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OBJECTIVE To explore the corridor for atlas pedicle screw placement perpendicular to the coronal plane and to develop patient-specific navigation templates for pedicle screw placement. METHODS This study is a retrospective analysis. A total of 71 patients (41 males and 30 females) were involved in this study from June 2016 to June 2018, and they were divided into a template group (39 patients) and a conventional group (32 patients). The CT-based 3D reconstruction models were analyzed in the template group. From the perspective of the 3D atlas in a coronal view, the pedicle corridor was obtained. Taking the center of the tangential circle of the pedicle as the entry point, we simulated screw placement perpendicular to the coronal plane. Then, the individual navigation template was designed and used in surgery. In the conventional group, free-hand pedicle screw placement was performed perpendicular to the coronal plane. The diameter of the maximum tangential circle and screw length of the pedicle corridor were measured in the template group. The surgical time, radiation exposure time, screw grading criteria and so on were evaluated and compared between the two groups after surgery. RESULTS ;The diameter of the maximum tangential circle and the distance between the entry point and posterior tubercle were significantly greater in males than in females. The operation was successfully completed in all patients, without aggravation of nerve injury, and the follow-up was 12-20 months, with an average of 15.6 months. A total of 78 screws were inserted in the template group, and 64 screws were inserted in the conventional group. The surgical times in the template group and conventional group were 76.47±24.44 min and 125.63±36.41 min, respectively. The radiation exposure times in the template group and conventional group were 3.51±1.77 and 10.15±4.95, respectively, and there was a significant difference between the two groups. In the template group, the deviation in the screw entry point and screw angle were 1.92±1.67 mm and 2.08±1.98°, respectively. The medial angle deviation between the left and right sides was 2.71±1.88° in the template group, which was significantly less than the deviation of 3.76±2.22° in the conventional group. CONCLUSION A pedicle screw trajectory perpendicular to the coronal plane can be quickly obtained based on the perspective of 3D models. The technique of screw placement perpendicular to the coronal plane assisted by navigation templates has a shorter operative time, lessintraoperative fluoroscopy and a higher safety of screw placement than traditional surgery.

Context Several small studies have suggested that the gut microbiome might influence osteoporosis, but there is little evidence from human metabolomics studies to explain this association. Objective This study examined the association of gut microbiome dysbiosis with osteoporosis and explored the potential pathways through which this association occurs using fecal and serum metabolomics. Methods We analyzed the composition of the gut microbiota by 16S rRNA profiling and bone mineral density using dual-energy X-ray absorptiometry in 1776 community-based adults. Targeted metabolomics in feces (15 categories) and serum (12 categories) were further analyzed in 971 participants using ultra-high-performance liquid chromatography coupled to tandem mass spectrometry. Results This study showed that osteoporosis was related to the beta diversity, taxonomy, and functional composition of the gut microbiota. The relative abundance of Actinobacillus, Blautia, Oscillospira, Bacteroides, and Phascolarctobacterium was positively associated with osteoporosis. However, Veillonellaceae other, Collinsella, and Ruminococcaceae other were inversely associated with the presence of osteoporosis. The association between microbiota biomarkers and osteoporosis was related to levels of peptidases and transcription machinery in microbial function. Fecal and serum metabolomics analyses suggested that tyrosine and tryptophan metabolism and valine, leucine, and isoleucine degradation were significantly linked to the identified microbiota biomarkers and to osteoporosis, respectively. Conclusion This large population-based study provided robust evidence connecting gut dysbiosis, fecal metabolomics, and serum metabolomics with osteoporosis. Our results suggest that gut dysbiosis and amino acid metabolism could be targets for intervention in osteoporosis.

Introduction Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swept rapidly throughout the world. So far, no therapeutics have yet proven to be effective. Ribavirin was recommended for the treatment of COVID-19 in China because of its in vitro activity. However, evidence supporting its clinical use with good efficacy is still lacking. Methods A total of 208 confirmed severe COVID-19 patients who were hospitalized in Wuhan Union West Campus between 1 February 2020 and 10 March 2020 were enrolled in the retrospective study. Patients were divided into two groups based on the use of ribavirin. The primary endpoint was the time to clinical improvement. The secondary endpoints included mortality, survival time, time to throat swab SARS-CoV-2 nucleic acid negative conversion, and the length of hospital stay. Results 68 patients were treated with ribavirin while 140 not. There were no significant between-group differences in demographic characteristics, baseline laboratory test results, treatment, and distribution of ordinal scale scores at enrollment, except for coexisting diseases especially cancer (ribavirin group vs no ribavirin group, P = 0.01). Treatment with ribavirin was not associated with a difference in the time to clinical improvement (P = 0.48, HR = 0.88, 95% CI = 0.63–1.25). There were also no significant differences between-group in SARS-CoV-2 nucleic acid negative conversion, mortality, survival time, and the length of hospital stay. Conclusions In hospitalized adult patients with severe COVID-19, no significant benefit was observed with ribavirin treatment.

