Full-space beam scanning based on transmission reflection switchable quadratic phase metasurface.

Beam scanning based on metasurfaces is widely discussed in recent years owing to its high integration, lightweight, and low cost. However, most of the reported beam scanning metasurfaces operate in either transmission or reflection mode. Here, we propose a full-space beam scanning metasurface based on transmission reflection switchable meta-atom and the quadratic phase distribution. As a validation, a metasurface array with 400 units (20 × 20) was experimentally demonstrated. Beam scanning of ± 35 ° was achieved in both transmission mode and reflection mode. A larger scanning angle (± 45 °) was further verified simulatively with a 900-units (30 × 30) array. The method provides an avenue for expanding the space of electromagnetic wave manipulation and may have great potential in wireless communication and radar detection.

Clinical significance of increased peripheral venous blood adipocyte-specific protein FABP4 after joint replacement.

A new method of diagnosing fat embolism (FE) at the molecular level was proposed, and the diagnostic value of adipocyte-specific protein fatty acid-binding protein 4 (Homo sapiens [human]) gene ID = 2167 (FABP4) for FE was preliminarily explored. Eight joint replacement patients, 5 internal medicine patients, and 6 healthy persons were recruited. Serum of internal medicine patients, healthy people, and patients before and 24 hours after joint replacement were taken as study samples. Subcutaneous adipose, intra-articular adipose and intramedullary yellow bone marrow of patients undergoing joint replacement were taken as study samples. The level of FABP4 in the above samples was detected by enzyme-linked immunoassay. Normal distribution was tested. Paired sample T test was used for self-control. Univariate analysis of variance was used for multigroup comparison.There was no significant difference in serum FABP4 level between healthy persons, medical patients, and preoperative patients. The FABP4 level in yellow bone marrow and subcutaneous adipose was significantly higher than that in serum of healthy people, medical patients, and preoperative patients. FABP4 level in the serum after joint replacement was significantly higher than that before joint replacement. FABP4 may be a specific indicator of FE diagnosis, but further studies are needed to confirm its clinical value.

Additive Interaction of MTHFR C677T and MTRR A66G Polymorphisms with Being Overweight/Obesity on the Risk of Type 2 Diabetes.

Although both methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms have been associated with type 2 diabetes (T2D), their interactions with being overweight/obesity on T2D risk remain unclear. To evaluate the associations of the two polymorphisms with T2D and their interactions with being overweight/obesity on T2D risk, a case-control study of 180 T2D patients and 350 healthy controls was conducted in northern China. Additive interaction was estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (S). After adjustments for age and gender, borderline significant associations of the MTHFR C677T and MTRR A66G polymorphisms with T2D were observed under recessive (OR = 1.43, 95% CI: 0.98-2.10) and dominant (OR = 1.43, 95% CI: 1.00-2.06) models, respectively. There was a significant interaction between the MTHFR 677TT genotype and being overweight/obesity on T2D risk (AP = 0.404, 95% CI: 0.047-0.761), in addition to the MTRR 66AG/GG genotypes (RERI = 1.703, 95% CI: 0.401-3.004; AP = 0.528, 95% CI: 0.223-0.834). Our findings suggest that individuals with the MTHFR 677TT or MTRR 66AG/GG genotypes are more susceptible to the detrimental effect of being overweight/obesity on T2D. Further large-scale studies are still needed to confirm our findings.

Combined genotype and haplotype distributions of MTHFR C677T and A1298C polymorphisms: A cross-sectional descriptive study of 13,473 Chinese adult women.

Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms are, independently and/or in combination, associated with many disorders. However, data on the combined genotype and haplotype distributions of the 2 polymorphisms in Chinese population were limited.We recruited 13,473 adult women from 9 Chinese provinces, collected buccal cell samples, and determined genotypes, to estimate the combined genotype and haplotype distributions of the MTHFR C677T and A1298C polymorphisms.In the total sample, the 6 common combined genotypes were CT/AA (29.5%), TT/AA (21.9%), CC/AA (15.4%), CC/AC (14.9%), CT/AC (13.7%), and CC/CC (3.4%); the 3 frequent haplotypes were 677T-1298A (43.6%), 677C-1298A (37.9%), and 677C-1298C (17.6%). Importantly, we observed that there were 51 (0.4%) individuals with the CT/CC genotype, 92 (0.7%) with the TT/AC genotype, 17 (0.1%) with the TT/CC genotype, and that the frequency of the 677T-1298C haplotype was 0.9%. In addition, the prevalence of some combined genotypes and haplotypes varied among populations residing in different areas and even showed apparent geographical gradients. Further linkage disequilibrium analysis showed that the D' and r values were 0.883 and 0.143, respectively.In summary, the findings of our study provide further strong evidence that the MTHFR C677T and A1298C polymorphisms are usually in trans and occasionally in cis configurations. The frequencies of mutant genotype combinations were relatively higher in Chinese population than other populations, and showed geographical variations. These baseline data would be useful for future related studies and for developing health management programs.

