Tailoring Interlayer Chiral Exchange by Azimuthal Symmetry Engineering.

Recent theoretical and experimental studies of the interlayer Dzyaloshinskii-Moriya interaction (DMI) have sparked great interest in its implementation into practical magnetic random-access memory (MRAM) devices, due to its capability to mediate long-range chiral spin textures. So far, experimental reports focused on the observation of interlayer DMI, leaving the development of strategies to control interlayer DMI's magnitude unaddressed. Here, we introduce an azimuthal symmetry engineering protocol capable of additive/subtractive tuning of interlayer DMI through the control of wedge deposition of separate layers and demonstrate its capability to mediate field-free spin-orbit torque (SOT) magnetization switching in both orthogonally magnetized and synthetic antiferromagnetically coupled systems. Furthermore, we showcase that the spatial inhomogeneity brought about by wedge deposition can be suppressed by specific azimuthal engineering design, ideal for practical implementation. Our findings provide guidelines for effective manipulations of interlayer DMI strength, beneficial for the future design of SOT-MRAM or other spintronic devices utilizing interlayer DMI.

Idiopathic multicentric Castleman disease (iMCD)-idiopathic plasmacytic lymphadenopathy: A distinct subtype of iMCD-not otherwise specified with different clinical features and better survival.

Idiopathic multicentric Castleman disease (iMCD) is subclassified into iMCD-thrombocytopenia, anasarca, reticulin fibrosis, renal dysfunction, organomegaly (TAFRO) and iMCD-not otherwise specified (NOS) according to the Castleman Disease Collaborative Network (CDCN) consensus criteria. With a deeper understanding of iMCD, a group of patients with iMCD-NOS characterised by polyclonal hypergammaglobulinaemia, plasmacytic/mixed-type lymph node histopathology and thrombocytosis has attracted attention. This group of patients has been previously described as having idiopathic plasmacytic lymphadenopathy (IPL). Whether these patients should be excluded from the current classification system lacks sufficient evidence. This retrospective analysis of 228 patients with iMCD-NOS identified 103 (45.2%) patients with iMCD-IPL. The clinical features and outcomes of patients with iMCD-IPL and iMCD-NOS without IPL were compared. Patients with iMCD-IPL showed a significantly higher inflammatory state but longer overall survival. No significant difference in overall survival was observed between severe and non-severe patients in the iMCD-IPL group according to the CDCN severity classification. Compared with lymphoma-like treatments, multiple myeloma-like and IL-6-blocking treatment approaches in the iMCD-IPL group resulted in significantly higher response rates and longer time to the next treatment. These findings highlight the particularities of iMCD-IPL and suggest that it should be considered a new subtype of iMCD-NOS.

Sirolimus is effective for refractory/relapsed idiopathic multicentric Castleman disease: A single-center, retrospective study.

Refractory/relapsed idiopathic multicentric Castleman disease (R/R iMCD) has limited treatment options. With studies showing increased mTOR activation in iMCD patients, sirolimus becomes an attractive and promising therapy for R/R iMCD. Here we report the results of a retrospective study involving 26 R/R iMCD patients treated with sirolimus-containing regimen. The median age at sirolimus initiation was 40.5 years (23-60), with a median prior treatment line of 2 (1-5). 18 patients (69.2%) achieved symptomatic and biochemical response, with a median time to at least overall partial remission of 1.9 months (0.5-14.6). The median follow-up time from sirolimus initiation was 11.7 months (1.6-50.7) and the median time to next treatment (TTNT) was 46.2 months. No patients died at the end of follow-up. Most of the patients in the cohort are in ongoing responses and continue sirolimus therapy. Sirolimus is well tolerated with minor adverse effects. In conclusion, sirolimus is effective for R/R iMCD patients with good tolerance.

Combining superpulse dynamic CO2 laser and supramolecular salicylic acid in the treatment of dense comedones with higher clearance in a shorter time: A prospective, randomized, split-face clinical trial.

