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End-stage kidney disease (ESKD) patients have a higher risk of antibiotic-associated encephalopathy (AAE) than other patients. We aimed to evaluate the prevalence, risk factors and outcomes of AAE in ESKD patients.A retrospective study of ESKD patients treated with intravenous antibiotics in our hospital from Jan. 1, 2006, to Dec. 31, 2015 was performed. AAE was diagnosed by the modified Delphi method. Control individuals were randomly selected from the remaining patients who did not exhibit neurologic symptoms. Logistic regression analysis was used to identify risk factors for AAE as well as the association between AAE and outcome.A total of 2104 patients were included in the study. The prevalence of AAE in our study was 4.4% (92/2104). The multivariate logistic regression analysis revealed that anuria (OR = 8.04, 95% CI: 4.13-15.65,The prevalence of AAE was 4.4% in ESKD patients and varied among different antibiotics. Anuria, history of central nervous system disorder and hypoalbuminemia were associated with AAE in ESKD patients. AAE is associated with worse outcomes in ESKD patients.

It had been suggested, after facilitating the hatching process, improved pregnancy outcomes could be attained in embryos with thick and hard zona. This study aimed to determine the effect of zona thinning on pregnancy outcomes in poor-quality frozen-thawed blastocysts. This retrospective study included 230 women (≤ 40 years) who underwent frozen embryo transfer of poor-quality blastocysts (scored 3BB). In total, 105 patients were in the assisted hatching group in which the zona was thinned by laser before transfer and 125 patients were in the control group in which the blastocysts were non-manipulated. Patients' demographics, cycle characteristics, and pregnancy outcomes were compared between the assisted hatching group and the control group. Further, regression analysis was applied to test the correlation between assisted hatching and live birth. All parameters in the patients' demographic characteristics and the cycle's characteristics were not significantly different between two groups. As for pregnancy outcomes, the second trimester pregnancy loss was significantly higher in the assisted hatching group (P = 0.035). Other pregnancy outcomes, including implantation rate, clinical pregnancy rate, biochemical miscarriage rate, the first trimester pregnancy loss, ongoing pregnancy rate, and live birth rate were comparable between two groups. The logistic regression analysis demonstrated no association between live birth and assisted hatching (univariate, OR = 0.787, P 0.05; multivariate, OR = 0.652, P 0.05), and the area under the receiver operating characteristic curve of the regression model was almost 0.7. It suggested that zona thinning may not be supposed to perform on poor-quality, frozen-thawed blastocysts. The indications of assisted hatching were still needed to further investigate.

Indoor air purifiers are increasingly marketed for their health benefits, but their cardiovascular effects remain unclear. We systematically reviewed and meta-analysed randomized controlled trials (RCTs) on the cardiovascular effects of indoor air purification interventions in humans of all ages. We searched Embase, Medline, PubMed, and Web of Science from inception to 22 August 2020. Fourteen cross-over RCTs (18 publications) were included. Systolic blood pressure (SBP) was significantly reduced after intervention (-2.28 [95% CI: -3.92, -0.64] mmHg). There were tendencies of reductions in diastolic blood pressure (-0.35 [-1.52, 0.83] mmHg), pulse pressure (PP) (-0.86 [-2.07, 0.34] mmHg), C-reactive protein (-0.23 [-0.63, 0.18] mg/L), and improvement in reactive hyperaemia index (RHI) (0.10 [-0.04, 0.24]) after indoor air purification, although the effects were not statistically significant. However, when restricting the analyses to RCTs using physical-type purifiers only, significant improvements in PP (-1.56 [-2.98, -0.15] mmHg) and RHI (0.13 [0.01, 0.25]) were observed. This study found potential evidence on the short-term cardiovascular benefits of using indoor air purifiers, especially for SBP, PP and RHI. However, under the Grading of Recommendations Assessment, Development and Evaluation framework, the overall certainty of evidence was very low, which discourage unsubstantiated claims on the cardiovascular benefits of air purifiers. We have also identified several key methodological limitations, including small sample size, short duration of intervention, and the lack of wash-out period. Further RCTs with larger sample size and longer follow-up duration are needed to clarify the cardiovascular benefits of air purification interventions.

Background: Recognizing the kinematic characteristics of lumbar facet joints is important for the prevention and treatment of lumbar degenerative diseases. Previous studies have been conducted in either the supine or standing position, and there are no measurements regarding the kinematic characteristics of the lumbar facet joints while sitting. The aim of this study was to measure and analyze lumbar facet joint motion characteristics while sitting.Methods: Ten subjects (5 males and 5 females) performed the movements of flexion-extension, left bending-right bending, and left rotation-right rotation in a sitting position. Dual Fluoroscopic Image System and computed tomography technique were used to measure the displacement and rotation angle of the lumbar facet joints of the subjects for analysis. The movement characteristics of L3-S1 were measured. Results: When the subjects were in sitting position, the lumbar vertebra mainly changed in Z axis and α, β angle when they performed flexion-extension activities. The displacement of the left facet joint was 4.65 ± 1.99 mm at L3-4, 1.89 ± 2.99 mm at L4-5, and 0.80 ± 2.27 mm at L5-S1 in the Z axis, and the displacement of the right facet joint was 3.20 ± 2.61 mm at L3-4, 1.71 ± 3.00 mm at L4-5, and 0.31 ± 1.69 mm at L5-S1 in the Z axis. The rotation in the α angle was 6.00 ± 4.49 ° at L3-4, 3.51 ± 5.24 ° at L4-5, and 0.97 ± 4.13 ° at L5-S1, which was significant different. The rotation in the β angle was 2.30 ± 2.94 °at L3-4, 0.16 ± 2.06 ° at L4-5, and 0.35 ± 1.74 °at L5-S1, which was significant different. When the lumbar spine performed the activity of left bending-right bending, there were changes in rotation mainly in the Z axis and β angle. The displacement of left facet joint in the Z axis was 1.34 ± 2.84 mm at L3-4, 2.11 ± 0.88 mm at L4-5 , and 0.72 ± 0.81 mm at L5-S1; the rotation in the β angle was 5.66 ± 2.70°at L3-4, 7.89 ± 2.59 ° at L4-5, and 1.28 ± 2.07 ° at L5-S1; when the lumbar spine performed the activity of left rotation-right rotation, there were changes in the β angle. The rotation of β angle was 4.09 ± 2.86 ° at L3-4, 2.14 ± 3.38 ° at L4-5, and 0.63 ± 1.85 ° at L5-S1.Conclusion: The lumbar facet joint motion in sitting position is different in each mode of motion. The horizontal displacement and rotation are predominant during flexion and extension activities, while there are different rotation in bending and rotation. The study shows the coupled motion of the lumbar facet joints while sitting, providing a new perspective on the kinematics of the lumbar spine and the etiology of lumbar degenerative diseases.

Objective To explore the clinical characteristics of Coronavirus Disease (COVID-19) patients with gastrointestinal symptoms. Methods The clinical data of 164 COVID-19 patients with gastrointestinal symptoms were extracted and analysed retrospectively. Results In total, 505 COVID-19 patients were divided into two groups: those with gastrointestinal symptoms (G group) and those without gastrointestinal symptoms (NG group). Common gastrointestinal symptoms included inappetence, diarrhoea, nausea, abdominal pain, and vomiting. Significantly higher proportions of patients with fever, dizziness, myalgia, and fatigue were noted in group G than in group NG. Compared with patients without fever, there was a significant difference between G group and NG group in moderate fever or above, while there was no significant difference between the two groups in low fever. The laboratory results showed that patients in the G group had significantly higher C-reactive protein, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase levels than those in the NG group. Moreover, the proportion of patients with severe pneumonia was significantly higher in the G group than in the NG group. Conclusion In Wuhan, the proportion of COVID-19 patients who experience gastrointestinal symptoms is relatively high. Patients who experience gastrointestinal symptoms are more likely to suffer from severe pneumonia, which may help clinicians identify patients at high risk of COVID-19 and thus reduce the incidence of this condition.

Tumor metastasis accounts for the majority of cancer-related deaths; it is therefore important to develop preclinical models that faithfully recapitulate disease progression. Here, we generated paired organoids derived from primary tumors and matched liver metastases in the same colorectal cancer (CRC) patients. Despite the fact that paired organoids exhibit comparable gene expression and cell morphology, organoids from metastatic lesions demonstrate more aggressive phenotypes, tumorigenesis, and metastatic capacity than those from primary lesions. Transcriptional analyses of the paired organoids reveal signature genes and pathways altered during the progression of CRC, including SOX2. Further study shows that inducible knockdown of SOX2 attenuated invasion, proliferation, and liver metastasis outgrowth. Taken together, we use patient-derived paired primary and metastatic cancer organoids to model CRC metastasis and illustrate that SOX2 is associated with CRC progression and may serve as a potential prognostic biomarker and therapeutic target of CRC.