Gender-specific interactions of MTHFR C677T and MTRR A66G polymorphisms with overweight/obesity on serum lipid levels in a Chinese Han population.

BACKGROUND: Little is known regarding the interactions of methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms with overweight/obesity on serum lipid profiles. The aim of the current study was to explore interactions between the two polymorphisms and overweight/obesity on four common lipid levels in a Chinese Han population and further to evaluate whether these interactions exhibit gender-specificity. METHODS: A total of 2239 participants (750 females and 1489 males) were enrolled into this study. The genotypes of the MTHFR C677T and MTRR A66G were determined by a TaqMan assay. Overweight and obesity were defined as a body mass index between 24 and 27.99 and ≥ 28 kg/m2, respectively. The interactions were examined by factorial design covariance analysis, and further multiple comparisons were conducted by Bonferroni correction. RESULTS: There was no significant difference in the genotypic and allelic frequencies between females and males (MTHFR 677 T allele: 54.47 % for females and 54.40 % for males; MTRR 66G allele: 24.73 % for females and 24.71 % for males). Interaction between the MTHFR C677T polymorphism and overweight/obesity on serum triglyceride levels, and interaction between the MTRR A66G polymorphism and overweight/obesity on serum high-density lipoprotein cholesterol levels were detected in women (P = 0.015 and P = 0.056, respectively). For female subjects with overweight/obesity, the serum triglyceride levels in MTHFR 677TT genotype [1.09 (0.78-1.50) mmol/L] were significantly higher as compared with MTHFR 677CC genotype [0.90 (0.60-1.15) mmol/L, P = 0.007], and the MTRR 66GG genotype carriers had higher serum high-density lipoprotein cholesterol levels than those with MTRR 66AG genotype (1.46 ± 0.50 vs. 1.19 ± 0.31 mmol/L, P = 0.058). Furthermore, in male subjects with overweight/obesity, the MTHFR 677CT genotype carriers had higher low-density lipoprotein cholesterol levels than those with MTHFR 677TT genotype (2.96 ± 1.07 vs. 2.74 ± 0.88 mmol/L, P = 0.015). CONCLUSIONS: Our results indicate that there exist interactive effects of the MTHFR C677T and MTRR A66G polymorphisms with overweight/obesity on some lipid traits in Chinese Han population, and the effects were gender-specific.

Interactions of Methylenetetrahydrofolate Reductase C677T Polymorphism with Environmental Factors on Hypertension Susceptibility.

Hypertension is considered to be the result of genes, environment, and their interactions. Among them age, sex, tobacco use, alcohol consumption, and being overweight/obesity are well documented environmental determinants, and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is nominated as a potential genetic candidate. However, the synergistic effect of the MTHFR C677T polymorphism with these environmental factors on the risk of hypertension has received little attention. The aim of this study was to explore the associations of the MTHFR C677T polymorphism, environmental factors, and their interactions with hypertension predisposition in a Northern Chinese Han population. A total of 708 participants were enrolled in the study. The genotypes of the MTHFR C677T were determined by a TaqMan assay. We found that participants of an older age, being overweight/obesity, with a smoking habit, drinking habit, or carrying the 677T allele were at an increased risk of hypertension. Additionally, there existed marginally significant interactions of the polymorphism with age and overweight/obesity. However, future large, well-designed studies in Chinese and other populations, as well as mechanistic studies, are still needed to validate our findings, especially considering that the interactions observed in our study were only marginally significant.

The Circulating Treg/Th17 Cell Ratio Is Correlated with Relapse and Treatment Response in Pulmonary Sarcoidosis Patients after Corticosteroid Withdrawal.

