Roxadustat reduces left ventricular mass index compared to rHuEPO in haemodialysis patients in a randomized controlled trial.

BACKGROUND: Left ventricular hypertrophy (LVH) is highly prevalent in haemodialysis (HD) patients and is associated with an increased risk of death. Roxadustat and recombinant human erythropoietin (rHuEPO, abbreviated as EPO) are the main treatment strategies for renal anaemia in HD patients, but it has not been clear whether there is a difference in their effect on LVH. METHODS: In this multi-centre, prospective, randomized trial of 12-month duration, study participants were randomized in a 1:1 ratio to the roxadustat group or the EPO group. The doses of both treatment regimens were adjusted so that the patients had a haemoglobin level of 10.0-12.0 g per dL. The primary study endpoint was the change from baseline to 12 months in the left ventricular mass index (LVMI, g/m2) measured by echocardiography. RESULTS: In total, 114 patients were enrolled. The mean age was 50 years, and the median dialysis duration was 33 months. Sixty-one patients were men, and 24 were diabetic. LVMI decreased from 116.18 ± 27.84 to 110.70 ± 25.74 g/m2 in the roxadustat group. However, it increased from 109.35 ± 23.41 to 114.99 ± 28.46 g/m2 in the EPO group, with a significant difference in the change in LVMI between the two groups [-5.48 (-11.60 to 0.65) vs. 5.65 (0.74 to 10.55), p < 0.05]. Changes in left ventricular mass, end-diastolic volume and 6-min walk test seemed superior in the roxadustat group. There were no significant differences in other cardiac geometry, biochemical parameters and major adverse cardiovascular events between the two groups. CONCLUSIONS: Compared to EPO, roxadustat is more helpful in the regression of LVH in HD patients.

A diet-wide association study for liver cancer risk: findings from a prospective cohort study in Chinese men.

Dietary factors have been extensively investigated as possible risk factors for liver cancer, but the evidence is inconclusive. Our study systematically assessed the association between 142 foods and nutrients and liver cancer risk in a Chinese population using a diet-wide association study. Based on data from 59,844 men in the Shanghai Men's Health Study (SMHS), we assessed the diet intake by dietary questionnaires. Cox regression was used to quantify the association between each food and nutrient and liver cancer risk. A false discovery rate (FDR) of 0.05 was used to select the foods and nutrients for validation. In the cohort, 431 liver cancer cases were identified during 712,373 person-years of follow-up. Retinol (HR per 1 SD increment = 1.09, 95% CI: 1.03-1.14) was associated with a higher risk of liver cancer, whereas onions (HR per 1 SD increment = 0.67, 95% CI: 0.54-0.84) and manganese (HR per 1 SD increment = 0.85, 95% CI: 0.78-0.94) were inversely associated with liver cancer risk. In the replication analysis, estimates for these foods and nutrients were similar in magnitude and direction. Our findings confirm that retinol, onions and manganese were associated with liver cancer risk, which provides reliable evidence between diet and liver cancer development.

Sex-specific impact of dietary patterns on liver cancer incidence: updated results from two population-based cohort studies in China.

PURPOSE: The associations between dietary patterns and liver cancer risk have received much attention, but evidence among the Chinese population is scarce. This study aims to update the results of two cohort studies and provide the sex-specific associations in the Chinese population. METHODS: This study was based on two cohorts from the Shanghai Men's Health Study (SMHS) and the Shanghai Women's Health Study (SWHS). Diet information was collected by validated food frequency questionnaires. Dietary patterns were derived by factor analysis. Cox regression model was utilized to estimate the hazard ratio (HR) and 95% confidence interval (CI) for associations between dietary patterns and liver cancer risk. RESULTS: During median follow-up years of 11.2 (male) and 17.1 (female) years, 427 males and 252 females were identified as incident primary liver cancer cases. In males, vegetable-based dietary pattern was inversely associated with liver cancer (HRQ4-Q1: 0.67, 95%CI 0.51-0.88, Ptrend < 0.001). Interaction analysis indicated that in males lower vegetable-based dietary pattern score and older age/medical history of chronic hepatitis combined increase the hazard of liver cancer more than the sum of them, with a 114% and 1061% higher risk, respectively. In females, the fruit-based dietary pattern was associated with a reduced risk of liver cancer (HRQ4-Q1: 0.63, 95%CI 0.42-0.95, Ptrend = 0.03). In both males and females, null associations were observed between the meat-based dietary pattern and the risk of liver cancer. CONCLUSION: A vegetable-based dietary pattern in males and a fruit-based dietary pattern in females tended to have a protective role on liver cancer risk. This study provided updated information that might be applied to guide public health action for the primary prevention of liver cancer.