The optimal assisted reproductive treatment strategy for infertile women with unilateral tubal obstruction remains uncertain. To investigate the role of intrauterine insemination (IUI) in the treatment of infertile women with unilateral tubal occlusion, the data of 148 couples were retrospectively collected and analyzed. Seventy-eight infertile women with unilateral occlusion diagnosed by hysterosalpingography (HSG) were categorized as the study group and 70 others with unexplained infertility as the control group. The study group was divided into a proximal occlusion subgroup and a mid-distal occlusion subgroup for further analysis. The main outcomes, namely the clinical pregnancy rate (CPR), ongoing pregnancy rate (OPR), and live birth rate (LBR) per cycle, were analyzed. Our results showed a tendency of lower CPR, OPR, and LBR in the study group than in the control group, without statistical significance. Further investigations revealed that the unilateral proximal occlusion subgroup had similar CPR, OPR, and LBR as the control group, while the unilateral mid-distal occlusion subgroup had significantly lower CPR (5.1% vs. 20.0%, P=0.035), OPR (5.1% vs. 20.0%, P=0.035), and LBR (5.1% vs. 20.0%, P=0.035) than the control group. In conclusion, the clinical outcomes of IUI were worse in patients with unilateral tubal occlusion than in those with unexplained infertility. This might be primarily caused by the worse outcome of patients with unilateral mid-distal tubal occlusion instead of proximal occlusion.

BackgroundSignificant progress has been made in cell replacement therapy for neural retinal diseases using retinal cells differentiated from human pluripotent stem cells. Low tumorigenicity and the ability to mature to form synaptic junctions make precursor cells a promising donor source. Here, we attempted to improve the yield of photoreceptor precursor cells in three-dimensional retinal organoids from human embryonic stem cells (hESCs).MethodsA CRX-tdTomato-tagged hESC line was generated to track retinal precursors in 3D retinal organoids. COCO, a multifunctional antagonist of the Wnt, TGF-β, and BMP pathways, was employed to 3D organoid differentiation schemes for enhanced photoreceptor precursor cells. Organoid fluorescence intensity measurement was used to monitor retinalization tendency with the number of precursors further checked by flow cytometry. Signature gene expression during organoid differentiation were assessed by qPCR and immunocytochemistry after COCO supplementation.ResultsCRX-positive cells can be spatiotemporally tracked by tdTomato without affecting retinalization during retinal organoid differentiation. Fluorescence intensity of organoids, which turned out highly consistent with flow cytometry measurement, allowed us to determine the differentiation efficiency of precursors during organoid culturing directly. Using COCO as an auxiliary supplement, rather than alone, can yield an increased number of photoreceptor precursors in the early stage of organoid differentiation. Over a longer time-frame, photoreceptor precursors enhanced their fate of cones and decreased fate of rods after treatment with COCO.ConclusionsTracing with the CRX-reporter system showed that in retinal organoids derived from human pluripotent stem cells, COCO increased the differentiation efficiency of photoreceptor precursors and cones.

Recently, growing evidence has shown that aberrant long non‐coding RNA (lncRNA) expression in conjunction with an impaired trophoblastic phenotype could implicate the pathological process of pre‐eclampsia (PE). However, only a small portion of lncRNAs has been characterized with regard to the function and molecular mechanisms involved in PE. There are still gaps in the available knowledge; as a result, there are currently only a few applicable treatments for PE in the context of lncRNA. Here, we found that lncRNA AGAP2‐AS1 is abnormally down‐regulated in severe PE placenta tissues. Using human trophoblasts, we established that AGAP2‐AS1 knockdown could inhibit trophoblasts proliferation and invasion and promote cell apoptosis. Further, we showed that overexpression of AGAP2‐AS1 substantially stimulated the development of the trophoblastic phenotype. Through high‐throughput sequencing analysis, we demonstrated that silencing of AGAP2‐AS1 favourably regulated various genes which are relevant to trophoblastic growth and invasion. Mechanistically, AGAP2‐AS1 promoted the suppressor protein, Jun dimerization protein 2 (JDP2), by sponging miR‐574‐5p. Resultantly, further impairment of the trophoblastic phenotype was achieved by way of inhibiting cell growth, apoptosis and invasion. We also determined that the expression of AGAP2‐AS1 could be mediated by FOXP1. Our results showed that the down‐regulated expression of lncRNA AGAP2‐AS1 might serve as a key suppressor in PE via inhibition of JDP2 at the post‐transcriptional level by competing for miR‐574; thus, this presents a novel therapeutic strategy for PE.

The surface glycoprotein (S protein) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was used to develop coronavirus disease 2019 (COVID-19) vaccines. However, SARS-CoV-2, especially the S protein, has undergone rapid evolution and mutation, which has remained to be determined. Here, we analyzed and compared the early (12 237) and the current (more than 10 million) SARS-CoV-2 strains to identify the mutation features and geographical distribution of the S gene and S protein. Results showed that in the early strains, most of the loci were with relative low mutation frequency except S: 23403 (4486 strains), while in the current strains, there was a surge in the mutation strains and frequency, with S: 23403 constantly being the highest one, but tremendously increased to approximately 1050 times. Furthermore, D614 (S: 23403) was one of the most highly frequent mutations in the S protein of Omicron as of March 2022, and most of the mutant strains were still from the United States, and the United Kingdom. Further analysis demonstrated that in the receptor-binding domain, most of the loci with low mutation frequency in the early strains, while S: 22995 was nowadays the most prevalent loci with 3 122 491 strains in the current strains. Overall, we compare the mutation features of the S region in SARS-CoV-2 strains between the early and the current stains, providing insight into further studies in concert with emerging SARS-CoV-2 variants for COVID-19 vaccines.

Background: The abnormal expression Dopamine D1 receptor (DRD1) gives rise to the dysfunction of dopaminergic neurotransmitter and may be associated with the occurrence of schizophrenia. Mi...

The dopamine transporter is coded by the SLC6A3 gene and plays an important role in regulation of the neurotransmitter dopamine. To detect the association between the SLC6A3 gene and the risk of schizophrenia, 31 case-control articles were included in this meta-analysis. There were 23 studies with 40 bp VNTR (3246 cases and 3639 controls), 4 studies with rs40184 (2020 cases and 1674 controls), rs6347 (1317 cases and 1917 controls), rs403636 (2045 cases and 1704 controls), and rs2975226 (849 cases and 904 controls); and 3 studies with rs12516948 (1920 cases and 1569 controls), rs27072 (984 cases and 1015 controls), rs6869645 (1142 cases and 1082 controls), rs37022 (1168 cases and 1091 controls), rs464049 (1169cases and 1096 controls), rs2652511 (707 cases and 714 controls), and rs3756450 (1176 cases and 1096 controls). Pooled, subgroup, and sensitivity analyses were performed, and the results were visualized by forest and funnel plots. In the dominant genetic model, the genotype AA+AT of rs2975226 in the Indian population (Pz = 0, odds ratio [OR] = 3.245, 95% confidence interval [CI] = 1.806–5.831), TT of rs464049 (Pz = 0.002, OR = 1.389, 95% CI = 1.129–1.708), and TT of rs3756450 (Pz = 0.014, OR = 1.251, 95% CI = 1.047–1.495) might be risk factors for schizophrenia. Additionally, no other single nucleotide polymorphisms were observed. These results indicate that more functional studies are warranted.

Breast cancer susceptibility gene 1 (BRCA1) has been implicated in modulating metabolism via transcriptional regulation. However, direct metabolic targets of BRCA1 and the underlying regulatory mechanisms are still unknown. Here, we identified several metabolic genes, including the gene which encodes glutamate‐oxaloacetate transaminase 2 (GOT2), a key enzyme for aspartate biosynthesis, which are repressed by BRCA1. We report that BRCA1 forms a co‐repressor complex with ZBRK1 that coordinately represses GOT 2 expression via a ZBRK1 recognition element in the promoter of GOT2. Impairment of this complex results in upregulation of GOT2, which in turn increases aspartate and alpha ketoglutarate production, leading to rapid cell proliferation of breast cancer cells. Importantly, we found that GOT2 can serve as an independent prognostic factor for overall survival and disease‐free survival of patients with breast cancer, especially triple‐negative breast cancer. Interestingly, we also demonstrated that GOT2 overexpression sensitized breast cancer cells to methotrexate, suggesting a promising precision therapeutic strategy for breast cancer treatment. In summary, our findings reveal that BRCA1 modulates aspartate biosynthesis through transcriptional repression of GOT2, and provides a biological basis for treatment choices in breast cancer.