OBJECTIVES: Pulmonary sarcoidosis is an immune-mediated disease, and some patients can be effectively treated with corticosteroids. However, nearly half of all sarcoidosis patients relapse after corticosteroid withdrawal. Different subsets of CD4+ helper T cells participate in the immunopathogenesis of sarcoidosis. Thus, the aims of our study were to investigate whether the circulating subsets of CD4+ helper T cells were associated with sarcoidosis relapse and with its remission after retreatment. Additionally, we identified a useful biomarker for predicting the relapse and remission of sarcoidosis patients. METHODS: Forty-two patients were enrolled in the present study who had previously been diagnosed with pulmonary sarcoidosis and treated with corticosteroids. The patients were allocated into either a stable group if they exhibited sustained remission (n = 22) or a relapse group if they experienced clinical or radiological recurrence after treatment withdrawal (n = 20). Peripheral blood cells were collected from these patients and analyzed to determine the frequencies of subsets of circulating CD4+ helper T cells by flow cytometry. The patients in the relapse group were retreated with corticosteroids and immunosuppressive agents and were then reevaluated to determine the frequencies of dynamic subsets of circulating CD4+ helper T cells after remission. RESULTS: The frequencies of circulating Tregs were significantly increased concomitant with a decrease in the circulating Th17 cell frequency in the relapsed patients compared with the stable patients. The Treg/Th17 ratio was negatively correlated with sarcoidosis activity and was sensitive to retreatment. In addition, the percentage of isolated CD45RO+Ki67+ Tregs was higher in the patients who were stable and in those who recovered after retreatment than in those who relapsed. CONCLUSIONS: An imbalance between Tregs and Th17 cells is associated with pulmonary sarcoidosis relapse after corticosteroid withdrawal. The circulating Treg/Th17 ratio could serve as an alternative marker for monitoring pulmonary sarcoidosis relapse after the end of corticosteroid treatment and for rapidly predicting the response to retreatment.

Pleural Effusion in Multiple Myeloma.

OBJECTIVE: Pleural effusion is rarely observed in patients with multiple myeloma (MM). Myeloma cell infiltration or invasion to the pleura is very rare. This study aimed to investigate the clinical characteristics of pleural effusion in patients with MM. METHODS: We retrospectively reviewed the medical records of patients diagnosed with pleural effusion, MM, and pleural effusion with MM between 2004 and 2014 at Beijing Jishuitan Hospital. The present study included patients with pleural effusion who underwent cytological, bacteriological, biochemical and other testing. The cytopathology of abnormal pleural effusion cells was not diagnostic, thus flow cytometry was performed. MM was defined using the diagnosis standard of NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) 2014 for MM. RESULTS: This study included 3,480 pleural effusion patients and 319 MM patients. There were 34 patients with both MM and pleural effusion (17 men and 17 women). The average age was 63 years (range, 48-84 years). Pleural effusion with MM was caused by congestive heart disease, chronic renal failure, hypoalbuminemia, pulmonary infarctions, cirrhosis, pulmonary arterial hypertension, parapneumonic effusion, tuberculous pleural effusion, and myelomatous pleural effusion (MPE). The diagnosis of MPE was confirmed by the detection of myeloma cells in the pleural fluid using flow cytometric analyses. There were only 2 MPE cases in our study. The first MPE case was a woman. The first clinical manifestation was pleural effusion, and the diagnosis was non-secretory MM, DSS stage IIIA (Durie-Salmon staging system); ISS stage I (the International Staging System). The second MPE case was a man who was diagnosed with MM IgA-κ, DSS stage IIIA; ISS stage II. CONCLUSION: The detection rate of MPE was very low. MPE tended to present with yellow exudates and the lack of physical and chemical characteristics. Furthermore, patients with MPE exhibited many yellow nodules on the pleura. These nodules were lobulated and had abundant blood supply. The routine pleural effusion pathological examination had low sensitivity. Flow cytometry may be more useful for improving the detection rate of MPE.

Are MTHFR C677T and MTRR A66G Polymorphisms Associated with Overweight/Obesity Risk? From a Case-Control to a Meta-Analysis of 30,327 Subjects.

