were included. Only one oral PDE4 inhibitor, apremilast, met the inclusion criteria. Overall, compared with the placebo, apremilast was associated with higher response rates in PASI-75 (RR, 3.22; 95% CI, 2.59-4.01), ScPGA of 0 or 1 (RR, 2.21; 95% CI, 1.69-2.91), PPPGA of 0 or 1 (RR 2.33; 95%CI, 1.16-4.66), and a significant decrease in NPASI (SMD, -0.46; 95% CI, -0.58 to -0.33). There were no significant differences in serious adverse events. Subgroup analyses showed that significantly more patients achieved PASI-75 after 16 weeks of therapy with apremilast of 20 mg bid (RR, 2.82; 95% CI, 2.01-3.95) and 30 mg bid (RR, 4.08; 95% CI, 3.12-5.33). Heterogeneity was not significant across studies. Conclusion: Apremilast is a safe and effective treatment for plaque psoriasis and psoriatic arthritis, especially for difficult-to-treat sites. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42022345700).

Febrile Ulceronecrotic Mucha-Habermann Disease: A Case Report and a Systematic Review.

The characteristics and treatments of febrile ulceronecrotic Mucha-Habermann disease (FUMHD) are not well-understood. We reported a FUMHD case, and searched Medline, Embase, Pubmed, Scopus, and Web of Science from inception to June 16, 2021, to perform a systematic review to synthesize its characteristics and treatments. Seventy-eight reports, including 84 people were eligible. Most of them were male (62/83, 74.7%), with high fever state (50/80, 62.5% had a high fever of 39°C or above), and with more positive skin bacterial cultures (31/41, 75.6%). Adults were associated with a higher risk of death (OR = 12.976, 95% CI: 1.049, 160.504, p = 0.046), but not positive blood bacterial cultures (p = 0.102). Systematic corticosteroids combination with other immunosuppressants (methotrexate or cyclosporine) were associated with significantly more effective cases (26/31 = 83.9%, χ2 = 4.065, p = 0.044). Furthermore, no significant differences between the low-dose and high-dose systematic corticosteroid groups were detected in treatment validation (p > 0.05). Overall, FUMHD was associated with male patients, high fever, and positive skin bacterial cultures. Early combination therapy with lower doses of corticosteroids and methotrexate or cyclosporine may be an optimal choice for the treatment of FUMHD.

Efficacy and safety profile of antioxidants in the treatment of atopic dermatitis: A systematic review and meta-analysis of randomized controlled trials.

The use of antioxidants in atopic dermatitis (AD) is controversial. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of antioxidants therapy in AD. Randomized clinical trials were identified from Medline, Embase, and Cochrane library. Changes from baseline in severity and itch score were extracted from individual studies and pooled using random-effects. Eighteen trials including 763 AD patients were eligible. Overall, antioxidants were associated with statistically significant reductions in diseases severity (p < 0.0001), but not with itch score (p = 0.59). No serious adverse events were recorded. Subgroup analyses revealed that antioxidants were associated with a significant reduction in severity score regardless of disease severity at baseline and treatment duration (p < 0.05). However, antioxidants had additional benefit only in children (p = 0.02) but not in adults (p = 0.30). Oral supplementation with vitamin D, combined vitamins D and E, combined vitamins A, D and E and topical vitamin B12 was associated with significantly lower severity score (p < 0.05). There was significant heterogeneity between studies (I2  = 50%; p = 0.003). The effect estimates did not change statistically after excluding sources of study heterogeneity. This meta-analysis suggests that antioxidants may be a safe and effective treatment for AD patients, especially when supplemented with oral vitamin D and topical vitamin B12 , as well as in pediatric patients.

Is replacing red meat with other protein sources associated with lower risks of coronary heart disease and all-cause mortality? A meta-analysis of prospective studies.