BackgroundThis study aimed to investigate fetal and maternal outcomes in women with active lupus nephritis (LN). Specifically, we compared women who had new-onset LN and those with pre-existing LN during pregnancy.MethodsPatients with active LN during pregnancy were divided into the new-onset group (LN first occurred during pregnancy) and the pre-existing group (a history of LN) on the basis of the onset time of LN. Data on clinical features, laboratory findings, and pregnancy outcome were collected and analyzed between the two groups. Multivariate logistic regression analysis was used to compare the effects of active LN on adverse pregnancy outcomes.ResultsWe studied 73 pregnancies in 69 women between 2010 and 2019. Of these, 38 pregnancies were in the pre-existing LN group and 35 were in the new-onset group. Patients with pre-existing LN had a higher risk of composite adverse fetal outcomes than those with new-onset LN [adjusted odds ratio (ORs), 44.59; 95% confidence interval (CI), 1.21–1664.82;P= 0.039]. However, the two groups had similar adverse maternal outcomes (ORs, 1.24; 95% CI, 0.36–4.29). Serum albumin and proteinuria significantly improved after pregnancy (P< 0.001). Kaplan–Meier analysis showed that the long-term renal outcome was similar between the two groups.ConclusionsPregnant patients with pre-existing LN were associated with a higher risk of composite adverse fetal outcomes than those with new-onset LN. However, these two groups of patients had similar adverse maternal outcomes. The long-term renal outcomes were not different after pregnancy between these two groups.

Background rs13405728 was identified as one of the most prevalent susceptibility loci for polycystic ovary syndrome (PCOS) in Han Chinese and Caucasian women. However, the target genes and potential mechanisms of the rs13405728 locus remain to be determined. Methods Three-dimensional (3D) genome interactions from the ovary tissue were characterized via high-through chromosome conformation capture (Hi-C) and Capture Hi-C technologies to identify putative targets at the rs13405728 locus. Combined analyses of eQTL, RNA-Seq, DNase-Seq, ChIP-Seq, and sing-cell sequencing were performed to explore the molecular roles of these target genes in PCOS. PCOS-like mice were applied to verify the expression patterns. Results Generally, STON1 and FSHR were identified as potential targets of the rs13405728 locus in 3D genomic interactions with epigenomic regulatory peaks, with STON1 (P=0.0423) and FSHR (P=0.0013) being highly expressed in PCOS patients. STON1 co-expressed genes were associated with metabolic processes (P=0.0008) in adipocytes (P=0.0001), which was validated in the fat tissue (P

The occurrence of 187 pharmaceuticals and personal care products (PPCPs) was investigated in bottled water samples (35 and 33 from Chinese and foreign brands, respectively). Forty-four compounds belonging to 14 PPCP categories were detected in 56 of the 68 bottled water samples. Further, more than 35% of water samples contained at least three PPCPs, and in one particular sample, 11 different PPCPs were detected. Macrolides constituted the most prevalent PPCP category, and salbutamol, erythromycin, and azithromycin showed the highest detection frequency (17.6%). The thermal stabilities of the 187 PPCPs were determined, and the results obtained showed that only 35 out of the 187 compounds were degraded by more than 50% after boiling for 5 min. Even though the risk quotients (RQs) of detected PPCPs showed low risk levels, the RQs of 13 compounds with RQs ≥ 0.0001 were 2–4 fold higher in infants than in other life stages. Moreover, further studies are necessary to evaluate the toxicity of PPCP mixtures, the effects of PPCPs on human intestinal microbiota, and their risk of induction of drug-resistant bacteria and drug-resistant genes.

Introduction Abnormal expression of ionotropic glutamate receptor NMDA type subunit 1, the key subunit of the NMDA receptor, may be related to many neuropsychiatric disorders. In this study, we explored the functional sequence of the 5′ regulatory region of the human GRIN1 gene and discussed the transcription factors that may regulate gene expression. Materials and Methods Twelve recombinant pGL3 vectors with gradually truncated fragment lengths were constructed, transfected into HEK-293, U87, and SK-N-SH cell lines, and analyzed through the luciferase reporter gene assay. JASPAR database is used to predict transcription factors. Results In SK-N-SH and U87 cell lines, regions from −337 to −159 bp, −704 to −556 bp inhibited gene expression, while −556 to −337 bp upregulated gene expression. In HEK-293 and U87 cell lines, the expression of fragment −1703 to + 188 bp was significantly increased compared to adjacent fragments −1539 to + 188 bp and −1843 to + 188 bp. The protein expressions of fragments −2162 to + 188 bp and −2025 to + 188 bp, −1539 to + 188 bp and −1215 to + 188 bp, −1215 to + 188 bp and −1066 to + 188 bp were significantly different in HEK-293 and SK-N-SH cells. According to the predictions of the JASPAR database, the transcription factors REST, EGR1, and CREB1/HIC2 may bind the DNA sequences of GRIN1 gene from the −337 to −159, −556 to −337, and −704 to −556, respectively. In addition, zinc finger transcription factors may regulate the expression of other differentially expressed fragments. Conclusions Abnormal transcription regulation in the proximal promoter region of GRIN1 (-704 to + 188 bp) may be involved in the course of neuropsychiatric diseases.

Graphical abstract Averaged 24-hour variation of fine particulate matter (PM2.5) concentrations (µg/m3) recorded in the personal, kitchen, living room, and ambient monitors across the three study sites in the warm and cool season., Highlights • We collected detailed fuel use, time-activity, and air pollution data from 477 Chinese adults. • Mix of solid and clean fuels was common for cooking or heating in rural areas. • Real-time PM2.5 data at personal, household, and ambient environments are presented. • PM2.5 levels in rural areas with solid fuel use were 2–3 times higher than in urban areas. • Personal, household and ambient PM2.5 levels were 2–3 times higher in the cool season., Background Previous studies of the health impact of ambient and household air pollution (AAP/HAP) have chiefly relied on self-reported and/or address-based exposure modelling data. We assessed the feasibility of collecting and integrating detailed personal exposure data in different settings and seasons. Methods/design We recruited 477 participants (mean age 58 years, 72% women) from three (two rural [Gansu/Henan] and one urban [Suzhou]) study areas in the China Kadoorie Biobank, based on their previously reported fuel use patterns. A time-resolved monitor (PATS+CO) was used to measure continuously for 120-hour the concentration of fine particulate matter (PM2.5) at personal and household (kitchen and living room) levels in warm (May-September 2017) and cool (November 2017–January 2018) seasons, along with questionnaires on participants’ characteristics (e.g. socio-demographic, and fuel use) and time-activity (48-hour). Parallel local ambient monitoring of particulate matter (PM1, PM2.5 and PM10) and gaseous pollutants (CO, ozone, nitrogen oxides) was conducted using regularly-calibrated devices. The air pollution exposure data were compared by study sites and seasons. Findings Overall 76% reported cooking at least weekly (regular-cooks), and 48% (urban 1%, rural 65%) used solid fuels (wood/coal) for cooking. Winter heating was more common in rural sites than in urban site (74–91% vs 17% daily), and mainly involved solid fuels. Mixed use of clean and solid fuels was common for cooking in rural areas (38%) but not for heating (0%). Overall, the measured mean PM2.5 levels were 2–3 fold higher in the cool than warm season, and in rural (e.g. kitchen: Gansuwarm_season = 142.3 µg/m3; Gansucool_season = 508.1 µg/m3; Henanwarm_season = 77.5 µg/m3; Henancool_season = 222.3 µg/m3) than urban sites (Suzhouwarm_season = 41.6 µg/m3; Suzhoucool_season = 81.6 µg/m3). The levels recorded tended to be the highest in kitchens, followed by personal, living room and outdoor. Time-resolved data show prominent peaks consistently recorded in the kitchen at typical cooking times, and sustained elevated PM2.5 levels (> 100 µg/m3) were observed in rural areas where use of solid fuels for heating was common. Discussion Personal air pollution exposure can be readily assessed using a low-cost time-resolved monitor in different settings, which, in combination with other personal and health outcome data, will enable reliable assessment of the long-term health effects of HAP/AAP exposures in general populations.

The association between non-high-density lipoprotein cholesterol (non-HDL-C) and mortality in patients undergoing peritoneal dialysis (PD) is unclear.The aim of this study was to evaluate the association of non-HDL-C with cardiovascular (CV) and all-cause mortality in PD patients.We conducted a prospective cohort study. A total of 1,616 incident PD patients from a single PD center in South China were followed for a median of 47.6 months. The independent association of non-HDL-C with CV and all-cause mortality was evaluated by a Cox regression analysis.During the follow-up period, 508 (31.4%) patients died, of which 249 (49.0%) were due to CV events. Atherosclerotic CV mortality accounted for 59.8% of CV mortality. In multivariable models, for 1-SD increase in non-HDL-C level, the hazard ratios (HRs) for CV and all-cause mortality were 1.52 [95% confidence interval (CI), 1.32-1.75; P 0.001)] and 1.24 (95% CI, 1.12-1.39; P 0.001), respectively. Furthermore, non-HDL-C was positively associated with atherosclerotic CV mortality (HR, 1.29; 95% CI, 1.09-1.52; P = 0.004) but not associated with nonatherosclerotic CV mortality (HR, 0.79; 95% CI, 0.59-1.05; P = 0.108). The quartile analyses showed a similar pattern to the continuous variable analyses of non-HDL-C levels for CV and all-cause mortality but did not demonstrate statistical significance for atherosclerotic or nonatherosclerotic CV mortality.An elevated non-HDL-C level was independently associated with an increased risk of CV mortality, especially atherosclerotic CV mortality, and all-cause mortality in incident PD patients.