OBJECTIVES: Dense comedones are common in patients with acne vulgaris, and promoting treatment can prevent the progression of acne lesions. However, the efficacy-time conflict makes the treatment challenging and the medication options are limited by the side effects. MATERIALS AND METHODS: Thirty-five patients with symmetrical dense comedones were enrolled and the two sides of the face were randomly assigned to receive 30% supramolecular salicylic acid (SSA) combined with CO2 laser or CO2 laser monotherapy at an interval of 2 weeks for six treatment sessions. Comedones count, porphyrin index (PI), texture index (TI), melanin index, erythema index, hydration index (HI), transepidermal water loss (TEWL), and side effects were recorded at each visit till the 12th week. RESULTS: Thirty-one patients completed the study. Comedones on the combined-SSA side were reduced more after six treatments, that the mean reduction rate of the combined-SSA side was 85.76%, and that of the CO2 laser-treated side was 62.32% (Pbetween < 0.001). Combining SSA also showed a better effect on reducing PI and TI than CO2 laser singly (Pbetween < 0.001). TEWL and HI between the two sides showed no significant differences after treatments. No permanent or severe side effects were observed on both side. CONCLUSIONS: The treatment combined CO2 laser with 30% SSA dealt with the efficacy-time conflict while significantly reducing comedones and improving skin texture in 12 weeks and no serious adverse reactions occurred. LIMITATIONS: It is a single-center study and the number of subjects was small.

Intracranial drainage versus extracranial shunt in the treatment of intracranial arachnoid cysts: a meta-analysis.

OBJECTIVE: To review the literature and analyze the efficacy and safety of two surgery procedures, intracranial drainage and extracranial shunt, for intracranial arachnoid cysts. METHODS: We searched the online Medlars, PubMed, and Cochrane Central electronic databases and collected studies of patients with intracranial arachnoid cysts treated with two surgical methods. RESULTS: The meta-analysis results shows that there were not statistically significant in clinical symptoms improvement, cyst reduction, the improvement of epilepsy, epidural hematoma, cerebrospinal fluid leak, and recurrence rate (P > 0.05, with RR values are 0.99, 0.94, 1.00, 0.94, 1.21, and 0.75 respectively). There was statistically significant in the occurrence rate of intracranial infection (P = 0.0004, RR = 0.28). The intracranial drainage group was lower than extracranial shunt group. CONCLUSION: The results indicated that the efficacy and safety of two surgery procedures are similar in the treatment of intracranial arachnoid cysts, but the intracranial drainage was better than extracranial shunt in reducing the risk of intracranial infection.

The KBTBD6/7-DRD2 axis regulates pituitary adenoma sensitivity to dopamine agonist treatment.

Pituitary adenoma (PA) is one of the most common intracranial tumors, and approximately 40% of all PAs are prolactinomas. Dopamine agonists (DAs), such as cabergoline (CAB), have been successfully used in the treatment of prolactinomas. The expression of dopamine type 2 receptor (DRD2) determines the therapeutic effect of DAs, but the molecular mechanisms of DRD2 regulation are not fully understood. In this study, we first demonstrated that DRD2 underwent proteasome-mediated degradation. We further employed the yeast two-hybrid system and identified kelch repeat and BTB (POZ) domain containing 7 (KBTBD7), a substrate adaptor for the CUL3-RING ubiquitin (Ub) ligase complex, as a DRD2-interacting protein. KBTBD6/7 directly interacted with, and ubiquitinated DRD2 at five ubiquitination sites (K221, K226, K241, K251, and K258). CAB, a high-affinity DRD2 agonist, induced DRD2 internalization, and cytoplasmic DRD2 was degraded via ubiquitination under the control of KBTBD6/7, the activity of which attenuated CAB-mediated inhibition of the AKT/mTOR pathway. KBTBD7 knockout (KO) mice were generated using the CRISPR-Cas9 technique, in which the static level of DRD2 protein was elevated in the pituitary gland, thalamus, and heart, compared to that of WT mice. Consistently, the expression of KBTBD6/7 was negatively correlated with that of DRD2 in human pituitary tumors. Moreover, KBTBD7 was highly expressed in dopamine-resistant prolactinomas, but at low levels in dopamine-sensitive prolactinomas. Knockdown of KBTBD6/7 sensitized MMQ cells and primary pituitary tumor cells to CAB treatment. Conversely, KBTBD7 overexpression increased CAB resistance of estrogen-induced in situ rat prolactinoma model. Together, our findings have uncovered the novel mechanism of DRD2 protein degradation and shown that the KBTBD6/7-DRD2 axis regulates PA sensitivity to DA treatment. KBTBD6/7 may thus become a promising therapeutic target for pituitary tumors.

[Fast-onset antidepressant potentials of essential oil of herbs].