Residential mobility and liver cancer risk: findings from a prospective cohort study in Chinese women.

BACKGROUND: Residential mobility is believed to influence the occurrence and development of cancer; however, the results are inconclusive. Furthermore, limited studies have been conducted on Asian populations. This study aimed to evaluate the relationship between residential mobility and liver cancer risk among Chinese women. METHODS: We enrolled 72,818 women from urban Shanghai between 1996 and 2000, and then followed them until the end of 2016. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the association between residential mobility and liver cancer risk. A linear trend test was conducted by ranking variables. A sensitivity analysis was also conducted, excluding participants with follow-up times of less than 2 years, to prevent potential bias. RESULTS: During the 1,269,765 person-years of follow-up, liver cancer was newly diagnosed in 259 patients. Domestic migration (HR = 1.47, 95% CI, 1.44-1.50), especially immigration to Shanghai (HR = 1.47, 95% CI, 1.44-1.50) was associated with an increased risk of liver cancer. In addition, migration frequency, age at initial migration and first immigration to Shanghai had linear trends with an increased liver cancer risk (Ptrend <0.001). The results were similar when excluding participants with less than two years of follow-up. CONCLUSIONS: The possible association between residential mobility and a higher risk of liver cancer in women could suggest the need for effective interventions to reduce adverse environmental exposures and enhance people's health.

New insights into biologic interpretation of bioinformatic pipelines for fish eDNA metabarcoding: A case study in Pearl River estuary.

Environmental DNA (eDNA) metabarcoding is an emerging tool for monitoring biological communities in aquatic ecosystems. The selection of bioinformatic pipelines significantly impacts the results of biodiversity assessments. However, there is currently no consensus on the appropriate bioinformatic pipelines for fish community analysis in eDNA metabarcoding. In this study, we compared three bioinformatic pipelines (Uparse, DADA2, and UNOISE3) using real and mock (constructed with 15/30 known fish) communities to investigate the differences in biological interpretation during the data analysis process in eDNA metabarcoding. Performance evaluation and diversity analyses revealed that the choice of bioinformatic pipeline could impact the biological results of metabarcoding experiments. Among the three pipelines, the operational taxonomic units (OTU)-based pipeline (Uparse) showed the best performance (sensitivity: 0.6250 ± 0.0166; compositional similarity: 0.4000 ± 0.0571), the highest richness (25-102) and minimal inter-group differences in alpha diversity. It suggested the OTU-based pipeline possessed superior capability in fish diversity monitoring compared to ASV/ZOTU-based pipeline. Additionally, the Bray-Curtis distance matrix achieved the highest discriminative effect in the PCoA (43.3%-53.89%) and inter-group analysis (P < 0.01), indicating it was better at distinguishing compositional differences or specific genera of fish community at different sampling sites than other distance matrices. These findings provide new insights into fish community monitoring through eDNA metabarcoding in estuarine environments.

Cumulative consumption of tea is associated with lower risk of liver cancer: Updated results from the Shanghai Women's Health Study.