Adrenocortical carcinoma is one of the aggressive malignancies and it originates from the cortex of adrenal gland. Dysregulation of long non-coding RNA plays important roles in the development of adrenocortical carcinoma. Here, we found that lncRNA ASB16-AS1 was down-regulated in adrenocortical carcinoma and ASB16-AS1 functions as tumor suppressor in vitro and in vivo. We then found that IGF1R and CDK6 are regulated by ASB16-AS1 in adrenocortical carcinoma cells by transcriptome RNA sequencing. ASB16-AS1 associates with RNA-binding protein HuR (ELAVL1) as revealed by RNA pull-down following mass spectrometry. Also, ASB16-AS1 inhibits HuR expression post-translationally by promoting its ubiquitination. ASB16-AS1 regulates IGF1R and CDK6 mRNA expression through RNA-binding protein HuR. We then found that inhibition of ASB16-AS1 attenuates the binding of ubiquitin E3 ligase BTRC to HuR and subsequently inhibits HuR protein unbiquitination and degradation. BTRC knock-down could reverse the effect of AB16-AS1 on HuR, CDK6, and IGF1R levels. Collectively, these results demonstrate that ASB16-AS1 regulates adrenocortical carcinoma cell proliferation and tackling the level of ASB16-AS1 may be developed to treat adrenocortical carcinoma.

Background The 5-hydroxytryptamine 1B receptor (5-HT1B) plays an essential role in the serotonin (5-HT) system and is widely involved in a variety of brain activities. HTR1B is the gene encoding 5-HT1B. Genome-wide association studies have shown that HTR1B polymorphisms are closely related to multiple mental and behavioral disorders; however, the functional mechanisms underlying these associations are unknown. This study investigated the effect of several HTR1B haplotypes on regulation of gene expression in vitro and the functional sequences in the 5′ regulatory region of HTR1B to determine their potential association with mental and behavioral disorders. Methods Six haplotypes consisting of rs4140535, rs1778258, rs17273700, rs1228814, rs11568817, and rs130058 and several truncated fragments of the 5′ regulatory region of HTR1B were transfected into SK-N-SH and HEK-293 cells. The relative fluorescence intensities of the different haplotypes and truncated fragments were detected using a dual-luciferase reporter assay system. Results Compared to the major haplotype T-G-T-C-T-A, the relative fluorescence intensities of haplotypes C-A-T-C-T-A, C-G-T-C-T-A, C-G-C-A-G-T, and C-G-T-A-T-A were significantly lower, and that of haplotype C-G-C-A-G-A was significantly higher. Furthermore, the effects of the rs4140535T allele, the rs17273700C-rs11568817G linkage combination, and the rs1228814A allele made their relative fluorescence intensities significantly higher than their counterparts at each locus. Conversely, the rs1778258A and rs130058T alleles decreased the relative fluorescence intensities. In addition, we found that regions from − 1587 to − 1371 bp (TSS, + 1), − 1149 to − 894 bp, − 39 to + 130 bp, + 130 to + 341 bp, and + 341 to + 505 bp upregulated gene expression. In contrast, regions − 603 to − 316 bp and + 130 to + 341 bp downregulated gene expression. Region + 341 to + 505 bp played a decisive role in gene transcription. Conclusions HTR1B 5′ regulatory region polymorphisms have regulatory effects on gene expression and potential correlate with several pathology and physiology conditions. This study suggests that a crucial sequence for transcription is located in region + 341 ~ + 505 bp. Regions − 1587 to − 1371 bp, − 1149 to − 894 bp, − 603 to − 316 bp, − 39 to + 130 bp, and + 130 to + 341 bp contain functional sequences that can promote or suppress the HTR1B gene expression.

Background Plasma fibrinogen is significantly associated with cardiovascular (CV) events and mortality in the general population. However, the association between plasma fibrinogen and mortality in patients undergoing peritoneal dialysis (PD) is unclear. Methods This was a prospective cohort study. A total of 1603 incident PD patients from a single center in South China were followed for a median of 46.7 months. A Cox regression analysis was used to evaluate the independent association of plasma fibrinogen with CV and all-cause mortality. Models were adjusted for age, sex, smoking, a history of CV events, diabetes, body mass index, systolic blood pressure, hemoglobin, blood platelet count, serum potassium, serum albumin, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, hypersensitive C-reactive protein, estimated glomerular filtration rate, antiplatelet agents and lipid-lowering drugs. Results The mean age was 47.4 ± 15.3 years, 955 (59.6%) patients were male, 319 (19.9%) had a history of CV events, and 410 (25.6%) had diabetes. The average plasma fibrinogen level was 4.12 ± 1.38 g/L. Of the 474 (29.6%) patients who died during follow-up, 235 (49.6%) died due to CV events. In multivariable models, the adjusted hazard ratios (HRs) for quartile 1, quartile 3, and quartile 4 versus quartile 2 were 1.18 (95% confidence interval [CI], 0.72–1.95, P = 0.51), 1.47 (95% CI, 0.93–2.33, P = 0.10), and 1.78 (95% CI, 1.15–2.77, P = 0.01) for CV mortality and 1.20 (95% CI, 0.86–1.68, P = 0.28), 1.29 (95% CI, 0.93–1.78, P = 0.13), and 1.53 (95% CI, 1.12–2.09, P = 0.007) for all-cause mortality, respectively. A nonlinear relationship between plasma fibrinogen and CV and all-cause mortality was observed. Conclusions An elevated plasma fibrinogen level was significantly associated with an increased risk of CV and all-cause mortality in patients undergoing PD.

Background: Few studies evaluated over 5-year outcomes of dialysis patients. This study examined 10-year all-cause mortality and death-censored technique failure in a cohort of incident peritoneal dialysis (PD) individuals. Methods: Five hundred and thirty-three incident PD individuals from 2006 to 2008 were prospectively followed up for more than 10 years until 2018. Clinical characteristics at PD initiation were collected. The primary outcome was all-cause mortality, and the secondary outcome was death-censored technique failure. Cox hazards models were fit using clinical characteristics at PD initiation. Results: The mean age starting PD for these participants was 48 ± 16 years; 130 (24%) patients had diabetic nephropathy. During follow-up, 208 patients died, and 84 patients experienced technique failures. The 1, 3, 5, and 10 years’ survival rates for incident PD patients were 93%, 81%, 64%, and 36%, respectively, and the technical survival rates were 98%, 93%, 85%, and 62%, respectively. Mortality risk was much higher after 3 years on PD. The peritonitis rate was 0.19 episodes per patient-year, and 7 (1.3%) patients had encapsulating peritoneal sclerosis (EPS) giving an incidence rate of 3.1 of 1000 patient-years. The main causes of death were cardiovascular events (97 of 208, 47%), and technique failure was mainly due to peritonitis (41 of 84, 49%). Older age, higher Charlson comorbidity index, and lower level of education were strongly associated with mortality, and diabetic nephropathy was an independent risk factor for technique failure. Conclusions: The 10-year’s survival and technique survival rates of incident PD patients were 36% and 62%. Long-term PD can be continued successfully with improved outcomes and low risk for EPS.

Endometriosis is a chronic inflammatory syndrome and nearly 6%‐10% of women are affected by it during the reproductive period. Previous studies have proved that microRNAs (miRNAs) are implicated in the pathogenesis of ovarian endometriosis. In this study, we aimed to investigate that restored miR‐488 would effectively inhibit the development of endometriosis. The microarray‐based data analysis was performed to screen endometriosis‐related differentially expressed genes (DEGs). The mouse model in endometriosis syndrome was established by being subcutaneously injected with Estradiol benzoate, and the ectopic endometrial tissues and normal endometrial tissues were collected. Additionally, the endometrial glandular epithelial cells were extracted from the endometrial glandular epithelial tissues from normal and endometriosis mice. In order to examine the role of miR‐488 in mice with endometriosis, we measured miR‐488 expression and expression levels of Frizzled‐7 (FZD7), cyclinD1, β‐catenin, and c‐Myc in vivo and in vitro. Finally, we detected the effect of miR‐488 on cell proliferation, apoptosis, migration and invasion in vitro. FZD7 was upregulated in human endometriosis. The data showed higher expression levels of FZD7, β‐catenin, c‐Myc and cyclinD1, and lower miR‐488 expression in mouse endometrial tissues. FZD7 was the target gene of miR‐488. Furthermore, elevated miR‐488 in isolated mouse endometrial glandular endometrial cells inhibited FZD7, the translocation of β‐catenin to nucleus, the activation of Wnt pathway, and the cell proliferation, migration and invasion. Collectively, these findings indicated that up‐regulated miR‐488 may reduce the proliferation, migration and invasion of endometrial glandular epithelial cells through inhibiting the activation of Wnt pathway by down‐regulating FZD7.