BackgroundPrevious studies suggested that acupuncture was a promising adjunct treatment for asthma. However, the underlying mechanism of acupuncture for asthma remains unclear. The present trial aimed to explore whether and how specific meridian acupuncture works in quality of life and symptomatic improvement by modulating brain function in asthma patients.Methods: A randomized controlled functional brain imaging trial is currently being conducted in Sichuan, China. In total 48 patients with mild to moderate, persistent asthma will be recruited randomly allocated to two acupuncture groups: acupuncturing at Lung Meridian and acupuncturing at Heart Meridian. The treatment period will last for 4 weeks. The Asthma quality of life questionnaire (AQLQ) is the primary outcome. Asthma control test (ACT), the rate of Peak expiratory flow (PEFR), Forced expiratory volume in 1 second (FEV1), Montreal cognitive assessment (MoCA), Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) will also assess the clinical efficacy of different interventions. Functional magnetic resonance imaging (fMRI) scans will be performed to detect cerebral activity changes in each group. The clinical data and fMRI data will be analyzed, respectively. Pearson correlation analysis will be used to assess the association between the changes of cerebral activity features and the improvement of clinical outcomes in each group.Discussion: The present study has been established on the “meridians-viscera relationship” theory of traditional Chinese medicine and modern central mechanism of acupuncture. The results of this trial would be useful to identify the efficiency of the specific meridian acupuncture for asthma. The investigation of its central mechanism would further expand our knowledge of the acupuncture for asthma. Trial registration: Chinese Clinical Trial Registry, ChiCTR1900027478. Registered on 15 November 2019.

To explore the clinical efficacy of assisted reproductive technology (ART) combined with progesterone capsules in the treatment of infertility caused by the diminished ovarian reserve (DOR) and its influence on serum FSH, E2, and LH levels of patients.In the manner of retrospective study, the data of 120 patients with infertility caused by DOR admitted to our hospital (February 2019-February 2020) were retrospectively analyzed, and the patients were equally divided into the experimental group and the control group according to the order of admission. All patients underwent in vitro fertilization and embryo transfer (IVF-ET), and the experimental group was received progesterone capsules at the same time. Ovarian-related indexes, follicular development, serum hormone levels, and pregnancy outcomes were compared between both groups.After treatment, compared with the control group, ovarian-related indexes and follicular development in the experimental group were conspicuously better (ART combined with progesterone capsules can improve serum hormone levels, ovarian function, follicular development, and clinical pregnancy rate for patients with infertility caused by DOR, which should be applied in practice.

Background Primary dysmenorrhea (PDM) is highly associated with mood symptoms. However, the neuropathology of these comorbidities is unclear. In the present study, we aimed to investigate the structural changes in the amygdala of patients with PDM during the pain-free phase using a surface-based shape analysis. Methods Forty-three PDM patients and forty healthy controls were recruited in the study, and all participants underwent structural magnetic resonance imaging scans during their periovulatory phase. FMRIB’s Integrated Registration and Segmentation Tool (FIRST) was employed to assess the subcortical volumetric and surface alterations in patients with PDM. Moreover, correlation and mediation analyses were used to detect the clinical significance of the subcortical morphometry alteration. Results PDM patients showed hypertrophic alteration of the amygdala in the left superficial nuclei and right basolateral and superficial nuclei but not for the whole amygdala volume. The hypertrophic amygdala was associated with disease duration, pain severity and anxiety symptoms during the menstrual period. Furthermore, the hypertrophic left amygdala could mediate the association between disease duration and anxiety severity. Conclusions The results of the current study demonstrated that the localized amygdala shape hypertrophy was present in PDM patients even in the pain-free phase. In addition, the mediator role of the hypertrophic amygdala indicates the potential target of amygdala for anxiety treatment in PDM treatment in the pain-free phase.

The short-term effects of long-acting somatostatin analogues (SSAs) on lipid profiles in patients with acromegaly are not well studied. We retrospectively analyzed the effects of SSAs on lipid profiles and associated cardiovascular risk factors in a cohort of 120 newly diagnosed acromegaly patients. In this study, 69 females and 51 males were included. These patients were treated with either octreotide LAR (OCT) or lanreotide SR (LAN) for 3 months. After SSAs treatment, both GH and IGF-1 significantly decreased (p0.05). Fasting insulin, fasting C-peptide, and HOMA-IR were significantly decreased after SSAs treatment. In conclusion, our current study revealed that short-term SSAs treatment improves lipid profiles and other cardiovascular risk factors in patients with acromegaly.