Prospective epidemiological studies have provided limited evidence for an association between tea consumption and liver cancer risk. Based on a population-based prospective cohort study in middle-aged Chinese women, we investigated the association between tea consumption and the risk of primary liver cancer. Detailed information on tea drinking habits and other potential confounders was obtained at the baseline interview. Incident liver cancer cases were identified through record linkage with the population-based cancer registry and verified through home visits and review of medical charts by medical experts. Multiple aspects of tea drinking habits including starting age, duration, intensity and cumulative consumption of any type of tea and green tea were considered. Multivariable-adjusted hazard ratios (aHRs) and their 95% confidence intervals (CIs) were derived from the Cox regression models. After a median follow-up time of 18.12 (interquartile range = 1.59) years, 253 incident liver cancer cases were identified from 71 841 cohort members. Compared with never tea drinkers, the risk of liver cancer for participants who have consumed over 30 kg of dried tea leaves cumulatively was 0.56 (95% CI: 0.32-0.97). For those who drank green tea only, the aHR was 0.54 (95% CI: 0.30-0.98). This updated study suggested an inverse association between cumulative consumption of tea, especially green tea and the risk of primary liver cancer.

Sex-Specific Correlation Analysis of Branched-Chain Amino Acids in Dietary Intakes and Plasma among Chinese Adults.

BACKGROUND: Previous findings about the influence of dietary intakes of the branched-chain amino acid (BCAA) on their plasma concentrations have been limited and inconsistent, and evidence from the Chinese population was lacking. OBJECTIVES: This study aimed to investigate the diet-plasma BCAA correlations in Chinese male and female adults. METHODS: This cross-sectional study was based on a nested case-control study within 2 prospective population-based cohorts in Shanghai, China. Diet information was collected by the food frequency questionnaires. Plasma BCAA concentrations were measured by ultraperformance liquid chromatography coupled with tandem mass spectrometry. Spearman correlations and linear regression models were conducted to examine the relationships between dietary BCAA intakes and plasma BCAA. The multivariable model was adjusted for age at the interview, total energy intake, time of blood collection from last meal, dietary patterns, body mass index (in kg/m2), type 2 diabetes, and physical activity. RESULTS: A total of 322 males (median age of 57.0 y) and 187 females (median age of 60.0 y) were included in this cross-sectional study. The geometric means of dietary intake of leucine, isoleucine, valine, and BCAA were 4937.7, 3029.6, 3268.5, and 11237.4 mg/d in males, and 4125.7, 2567.8, 2754.3, and 9449.4 mg/d in females. The geometric means of plasma concentrations of leucine, isoleucine, valine, and BCAA were 181.9, 65.0, 219.8, and 469.4 µM/L in males and 161.6, 61.1, 206.5, and 431.6 µM/L in females. Only leucine (r = 0.1660, P = 0.0028) and total BCAA (r = 0.1348, P = 0.0155) in males exhibited weak positive correlation coefficients. After adjustment for the covariates, leucine, isoleucine, valine, and total BCAA in dietary intakes and plasma were not correlated in both males and females. CONCLUSIONS: In Chinese male and female adults, dietary intakes are not major determinants of plasma concentrations of BCAA, and plasma concentrations might not be reflected by usual dietary intakes of BCAA.

Relationship between IL-17A gene polymorphism and susceptibility to Kawasaki disease. / IL-17AåŸºå› rs3819025ä½ç‚¹å¤šæ€æ€§ä¸Žå·å´Žç— çš„ç›¸å ³æ€§ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: Kawasaki disease (KD) is the most common autoimmune vasculitis syndrome in children, which supposed be a complex polygenic disorder. Interleukin-17 (IL-17) is a member of the pro-inflammatory cytokine family, which has a strong pro-inflammatory effect and can participate in various acute and chronic inflammatory responses. This study aims to investigate the relationship between the single-nucleotide polymorphism (SNP) locus rs3819025 in the IL-17A gene and the susceptibility to KD. METHODS: A total of 120 patients with KD who met the diagnostic criteria (the KD group) and 120 healthy children (the control group) were enrolled retrospectively in this study. Polymerase chain reaction (PCR) and DNA direct sequencing were used to detect the SNPs of children in the 2 groups. RESULTS: The frequencies of GG, GA, and AA genotypes of rs3819025 locus in the IL-17A gene in the KD group were 82.5%, 17.5%, and 0, respectively, and the frequencies of GG, GA, and AA genotypes in the control group were 72.5%, 22.5%, and 5.0%, respectively. There were significant differences in both genotype (χ2=7.524, P=0.023). The allele frequencies G and A of rs3819025 locus in the KD group were 91.25% and 8.75%, respectively, while those in the control group were 83.75% and 16.25%, respectively. There was significant difference between the 2 groups (χ2=6.171, P=0.013). The distribution frequencies of GG or GA genotype and G or A allele were 88.46% or 11.54% and 94.23% or 5.77% in the KD group with coronary artery lesion, respectively. The distribution frequencies of GG or GA genotype and G or A allele were 78.72% or 21.28% and 89.36% or 10.64% in the KD group without coronary artery lesion, respectively. There were no significant differences in genotype and allele frequencies of rs3819025 between the KD with coronary artery lesion group and the KD group without coronary artery lesion (both P>0.05). Besides, children with the allele A had a 2.023 times higher risk of KD than those without the allele A (χ2=6.171, P=0.013; OR=2.023, 95% CI 1.151 to 3.557). CONCLUSIONS: The locus rs3819025 in the IL-17A gene is associated with the pathogenesis of KD. The allele A of the locus rs3819025 in the IL-17A gene may be a risk factor for KD.