ContextThe H19 long noncoding RNA (lncRNA) belongs to a highly conserved, imprinted gene cluster involved in embryonic development and growth control. We previously described a novel mechanism whereby the Anti-mullerian hormone (Amh)appears to be regulated byH19.However, the relationship between circulatingH19and markers of ovarian reserve including AMH not been investigated.ObjectiveTo determine whetherH19expression is altered in women with decreased ovarian reserve.DesignExperimental study.SettingYale School of Medicine (New Haven, USA) and Gazi University School of Medicine (Ankara, Turkey).Patients or other participantsA total of 141 women undergoing infertility evaluation and treatment.InterventionCollection of discarded blood samples and cumulus cells at the time of baseline infertility evaluation and transvaginal oocyte retrieval, respectively.Main outcome measureSerum and cumulus cellH19expression.ResultsWomen with diminished ovarian reserve (as determined by AMH) had significantly lower serum H19 expression levels as compared to controls (p p ConclusionIn this study, we show that downregulation ofH19in serum and cumulus cells is closely associated with decreased ovarian reserve, as measured by decreased AMH levels and reduced oocyte yield at oocyte retrieval. Further study with expanded sample sizes is necessary to determine whetherH19may be of use as a novel biomarker for diminished ovarian reserve.

Few studies have investigated the short-term effect of personal temperature exposure on blood oxygen saturation (SpO2). We conducted this longitudinal panel study with real-time monitoring of SpO2 ...

Background: The CACNA1C gene was defined as a risk gene for schizophrenia in a large genome-wide association study of European ancestry performed by the Psychiatric Genomics Consortium. Previous meta-analyses focused on the association between the CACNA1C gene rs1006737 and schizophrenia. The present study focused on whether there was a racial difference in the effect of the CACNA1C gene rs1006737 on schizophrenia. rs2007044 and rs4765905 were analyzed for their effect on the risk of schizophrenia. Methods: Pooled, subgroup, sensitivity, and publication bias analysis were conducted.Results: A total of 18 studies met the inclusion criteria, including fourteen rs1006737 studies (15,213 cases, 19,412 controls), three rs2007044 studies (6,007 cases, 6,518 controls), and two rs4765905 studies (2,435 cases, 2,639 controls). An allele model study also related rs2007044 and rs4765905 to schizophrenia. The overall meta-analysis for rs1006737, which included the allele contrast, dominant, recessive, codominance, and complete overdominance models, showed significant differences between rs1006737 and schizophrenia. However, the race-based subgroup analysis for rs1006737 found that the genotypes GG and GG + GA were only protective factors for schizophrenia in European populations. In contrast, the rs1006737 GA genotype only reduced the risk of schizophrenia in Asian populations. Conclusions: Rs1006737, rs2007044, and rs4765905 of the CACNA1C gene were associated with susceptibility to schizophrenia. However, the influence model for rs1006737 on schizophrenia in Asian and European populations demonstrated both similarities and differences between the two populations.

Background The HTR1B gene encodes the 5-hydroxytryptamine (5-HT1B) receptor, which is involved in a variety of brain activities and mental disorders. The regulatory effects of non-coding regions on genomic DNA are one of many reasons for the cause of genetic-related diseases. Post-transcriptional regulation that depends on the function of 3' regulatory regions plays a particularly important role. This study investigated the effects, on reporter gene expression, of several haplotypes of the HTR1B gene (rs6297, rs3827804, rs140792648, rs9361234, rs76194807, rs58138557, and rs13212041) and truncated fragments in order to analyze the function of the 3' region of HTR1B. Methods Seven haplotypes, consisting of rs6297, rs3827804, rs140792648, rs9361234, rs76194807, rs58138557, and rs13212041, and truncated fragments of the HTR1B gene 3' region were transfected into SK-N-SH, HEK-293, and U87 cell lines. The relative fluorescence intensities were detected by a dual luciferase reporter assay system.Results We found that the haplotype, AG_CT_A, enhanced the expression level compared to the main haplotype; AG_CG_A; GG_CG_G decreased the expression level. Two alleles, rs76194807T and rs6297G, exhibited different relative luciferase intensities compared to their counterparts at each locus. We also found that +2440 ~ +2769 bp and +1953 ~ +2311 bp regions both had negative effects on gene expression.ConclusionsThe 3' region of HTR1B has a regulatory effect on gene expression, which is likely closely associated with the interpretation of HTR1B-related disorders. In addition, the HTR1B 3' region includes several effector binding sites that induce an inhibitory effect on gene expression.

Introduction: Very early withdrawal from treatment in patients undergoing peritoneal dialysis (PD) is an increasingly important, but poorly understood, issue. Here, we identified the reasons and risk factors for very early withdrawal from PD. Methods: Incident PD patients from The First Affiliated Hospital of Sun Yat-sen University above 18 years who started treatment between January 1 2006 and December 31 2011 were included. Cessation of PD therapy within the first 90 days after beginning dialysis was classified as very early withdrawal. Results: Totally 1444 patients were enrolled. Of these, 71 (4.9%) withdrew from PD therapy during the first 90 days. Primary reasons for very early withdrawal included death (34 patients, 47.9%), transplantation (21 patients, 29.6%) and transfer to hemodialysis (14 patients, 19.7%). The leading reasons for death were cardiovascular and infectious disease, accounting for 41.2% (14 patients) and 23.5% (8 patients) of total deaths, respectively. Dialysate leakage (six patients, 42.9%) and catheter dysfunction (five patients, 35.7%) were the main reasons for transfer to hemodialysis. In multivariate analysis, predictors for very early PD withdrawal were older age (per decade increasing; hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.03–1.45; p = .019), higher systolic blood pressure (per 10 mmHg increasing; HR, 1.35; 95% CI, 1.20–1.50; p

Multidrug resistance (MDR) is the leading cause of failure for breast cancer in the clinic. Thus far, polymer–lipid hybrid nanoparticles (PLN) loaded chemotherapeutic agents has been used to overcome MDR in breast cancer. In this study, we prepared psoralen polymer–lipid hybrid nanoparticles (PSO-PLN) to reverse drug resistant MCF-7/ADR cells in vitro and in vivo. PSO-PLN was prepared by the emulsification evaporation-low temperature solidification method. The formulation, water solubility and bioavailability, particle size, zeta potential and entrapment efficiency, and in vitro release experiments were optimized in order to improve the activity of PSO to reverse MDR. Optimal formulation: soybean phospholipids 50 mg, poly(lactic-co-glycolic) acid (PLGA) 15 mg, PSO 3 mg, and Tween-80 1%. The PSO-PLN possessed a round appearance, uniform size, exhibited no adhesion. The average particle size was 93.59 ± 2.87 nm, the dispersion co-efficient was 0.249 ± 0.06, the zeta potential was 25.47 ± 2.84 mV. In vitro analyses revealed that PSO resistance index was 3.2, and PSO-PLN resistance index was 5.6, indicating that PSO-PLN versus MCF-7/ADR reversal effect was significant. Moreover, PSO-PLN is somewhat targeted to the liver, and has an antitumor effect in the xenograft model of drug-resistant MCF-7/ADR cells. In conclusion, PSO-PLN not only reverses MDR but also improves therapeutic efficiency by enhancing sustained release of PSO.