CONTEXT: A high amount of red meat consumption has been associated with higher risks of coronary heart disease (CHD) and all-cause mortality in a single food-exposure model. However, this model may overlook the potentially differential influence of red meat on these outcomes depending on the foods replaced by red meat. OBJECTIVE: A PRISMA-compliant meta-analysis of prospective observational studies was performed to quantify the risks of CHD and all-cause mortality associated with the replacement of total, unprocessed, or processed red meat with fish/seafood, poultry, dairy, eggs, nuts, and legumes. DATA SOURCES: The PubMed and Web of Science databases were searched to identify relevant articles published in any language from database inception to October 30, 2021. DATA EXTRACTION: The prospective observational studies were considered relevant if they reported relative risks (RRs) and 95%CIs for the associations of interest. DATA ANALYSIS: Thirteen articles were included. A random-effects model was used to estimate the summary RRs and 95%CIs for the associations of interest. Replacing total red meat with poultry (RR, 0.88, 95%CI, 0.82-0.96; I2 = 0%), dairy (RR, 0.90, 95%CI, 0.88-0.92; I2 = 0%), eggs (RR, 0.86, 95%CI, 0.79-0.94; I2 = 7.1%), nuts (RR, 0.84, 95%CI, 0.74-0.95; I2 = 66.8%), or legumes (RR, 0.84, 95%CI, 0.74-0.95; I2 = 7.3%) was associated with a lower risk of CHD, whereas substituting fish/seafood (RR, 0.91, 95%CI, 0.79-1.04; I2 = 69.5%) for total red meat was not associated with the risk of CHD. The replacement of total red meat with fish/seafood (RR, 0.92, 95%CI, 0.89-0.96; I2 = 86.9%), poultry (RR, 0.92, 95%CI, 0.90-0.95; I2 = 61.6%), eggs (RR, 0.91, 95%CI, 0.87-0.95; I2 = 33.8%), or nuts (RR, 0.92, 95%CI, 0.87-0.97; I2 = 81.9%) was associated with a lower risk of all-cause mortality, whereas the substitution of dairy (RR, 0.97, 95%CI, 0.93-1.01; I2 = 33.9%) or legumes (RR, 0.97, 95%CI, 0.93-1.01; I2 = 53.5%) for total red meat was not associated with the risk of all-cause mortality. Lower risks of CHD and all-cause mortality were more consistently observed for processed red meat replacements than for unprocessed red meat replacements. The results did not materially change when the analyses of total, processed, and unprocessed red meat were restricted to the studies that used a uniform substitution amount per unit of 1 serving/d. CONCLUSION: Keeping red meat, particularly processed red meat, consumption to a minimum along with increasing healthier alternative protein sources to replace red meat in the diet may contribute to the prevention of CHD and premature death. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021259446.

The Effects of Milk Supplementation on Bone Health Indices in Adults: A Meta-Analysis of Randomized Controlled Trials.

Milk contains a number of bone-beneficial nutrients. However, milk, due to the D-galactose content, might have unfavorable effects on bone health. A meta-analysis of randomized controlled trials (RCTs) was performed to clarify the effects of milk supplementation on bone mineral density (BMD), bone turnover markers [N-terminal telopeptide of type I collagen (NTx), C-terminal telopeptide of type 1 collagen (CTx), osteocalcin, bone alkaline phosphatase (BALP), and procollagen type 1 N-propeptide (P1NP)], and hormonal indices related to bone metabolism [parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], and insulin-like growth factor 1 (IGF-1)] in adults. The PubMed and Web of Science databases were searched. A random-effects model was used to estimate the pooled effect sizes. A total of 20 RCTs were included. The trial duration ranged from 1 mo to 36 mo. Milk supplementation resulted in a small but significant increase in BMD at the hip (+0.004 g/cm2; n = 9 RCTs) and lumbar spine (+0.025 g/cm2; n = 7), but did not significantly affect whole-body BMD (n = 3) and femoral neck BMD (n = 7). Milk supplementation reduced the concentrations of P1NP (-5.20 ng/mL; n = 9), CTx (-0.16 ng/mL; n = 9), and NTx (-8.66 nmol bone collagen equivalents/mmol creatinine; n = 3). The concentrations of osteocalcin (n = 9) and BALP (n = 3) were not affected by milk supplementation. Reduced parathyroid hormone PTH (-1.01 pg/mL; n = 13) concentrations and increased IGF-1 (+1.79 nmol/l; n = 4) concentrations were observed with milk supplementation. 25(OH)D (+3.73 ng/mL; n = 11) concentrations were increased with vitamin-D fortified milk supplementation. The addition of milk to the diet may potentially increase the likelihood of preventing bone loss by restoring bone homeostasis through the modulation of the calcium-vitamin D-PTH axis, bone remodeling rate, and growth hormone/IGF-1 axis.