Several studies have examined the associations of methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms with being overweight/obesity. However, the results are still controversial. We therefore conducted a case-control study (517 cases and 741 controls) in a Chinese Han population and then performed a meta-analysis by combining previous studies (5431 cases and 24,896 controls). In our case-control study, the MTHFR C677T polymorphism was not significantly associated with being overweight/obesity when examining homozygous codominant, heterozygous codominant, dominant, recessive and allelic genetic models. The following meta-analysis confirmed our case-control results. Heterogeneity was minimal in the overall analysis, and sensitivity analyses and publication bias tests indicated that the meta-analytic results were reliable. Similarly, both the case-control study and meta-analysis found no significant association between the MTRR A66G polymorphism and being overweight/obesity. However, sensitivity analyses showed that the associations between the MTRR A66G polymorphism and being overweight/obesity became significant in the dominant, heterozygous codominant and allelic models after excluding our case-control study. The results from our case-control study and meta-analysis suggest that both of the two polymorphisms are not associated with being overweight/obesity. Further large-scale population-based studies, especially for the MTRR A66G polymorphism, are still needed to confirm or refute our findings.

[Surgical lung biopsy for the management of diffuse interstitial lung disease].

OBJECTIVE: To evaluate the role of surgical lung biopsy (SLB) in the management of diffuse interstitial lung disease (DILD) with no specific diagnosis. METHODS: We conducted a retrospective analysis of 179 cases with DILD of non-specific diagnosis after non-invasive methods and minimally invasive processes, including bronchoscopy and CT-guided lung biopsy, were performed SLB at Peking Union Medical College Hospital between 2006 and 2012. Patient demographics, surgical approach, number and site of biopsies, post-operative complications and postoperative pathological diagnosis and treatment were analyzed. RESULTS: Of 179 cases, there were 91 males (50.8%) and 88 females (49.2%), with a median age of 47.3 years (range 16-76). There were 6 cases(3.4%) who were younger than 20 years and 25 cases(14%) older than 60 years. From 2006 to 2012, every year there were 16 case (8.9%), 17 cases(9.5%), 19 cases (10.6%), 44 cases (24.6%), 33 cases(18.4%), 31 cases (17.3%) and 19 cases (10.6%) respectively. The total median hospital stay was 33.4 days (range 6-76) and the mean postoperative stay was 18.6 days (range 2-56). The mean duration for chest drainage was 3.2 days (range 2-18). Among them, 150 cases were arranged with video-assisted thoracoscopy surgery (VATS) and 29 cases were arranged with minithoracotomy. The number of biopsies taken was ranged from one to four and there were 126 cases (70.4%) had more than one biopsy. The biopsy was performed in left lingular lobe (54 cases/30.2%), left natural upper lobe (16 cases/8.9%), left inferior basal segments (56 cases/31.3%), right upper lobe (30 cases/16.7%), right meddle lobe (40case/22.3%) and right inferior basal segments (56 case/31.3%) respectively. Definitive pathological diagnosis was reached in 103 cases (57.5%), diagnosis was reached after combination of pathological, clinical and radiological manifestations in 32 cases (17.9%) and there were 44 cases (24.6%) could not achieved diagnosis even after the SLB. Chronic extrinsic allergic alveolitis was the most common diagnosis (33/24.4%), following nonspecific interstitial pneumonia (27/20%) for the 135 cases with a definite diagnosis. Among 179 cases, there were 114 cases had a change in their treatment following the results of SLB. There were 16 cases had a fever after surgery and antibiotics were administrated for eleven of them. Other complication were included delayed wound healing (>10 days after surgery, 6 cases), thoracic hemorrhage (5 cases), chest tube re-indwelling because of pneumothorax (4 cases), delayed weaning of ventilator (>3 days after surgery, 4 cases), respiratory failure (3 cases), and thoracic infection (2 cases). There were two cases died within 30 days following surgery because of respiratory failure. CONCLUSIONS: Most of the DILD patients who were arranged with SLB were young and middle-aged cases. The left lingular lobe, right meddle lobe and both inferior lobes were the preferred biopsy sites. The results of biopsy surgery could provides a diagnosis for most of the DILD patients and could modulate the treatment for more than half of them. Fever and delayed wound healing were the major complications. The SLB related mortality was low. SLB was suggested to the undiagnosed DILD patients.

[Effects of fasudil on bleomycin-induced pulmonary fibrosis in mice and on the biological behaviors in NIH3T3 mouse fibroblast cell line].