Background. The tumor microenvironment (TME) plays a significant role in the progression and prognosis of acute myeloid leukemia (AML). This study is aimed at exploring TME-associated biomarkers and identify their potential mechanism in the microenvironment of AML. Method. In this study, the stromal, immune, and ESTIMATE scores of AML patients were evaluated with the ESTIMATE and CIBERSORT algorithms; then, the AML samples were divided into high- and low-score groups. We evaluated the association between clinicopathological characteristics, survival rate, and the stromal/immune/ESTIMATE scores. Furthermore, we identified TME-associated differentially expressed genes (DEGs) then carried out pathway enrichment analysis, protein-protein interaction (PPI) network, Cox regression analysis, and Kaplan-Meier survival analysis to select the most crucial genes. In addition, we further explored the potential mechanism of HCK in the AML microenvironment. Results. We identified 624 TME-associated DEGs and found that HCK was the most promising biomarker associated with AML. The results of the gene set enrichment analysis (GSEA) indicated that HCK was mainly involved in immune and inflammation-related signaling pathways. In addition, CIBERSORT analysis showed that HCK was closely related to tumor immune infiltration, with HCK expression associated with various infiltrating immune cells, including B cells, T cells, tumor-associated macrophages (TAM), NK cells, plasma cells, eosinophils, and neutrophils. Furthermore, HCK expression was closely related with ELN risk stratification in patients with AML. Conclusion. HCK could regulate immune cell infiltration in the microenvironment of AML and may act as a potential biomarker for the treatment and prognosis of AML patients.

The effect of vitamin D (VD) on the risk of preeclampsia (PE) is uncertain. Few of previous studies focused on the relationship between dietary VD intake and PE risk. Therefore, we conducted this 1:1 matched case–control study to explore the association of dietary VD intake and serum VD concentrations with PE risk in Chinese pregnant women. A total of 440 pairs of participants were recruited during March 2016 to June 2019. Dietary information was obtained using a seventy-eight-item semi-quantitative FFQ. Serum concentrations of 25(OH)D2 and 25(OH)D3 were measured by liquid chromatography–tandem MS. Multivariate conditional logistic regression was used to estimate OR and 95 % CI. Restricted cubic splines (RCS) were plotted to evaluate the dose–response relationship of dietary VD intake and serum VD concentrations with PE risk. Compared with the lowest quartile, the OR of the highest quartile were 0·45 (95 % CI 0·29, 0·71, Ptrend = 0·001) for VD dietary intake and 0·26 (95 % CI 0·11, 0·60, Ptrend = 0·003) for serum levels after adjusting for confounders. In addition, the RCS analysis suggested a reverse J-shaped relationship between dietary VD intake and PE risk (P-nonlinearity = 0·02). A similar association was also found between serum concentrations of total 25(OH)D and PE risk (P-nonlinearity = 0·02). In conclusion, this study provides evidence that higher dietary intake and serum levels of VD are associated with the lower risk of PE in Chinese pregnant women.

Objective Recent neuroimaging studies have found that brain function is abnormal in primary dysmenorrhea (PDM). The present study aimed to explore frequency-specific brain alterations and their occurrence in the PDM. Methods Forty-seven patients with PDM and 36 matched healthy controls were enrolled in the study and underwent resting-state functional magnetic resonance imaging. The alterations in brain function in patients with PDM were assessed with different frequency filter bands (Slow5, Slow4, Slow3, and full low frequency) and a functional connectivity density (FCD) approach. The clinical significance of the altered FCD was then explored. Additionally, mediation analysis was used to detect the altered FCD-mediated clinical relationships in PDM. Results Frequency-specific FCD alterations have been observed in patients with PDM, especially in the central executive, default mode, and sensorimotor networks and in the hippocampus. The altered full low-frequency FCD in the hippocampus was associated with the duration of disease and pain severity scores. The altered Slow5 FCD in the second somatosensory area (S2) was associated with the severity of pain in PDM. Furthermore, the FCD in S2 mediated the duration associated with pain symptoms in PDM. Conclusion The present study identified frequency-specific FCD alterations in PDM and suggested that the S2 area is a potential treatment target for PDM.

Background and objective: soy protein and soy isoflavones have been suggested to be associated with improved cardiovascular risk factors (e.g., lipid profiles and uric acid (UA)), but few studies have been conducted among women with impaired glucose regulation (IGR). This study is aimed to evaluate the effect of isolated daidzein and genistein on lipid profiles, high sensitive C-reactive protein (hs-CRP), and uric acid (UA) among Chinese women with IGR. Methods and results: this randomized, double-blind, and placebo-controlled trial was conducted in 165 Chinese women aged 30–70 years with IGR. Participants were randomly assigned to one of the three groups: 0 mg of daidzein and genistein with 10 g soy protein (placebo group), 50 mg of daidzein with 10 g soy protein (daidzein group), or 50 mg of genistein with 10 g soy protein (genistein group) supplementation for 24 weeks. Fasting serum total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), lipoprotein a (LP (a)), hs-CRP, and UA were assessed at baseline, 12, and 24 weeks after intervention. The results showed no significant differences in the changes (%) of TC, TG, HDL-C, LDL-C, LP (a), hs-CRP, and UA between the three treatment groups at weeks 12 or 24 (all P > 0.05). Conclusion: neither isolated daidzein nor genistein had a significant effect on cardiovascular health in Chinese women with IGR.