Joint impact of BMI, physical activity and diet on type 2 diabetes: Findings from two population-based cohorts in China.

AIMS: Limited epidemiological data on the combined impact of several lifestyle factors on type 2 diabetes (T2D) incidence was reported in Chinese population. This study aimed to examine how combinations of BMI, physical activity and diet relate to T2D incidence and estimate corresponding population attributable risk in the general population. METHODS: A total of 56,691 male and 70,849 female participants aged 40-74 years old in two population-based cohorts from the Shanghai Men's and Women's Health Studies were used for analysis. The Cox regression model was used to estimate the association between lifestyle factors collected at baseline and T2D incidence. Multivariable-adjusted population attributable risks were calculated for specific combinations of lifestyle factors. RESULTS: There were 3315 male and 5925 female incident T2D, with corresponding density incidence rates of 6.39 and 6.04 per 1000 person-years. If the healthiest group of healthy lifestyle index (HLI) was used as a reference, the hazard ratios (95% confidence intervals) of T2D increased monotonically in men [2.04 (1.75, 2.38); 2.94 (2.53, 3.42); 4.31 (3.66, 5.07)] and women [1.85 (1.64, 2.08); 2.79 (2.49, 3.13); 4.14 (3.66, 4.67)]. One point increase of HLI was related to 35% and 35% lower risk in men and women. About 52.7% and 58.4% cases in men and women could have been avoided if participants had been adherent to a healthy lifestyle of maintaining healthy body weight, eating a healthy diet and keeping physically active. CONCLUSIONS: An increased number of healthy lifestyle factors were associated with a decreased risk of T2D in the Chinese population. Future interventions targeted at combined healthy lifestyle factors are needed to reduce the burden of T2D.

Dietary fat intake and liver cancer incidence: A population-based cohort study in Chinese men.

To date, limited studies have focused on the association between dietary fat and liver cancer risk, especially in China. Our study aims to evaluate the association between dietary fat intake and liver cancer incidence risk in men. Dietary fat intake was obtained through a validated food frequency questionnaire in a Chinese prospective cohort. The Cox regression model was utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). After exclusion, 59 998 recruitments were finally analyzed with a total follow-up time of 714 339 person-years, 431 incident liver cancer cases were newly identified among them. The adjusted HRs (95% CIs) for the highest vs lowest quartile of total fat, saturated fat, monounsaturated fat (MUFA), and polyunsaturated fat (PUFA) were 1.33 (1.01-1.75), 1.50 (1.13-1.97), 1.26 (0.96-1.65), and 1.41 (1.07-1.86), and the corresponding P-trend values were .008, .005, .034, and .005, respectively. In the secondary analysis among participants tested for hepatitis B virus, we found that higher intakes of saturated fat and PUFA were also associated with increased liver cancer risks. Besides, high risks of per standard deviation alterations of the total fat, saturated fat and MUFA were detected in liver cancer, and these results were similar to those concluded from the full-cohort analysis. In conclusion, dietary intakes of total fat, saturated fat, PUFA, and probably MUFA might increase liver cancer risks. Our study provides suggestive advice to public administration on dietary suggestions, and related measures taken from managing dietary fat intake might reduce liver cancer incidence.