The existing antidepressants demonstrated delayed onset of clinical effects, so fast-onset antidepressants are required. Essential oil of herbs showed potentials fast-onset antidepressant potential. First, its aromatic odor can directly activate olfactory nerves; its high lipophilicity causes a high blood-brain barrier penetration rate; and its high volatility is suitable for nasal-brain targeting and inhalation delivery. Therefore, essential oils can rapidly regulate brain functions by multiple ways, suggesting a fast-onset antidepressant potential. Second, the advance of studies on chemistry and pharmacology of antidepressant essential oils demonstrated chemical substances, antidepressant effects and possible action mechanisms of antidepressant essential oils. Third, the effect of essential oils' antidepressant components on fast-onset antidepressant targets was investigated. It was found that chemical constituents of essential oils antagonized NMDA receptor activities, suggesting that essential oils have fast-onset antidepressant effect. Finally, characteristics of essential oils, fast-onset antidepressant targets and drug delivery methods are integrated to give full play to essential oils' fast-onset antidepressant advantage and provide a new direction for new drug discovery.

[Aortic and Mitral Annuli Coupling and Its Association with Cardiac Function in Patients with Dilated Cardiomyopathy.]

OBJECTIVES: To compare the mitral and aortic annuli excursion (AE) and aortomitral angle (AMA) variations between patients with and without dilated cardiomyopathy (DCM) using speckle tracking echocardiography (STE),and determine the role of annuli dynamics and coupling behaviors in the left ventricular function. METHODS: Thirty-five patients with DCM and thirty-five age and sex matched healthy adults underwent transthoracic echocardiographic examinations.In the parasternal long-axis view,the AE and AMA variations were measured using Philips QLAB 9.0 software.In the apical four chamber view,the left ventricular ejection fraction (LVEF),longitudinal,circumferential,and radial strain were measured using Tomtec Arene 1.0 software. RESULTS: The DCM patients had significantly smaller AE and AMAmax-min,bigger AMAmax and AMAmin,and varied cardiac cycle compared with the healthy adults.The AMA of DCM patients increased to its maximal value earlier in diastole with little variation.AE was positively correlated with LVEF and multidirectional strain.AMAmax and AMAmin were negatively correlated with AE,LVEF and multidirectional strain (P<0.05).Significant correlations were also found between AMAmax-min and AE,LVEF and multidirectional strain (P<0.05). CONCLUSIONS: AE,AMA,LVEF and multidirectional strain can be quantified using STE.The coupling of mitral and aortic annuli in DCM patients is abnormal and correlated well with left ventricular systolic function.AE and AMA can be conveniently used for estimation of integral and regional cardiac function.

A novel sesquiterpene and three new phenolic compounds from the rhizomes of Acorus tatarinowii Schott.

A novel sesquiterpene with an unprecedented epoxy lactone skeleton, named tatarinolactone, together with two new amides, a new biphenylpropanoid and two known lignans were isolated from the rhizomes of Acorus tatarinowii Schott. Their structures were identified as 6,7,8-trihydroxy-4α-isobutyl-4,7-dimethylhexahydro-6,8α-epoxychromen-2(3H)-one (1), (E)-methyl 4-[3-(4-hydroxy-3-methoxyphenyl)acrylamido]butanoate (2), (Z)-methyl 4-[3-(4-hydroxy-3-methoxyphenyl)acrylamido]butanoate enol isomer (3), (R)-4-hydroxy-3-[1-hydroxy-3-(4-hydroxy-3-methoxyphenyl)propan-2-yl]-5-methoxybenzoic acid (4), (2S,3R)-ceplignan (5), and (2R,3S)-ceplignan (6), respectively, based on extensive spectroscopic analysis and by comparison to the known compounds. To test their effects on serotonin transporters, a high content assay using hSERT-HEK293 cell line was adopted. Results indicated that compounds 1 and 4 significantly inhibited SERT activity, while compounds 2, 3, 5, and 6 significantly enhanced SERT activity, which partly explain the traditional uses of the rhizomes of Acorus tatarinowii Schott in treatments of neuropsychiatric and digestive disorders.

A prospective study of zanubrutinib, a Bruton tyrosine kinase inhibitor, in relapsed/refractory idiopathic multicentric Castleman disease.