An outdoor solar assisted large-scale cleaning system (SALSCS) was constructed to mitigate the levels of fine particulate matter (PM2.5) in urban areas of Xi'an China, providing a quasi-experimental opportunity to examine the biologic responses to the changes in pollution level. We conducted this outdoor SALSCS based real-world quasi-interventional study to examine the associations of the SALSCS intervention and changes in air pollution levels with the biomarkers of systemic inflammation and oxidative stress in healthy elders. We measured the levels of 8-hydrox-2-deoxyguanosine (8-OHdG), Interlukin-6 (IL-6), as well as tumor necrosis factor alpha (TNF-α) from urine samples, and IL-6 from saliva samples of 123 healthy retired participants from interventional/control residential areas in two sampling campaigns. We collected daily 24-h PM2.5 samples in two residential areas during the study periods using mini-volume samplers. Data on PM10, gaseous pollutants and weather factors were collected from the nearest national air quality monitoring stations. We used linear mixed-effect models to examine the percent change in each biomarker associated with the SALSCS intervention and air pollution levels, after adjusting for time trend, seasonality, weather factors and personal characteristics. Results showed that the SALSCS intervention was significantly associated with decreases in the geometric mean of biomarkers by 47.6% (95% confidence interval: 16.5–67.2%) for 8-OHdG, 66% (31.0–83.3%) for TNF-α, 41.7% (0.2–65.9%) and 43.4% (13.6–62.9%) for urinary and salivary IL-6, respectively. An inter-quartile range increase of ambient PM2.5 exposure averaged on the day of the collection of bio-samples and the day before (34.1 μg/m3) was associated, albeit non-significantly so, with 22.8%–37.9% increases in the geometric mean of these biomarkers. This study demonstrated that the SALSCS intervention and decreased ambient air pollution exposure results in lower burden of systemic inflammation and oxidative stress in older adults.

To investigate the capacity of biphasic cardiac CT (CCT) for qualitative and quantitative evaluation of different grades of left atrial appendage spontaneous echo contrast (LAASEC). The study included 267 inpatients with confirmed atrial fibrillation who underwent both CCT and transesophageal echocardiography (TEE). CT numbers for LAA, ascending aorta (AA), and left atrium (LA) were identified, and ROC curves for LAA, LAA/AA, and LAA/LA were plotted. With TEE as the standard, the sensitivity, specificity, PPV, NPV, and accuracy of CCT for LAASEC grade ≥ 1 were 60.3, 92.9, 92.4, 64.8, and 75.7%; and for grade ≥ 2 were 100.0, 84.4, 71.4, 100.0, and 88.8% respectively. The values of LAA, LAA/AA, and LAA/LA were significantly larger in LAASEC grade 0 versus 1 and in grade 1 versus 2, but were similar in grades 2 and 3 or in grades 3 and 4. The values of LAA/AA were larger in grade 2 versus 4. When the cutoff value for LAA/AA = 0.897, sensitivity, specificity, PPV, NPV, and accuracy of CCT for LAASEC grade ≥ 1 was 89.6, 83.2, 87.9, 85.5, and 86.9% and with a cutoff for LAA/AA of 0.524, the sensitivity, specificity, PPV, NPV, and accuracy for LAASEC grade ≥ 2 was 98.7, 92.7, 84.1, 99.4, and 94.4%. Although CCT showed limited diagnostic accuracy for grade 1 LAASEC, grade ≥ 2 LAASEC could be excluded when there was no LAA filling defect on first-phase CCT, and TEE can be avoided. CCT has an excellent accuracy in diagnosing LAASEC, and quantitative analysis (in particular LAA/AA) is superior.

The aim of this study was to explore whether schizophrenia occurrence is associated with polymorphisms in the 5′ regulatory region of GABRB3 (gamma-aminobutyric acid type A receptor beta 3, subunit gene). The study included 324 patients with schizophrenia and 327 unaffected participants; all individuals were northern Han Chinese. Genotype and haplotype frequency distributions were compared for the 2 groups by means of PCR amplification and direct sequencing of the promoter region of GABRB3. The genotype distribution among control participants was in accordance with the Hardy-Weinberg equilibrium. Five common single-nucleotide polymorphism (SNP) sites were detected in the 5′ promoter region of GABRB3: rs4243768, rs7171660, rs4363842, rs4906902, and rs8179184. Only rs8179184 and rs4906902 differed significantly in frequency between controls and cases (P

Schizophrenia is a serious neurodevelopmental disorder. Genetics is an important factor leading to schizophrenia, but its exact role is still unclear. Many studies have focused on neurotransmitters and regulators that participate in the processes mediated by these neurotransmitters. Alcohol dehydrogenase may not only catalyze the oxidation of retinol and ethanol but also be involved in a variety of neurotransmitter metabolic pathways. Therefore, our study investigated whether ADH7 gene variations in the Chinese Han population were associated with schizophrenia. Genomic DNA was extracted from a cohort of 275 schizophrenic patients (136 men and 139 women) and 313 healthy controls (160 men and 153 women) from the Northern Han Chinese population. The Hardy-Weinberg equilibrium test and linkage disequilibrium analysis were performed. Differences in genotypes, alleles, and haplotypes between the schizophrenic and control groups were determined using the chi-square test and correlation analysis. The distribution of the CC + TT genotype of rs284787 was statistically different between the case and control groups (p = 0.026, OR = 1.448); however, the difference disappeared after Bonferroni correction. Linkage analysis indicated that rs739147, rs284787, rs3805329, rs894369, rs3805331, and rs284786 were closely linked in one block. The haplotype analysis found no association between the composed haplotypes and the occurrence of schizophrenia. Our study showed that the ADH7 gene was not associated with the risk of schizophrenia. Additional studies with larger cohorts of different ethnicities are needed to validate our findings.

Following the discovery and emergence of the plasmid-mediated colistin resistance gene, mcr-1, the Chinese government formally banned colistin as an animal growth promoter on April 30, 2017. Herein, we report patterns in colistin resistance and mcr-1 abundance in Escherichia coli from animals and humans between 2015 and 2019, to evaluate the effects of the colistin withdrawal.We did an epidemiology comparative study to investigate: annual production and sales of colistin in agriculture across mainland China according to data from the China Veterinary Drug Association from 2015 to 2018; the prevalence of colistin-resistant E coli (CREC) in pigs and chickens in 23 Chinese provinces and municipalities as reported in the China Surveillance on Antimicrobial Resistance of Animal Origin database from Jan 1, 2015, to Dec 31, 2016, and Jan 1, 2017, to Dec 31, 2018; the presence of residual colistin and mcr-1 in faeces from 118 animal farms (60 pig, 29 chicken, and 29 cattle) across four provinces over July 1, 2017, to August 31, 2017, and July 1, 2018 to August 31, 2018; the prevalence of mcr-1-positive E coli (MCRPEC) carriage in healthy individuals attending routine hospital examinations across 24 provinces and municipalities from June 1 to July 30, 2019, comparing with equivalent 2016 data (June 1 to September 30) from our previous study in the same hospitals; and the patterns in CREC prevalence among hospital E coli infections across 26 provinces and municipalities from Jan 1, 2015, to Dec 31, 2016, and Jan 1, 2018, to Dec 31, 2019, reported on the China Antimicrobial Surveillance Network.After the ban on colistin as a growth promoter, marked reductions were observed in the production (27 170 tonnes in 2015 vs 2497 tonnes in 2018) and sale (US$71·5 million in 2015 vs US$8·0 million in 2018) of colistin sulfate premix. Across 118 farms in four provinces, mean colistin residue concentration was 191·1 μg/kg (SD 934·1) in 2017 versus 7·5 μg/kg (50·0) in 2018 (p0·0001), and the median relative abundance of mcr-1 per 16S RNA was 0·0009 [IQR 0·0001-0·0059] in 2017 versus 0·0002 [0·0000-0·0020] in 2018 (p=0·0001). Across 23 provinces and municipalities, CREC was identified in pig faeces in 1153 (34·0%) of 3396 samples in 2015-16 versus 142 (5·1%) of 2781 in 2017-18 (p0·0001); and in chickens in 474 (18·1%) of 2614 samples in 2015-16 versus 143 (5·0%) of 2887 in 2017-18 (p0·0001). In hospitals across 24 provincial capital cities and municipalities, human carriage of MCRPEC was identified in 644 (14·3%) of 4498 samples in 2016 versus 357 (6·3%) of 5657 in 2019 (p0·0001). Clinical CREC infections in 26 provinces and municipalities comprised 1059 (1·7%) of 62 737 E coli infections in 2015-16 versus 794 (1·3%) of 59 385 in 2018-19 (p0·0001).The colistin withdrawal policy and the decreasing use of colistin in agriculture have had a significant effect on reducing colistin resistance in both animals and humans in China. However, continuous colistin monitoring is essential, in particular to act as an early warning system for colistin stewardship in Chinese hospitals.National Key Research and Development Program of China, National Natural Science Foundation of China, and UK Medical Research Council.