Evaluation of the etiology and risk factors for maternal sepsis: A single center study in Guangzhou, China.

BACKGROUND: Maternal sepsis is a major cause of gestational morbidity and neonatal mortality worldwide and particularly in China. AIM: To evaluate the etiology of maternal sepsis and further identify its risk factors. METHODS: In this retrospective study, we evaluated 70698 obstetric patients who were admitted to the Third Affiliated Hospital of Guangzhou Medical University between January 1, 2009 and June 30, 2018. Subjects were divided into sepsis group and non-sepsis group based on the incidence of sepsis. Data about medical history (surgical and obstetric history) and demographic information were collected. The Mann-Whitney U test was used to compare patient age, gestational age and duration of hospitalization between the two groups. Univariate and multivariate logistic regression models were used to analyze the etiology and the risk factors for maternal sepsis. Unadjusted and adjusted odds ratios (OR) are reported. RESULTS: A total of 561 of 70698 obstetric patients were diagnosed with infection; of the infected patients, 492 had non-sepsis associated infection (87.7%), while 69 had sepsis (12.3%). The morbidity rate of maternal sepsis was 9.76/10000; the fatality rate in the sepsis group was 11.6% (8/69). Emergency admission (OR = 2.183) or transfer (OR = 2.870), irregular prenatal care (OR = 2.953), labor induction (OR = 4.665), cervical cerclage (OR = 14.214), first trimester (OR = 6.806) and second trimester (OR = 2.09) were significant risk factors for maternal sepsis. CONCLUSION: Mode of admission, poor prenatal care, labor induction, cervical cerclage, first trimester and second trimester pregnancy were risk factors for maternal sepsis. Escherichia coli was the most common causative organism for maternal sepsis, and the uterus was the most common site of infection.

Vitamin A deficiency exacerbates extrinsic atopic dermatitis development by potentiating type 2 helper T cell-type inflammation and mast cell activation.

BACKGROUND: Vitamin A deficiency (VAD) has been hypothesized to play a role in the pathophysiology of atopic dermatitis (AD). OBJECTIVE: We sought to verify whether VAD can exacerbate AD development, and explore the possible pathophysiologic mechanism. METHODS: We detected serum vitamin A (VA) concentration in different phenotypes of AD infants (intrinsic AD, iAD and extrinsic AD, eAD), and established ovalbumin (OVA) percutaneous sensitized AD model and passive cutaneous anaphylaxis (PCA) model on VAD and vitamin A supplementation (VAS) model in wild-type mice (C57BL/6) and established AD model on both normal VA (VAN) and VAD feeding mast cell deficiency mice (ckitw-sh/w-sh ). RESULTS: The average serum VA concentration of eAD was significantly lower than that of iAD, as well as healthy controls. In OVA-induced C57BL/6 mouse AD model, compared with VAN group, VAD mice manifested significantly more mast cells accumulation in the skin lesions, more severe Th2-mediated inflammation, including higher serum IgG1 and IgE levels, more IL-4, IL-13 mRNA expression in OVA-sensitized skin, and lower Th1 immune response, including lower serum IgG2a and IFN-γ mRNA expression in the skin. But there was no significant difference in the expression of IL-17 mRNA between OVA-treated skin of VAN and VAD mice. However, in OVA-induced ckitw-sh/w-sh mouse AD model, we did not find any significant differences in the above measurements between VAD and VAN group. In PCA model, VAD mice showed remarkable more blue dye leakage than that in VAN mice. Compared with VAD group, the above-mentioned inflammatory measurements in VAS group and VAN group were similar in OVA-induced AD model mice. CONCLUSIONS AND CLINICAL RELEVANCE: VAD can exacerbate extrinsic AD by augmenting Th2-mediated inflammation and mast cell activation. Therapeutic VAS can rescue VAD-aggravated eAD. It may provide a new strategy for future prevention or treatment of atopic dermatitis.