Relapsed and refractory (R/R) idiopathic multicentric Castleman disease (iMCD) is a clinical challenge with no standard treatment. In this preliminary clinical trial, we investigated the efficacy and safety profiles of a Bruton tyrosine kinase inhibitor (BTKi), zanubrutinib, in patients with R/R iMCD. The primary endpoint was the overall response rate at Week 12 according to the Castleman Disease Collaborative Network (CDCN) response criteria. The trial was terminated early due to a lack of treatment response in the first enrolled 5 patients. Although 3 patients achieved symptomatic response, none of the 5 patients had an overall response by Week 12. One patient had progressive disease and the other 4 had stable disease. The study drug was well tolerated without grade 2 or higher adverse events. Our findings suggest that BTKi therapy is not effective for iMCD, and further attempts at single-agent therapy with zanubrutinib or other BTKis for iMCD should be considered with caution and probably avoided. This trial was registered at www.clinialtrials.gov as #NCT04743687.

Comparative analysis of primate and pig cells reveals primate-specific PINK1 expression and phosphorylation.

PTEN-induced putative kinase 1 (PINK1), a mitochondrial kinase that phosphorylates Parkin and other proteins, plays a crucial role in mitophagy and protection against neurodegeneration. Mutations in PINK1 and Parkin can lead to loss of function and early onset Parkinson's disease. However, there is a lack of strong in vivo evidence in rodent models to support the theory that loss of PINK1 affects mitophagy and induces neurodegeneration. Additionally, PINK1 knockout pigs ( Sus scrofa) do not appear to exhibit neurodegeneration. In our recent work involving non-human primates, we found that PINK1 is selectively expressed in primate brains, while absent in rodent brains. To extend this to other species, we used multiple antibodies to examine the expression of PINK1 in pig tissues. In contrast to tissues from cynomolgus monkeys ( Macaca fascicularis), our data did not convincingly demonstrate detectable PINK1 expression in pig tissues. Knockdown of PINK1 in cultured pig cells did not result in altered Parkin and BAD phosphorylation, as observed in cultured monkey cells. A comparison of monkey and pig striatum revealed more PINK1-phosphorylated substrates in the monkey brain. Consistently, PINK1 knockout in pigs did not lead to obvious changes in the phosphorylation of Parkin and BAD. These findings provide new evidence that PINK1 expression is specific to primates, underscoring the importance of non-human primates in investigating PINK1 function and pathology related to PINK1 deficiency.

Quality of life of patients with neurodermatitis.

BACKGROUND: Neurodermatitis is a common chronic skin disease. Although not life-threatening, it can produce an important psychosocial burden, sleep disturbance and sexual dysfunction. Patients with neurodermatitis tend to have poor social skills or interpersonal resources and a lack of flexibility. However quality of life (QoL) of patients with neurodermatitis has seldom investigated. The objective of this study is to assess the impact of neurodermatitis on patients' QoL using the Dermatology Life Quality Index questionnaire, and assess its feasibility and internal consistency. METHODS: One hundred and fifty consecutive outpatients seeking treatment for neurodermatitis and 250 patients with psoriasis in the Department of Dermatology, the Second Hospital of Xi'an Jiaotong University, were assessed for eligibility for this prospective study from July 1, 2011 to September 30, 2011. Demographic data and disease-related characteristics were collected. RESULTS: The overall mean DLQI score for neurodermatits (9.34) was lower than that for psoriasis (13.32) (P < 0.001). Patients with neurodermatitis scored significantly lower for all items except Q1 (symptoms) and Q9 (sexual difficulties). No strong relationship between disease-related characteristics and quality of life could be found. The inter-item correlation averaged 0.415 and Cronbach's alpha was 0.889, indicating high internal consistency. CONCLUSION: This is the first study to attempt to measure the impact of neurodermatitis for both male and female patients on QoL. Neurodermatitis moderately affected the QoL of the patients.

Attenuated Microcirculation in Small Metastatic Tumors in Murine Liver.