What is known and objective Tacrolimus (FK506), an effective and potent calcineurin inhibitor, is the cornerstone of immunosuppression after kidney transplantation. Wuzhi capsule (WZC), a prescribed ethanol extract of Nan-Wuweizi (Schisandra sphenanthera), is widely prescribed for kidney transplant recipients for the maintenance of tacrolimus concentration in clinical settings. Previous studies have demonstrated that WZC can increase the blood concentration of tacrolimus. However, it remains controversial whether to use WZC can be used to increase tacrolimus concentration in clinical practice. Our study aimed to evaluate the efficacy and safety of WZC combined with tacrolimus in the treatment of kidney transplant recipients. Methods One hundred and ninety four Chinese kidney transplant recipients were included in this retrospective study. The recipients were divided into two groups (non-WZC group and WZC group). We investigated the effects of WZC on tacrolimus in terms of tacrolimus metabolism, laboratory tests, pharmacogenomics, renal function and adverse reactions. Results and discussion The concentration/dose (C0 /D) of tacrolimus was significantly higher in the WZC group than the non-WZC group. The laboratory findings of blood routine tests, liver and kidney function were not significantly different between the two groups. The CYP3A5 genotype showed clearly associated with tacrolimus C0 /D, whereas no significant difference was observed in patients with CYP3A4*1B, CYP3A4*22, ABCB1, ABCC2, POR*28 or PXR alleles. The improvement of C0 /D by administration of WZC was significant in CYP3A5 expressers compared to non-expressers. Furthermore, the WZC group had a remarkably higher proportion of subjects who reached the target tacrolimus concentration than the non-WZC group. No significant differences in renal function and adverse reactions were observed between the groups. What is new and conclusion Wuzhi capsule can increase tacrolimus concentration without negative effects on renal function and adverse reactions, especially in CYP3A5 expressers. Efficient and economical synergistic effects can be achieved by the combined administration of WZC in kidney transplant recipients.

ObjectiveTo investigate the dynamic functional connectivity of thalamocortical networks in interictal migraine patients and whether clinical features are associated with abnormal connectivity.MethodsWe investigated dynamic functional network connectivity (dFNC) of the migraine brain in 89 interictal migraine patients and 70 healthy controls. We focused on the temporal properties of thalamocortical connectivity using sliding window cross-correlation, clustering state analysis, and graph-theory methods. Relationships between clinical symptoms and abnormal dFNC were evaluated using a multivariate linear regression model.ResultsFive dFNC brain states were identified to characterize and compare dynamic functional connectivity patterns. We demonstrated that migraineurs spent more time in a strongly interconnected between-network state, but they spent less time in a sparsely connected state. Interestingly, we found that abnormal posterior thalamus (pulvinar nucleus) dFNC with the visual cortex and the precuneus were significantly correlated with headache frequency of migraine. Further topologic measures revealed that migraineurs had significantly lower efficiency of information transfer in both global and local dFNC.ConclusionOur results demonstrated a transient pathologic state with atypical thalamocortical connectivity in migraineurs and extended current findings regarding abnormal thalamocortical networks and dysrhythmia in migraine.

Xist is an X-linked ribonucleic acid (RNA) gene responsible for the cis induction of X chromosome inactivation (XCI). In cloned mammalian embryos, Xist is ectopically activated at the morula to blastocyst stage on the X chromosome that is supposed to be active, thus resulting in abnormal XCI. Suppression of erroneous Xist expression by injecting small interfering RNA (siRNA) remarkably increased the developmental efficiency of cloned male mouse embryos by approximately 10-fold. However, injection of anti-Xist siRNA resulted in only a slight increase in the developmental ability of injected cloned male pig embryos because the blocking effect of the injected siRNA was not maintained beyond the morula stage, which is 5 days post-activation. To develop a more effective approach for suppressing the ectopic expression of Xist in cloned pig embryos, we compared the silencing effect of short hairpin RNA (shRNA) and siRNA on Xist expression and the effects of these two Xist knockdown methods on the developmental competence of cloned male pig embryos. Results indicated that an shRNA-based RNA interference (RNAi) has a longer blocking effect on Xist expression than an siRNA-mediated RNAi. Injection of anti-Xist shRNA plasmid into two-cell-stage cloned male pig embryos effectively suppressed Xist expression, rescued XCI at the blastocyst stage, and improved the in vitro developmental ability of injected cloned embryos. These positive effects, however, were not observed in cloned male pig embryos injected with anti-Xist siRNA. This study demonstrates that vector-based rather than siRNA-mediated RNAi of Xist expression can be employed to improve pig cloning efficiency.