OBJECTIVE: To determine the beneficial effects and mechanisms of fasudil, a selective ROCK inhibitor, on bleomycin-induced pulmonary fibrosis in mice and to determine the effects and mechanisms of fasudil on the biological behaviors in NIH3T3 mouse fibroblast cell line. METHODS: The BPF model was induced by a single dosage of 2.5 mg/kg bleomycin intratracheal injection in mice and fasudil intraperitoneal injection was given to the mice. The fibrosis degree was determined pathologically by using the Ashcroft scoring method and biochemically by hydroxyproline assay in lung tissue. NIH3T3 mouse fibroblast cell line was cultured in vitro and fasudil was given to the cell. The proliferation activity in NIH3T3 cells were detected by MTT assay and flat colony forming experiment. The migration activity in NIH3T3 cells were detected by scratch test and transwell chamber experiment. The expression of CyclinD1, MMP2 and TIMP1 mRNA in NIH3T3 cells was detected by RT-PCR. The expression of CyclinD1, MMP2 and TIMP1 protein and the level of MYPT1 phosphorylation in NIH3T3 cells was detected by Western blot. RESULTS: Compare to the mice administrated by bleomycin, the Ashcroft score and hydroxyproline content were significantly decreased in the mice administered fasudil. Administration of fasudil can reduce the ability of proliferation and migration in a dose-dependent manner in NIH3T3 cells. The effect of fasudil was possibly related to increase the production of TIMP1 and decrease the production of CyclinD1 and MMP2. CONCLUSIONS: Administration of fasudil can attenuate pulmonary fibrosis both in vivo and in vitro. These findings suggest that fasudil may be a potential therapeutic candidate for the treatment of pulmonary fibrosis.

Associations of MTHFR C677T and MTRR A66G gene polymorphisms with metabolic syndrome: a case-control study in Northern China.

Prior evidence indicates that homocysteine plays a role in the development of metabolic syndrome (MetS). Methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms are common genetic determinants of homocysteine levels. To investigate the associations of the MTHFR C677T and MTRR A66G polymorphisms with MetS, 692 Chinese Han subjects with MetS and 878 controls were recruited. The component traits of MetS and the MTHFR C677T and MTRR A66G genotypes were determined. A significant association was observed between the MTHFR 677T allele and increased risk of MetS, high fasting blood glucose, high waist circumference, and increasing number of MetS components. The MTRR A66G polymorphism was associated with an increased risk of MetS when combined with the MTHFR 677TT genotype, although there was no association found between MetS and MTRR A66G alone. Furthermore, the MTRR 66GG genotype was associated with high fasting blood glucose and triglycerides. Our data suggest that the MTHFR 677T allele may contribute to an increased risk of MetS in the northern Chinese Han population. The MTRR A66G polymorphism is not associated with MetS. However, it may exacerbate the effect of the MTHFR C677T variant alone. Further large prospective population-based studies are required to confirm our findings.

Vector analyses of linearly and circularly polarized Bessel beams using Hertz vector potentials.

Using the transverse Hertz vector potentials, vector analyses of linearly and circularly polarized Bessel beams of arbitrary orders are presented in this paper. Expressions for the electric and magnetic fields of vector Bessel beams in free space that are rigorous solutions to the vector Helmholtz equation are derived. Their respective time averaged energy density and Poynting vector are also obtained, in order to exhibit their non-diffracting properties. Polarization patterns and magnitude profiles with different parameters are displayed. Particular emphasis is placed on the cases where the ratio of wave number over its transverse component k/kt approximately equals to one and largely exceeds it, which corresponding to the nonparaxial and paraxial condition, respectively. These results allow us to recognize that the vector Bessel beams exhibit new and important features, compared with the scalar fields.

Intrapulmonary concentration of levofloxacin in patients with idiopathic pulmonary fibrosis.

Patients with idiopathic pulmonary fibrosis (IPF) have significantly impaired pulmonary diffusion, which may affect the pulmonary concentration of many drugs, including antibiotics. In this study, we compared the difference in pulmonary levofloxacin (LVFX) concentration between patients with normal lung function and IPF. The IPF group included 10 patients with a proven diagnosis of IPF and a diffusing capacity for carbon monoxide ranging from 40% to 70% of predicted values. The control group included 10 patients with normal pulmonary function. Blood and bronchoalveolar lavage fluid (BALF) were taken at 3-3.5 h after fasting. LVFX (500 mg) was administered orally. LVFX concentrations in the serum and BALF were determined using HPLC-MS/MC. The level of LVFX in alveolar epithelial lining fluid (ELF) was calculated using the following formula: LVFX ELF = LVFX BALF × (Urea serum/Urea BALF). No significant differences in age, body weight, height, and calculated creatinine clearance and BALF retrieval rate were observed between groups. LVFX serum concentrations in the IPF and control groups were (5.97 ± 1.28) µg/ml and (6.84 ± 3.43) µg/ml, respectively (P = 0.4727). ELF concentration of LVFX in the control group was (27.81 ± 21.36) µg/ml, while the concentration in the IPF group was (10.17 ± 2.46) µg/ml, less than half of that in the controls (P = 0.0058). The intrapulmonary concentration of LVFX in IPF patients was lower than those with normal lung function. Notably, however, the ELF LVFX concentration following 500 mg once-daily exceeded the MIC90 of common respiratory pathogens. Excellent antibacterial efficacy of LVFX can be expected for IPF patients in the treatment of respiratory tract infections.