Background We investigated the characteristics of antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (ANCA-GN) and immunoglobulin G4 (IgG4)-related kidney disease (IgG4-RKD) overlap syndrome. Methods This is a 2-center study with 19 patients. Results Fifteen patients were classified as microscopic polyangiitis (MPA). The initial serum creatinine levels were 320.9 ± 191.4 μmol/l and the BVAS was 19.7 ± 7.4 at diagnosis. Hematuria was absent or slight in 13 (68.4%) cases. Renal histology of these patients revealed concurrent ANCA-GN and IgG4-RKD. Regarding the histological classification of ANCA-GN, 9 (47.4%), 8 (42.1%), 1 (5.3%) and 1 (5.3%) patients were classified as focal, crescentic, mixed and sclerotic ANCA-GN, respectively. MPO-ANCA could be detected in 17/19 (89.5%) patients. IgG subclasses of MPO-ANCA were tested in 10 patients, and all were positive for IgG4-MPO-ANCA. In patients with combined ANCA-GN and IgG4-RKD, the percentage of positive IgG1-MPO-ANCA was significantly lower than the control group of 20 AAV patients without IgG4-RKD (P = 0.002), and the percentage of positive IgG4-MPO-ANCA was higher than the control group, but this difference was not statistically significant (P = 0.14). Conclusions ANCA-GN and IgG4-RKD overlap syndrome concerned mainly MPO-ANCA positive patients. The IgG subclass analysis of MPO-ANCA showed lower percentage of IgG1 subclass. The association between ANCA-GN and IgG4-RKD is possible and represents a special entity.

At present, the precise role of human menopausal gonadotropin (HMG) and recombinant luteinizing hormone (rLH) supplementation at an early time of follicular phase on in vitro fertilization (IVF)/intra cytoplasmatic sperm injection (ICSI) outcomes remains uncertain. Here infertile women of normal ovarian function undergoing their first cycle of IVF/ICSI were studied and were randomly allocated into 3 groups. Group 1, ovarian stimulation with 150IU recombinant follicle-stimulating hormone (FSH) alone. Group 2, patients received 75IU rFSH and 75IU HMG. Group 3 patients were given 150IU rFSH and 75IU rLH. There were no significant differences in the clinical characteristics, ovarian response, the biochemical, clinical and ongoing pregnancy rates among the 3 groups. No significant differences were found in biochemical, clinical and ongoing pregnancy rates between the patients whose LH levels were lower than 0.75 mIU/ml and those above this threshold in group 1. Furthermore, there were also no significant differences in biochemical, clinical and ongoing pregnancy rates among the 3 group patients whose LH level lower than 0.75 mIU/ml. The results showed that either the addition of HMG or rLH supplementation at an early time of follicular phase produce no significant benefit on IVF outcome in patients with normal ovarian function.

Although retinal and cerebral microvessels share similar embryological, anatomical and physiological characteristics, the correlation between retinopathy and leukoaraiosis (LA), a type of brain microvascular disease, is unclear. In the present study, the sample included 213 patients admitted to the department of neurology from January 2012 through October 2012. MRI and retinal photography were performed within 48hours of hospitalization, and patient demographics, comorbidities, preadmission medications and laboratory data were collected. MRI images were used to divide the patients into LA and non-LA groups. Using multivariate binary logistic regression, the effects of retinopathy on LA were investigated. Of the 213 patients enrolled, 168 were included in this study (LA, n=108; non-LA, n=60). Hypertension, coronary heart disease and carotid artery plaque were more common in the LA group, and these patients showed higher blood levels of C-reactive protein, homocysteine and triglycerides. The incidence of retinopathy was significantly increased in the LA group compared with the non-LA group, and there was a significant correlation between the severity of LA and incidence of retinopathy. Retinopathy is an independent risk factor for LA and can significantly increase the risk of LA when combined with age, coronary heart disease, C-reactive protein, carotid artery plaque or systolic pressure. Taken together, retinopathy is associated with LA in patients with anterior circulation infarcts. Retinopathy is an independent risk factor for LA and an increase the risk of LA, and thus facilitating the evaluation of LA.

Nowadays prevalence of restless legs syndrome (RLS) in chronic kidney disease (CKD) patients was reported in many studies, while the results varied. The aim of our study was to investigate the prevalence of RLS in this population, considering different data collecting measures and diagnostic criteria.MEDLINE, Embase, PsycINFO, and Scopus databases were searched for relevant studies. We limited the analyses to studies using clinical interview or questionnaire for diagnosis. Univariate meta-regression analysis was preformed to assess the effects of the disease-related covariates on prevalence estimates. Comprehensive Meta-Analysis 2.0 was used to perform the meta-analysis.Fifty-one studies were included in the analysis. Prevalence of RLS was varied by renal function and diagnostic methods. Overall prevalence in CKD populations was 24.2% (95%CI, 20.1-28.7). Pooled prevalence of RLS was higher in patients diagnosed by questionnaire than by clinical interview [26.2% (95%CI, 17.9-36.5) vs. 23.6% (95%CI, 19.6-28.1)]. When grouped by CKD setting, the prevalence was 28.4% (95%CI, 24.6-32.6) in dialysis patients, followed by early stages patients [9.9% (95%CI, 5.4-17.5)], and kidney transplant recipients [6.7% (95%CI, 5.6-7.8)].Our meta-analysis suggested that more than one-quarter of CKD sufferers, especially those who were on dialysis, were plagued by RLS. Higher sensitivity of diagnostic criteria in interview may be valuable for timely treatment.

The envelope domain III (EDIII) of the dengue virus (DENV) has been confirmed to be involved in receptor binding. It is the target of specific neutralizing antibodies, and is considered to be a promising subunit dengue vaccine candidate. However, several recent studies have shown that anti‑EDIII antibodies contribute little to the neutralizing or enhancing ability of human DENV‑infected serum. The present study involved an analysis of the neutralization and antibody‑dependent enhancement (ADE) activities of EDIII‑reactive antibodies in human convalescent sera from patients with primary DENV‑1 infection and rabbit antiserum immunized with recombinant DENV‑1 EDIII protein. The results indicated that serum neutralization was not associated with titres of EDIII‑binding antibodies in the human DENV‑1‑infected sera. The depletion of anti‑EDIII antibodies from these serum samples revealed that the anti‑EDIII antibodies of the patients contributed little to neutralization and ADE. However, the EDIII‑reactive antibodies from the rabbit antiserum exhibited protective abilities of neutralization at a high dilution (~1:50,000) and ADE at a low dilution (~1:5,000) for the homotypic DENV infection. Notably, the rabbit antiserum displayed ADE activity only at a dilution of 1:40 for the heterotypic virus infection, which suggests that EDIII‑reactive antibodies may be safe in secondary infection with heterotypic viruses. These results suggest that DENV EDIII is not the predominant antigen of the DENV infection process; however, purified or recombinant DENV EDIII may be used as a subunit vaccine to provoke an effective and safe antibody response.

Giosgenin is a naturally steroidal saponin exhibiting a variety of biological activities including antitumor ones. A series of novel diosgenyl quaternary ammonium derivatives were designed and synthesized to develop potential anti-tumor agents in our research. All novel derivatives were characterized by 1H NMR, 13C NMR and HR-MS, and evaluated for their in vitro anti-proliferative activities using MTT assay. The human cancer cell lines were A549 (Human lung cancer cell), H1975 (Human lung adenocarcinoma cell), A431 (Human skin squamous cell carcinoma), HCT-116 (Human colorectal adenocarcinoma cell), Aspc-1 (Human metastatic pancreatic cancer cell), Ramos (Human B lymphoma cell), HBE (Human bronchial epithelioid cell) and LO2 (Human normal hepatocyte).

A multi-residue method has been developed for the identification and quantification of 78 compounds from seven different classes of veterinary drugs in eggs. This method was based on dispersive solid phase extraction where mixed-mode cation exchange sorbent was used to combine the isolation of compounds and sample purification. The analysis was performed using ultra-high performance liquid chromatography-tandem mass spectrometry, and the chromatographic run time of one injection was 9.5 min. The mean recovery ranged from 70.5% to 119.2% and inter-day relative standard deviation was less than 17.0%. The limit of quantification ranged between 0.1 and 1 μg/kg, which was sufficient to support surveillance monitoring. Lastly, the method was successfully used to detect residues of veterinary drug in real samples. The dietary exposure risk was subsequently assessed using the results of the survey, indicating that the evaluated daily intake and percentage of acceptable daily intake were at toxicologically acceptable levels.

The non-receptor protein tyrosine phosphatase (PTP) SHP2, encoded by PTPN11, plays an essential role in RAS-mitogen-activated protein kinase (MAPK) signaling during normal development. It has been perplexing as to why both enzymatically activating and inactivating mutations in PTPN11 result in human developmental disorders with overlapping clinical manifestations. Here, we uncover a common liquid-liquid phase separation (LLPS) behavior shared by these disease-associated SHP2 mutants. SHP2 LLPS is mediated by the conserved well-folded PTP domain through multivalent electrostatic interactions and regulated by an intrinsic autoinhibitory mechanism through conformational changes. SHP2 allosteric inhibitors can attenuate LLPS of SHP2 mutants, which boosts SHP2 PTP activity. Moreover, disease-associated SHP2 mutants can recruit and activate wild-type (WT) SHP2 in LLPS to promote MAPK activation. These results not only suggest that LLPS serves as a gain-of-function mechanism involved in the pathogenesis of SHP2-associated human diseases but also provide evidence that PTP may be regulated by LLPS that can be therapeutically targeted.