Introduction: Several studies have identified a number of genes associated with Parkinson’s disease (PD). Genomic rearrangements (exon dosage variations) in these genes have emerged as significant, causing mutations. However, exon dosage variations in several PD genes were rarely investigated in Chinese patients. Objective: This study was aimed at determining the prevalence of PD-causing genes’ exon rearrangements in Chinese sporadic early-onset PD (EOPD) patients. Methods: A total of 150 Chinese sporadic EOPD patients and 100 healthy controls were enrolled. Multiplex ligation-dependent probe amplification (MLPA) was used to detect exon dosage in PD genes, including SNCA, PARKIN, UCHL1, PINK1, DJ1, LRRK2, and ATP13A2. Positive results were verified by real-time quantitative polymerase chain reaction. And exon sequencing was employed to screen for subtle mutations. Novel exon dosage variations were screened in families and controls. Results: PARKIN exon rearrangements were detected in 10 (6.7%) patients, including a novel heterozygous duplication of PARKIN exons 1–4. Clinical investigation showed that the percentage of individuals with PARKIN exon rearrangements was higher in the younger patients. Notably, the MLPA screening detected a heterozygous deletion of UCHL1 exon 1 in a patient. MLPA analysis in the family detected the deletion in an asymptomatic sister, indicating incomplete penetrance. Conclusion: Exon copy number variations (CNVs) in the PARKIN gene are relatively common among Chinese sporadic EOPD patients, whereas exon CNVs in other known PD genes can also be detected. Our findings demonstrate that it is important to perform exon dosage analysis for several known PD genes to obtain a better mechanistic insight into PD pathogenesis.

Background Acupuncture or moxibustion has been proven to be effective for patients with primary dysmenorrhea (PDM). However, the respective advantages and potential central mechanism of acupuncture and moxibustion are worthy of investigating to promote their further application. Methods In this randomized controlled neuroimaging trial, 72 patients with PDM will be randomly assigned to three groups: acupuncture treatment group, moxibustion treatment group, and waiting list group. The acupuncture treatment group and moxibustion treatment group will receive acupuncture or moxibustion, respectively, for a total of 3 sessions over 3 consecutive menstrual cycles, and the waiting list group will not take acupuncture or moxibustion during these 3 menstrual cycles. The COX Menstrual Symptom Scale (CMSS), visual analog scale (VAS), and Pain Catastrophizing Scale (PCS) will be used to evaluate the clinical efficacy. The Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), and 36-Item Short Form Health Survey (SF-36) will be used to assess the mental state and quality of life at baseline and at the end of treatment. Functional magnetic resonance imaging (fMRI) will be performed for detecting the cerebral activity changes at baseline and at the end of the treatment. The clinical data and imaging data will be analyzed among the groups. Correlation analysis will be conducted to investigate the relationship between brain functional changes and symptom improvement. Discussion The application of the randomized controlled neuroimaging trial will provide objective and valid evidence about how acupuncture and moxibustion treatment relieve menstrual pain. The results of this study would be useful to confirm the potential similarities and differences between acupuncture and moxibustion in clinical efficacy and central mechanism for patients with PDM. Trial registration Chinese Clinical Trial Registry ChiCTR2100043732. Registered on 27 February 2021

To examine the association between blood urea nitrogen (BUN) and risk of type 2 diabetes (T2DM) among Chinese adults, we performed an ongoing cohort study of 38578 Chinese adults (56.3% males; average age, 41.6 y) who underwent repeated health check-up examinations between 2009 and 2016 and without T2DM at baseline. During follow-up, incident T2DM cases were identified based on self-report, medication use, measurements of fasting plasma glucose, 2 h post oral glucose, or haemoglobinA1c. 2009 (5.2%) cases confirmed with incident T2DM were identified during median follow-up of 3.1 years. With increasing quartiles of BUN levels, the incidences of T2DM gradually increased with 0.69%, 1.11%, 1.53%, and 1.87% for quartile 1 to quartile 4 (p trend

Our aim is to conduct a meta-analysis comparing clinical outcomes between the mild ovarian stimulation cycle versus an artificial cycle (AC) for frozen embryo transfer (FET) in patients with polycystic ovary syndrome (PCOS). We systematically searched the databases of PubMed, EMBASE and the Cochrane Library from inception to January 2020. The outcomes were live birth rate (LBR), ongoing pregnancy rate (OPR), clinical pregnancy rate (CPR), embryo implantation rate (IR) and miscarriage rate (MR). The mild ovarian stimulation cycle and AC were compared according to risk ratios and 95% confidence intervals using a fixed or random effects model. Four retrospective studies describing the clinical outcomes were included. We found no significant difference in LBR, OPR, CPR, IR or MR between the mild ovarian stimulation cycle and AC protocols, whereas a lower MR was found for the letrozole-stimulated cycle than the AC. The letrozole-stimulated cycle for endometrial preparation in PCOS patients undergoing FET may lower the MR more than the AC. PCOS patients using the mild ovarian stimulation cycle for endometrial preparation undergoing FET had similar LBR, OPR, CPR and IR compared with the AC. The letrozole-stimulated protocol may be a reasonable choice for endometrial preparation before FET for women with PCOS.