L1CAM mutations in three fetuses diagnosed by medical exome sequencing.

OBJECTIVE: The L1 cell adhesion molecule (L1CAM) gene, encodes the L1 cell adhesion molecule, is involved in the central nervous system development. Its mutations result in L1 syndrome which is associated with brain malformation and nervous developmental delay. CASE REPORT: We presented three fetuses with hydrocephalus and agenesis of the corpus callosum detected by ultrasound, followed by medical exome sequencing (MES) test with L1CAM mutations: two known missense mutation c.551G > A (p. R184Q) and c.1354G > A (p. G452R), and a novel frameshift mutation c.1322delG which causes the early termination of translation (p. G441Afs∗72). By utilizing multiple computational analysis, all the variants were scored to be likely pathogenic. CONCLUSION: Combined use of ultrasound and MES to identify the molecular etiology of fetal anomalies may contribute to expanding our knowledge of the clinical phenotype of L1 syndrome observed in the south Chinese population.

Prenatal diagnose of a fetus with Harlequin ichthyosis in a Chinese family.

OBJECTIVE: Harlequin ichthyosis (HI) was the most severe form of ichthyoses, which leaded to neonatal death in 50% of cases. It was the result of mutations in ABCA12 gene. With the development of ultrasound skills and genetic analysis, HI could be prenatal diagnosed. CASE REPORT: Here, we reported a case of HI, which was prenatal diagnosed by ultrasound examination and genetic analysis. The fetus was found that severe ectropion, eclabium, flattened nose, and rudimentary ears by ultrasound at 20 weeks gestation. A molecular genetic analysis was performed and revealed two mutations in the ABCA12 gene. One of two mutations were not reported in the past. The fetus was terminated. CONCLUSION: HI was associated with the poor prognosis of HI neonates. Prenatal ultrasound and genetic analysis were important for prenatal diagnosis of HI and were helpful to give sufficient prenatal counsels for the family with HI baby.

Evaluation of the Validity and Reliability of the Chinese Healthy Eating Index.

The Chinese Healthy Eating Index (CHEI) is a measuring instrument of diet quality in accordance with the Dietary Guidelines for Chinese (DGC)-2016. The objective of the study was to evaluate the validity and reliability of the CHEI. Data from 12,473 adults from the China Health and Nutrition Survey (CHNS)-2011, including 3-day-24-h dietary recalls were used in this study. The CHEI was assessed by four exemplary menus developed by the DGC-2016, the general linear models, the independent t-test and the Mann-Whitney U-test, the Spearman's correlation analysis, the principal components analysis (PCA), the Cronbach's coefficient, and the Pearson correlation with nutrient intakes. A higher CHEI score was linked with lower exposure to known risk factors of Chinese diets. The CHEI scored nearly perfect for exemplary menus for adult men (99.8), adult women (99.7), and the healthy elderly (99.1), but not for young children (91.2). The CHEI was able to distinguish the difference in diet quality between smokers and non-smokers (P < 0.0001), people with higher and lower education levels (P < 0.0001), and people living in urban and rural areas (P < 0.0001). Low correlations with energy intake for the CHEI total and component scores (|r| < 0.34, P < 0.01) supported the index assessed diet quality independently of diet quantity. The PCA indicated that underlying multiple dimensions compose the CHEI, and Cronbach's coefficient α was 0.22. Components of dairy, fruits and cooking oils had the greatest impact on the total score. People with a higher CHEI score had not only a higher absolute intake of nutrients (P < 0.001), but also a more nutrient-dense diet (P < 0.001). Our findings support the validity and reliability of the CHEI when using the 3-day-24-h recalls.

Association between Phthalate Exposure and the Use of Plastic Containers in Shanghai Adults.