ObjectiveSchizophrenia is a severe neurodevelopmental disorder with a complex genetic and environmental etiology. The gene encoding EF-hand domain-containing protein D2 ( EFHD2) may be a genetic risk locus for schizophrenia.MethodsWe genotyped four EFHD2 single-nucleotide polymorphisms (281 schizophrenia cases [SCZ], 321 controls) from northern Chinese Han individuals using Sanger sequencing and polymerase chain reaction-restriction fragment length polymorphism analysis. Differences existed in genotype, allele, and haplotype frequency distributions between SCZ and control groups.ResultsThe rs2473357 genotype and allele frequency distributions differed between SCZ and controls; however, this difference disappeared after Bonferroni correction. Differences in rs2473357 genotype and allele frequency distributions between SCZ and controls were more pronounced in men than in women. The G allele increased schizophrenia risk (odds ratio = 1.807, 95% confidence interval = 1.164–2.803). Among six haplotypes (G–, A–, G-insC, A-C, G-C, and G-T), the G– haplotype frequency distribution differed between SCZ and controls in women; the A-C and G-C haplotype frequency distributions differed between SCZ and controls in men.ConclusionsEFHD2 may be involved in schizophrenia. Sex differences in EFHD2 genotype and allele frequency distributions existed among schizophrenia patients. Further research is needed to determine the role of EFHD2 in schizophrenia.

Patients with chronic obstructive pulmonary disease (COPD) often experience deteriorating gaseous exchange which in turn may result in declines in blood oxygen saturation (SpO2). Increasing evidence has also shown that elevated levels of fine particulate matter (PM2.5) may contribute to COPD pathogenesis. However, the acute effects of PM2.5 on SpO2 among COPD patients remain unclear, especially for its time course. Therefore, we conducted this panel study with 3-day real-time monitoring for personal PM2.5 exposure and concurrent SpO2 of 39 participants (20 COPD patients, 19 healthy participants), aged 60 to 90 years, in Hong Kong to explore the acute effects of personal PM2.5 exposure on SpO2 (within minutes to hours). We applied a linear mixed effect model to examine the associations between personal PM2.5 and SpO2, while adjusting for temporal trend, personal characteristics, weather conditions, and co-exposure to gaseous pollutants (ambient ozone, nitrogen dioxides, carbon monoxide, and atmospheric pressure). We found that short-term exposure to PM2.5 might result in acute declines of SpO2 within minutes, and the effects would last for several hours. An interquartile range increase of personal PM2.5 exposure (17.2 μg/m3) was associated with −0.19% (95% CI: −0.26% to −0.12%) changes of concurrent SpO2 for all participants. The most significant decline was observed at lag0-3 h, and then became insignificant at lag0-12 h. At lag0-1 h, estimated mean changes of SpO2 were −0.40% (95% CI: −0.55% to −0.24%) for COPD patients and −0.09% (95% CI: −0.23% to 0.06%) for healthy participants. Compared with healthy participants, the effects of PM2.5 exposure on SpO2 for COPD patients were slightly stronger and more acute. Reducing PM2.5 concentrations might be a useful approach to improve health status and reduce exacerbations for COPD patients.

Background Schizophrenia is a severe neurodevelopmental disorder with a complex genetic and environmental etiology. Abnormal glutamate ionotropic N-methyl-D-aspartate receptor (NMDA) type subunit 1 (NR1) may be a potential cause of schizophrenia. Methods We conducted a case-control study to investigate the association between the GRIN1 gene, which encodes the NR1 subunit, and the risk of schizophrenia in a northern Chinese Han population using Sanger DNA sequencing. The dual luciferase reporter assay was used to detect the influence of two different haplotypes on GRIN1 gene expression. Results Seven SNPs (single nucleotide polymorphisms), including rs112421622 (− 2019 T/C), rs138961287 (− 1962--1961insT), rs117783907 (−1945G/T), rs181682830 (−1934G/A), rs7032504 (-1742C/T), rs144123109 (−1140G/A), and rs11146020 (−855G/C) were detected in the study population. Rs117783907 (−1945G/T) was associated with the occurrence of schizophrenia as a protective factor. The genotype frequencies of rs138961287 (− 1962--1961insT) and rs11146020 (−855G/C) were statistically different between cases and controls (p

Background Conflicting results have been reported from studies evaluating serum uric acid (SUA) levels as an independent risk factor for cardiovascular mortality in patients with chronic kidney disease (CKD). Methods We systematically searched MEDLINE, Web of Science, and bibliographies of retrieved articles to identify studies reporting on the association between SUA levels and cardiovascular mortality in patients with CKD. Random-effects models were used to calculate the pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI). Results We included 11 studies with an overall sample of 27,081 patients with CKD in this meta-analysis. By meta-analysis, restricted to 7 studies (n = 11,050), patients with the highest SUA were associated with an increased risk of cardiovascular mortality (HR 1.47, 95% CI 1.11–1.96) compared with patients with the lowest SUA. There was no indication of publication bias or significant heterogeneity (I2 = 40.4%; P = 0.109). Meta-analysis of 10 studies (n = 26,660) indicated that every 1 mg/dl increase in SUA levels increased a 12% risk in cardiovascular mortality (HR 1.12, 95% CI 1.02–1.24), with significant heterogeneity (I2 = 79.2%, P

To explore the image quality (IQ) and diagnostic value of 70 kVp turbo high-pitch coronary CT angiography (THP-CCTA) using automated tube voltage selection (ATVS) and 30 mL of low-concentration contrast agent. Patients who underwent 70 kVp THP-CCTA using ATVS with 30 mL of contrast agent (group A) were prospectively enrolled, and those who underwent conventional CCTA (100/120 kVp, prospective sequential mode with 65–75 mL of contrast agent) (group B) were retrospectively selected for study. IQ was assessed subjectively on a 5-point scale, and diagnostic value was assessed based on invasive coronary angiography as the gold standard. Heart rate (HR), HR fluctuation (HRF), body mass index (BMI), effective radiation dose (ED), and iodine uptake (IU) were recorded. A total of 796 patients (398/398 in groups A/B) were included. Between-group differences in age, gender, BMI, HR, HRF, and IQ values were not significant. The ED/IU values were 0.3 ± 0.1 mSv/9.0 ± 0.0 g and 5.8 ± 1.8 mSv/22.9 ± 1.0 g in groups A and B, respectively (p

Prostate cancer is one of the most frequent malignancies affecting men. Long non-coding RNAs (lncRNAs) are involved in the pathogenesis of prostate cancer. LncRNA LOXL1-AS1 participates in the pathogenesis of the exfoliation syndrome. However, the role of LOXL1-AS1 in cancer remains largely unknown. Here, we found that LOXL1-AS1 down-regulation inhibited prostate cancer cell proliferation and cell cycle progression. RNA sequencing analysis revealed that it regulates the expression of cell cycle-related genes. LOXL1-AS1 is predominantly distributed in the cytoplasm, where it interacts with miR-541-3p. In addition, miR-541-3p targets the cell cycle regulator CCND1 in prostate cancer cells. LOXL1-AS1 down-regulation inhibits the expression of CCND1 and cell cycle progression, whereas these effects are abolished upon miR-541-3p suppression. In summary, our study revealed that LOXL1-AS1 regulates prostate cancer cell proliferation and cell cycle progression through miR-541-3p and CCND1. Modulation of their levels may be used to treat prostate cancer.

Background Epidemiological studies found that genetic factors are among the causes of schizophrenia, exclusively the genes involved in the dopamine system. Prior to this, the role of dopamine receptor D2 (DRD2) gene promoter polymorphisms and schizophrenia has been studied extensively, but there are still some uncertainties about these associations. The present study is focusing on the association between the DRD2 gene promoter region polymorphisms and schizophrenia in the northern Chinese Han population. Methods We sequenced 2,111‐bp fragment of DRD2 gene promoter region in 306 schizophrenic patients and 324 healthy controls to find association between DRD2 and schizophrenia. SPSS version 18 0.0 was used to calculate odds ratios (OR), 95% confidence intervals (CIs).The Hardy–Weinberg equilibrium test and the confirmation of haplotypes were calculated using Haploview version 4.1. The association of schizophrenic risk of DRD2 genotypes, alleles, and haplotypes between case and control groups was calculated using the chi‐squared test. PS program was used to calculate the Power analysis. Results The genotype frequencies of rs7116768 (p = 0.025) and rs1799732 (p = 0.042) were associated meagerly. After Bonferroni correction, there was no association found between DRD2 gene promoter region with schizophrenia risk in the northern Chinese Han population. Conclusions In this study, we did not find any significant difference between schizophrenia and the polymorphisms of DRD2 gene promoter region. A more forceful conclusion remains to be verified by further confirmatory experiments.