Coffee drinking and cancer risk: an umbrella review of meta-analyses of observational studies.

BACKGROUND: Epidemiological studies on the association between coffee intake and cancer risk have yielded inconsistent results. To summarize and appraise the quality of the current evidence, we conducted an umbrella review of existing findings from meta-analyses of observational studies. METHODS: We searched PubMed, Embase, Web of Science and the Cochrane database to obtain systematic reviews and meta-analyses of associations between coffee intake and cancer incidence. For each association, we estimated the summary effect size using the fixed- and random-effects model, the 95% confidence interval, and the 95% prediction interval. We also assessed heterogeneity, evidence of small-study effects, and excess significance bias. RESULTS: Twenty-eight individual meta-analyses including 36 summary associations for 26 cancer sites were retrieved for this umbrella review. A total of 17 meta-analyses were significant at P ≤ 0.05 in the random-effects model. For the highest versus lowest categories, 4 of 26 associations had a more stringent P value (P ≤ 10- 6). Associations for five cancers were significant in dose-response analyses. Most studies (69%) showed low heterogeneity (I2 ≤ 50%). Three and six associations had evidence of excessive significance bias and publication bias, respectively. Coffee intake was inversely related to the risk of liver cancer and endometrial cancer and was characterized by dose-response relationships. There were no substantial changes when we restricted analyses to meta-analysis of cohort studies. CONCLUSIONS: There is highly suggestive evidence for an inverse association between coffee intake and risk of liver and endometrial cancer. Further research is needed to provide more robust evidence for cancer at other sites.

Identification and validation of differential expression of miR-455-5p in plasma of children with Kawasaki disease. / å·å´Žç— æ‚£å„¿è¡€æµ†å·®å¼‚è¡¨è¾¾miR-455-5p的鉴定及验证.

OBJECTIVES: To provide clues for further study of the relationship between miRNAs and Kawasaki disease (KD) development, and to provide molecular markers for ultimately improve the rate of early diagnosis for KD. METHODS: We collected acute, recovery KD children's plasma and normal samples, then used the miRNAs Assay Chip to screen the differentially expressed miRNAs in the plasma from KD children. Subsequently, miR-455-5p, which had identified via miRNAs assay chip, was validated by quantitative real-time PCR via independent cohort. RESULTS: According to the results of miRNAs Assay chip, we identified a miRNAs panel including 5 miRNAs significantly up-regulated and 5 miRNAs remarkably down-regulated in the plasma from KD children compared to the normal control; miR-455-5p in both of acute and recovery KD children's plasma was remarkably lower than that in the normal control (P<0.001, P=0.013, respectively), and miR-455-5p was also significantly lower than that in the recovery of KD children (P=0.007) by independent cohort validation. CONCLUSIONS: There are significantly differentially expressed circulating miRNAs between the KD children and normal control. We identified 10 miRNAs dysregulation in the KD children's plasma compared with the normal group. Circulating miR-455-5p in both of acute and recovery KD children's plasma is remarkably lower than that in the normal control, and miR-455-5p may considered as a marker to show the recovery process of KD children. Plasma specific circulating miRNAs play an important role in the early diagnosis of KD and become the new molecular marker of KD in the future.

Femtosecond laser micro-machining enabled all-fiber mode selective converter.

We demonstrate a compact all-fiber mode selective converter enabled by femtosecond laser micro-machining on the few-mode fiber (FMF) facet. By introducing a micro-structure into the FMF core, we can achieve a π spatial phase difference to the fundamental mode of light to be converted. Theoretical optimization reveals that various high-order modes, including LP11, LP02, and LP21 modes, can be selectively converted by various micro-structures on the FMF facet, with a mode extinction ratio of more than 25 dB and mode coupling efficiency of better than 45% over the C-band. Finally, a proof-of-concept experiment is conducted by inscribing a micro-slot on the two-mode fiber facet for the LP01 to LP11 mode conversion. A micro-slot with a width of 6.7 µm and a depth of 5.4 µm is fabricated under the optimal femtosecond laser parameters. A LP01 to LP11 mode conversion with an average insertion loss of 2.7 dB is realized over the C-band, together with a mode intensity profile correlation efficient of more than 65%. Efficient higher-order mode conversion is feasible with a precise femtosecond laser micro-machining.