To explore how baseline resting-state cerebral function predicts clinical outcomes of acupuncture treatment for migraine.One hundred migraine patients and 46 healthy subjects were recruited. Patients were randomized into the acupuncture, sham acupuncture, and waiting list groups. Resting-state functional magnetic resonance imaging data were collected at baseline and after 1 month of longitudinal acupuncture treatments. Fractional amplitude of low-frequency fluctuations (fALFF) calculations were applied to explore the associations between baseline fALFF and changes in clinical variables in the acupuncture treatment group and the waiting list group.Compared with healthy subjects, migraine patients had lower fALFF in the left rostral ventromedial medulla, right thalamus, left amygdala, and right angular gyrus. Regression analyses revealed that baseline fALFF values in the left middle frontal gyrus, left superior temporal gyrus, and middle temporal gyrus were positively associated with headache intensity changes in the acupuncture treatment group, while baseline fALFF values in the bilateral lingual gyrus and cuneus were negatively associated with headache intensity changes in this group.The baseline fALFF values of brain regions associated with cognitive pain modulation, but not migraine severity, may predict future headache intensity improvement levels in migraine patients receiving acupuncture treatment.

Background Poor personal hygiene increases disease risk, however, the prevalence of hygiene practices among adolescents is poorly described in low- and middle-income countries (LMICs). We aimed to assess the hygiene practices among young adolescents in LMICs using data from the Global School-based Student Health Surveys (GSHS). Methods This population-based study analysed the GSHS data for adolescents aged 12-15 years from 75 LMICs. Data were collected between 2003 and 2015 using standardised, anonymous, self-reported questionnaires. This report focuses on hygiene related behaviours such as tooth brushing, washing hands after using the toilet, washing hands before eating and washing hands with soap. The weighted prevalence and 95% confidential intervals (CIs) for the hygiene practices, and overall and regional estimates were calculated with random-effects meta-analysis. Results A total of 181 848 young adolescents from 75 LIMCs with available hygiene data were analysed. The overall prevalence for never washing hands were 7.4% (95% confidence interval (CI) = 4.4-10.3) for before eating, 5.9% (95% CI = 3.8-7.9) for after using the toilet, and 9.0% (95% CI = 6.2-11.8) for with soap. For tooth brushing, the overall prevalence estimates were 8.6% (95% CI = 5.5-11.7) for never brushing teeth, 80.9% (95% CI = 74.7-87.1) for 1-3 times per day, and 9.7% (95% CI = 5.8-13.6) for >3 times per day. However, the prevalence of different hygiene practices varied significantly among countries and regions (all P values 20%, was still observed in several LMICs (eg, 12 countries for never washing hands and 4 for never brushing teeth). Conclusions The hygiene practices of young adolescents aged 12-15 years were generally frequent, but poor status was still observed in several LMICs. These findings emphases the need for hygiene and health education targeting young adolescents in LMICs.

Heat stress is directly correlated to mammary gland dysfunction in dairy cows, especially in summer. Abnormally high environmental temperature induces oxidative stress and apoptosis in bovine mammary epithelial cells (BMECs). Nicotinamide mononucleotide (NMN) has beneficial effects in maintaining the cellular physiological functions. In this study, we evaluate the protective effect of NMN on heat stress-induced apoptosis of BMECs and explore the potential underlying mechanisms. Our results showed that heat stress considerably decreased cell viability in BMECs, whereas pretreatment of BMECs with NMN (150 μM) for 24 h significantly alleviated the negative effects of heat stress on cells. NMN protected BMECs from heat stress-induced oxidative stress by inhibiting the excessive accumulation of reactive oxygen species (ROS) and increasing the activity of antioxidant enzymes. It also inhibited apoptosis by reducing the ratio of Bax/Bcl2 and blocking proteolytic the cleavage of Caspase-3 in heat stressed-BMECs. Importantly, NMN treatment could reduce mitochondrial damage through mediating the expression of mitochondrial fission and fusion-related genes, including Dynamin related protein 1 (Drp1), Mitochondrial fission 1 protein (Fis1), and Mitofusin1, 2 (MFN1, 2); and suppress endoplasmic reticulum stress through unfolded protein response regulator Glucose regulated protein 78 (GRP78), and downstream elements Recombinant activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP). Above all, our results demonstrate that NMN supplemention attenuates heat stress-induced oxidative stress and apoptosis in BMECs by maintaining mitochondrial fission and fusion, and regulating endoplasmic reticulum stress, which provides the convincing evidence that NMN has valuable potential in alleviating mammary gland injury of dairy cows caused by environmental heat stress.