OBJECTIVE: Consuming phthalates may be due to the presence of food contact materials, such as plastic containers. In this study, we investigated the association between plastic container use and phthalate exposure in 2,140 Shanghai adults. METHODS: Participants completed a questionnaire on the frequency of using plastic containers in different scenarios in the previous year (e.g., daily, weekly) and on the consumption of plastic-packaged foods in the previous three days (yes or no). Urinary phthalate metabolites were used to assess the association between phthalate exposure and the use of plastic containers. RESULTS: The metabolites of di-(2-ethylhexyl) phthalate (DEHP) were the most frequently detected in urine. The results revealed that phthalate exposure was associated with consumption of plastic-packaged breakfast or processed food items in the previous three days. The consumption of these two food items had strong synergistic effects on increasing urinary concentrations of most phthalate metabolites. CONCLUSION: Our results of plastic-packaged breakfast and processed food may be explained by the use of flexible plastic containers, indicating the importance of risk assessment for the application of flexible plastic containers.

The Development of a Chinese Healthy Eating Index and Its Application in the General Population.

The objective of this study was to develop a Chinese Healthy Eating Index (CHEI) based on the updated Dietary Guidelines for Chinese (DGC-2016) and to apply it in the 2011 China Health and Nutrition Survey (CHNS-2011) to assess diet quality and its association with typical sociodemographic/economic factors. Data from 14,584 participants (≥2 years) from the CHNS-2011, including three 24-h dietary recalls and additional variables, were used to develop the CHEI. The standard portion size was applied to quantify food consumption. The CHEI was designed as a continuous scoring system, comprising 17 components; the maximum total score is 100. The mean, 1st and 99th percentiles of the CHEI score were 52.4, 27.6 and 78.3, respectively. Young and middle-aged adults scored better than the elderly. Diet insufficiency was chiefly manifested in fruits, dairy, whole grains and poultry; diet excess was mainly reflected in red meat, cooking oils and sodium. The CHEI was positively associated with education and urbanization levels; current smokers and unmarried people obtained relative low CHEI scores. Occupation and body mass index (BMI) were also related to the CHEI. Our findings indicate that the CHEI is capable of recognizing differences in diet quality among the Chinese, and it is sensitive to typical sociodemographic/economic factors.

Effects of decabrominated diphenyl ether (PBDE-209) in regulation of growth and apoptosis of breast, ovarian, and cervical cancer cells.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs), commonly used in building materials, electronics, plastics, polyurethane foams, and textiles, are health hazards found in the environment. OBJECTIVE: In this study we investigated the effects of PBDE-209, a deca-PBDE, on the regulation of growth and apoptosis of breast, ovarian, and cervical cancer cells as well as the underlying protein alterations. METHODS: We used MCF-7 and MCF-7/ADR (multidrug-resistant MCF-7) breast cancer cell lines, the HeLa cervical cancer cell line, the OVCAR-3 ovarian cancer cell line, and the normal CHO (Chinese hamster ovary) cell line to assess the effects of PBDE-209 using cell viability, immunofluorescence, and flow cytometric assays. Western blot assays were used to detect changes in protein expression. To assess the effects of PBDE-209 on apoptosis, we used the protein kinase Cα (PKCα) inhibitor Gö 6976, the extracellular signal-regulated kinase (ERK) inhibitor PD98059, and tamoxifen. RESULTS: Our data indicate that PBDE-209 increased viability and proliferation of the tumor cell lines and in CHO cells in a dose- and time-dependent manner. PBDE-209 also altered cell cycle distribution by inducing the S phase or G2/M phase. Furthermore, PBDE-209 partially suppressed tamoxifen-induced cell apoptosis in the breast cancer cell lines (MCF-7 and MCF-7/ADR) but suppressed Gö 6976- and PD98059-induced apoptosis in all cell lines. At the molecular level, PBDE-209 enhanced PKCα and ERK1/2 phosphorylation in the cell lines. CONCLUSIONS: Our data demonstrate that PBDE-209 is able to promote proliferation of various cancer cells from the female reproductive system and normal ovarian CHO cells. Furthermore, it reduced tamoxifen, PKCα, and ERK inhibition-induced apoptosis. Finally, PBDE-209 up-regulated phosphorylation of PKCα and ERK1/2 proteins in tumor cells and in CHO cells.