Association of miR-146a Gene Polymorphism at loci rs2910164 G/C, rs57095329 A/G, and rs6864584 T/C with Susceptibility to Kawasaki Disease in Chinese Children.

OBJECTIVE: To investigate the genetic association of miR-146a gene polymorphisms at loci rs2910164 G/C, rs57095329 A/G, and rs6864584 T/C in patients with Kawasaki disease (KD) and coronary artery lesions (CAL). METHODS: There were 120 patients with KD and 126 healthy subjects in this study. The genotype of loci rs2910164 G/C, rs57095329 A/G, and rs6864584 T/C of miR-146a gene were detected by polymerase chain reaction-sequence-based typing. RESULTS: For miR-146a gene polymorphisms at loci rs2910164 G/C, rs57095329 A/G, and rs6864584 T/C, there were no significant difference of genotype frequencies and allele frequencies between KD group and healthy control group, or between the IVIG-resistant group and IVIG-sensitive group (P > 0.05). In KD with coronary artery lesions (KD-CAL) group, the genotype frequencies of GG were higher than that in KD without coronary artery lesion (KD-WO) group at locus rs2910164 G/C polymorphisms of miR-146a gene (χ2 = 6.660, P = 0.036), patients with KD carried genotype of GG were at 3.636 times higher risk of getting coronary artery lesions than those of non-carriers (χ2 = 6.455, P = 0.018, OR = 3.636, 95%CI = 1.280-10.262). While there was no significant difference of allele frequency of G and C between KD-CAL group and KD-WO group (P > 0.05). In KD-CAL group, the allele frequency of A was higher than that in KD-WO group at locus rs57095329 A/G polymorphisms of miR-146a gene (χ2 = 4.745, P = 0.035), carriers with allele A were at 2.422 times higher risk of getting coronary artery lesions than those of non-carriers (χ2 = 4.745, P = 0.035, OR = 2.422, 95%CI = 1.073-5.465), while there was no significant difference of genotype frequency of AA, AG, and GG types between KD-CAL group and KD-WO group (P > 0.05). There was no significant difference of genotype frequencies of TT, TC, and CC types and allele frequencies of T and C types between KD-CAL group and KD-WO group at locus rs6864584 T/C polymorphisms of miR-146a gene (P > 0.05). CONCLUSIONS: The significant association has been found between the genotype and allele frequency of the miR-146a gene loci rs2910164 G/C and rs57095329 A/G, the genotype GG of rs2910164 G/C, and allele A of rs57095329 A/G were risk factors for getting coronary artery lesions.

Polymorphisms in endothelial protein C receptor gene and Kawasaki disease susceptibility in a Chinese children.

OBJECTIVE: To investigate association between the single nucleotide polymorphisms of endothelial protein C receptor (EPCR) gene and the risk of Kawasaki disease (KD) in a Chinese children.
 Methods: A total of 103 KD patients including 23 patients with coronary artery lesions (CAL) and 158 controls were recruited. Seven tagging SNPs (rs6088738, rs2069940, rs2069945, rs2069952, rs867186, rs9574, and rs1415774) of EPCR gene were selected for TaqMan allelic discrimination assay. The plasma soluble EPCR (sEPCR) levels of 53 KD and 52 healthy children were detected by ELISA.
 Results: We found a significant association between rs2069952, rs9574 or rs1415774 and higher probability for the occurrence of KD but not CAL formation. Interestingly, males with these 3 SNPs and rs2069945 SNPs bore a much greater risk of KD than females. The level of plasma sEPCR in children with KD didnot predict the formation of CAL. However, the allele G of rs867186 in EPCR was associated with the increased level of plasma sEPCR in KD patients.
 Conclusion: The SNPs of EPCR are associated with KD susceptibility in a Chinese Han children.