Metastatic cancer disease is the major cause of death in cancer patients. Because those small secondary tumors are clinically hardly detectable in their early stages, little is known about drug biodistribution and permeation into those metastatic tumors potentially contributing to insufficient clinical success against metastatic disease. Our recent studies indicated that breast cancer liver metastases may have compromised perfusion of intratumoral capillaries hindering the delivery of therapeutics for yet unknown reasons. To understand the microcirculation of small liver metastases, we have utilized computational simulations to study perfusion and oxygen concentration fields in and around the metastases smaller than 700 µm in size at the locations of portal vessels, central vein, and liver lobule acinus. Despite tumor vascularization, the results show that blood flow in those tumors can be substantially reduced indicating the presence of inadequate blood pressure gradients across tumors. A low blood pressure may contribute to the collapsed intratumoral capillary lumen limiting tumor perfusion that phenomenologically corroborates with our previously published in vivo studies. Tumors that are smaller than the liver lobule size and originating at different lobule locations may possess a different microcirculation environment and tumor perfusion. The acinus and portal vessel locations in the lobule were found to be the most beneficial to tumor growth based on tumor access to blood flow and intratumoral oxygen. These findings suggest that microcirculation states of small metastatic tumors can potentially contribute to physiological barriers preventing efficient delivery of therapeutic substances into small tumors.

A potential impact of SARS-CoV-2 on pituitary glands and pituitary neuroendocrine tumors.

INTRODUCTION: Angiotensin-converting enzyme 2 (ACE2) is the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The effects of SARS-CoV-2 on normal pituitary glands function or pituitary neuroendocrine tumors (PitNETs) have not yet been elucidated. Thus, the present study aimed to investigate the potential risks of SARS-CoV-2 infection on the impairment of pituitary glands and the development of PitNETs. METHODS: PitNETs tissues were obtained from 114 patients, and normal pituitary gland tissues were obtained from the autopsy. The mRNA levels of ACE2 and angiotensin II receptor type 1 (AGTR1) were examined by quantitative real-time PCR. Immunohistochemical staining was performed for ACE2 in 69 PitNETs and 3 normal pituitary glands. The primary tumor cells and pituitary cell lines (MMQ, GH3 and AtT-20/D16v-F2) were treated with diminazene aceturate (DIZE), an ACE2 agonist, with various dose regimens. The pituitary hormones between 43 patients with SARS-CoV-2 infection were compared with 45 healthy controls. RESULTS: Pituitary glands and the majority of PitNET tissues showed low/negative ACE2 expression at both the mRNA and protein levels, while AGTR1 showed high expression in normal pituitary and corticotroph adenomas. ACE2 agonist increased the secretion of ACTH in AtT-20/D16v-F2 cells through downregulating AGTR1. The level of serum adrenocorticotropic hormone (ACTH) was significantly increased in COVID-19 patients compared to normal controls (p < 0.001), but was dramatically decreased in critical cases compared to non-critical patients (p = 0.003). CONCLUSIONS: This study revealed a potential impact of SARS-CoV-2 infection on corticotroph cells and adenomas.

Seed- and Soil-Dependent Differences in Murine Breast Tumor Microenvironments Dictate Anti-PD-L1 IgG Delivery and Therapeutic Efficacy.

We sought to determine if Stephen Paget's "seed and soil" hypothesis of organ-preference patterns of cancer metastasis can explain the development of heterogeneity in a tumor microenvironment (TME) as well as immunotherapeutic delivery and efficacy. We established single-cell-derived clones (clones 1 and 16) from parental 4T1 murine breast cancer cells to create orthotopic primary and liver metastasis models to deconvolute polyclonal complexity cancer cells and the difference in TME-derived heterogeneities. Tumor-bearing mice were treated with anti-PD-L1 IgG or a control antibody, and immunofluorescent imaging and quantification were then performed to evaluate the therapeutic efficacy on tumor growth, the delivery of therapy to tumors, the development of blood vessels, the expression of PD-L1, the accumulation of immune cells, and the amount of coagulation inside tumors. The quantification showed an inverse correlation between the amount of delivered therapy and therapeutic efficacy in parental-cell-derived tumors. In contrast, tumors originating from clone 16 cells accumulated a significantly greater amount of therapy and responded better than clone-1-derived tumors. This difference was greater when tumors grew in the liver than the primary site. A similar trend was found in PD-L1 expression and immune cell accumulation. However, the change in the number of blood vessels was not significant. In addition, the amount of coagulation was more abundant in clone-1-derived tumors when compared to others. Thus, our findings reconfirmed the seed- and soil-dependent differences in PD-L1 expression, therapeutic delivery, immune cell accumulation, and tumor coagulation, which can constitute a heterogeneous delivery and response of immunotherapy in polyclonal tumors growing in different organs.

Relationship between growth hormone 1 genetic polymorphism and susceptibility to colorectal cancer.