Prevalence of hyperhomocysteinemia in China: a systematic review and meta-analysis.

Hyperhomocysteinemia (HHcy, total homocysteine concentrations > 15 µmol/L) has been associated with increased risk of many diseases. A systematic review was performed to summarize the prevalence of HHcy in China. We searched multiple international and Chinese scientific databases for relevant literature, and further manually screened reference lists and corresponded with original authors. Pooled prevalence of HHcy was calculated using random effects model. Subgroup analysis, meta-regression and sensitivity analysis were also performed. A total of 36 studies consisting 60,754 subjects (57.3% male; age range, 3-97 years) were finally included. The overall pooled prevalence of HHcy was 27.5%. Geographically, the prevalence was high in north areas, intermediate in central areas, and low in south areas, and was higher in inland versus coastal areas. The prevalence increased with age and was significantly higher in men than in women. Rural residents had a slightly higher HHcy prevalence than urban residents, and the studies conducted during 2006 to 2012 presented a higher HHcy prevalence than those during 1990 to 2005. In summary, the prevalence of HHcy in China is high, particularly in northern populations, the inlanders, males, and the elderly. Homocysteine-lowering strategies are necessary to reduce this highly preventable disorder.

Imbalance between Th17 and regulatory T-Cells in sarcoidosis.

Sarcoidosis is a systemic granulomatous disease, which is thought to result from an aberrant immune response. CD4+ T lymphocytes play an important role in the development of granulomas. Previously, the immunopathogenesis of sarcoidosis was focused on Th1/Th2 disturbances. The aim of this study was to evaluate the balance between newer CD4+ T lymphocytes, i.e., Treg and Th17 cells. In our studies, a decrease in Treg cells and an increase in Th17 cells were observed in the peripheral blood and BALF of sarcoidosis patients. A significant increase in the Th17/Treg cell ratio was observed in sarcoidosis patients. After treatment with prednisone, the expression of Foxp3 mRNA was elevated in the peripheral blood, and expression of (ROR)γt mRNA showed a downward trend. These findings suggest that sarcoidosis is associated with an imbalance between Th17 and Treg cells in peripheral blood and BALF. Therefore, targeting the cytokines that affect the Th17/Treg ratio could provide a new promising therapy for pulmonary sarcoidosis.

Geographical distribution of MTHFR C677T, A1298C and MTRR A66G gene polymorphisms in China: findings from 15357 adults of Han nationality.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C and methionine synthase reductase (MTRR) A66G polymorphisms are important genetic determinants for homocysteine (Hcy) levels, and are associated with several disorders. These polymorphisms are heterogeneously distributed worldwide. Our objective was to explore the geographical distributions of these polymorphisms in China. METHODOLOGIES: 15357 healthy adults were recruited from 10 regions. Buccal samples were collected and genomic DNA was isolated. Genotyping was performed using the fluorogenic 5'-nuclease assay. PRINCIPAL FINDINGS: The prevalence of the three polymorphisms among different populations from China varied significantly and showed apparent geographical gradients. For MTHFR C677T, the frequencies of the 677T allele and the 677TT genotype were significantly higher among northern populations and ranged from the lowest values (24.0% and 6.4%, respectively) in Hainan (southern) to the highest values (63.1% and 40.8%, respectively) in Shandong (northern). For MTHFR A1298C, the 1298C allele and the 1298CC genotype frequencies were significantly higher among southern populations and increased from low values (13.1% and 1.4%, respectively) in Shandong to high values (25.7% and 6.7%, respectively) in Hainan. For A66G, the 66G allele and the 66GG genotype frequencies increased from lower values (23.7% and 5.4%, respectively) in Shandong to higher values (29.2% and 8.6%, respectively) in Hainan. The overall frequency of the 677T allele, 677TT genotype, 1298C allele, 1298CC genotype, 66G allele and 66GG genotype in the Chinese Han population was 45.2%, 23.2%, 18.6%, 3.9%, 25.7%, and 6.6%, respectively. No gender differences were found in the prevalence of both the MTHFR C677T and MTRR A66G polymorphisms. CONCLUSIONS: This study indicates that there are marked geographical variations in the prevalence of the three polymorphisms among Chinese Han populations. Our baseline data may be useful for future researches in related fields.