This study aimed to determine the levels of health-related behaviours (physical activity, screen exposure and sleep status) among Chinese students from primary, secondary and high schools during the pandemic of COVID-19, as well as their changes compared with their status before the pandemic. A cross-sectional online survey of 10,933 students was conducted among 10 schools in Guangzhou, China, between 8th and 15th March, 2020. After getting the informed consent from student’s caregivers, an online questionnaire was designed and used to obtain time spending on health-related behaviours during the pandemic of COVID-19, as well as the changes compared with 3 months before the pandemic, which was completed by students themselves or their caregivers. Students were stratified by regions (urban, suburban, exurban), gender (boys and girls), and grades (lower grades of primary school, higher grades of primary schools, secondary schools and high schools). Data were expressed as number and percentages and Chi-square test was used to analyse difference between groups. Overall, the response rate of questionnaire was 95.3% (10,416/10,933). The median age of included students was 13.0 (10.0, 16.0) years and 50.1% (n = 5,219) were boys. 41.4%, 53.6% and 53.7% of total students reported less than 15 min per day in light, moderate and vigorous activities and 58.7% (n = 6,113) reported decreased participation in physical activity compared with the time before pandemic. Over 5 h of screen time spending on online study was reported by 44.6% (n = 4,649) of respondents, particular among high school students (81.0%). 76.9% of students reported increased screen time compared with the time before pandemic. Inadequate sleep was identified among 38.5% of students and the proportion was highest in high school students (56.9%). Our study indicated that, during the COVID-19 pandemic, the school closure exerted tremendous negative effects on school-aged children’s health habits, including less physical activity, longer screen exposure and irregular sleeping pattern.

Purpose Researches revealed that probiotics maybe a potential strategy for COVID-19, whereas there is a lack of related evidence. This study aims to analyze the role of probiotics on severe COVID-19 patients. Methods In the current retrospective single-center study, we collected data of 311 consecutive severe patients with confirmed COVID-19 in Wuhan Union Hospital from Feb 3rd to Feb 20th, 2020. Epidemiological, clinical and medication characteristics were compared and analyzed between patients with or without probiotics. Results In total, 93 of the 123 patients (75.61%) who were treated with probiotics survived to hospital discharge with the median inpatient day of 32 days and mean virus clearance time of 23 days, which were significantly longer than those of patients without probiotics. There were no bias in laboratory parameters, except for IL-6 and ESR, which were significantly higher in patients treated probiotics. We tracked the dynamic changes of 8 selected laboratory parameters (IL-6, CRP, total T lymphocytes, NK cells, B lymphocyte, CD4 + T cells, CD8 + T cells and CD4/CD8 ratio) and found that probiotics could not reduce the increased IL-6 levels but possessed the ability to moderate the immunity and decreased the incidence of secondary infection in COVID-19 patients. Conclusions Probiotics could be an effective strategy for the treatment of COVID-19 patients to reduce the secondary infection and moderated the immunity.

Saturated fatty acids with different chain lengths have different biological activities, but little is known about very-long-chain saturated fatty acids (VLCSFAs). This study investigated the associations between the circulating VLCSFAs and cardiovascular health. This community-based cohort study included 2198 adults without carotid artery plaques (CAPs) at baseline. The percentage of baseline erythrocyte VLCSFA (arachidic acid (C20:0), behenic acid (C22:0), and lignoceric acid (C24:0)) was measured by gas chromatography. The presence of CAPs was determined at baseline and every 3 years thereafter by ultrasound examination. A meta-analysis was conducted to summarize the pooled associations between circulating VLCSFAs and the risk of cardiovascular diseases (CVDs). During a median of 7.2 years of follow-up, 573 women (35.1%) and 281 men (49.6%) were identified as CAP incident cases. VLCSFAs were inversely related with CAP risk in women (all p-trend &lt, 0.05) but not in men. Multivariate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of CAPs for the highest (vs. lowest) quartile were 0.80 (0.63&ndash, 1.01) for C20:0, 0.71 (0.56&ndash, 0.89) for C22:0, 0.75 (0.59&ndash, 0.94) for C24:0, and 0.69 (0.55&ndash, 0.87) for total VLCSFAs in women. The pooled HRs (95% CIs) of CVDs for the highest (vs. lowest) circulating VLCSFAs from seven studies including 8592 participants and 3172 CVD events were 0.67 (0.57&ndash, 0.79) for C20:0, 0.66 (0.48&ndash, 0.90) for C22:0, and 0.57 (0.42&ndash, 0.79) for C24:0, respectively. Our findings suggested that circulating VLCSFAs were inversely associated with cardiovascular health.