Atypical Skeletal Muscle Profiles in Human Immunodeficiency Virus-Infected Asymptomatic Middle-Aged Adults.

Background: Human immunodeficiency virus (HIV)-infected individuals are at increased risk of age-associated functional impairment, even with effective antiretroviral therapy (ART). A concurrent characterization of skeletal muscle, physical function, and immune phenotype in aviremic middle-aged HIV-infected adults represents a knowledge gap in prognostic biomarker discovery. Methods: We undertook a prospective observational study of 170 middle-aged, HIV-infected ambulatory men and women with CD4+ T-cell counts of at least 350/µL and undetectable plasma viremia while on effective ART, and uninfected control participants. We measured biomarkers for inflammation and immune activation, fatigue, the Veterans Aging Cohort Study mortality index, and physical function. A subset also received a skeletal muscle biopsy and computed tomography scan. Results: Compared to the uninfected participants, HIV-infected participants displayed increased immune activation (P < .001), inflammation (P = .001), and fatigue (P = .010), and in a regression model adjusting for age and sex displayed deficits in stair-climb power (P < .001), gait speed (P = .036), and predicted metabolic equivalents (P = .019). Skeletal muscle displayed reduced nuclear peroxisome proliferator-activated receptor-γ coactivator 1α-positive myonuclei (P = .006), and increased internalized myonuclei (P < .001) that correlated with immune activation (P = .003) and leukocyte infiltration (P < .001). Internalized myonuclei improved a model for HIV discrimination, increasing the C-statistic from 0.84 to 0.90. Conclusions: Asymptomatic HIV-infected middle-aged adults display atypical skeletal muscle profiles, subclinical deficits in physical function, and persistent inflammation and immune activation. Identifying biomarker profiles for muscle dysregulation and risk for future functional decline in the HIV-infected population will be key to developing and monitoring preventive interventions. Clinical Trials Registration: NCT03011957.

Mechanisms responsible for reduced erythropoiesis during androgen deprivation therapy in men with prostate cancer.

Androgen deprivation therapy (ADT) is a mainstay of treatment for prostate cancer (PCa). As androgens stimulate erythropoiesis, ADT is associated with a reduction in hematocrit, which in turn contributes to fatigue and related morbidity. However, the mechanisms involved in ADT-induced reduction in erythropoiesis remain unclear. We conducted a 6-mo prospective cohort study and enrolled men with PCa about to undergo ADT (ADT-Group) and a control group of men who had previously undergone prostatectomy for localized PCa and were in remission (Non-ADT Group). All participants had normal testosterone levels at baseline. Fasting blood samples were collected at baseline, 12 wk, and 24 wk after initiation of ADT; samples were obtained at the same intervals from enrollment in the Non-ADT group. Blood count, iron studies, erythropoietin, erythroferrone, and hepcidin levels were measured. Seventy participants formed the analytical sample (31 ADT, 39 Non-ADT). ADT was associated with a significant reduction in erythrocyte count (estimated mean difference = -0.2×106 cells/µl, 95%CI = -0.3 to -0.1×106 cells/µl, P < 0.001), hematocrit (-1.9%, 95%CI = -2.7 to -1.1%, P < 0.001), and hemoglobin (-0.6 g/dl, 95%CI = -0.8 to -0.3 g/dl, P < 0.001). Serum hepcidin concentration increased in the ADT-group (18 ng/ml, P < 0.001); however, iron concentrations did not change (-1.1 µg/dl, P = 0.837). Ferritin levels increased in men on ADT (60 ng/ml, P < 0.001). Iron binding capacity, transferrin saturation, erythroferrone, and erythropoietin did not change. Nine men undergoing ADT developed new-onset anemia. In conclusion, reduced proliferation of marrow erythroid progenitors leads to ADT-induced reduction in erythropoiesis. Future studies should evaluate the role of selective androgen receptor modulators in the treatment of ADT-induced anemia.

Spectrum of Ankyrin Mutations in Hereditary Spherocytosis: A Case Report and Review of the Literature.