[Therapeutic effects and the underlying mechanism of umbilical cord-derived mesenchymal stem cells for bleomycin induced lung injury in rats].

OBJECTIVE: To study the efficacy of umbilical cord-derived mesenchymal stem cells (UC-MSCs) for bleomycin-induced pulmonary fibrosis in mice. METHODS: UC-MSCs were isolated from the umbilical cord after parental consent. One hundred C57BL/6 mice were randomly divided into 4 groups (12 of these for preliminary experiment). Mice in the control group (n = 20) were instilled with PBS via trachea and NS was injected via the tail vein after 3 days. Mice in the stem cell group (n = 20) were instilled with PBS via trachea and were injected with MSC via the tail vein after 3 days. Mice in the bleomycin group (n = 24) were instilled with bleomycin via trachea and NS was injected via the tail vein after 3 days. Mice in the bleomycin plus stem cell group (n = 24) were instilled with bleomycin via trachea and were injected with MSCs via the tail vein after 3 days. All of the mice were sacrificed at the 21(th) day, and the lungs were immediately fixed with 4% paraformaldehyde for 48 h, embedded in paraffin and sectioned at 5 µmol/L thickness. The sections were stained with hematoxylin and eosin (H&E) and Masson-trichrome. Histopathological scoring of pulmonary fibrosis was performed according to Ashcroft's method. The concentrations of matrix metalloproteinases-2 and tissue inhibitor of metalloproteinase-1were determined using immunohistochemistry. RESULTS: Compared with the bleomycin group, MSC transplantation significantly reduced pulmonary inflammation, fibrosis and deposition of collagen in the bleomycin plus stem cell group [(1.55 ± 0.51) vs (2.16 ± 0.77), and (1.45 ± 0.60) vs (2.32 ± 0.82), respectively, P < 0.05]. There was no difference between the control group and the stem cell group [(0.35 ± 0.49) vs (0.37 ± 0.50), P > 0.05]. The expression of MMP-2 in the bleomycin plus stem cell group was lower than the bleomycin group [(1.59 ± 0.59) vs (2.37 ± 0.68), P < 0.05], but there was no difference between the control group and the stem cell group [(0.80 ± 0.69) vs (0.84 ± 0.77), P > 0.05]. The expression of TIMP-1 in the bleomycin plus stem cell group was higher than the bleomycin group [(1.95 ± 0.58) vs (0.79 ± 0.71), P < 0.05], but there was no difference between the control group and the stem cell group [(1.10 ± 0.72) vs (1.32 ± 0.58), P > 0.05]. CONCLUSION: UC-MSC transplantation could relieve bleomycin-induced fibrosing alveolitis in mice. The mechanism might be related to the expression of MMP-2 and TIMP-1. UC-MSC had no effect on normal lungs.

Adverse events of pirfenidone for the treatment of pulmonary fibrosis: a meta-analysis of randomized controlled trials.

BACKGROUND: Pirfenidone (PFD) is a novel antifibrotic agent approved for patients with pulmonary fibrosis. However, there are concerns regarding toxicity of the drug. In this meta-analysis, we analyzed the adverse events (AEs) of PFD for the treatment of pulmonary fibrosis. METHODS: We performed a systematic search of PubMed, Embase, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials for trials published between January 1999 and October 2011. Data extracted from literature were analyzed with Review manager 5.0.24. RESULTS: The results of six randomized controlled trials (1073 participants) revealed that the number of individuals who discontinued PFD therapy was significantly higher than patients receiving placebo. The PFD group had a significantly higher rate of gastrointestinal (nausea, dyspepsia, diarrhea, and anorexia), neurological (dizziness and fatigue), and dermatological (photosensitivity and rash) AEs compared to the placebo group. CONCLUSIONS: PFD used for the treatment of pulmonary fibrosis is not so safe or well-tolerated. Notably, gastrointestinal, neurological and dermatological adverse effects were more common in patients receiving PFD therapy, and therefore appropriate precaution is needed.