The aim of this study was to evaluate the relationship between smoking, alcohol drinking and genetic polymorphism of the growth hormone 1 gene (GH1) T1663A with reference to colorectal cancer. We conducted a case-control study with 315 cases of colorectal cancer and 438 population-based controls in the Jiangsu Province, China. GH1 T1663A genotypes were identified using PCR-RFLP (restriction fragment length polymorphism) methods. Information on smoking and drinking was collected using a questionnaire. Odds ratios (ORs) were estimated with an unconditional logistic model. The distribution of T/T and A/A genotypes was significantly different between controls and cases (chi(2)(MH)=3.877, P=0.049). Compared with the GH1 T/T genotype, the A/A genotype was at a decreased risk of developing colorectal cancer (sex-, age-, body mass index-, smoking- and alcohol drinking-adjusted OR=0.56, 95% confidence interval: 0.34-0.90). Smoking was not associated with the risk of colorectal cancer, whereas alcohol drinking was associated with an increased risk of colorectal cancer. Among nonsmokers or nondrinkers, individuals who had the GH1 A/A genotype were at a decreased risk of developing colorectal cancer compared with individuals who had the GH1 T allele. These results show that the GH1 T1663A A/A genotype can decrease the risk for colorectal cancer.

Alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 genotypes, alcohol drinking and the risk for esophageal cancer in a Chinese population.

To investigate the relationship among alcohol dehydrogenase-2 (ADH2) and aldehyde dehydrogenase-2 (ALDH2) genetic polymorphisms, alcohol consumption and the susceptibility to esophageal cancer in a Chinese population, we conducted a case-control study with 221 cases and 191 population-based controls in the Taixing city of Jiangsu Province of China. ADH2 and ALDH2 genotypes were examined using PCR and denaturing high-performance liquid chromatography. Alcohol drinkers with the ALDH2 A allele showed a significantly increased risk of esophageal cancer compared with drinkers with the ALDH2 G/G genotype (odds ratio (OR)=3.08, 95% confidence interval (CI): 1.65-5.78) or nondrinkers with any genotype (OR=3.05, 95% CI: 1.49-6.25). Drinkers with the ALDH2 A allele and a cumulative amount of alcohol consumption > or =2.5 (kg * years) were at a significantly higher risk of developing esophageal cancer (OR=11.93, 95% CI: 3.17-44.90) compared with individuals with ALDH2 G/G genotypes and a cumulative amount of alcohol consumption <2.5 (kg * years). A dose-dependent positive result was found between cumulative amount of alcohol consumption and risk of esophageal cancer in individuals carrying the ALDH2 A allele (P=0.023) and the homozygous ALDH2 G allele (P=0.047). Compared with individuals carrying both ALDH2 G/G and ADH2 A/A alleles and with a cumulative amount of alcohol consumption <2.5 (kg * years), drinkers carrying both ALDH2 A and ADH2 G alleles and with a cumulative amount of alcohol consumption > or =2.5 (kg * years) showed a significantly elevated risk of esophageal cancer (OR=53.15, 95% CI: 4.24-666.84). This result suggests that to help lower their risk for esophageal cancer, persons carrying the ALDH2 A allele should be encouraged to reduce their consumption of alcoholic beverages.

Prevalence and sex- and age-related risk of pulmonary embolism in in-hospital patients with atrial fibrillation: a multicenter retrospective study from China.

BACKGROUND: This study was designed to explore the prevalence of pulmonary embolism (PE) and sex and age-related risk of incident PE in in-hospital patients with atrial fibrillation (AF) in China. METHODS: A retrospective cohort of 15,688 AF patients (mean age: 72.56 years; 55.7% male) was identified from 2008 to 2018 in our hospitals. The prevalence and incidence of PE over a 2.28-year follow-up were studied. Unadjusted, age or sex-adjusted, and multivariate Cox regression were used to explore the risk of PE in the studied patients. RESULTS: One hundred eighty-two AF patients (1.2%) had PE at their first hospitalizations. Over a mean follow-up of 2.28 years, 85 patients developed PE, with an incidence of 0.24% per person-year. PE was more likely to occur in female and older patients with AF according to the unadjusted, age or sex-adjusted, and multivariate Cox regression analysis (all P<0.05). Moreover, a significant higher risk of PE was seen in female and older patients in AF using Kaplan-Meier analysis, respectively (log-rank: both P<0.001). CONCLUSIONS: In the current AF cohort, the prevalence of PE was 1.2% and the incidence of PE was 0.24% per person-year during a mean follow-up of 2.28 years. Female and older patients were more likely to experience PE compared to male and younger patients.