BACKGROUND/AIMS: Hereditary spherocytosis (HS) is a common pediatric hemolytic anemia caused by congenital red blood cell defects. HS due to ankyrin 1 (ANK1) mutations is the most common type. We explored an ANK1 mutation from an HS patient and reviewed the literature. METHODS: We detected the mutation in a Chinese family in which 2 members were diagnosed with HS by next-generation sequencing. The proband was diagnosed with HS in the newborn period, based on clinical manifestations, laboratory data, and family history. The mutation spectrum of the ANK1 gene was summarized based on 85 patients diagnosed with HS carrying ANK1 mutations, and the ANK1 mutation spectrum was summarized and analyzed. RESULTS: We identified a novel mutation affecting ANK1 gene splicing (a splicing mutation) in both the patient and her mother, which is a substitution of T>G 2 nt after exon 25 in intron 26. The study expands our knowledge of the ANK1 gene mutation spectrum, providing a molecular basis for HS. CONCLUSION: A novel ANK1 mutation (NM_000037.3, c.2960+2T>G, intron 26) that is potentially associated with HS was identified. To date, 80 ANK1 mutations have been reported to be associated with HS in humans.

Epidemiology of childhood asthma in mainland China (1988-2014): A meta-analysis.

BACKGROUND: After the promotion of the two-child policy in recent years, the population of children in mainland China was bound to have a rapid growth, which would bring great challenges to public health. A number of cross-sectional studies on the epidemic of childhood asthma in mainland China were recently conducted, and varied prevalences were reported. Thus, knowing the epidemiology of childhood asthma in mainland China is of great necessity. OBJECTIVE: Our study aimed to summarize the pooled prevalence of childhood asthma in mainland China and its time trend, gender difference, regional distribution, and age structure. METHODS: Studies that reported the prevalence of childhood asthma in mainland China were identified via a systematic data base search through July 1, 2016. Meta-analysis was used to estimate the prevalence of childhood asthma and its subgroups, including gender, age groups, years, and regions. The regional distribution of the prevalence was set by province with the help of a geographic mapping software. The autoregressive integrated moving average model was used to predict the current prevalence of asthma. RESULTS: A total of 117 studies published from 1988 to 2014 in mainland China with a total sample size of 2,678,696 were included. The overall current prevalence and lifetime prevalence of childhood asthma was 2.112% (95% confidence interval [CI], 1.977-2.247%) and 2.502% (95% CI, 2.166-2.838%), respectively. The difference of the prevalences between male and female patients was significant: odds ratio 1.54 (95% CI, 1.47-1.62) for the current prevalence and odds ratio 1.61 (95% CI, 1.47-1.77) for the lifetime prevalence. CONCLUSION: The prevalence of childhood asthma in mainland China was low but has been increasing remarkably since 1998. Boys are more likely to have asthma throughout most of their childhood. Preschoolers (3-6 years old) showed a higher prevalence than the other age groups. The current prevalence of childhood asthma probably increased slightly from 2017 to 2019.

[Correlation between -31 T/C polymorphisms of interleukin-1ß gene and Kawasaki disease].

OBJECTIVE: To explore the correlation between the -31T/C polymorphisms of IL-1ß gene and thesusceptibility of Kawasaki disease (KD).
 Methods: The polymorphism at -31C/T site of IL-1ß gene was genotyped with the method of polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) in 100 KD patients (KD group) and 100 healthy children (control group). The differences in genotype distribution and allele frequency between the KD group and the control group were analyzed by χ2 test.
 Results: There were significant differences in genotype and allele frequencies for IL-1ß gene polymorphism at -31C/T site between the KD group and the control group (all P<0.05). The risk of KD in the KD group with TT genotype was 0.37 times as that with the CT and CC genotypes (χ2=5.65, P<0.005, OR=0.37, 95%CI 0.16 to 0.85). But there was no significant difference in genotype and allele frequencies for IL-1ß genepolymorphism at -31 site between the KD group with coronary artery lesion and the KD group without coronary artery lesion(all P>0.05).
 Conclusion: The polymorphism at -31T/C site of IL-1ß gene is associated with genetic susceptibility of KD. The KD patients with TT genotype are at low risk.