MTHFR polymorphisms, dietary folate intake and breast cancer risk in Chinese women.

To evaluate the relationship between dietary folate intake and genetic polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) with reference to breast cancer risk, we conducted a case-control study with 669 cases and 682 population-based controls in the Jiangsu Province of China. MTHFR C677T and A1298C genotypes were identified using PCR-RFLP (restrictrion fragment length polymorphism) methods. Dietary folate intake was assessed using an 83-item food frequency questionnaire. Odds ratios (ORs) were estimated with an unconditional logistic model. The frequencies of MTHFR C677T C/C, C/T and T/T genotypes were 32.37, 48.88 and 18.75% in cases and 37.66, 48.24 and 14.10% in controls, respectively. The difference in distribution was significant (chi(2)=6.616, P=0.037), the T/T genotype being associated with an elevated OR (adjusted for age, menopausal status, body mass index (BMI), income, work intensity and status of smoking and drinking) for breast cancer (1.62, 95% confidence interval (95% CI): 1.14-2.30). The frequencies of MTHFR A1298C A/A, A/C and C/C were 71.47, 27.08 and 1.44% in cases and 68.11, 30.13 and 1.76% in controls, respectively, with no significant differences being found (chi(2)=1.716, P=0.424). A significant inverse relationship was observed between folate intake and breast cancer risk. Compared with the lowest tertile of folate intake, the adjusted OR for breast cancer in the top tertile was 0.70 (95% CI: 0.53-0.92). However, no significant interaction was observed between folate intake and the MTHFR C677T polymorphism. Among individuals with the MTHFR A1298C A/A genotype, adjusted ORs for breast cancer were 0.89 (0.62-1.27) and 1.69 (1.20-2.36) for the second to the third tertile of folate intake compared with the highest folate intake group (tread test, P=0.0008). The findings of this study suggest that MTHFR genetic polymorphisms and dietary intake of folate may modify susceptibility to breast cancer.

[MTHFR polymorphisms, dietary folate intake and risks to breast cancer].

OBJECTIVE: To evaluate the relationship between dietary folate intake and genetic polymorphisms of 5, 10-methylenetetrahydrofolate reductase (MTHFR) with reference to breast cancer risk. METHODS: A case-control study was conducted with 669 cases and 682 population-based controls in Jiangsu province of China. MTHFR C677T and A1298C genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Dietary folate intake was assessed by using an 83-item food frequency questionnaire. Odds ratios (OR) were estimated with an unconditional logistic model. RESULTS: The frequencies of MTHFR C677T C/C, C/T and T/T genotypes were 32.37% (202/624), 48.88% (305/624) and 18.75% (117/624) in cases and 37.66% (235/624), 48.24% (301/624) and 14. 10% (88/624) in controls, respectively. The difference in distribution was significant (chi2 = 6.616, P = 0.037), the T/T genotype being associated with an elevated OR for breast cancer (1.62, 95% CI: 1.14 -2.30). The frequencies of MTHFR A1298C A/A, A/C and C/C were 71.47% (446/624), 27.08% (169/624) and 1.44% (9/624) in cases and 68.11%(425/624), 30.13% (188/624) and 1.76% (11/624)in controls,with no significant differences found (chi2 = 1.716, P= 0.424). Folate intake of cases [(263.00 +/- 137.38) microg/d] was significantly lower than that of controls [(285.12 +/- 149.61) microg/d] (t = -2. 830, P =0.005). Compared with the lowest tertile (< or = 199.08 microg/d) of folate intake, the adjusted OR for breast cancer in the top tertile (> or = 315.11 microg/d) was 0.70 (95% CI: 0.53 -0.92). Among individuals with the MTHFR A1298C A/A genotype,adjusted OR for breast cancer were 0.89 (95% CI: 0.62 - 1.27) and 1.69 (95% CI: 1.20 - 2.36) for the second to the third tertile of folate intake compared with the highest folate intake group (X2trend = 11.372, P = 0.001). CONCLUSION: The findings of the present study suggest that MTHFR genetic polymorphisms,and dietary intake of folate may modify susceptibility to breast cancer.