OBJECTIVE To examine the association of erythrocyte n-6 polyunsaturated fatty acid (PUFA) biomarkers with incident type 2 diabetes and explore the potential role of gut microbiota in the association. RESEARCH DESIGN AND METHODS We evaluated 2,731 participants without type 2 diabetes recruited between 2008 and 2013 in the Guangzhou Nutrition and Health Study (Guangzhou, China). Case subjects with type 2 diabetes were identified with clinical and biochemical information collected at follow-up visits. Using stool samples collected during the follow-up in the subset (n = 1,591), 16S rRNA profiling was conducted. Using multivariable-adjusted Poisson or linear regression, we examined associations of erythrocyte n-6 PUFA biomarkers with incident type 2 diabetes and diversity and composition of gut microbiota. RESULTS Over 6.2 years of follow-up, 276 case subjects with type 2 diabetes were identified (risk 0.10). Higher levels of erythrocyte γ-linolenic acid (GLA), but not linoleic or arachidonic acid, were associated with higher type 2 diabetes incidence. Comparing the top to the bottom quartile groups of GLA levels, relative risk was 1.72 (95% CI 1.21, 2.44) adjusted for potential confounders. Baseline GLA was inversely associated with gut microbial richness and diversity (α-diversity, both P < 0.05) during follow-up and significantly associated with microbiota β-diversity (P = 0.002). α-Diversity acted as a potential mediator in the association between GLA and type 2 diabetes (P < 0.05). Seven genera (Butyrivibrio, Blautia, Oscillospira, Odoribacter, S24-7 other, Rikenellaceae other, and Clostridiales other) were enriched in quartile 1 of GLA and in participants without type 2 diabetes. CONCLUSIONS Relative concentrations of erythrocyte GLA were positively associated with incident type 2 diabetes in a Chinese population and also with gut microbial profiles. These results highlight that gut microbiota may play an important role linking n-6 PUFA metabolism and type 2 diabetes etiology.

On March 11, 2020, the World Health Organization declared its assessment of coronavirus disease 2019 (COVID-19) as a global pandemic. However, specific anti-severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) drugs are still under development, and patients are managed by multiple complementary treatments. We performed a retrospective analysis to compare and evaluate the effect of low molecular weight heparin (LMWH) treatment on disease progression. For this purpose, the clinical records and laboratory indicators were extracted from electronic medical records of 42 patients with COVID-19 (21 of whom were treated with LMWH, and 21 without LMWH) hospitalized (Union Hospital of Huazhong University of Science and Technology) from February 1 to March 15, 2020. Changes in the percentage of lymphocytes before and after LMWH treatment were significantly different from those in the control group (P = 0.011). Likewise, changes in the levels of D-dimer and fibrinogen degradation products in the LMWH group before and after treatment were significantly different from those in the control group (P = 0.035). Remarkably, IL-6 levels were significantly reduced after LMWH treatment (P = 0.006), indicating that, besides other beneficial properties, LMWH may exert an anti-inflammatory effect and attenuate in part the "cytokine storm" induced by the virus. Our results support the use of LMWH as a potential therapeutic drug for the treatment of COVID-19, paving the way for a subsequent well-controlled clinical study. De tre första författarna delar förstaförfattarskapet.

Tryptanthrin is an indole quinazoline alkaloid from the indigo-bearing plants, such as Isatis indigotica Fort. Typically, this natural compound shows a variety of pharmacological activities such as antitumor, antibacterial, anti-inflammatory and antioxidant effects. This study was conducted to assess the antitumor activity of tryptanthrin in breast cancer models both in vitro and in vivo, and to explore the important role of the inflammatory tumor microenvironment (TME) in the antitumor effects of tryptanthrin. Human breast adenocarcinoma MCF-7 cells were used to assess the antitumor effect of tryptanthrin in vitro. MTT assay and colony formation assay were carried out to monitor the antiproliferative effect of tryptanthrin (1.56~50.0 μmol L−1) on inhibiting the proliferation and colony formation of MCF-7 cells, respectively. The migration and invasion of MCF-7 cells were evaluated by wound healing assay and Transwell chamber assay, respectively. Moreover, the 4T1 murine breast cancer model was established to examine the pharmacological activity of tryptanthrin, and three groups with different doses of tryptanthrin (25, 50 and 100 mg kg−1) were set in study. Additionally, tumor volumes and organ coefficients were measured and calculated. After two weeks of tryptanthrin treatment, samples from serum, tumor tissue and different organs from tumor-bearing mice were collected, and the enzyme-linked immunosorbent assay (ELISA) was performed to assess the regulation of inflammatory molecules in mouse serum. Additionally, pathological examinations of tumor tissues and organs from mice were evaluated through hematoxylin and eosin (H&E) staining. The expression of inflammatory proteins in tumor tissues was measured by immunohistochemistry (IHC) and Western blotting. Tryptanthrin inhibited the proliferation, migration and invasion of MCF-7 cells, up-regulated the protein level of E-cadherin, and down-regulated those of MMP-2 and Snail, as suggested by the MCF-7 cell experiment. According to the results from in vivo experiment, tryptanthrin was effective in inhibiting tumor growth, and it showed favorable safety without inducing the fluctuations of body mass and organ coefficient (p > 0.05). In addition, tryptanthrin also suppressed the expression levels of NOS1, COX-2 and NF-κB in mouse tumor tissues, and regulated those of IL-2, IL-10 and TNF-α in the serum of tumor cells-transplanted mice. Tryptanthrin exerted its anti-breast cancer activities through modulating the inflammatory TME both in vitro and in vivo.

Aims: Cervical cancer is the second most common cause of cancer-related deaths in developing nations. Human papillomavirus prophylactic vaccines are not widely available, and there are shortages of...

Findings for the roles of dairy products, Ca and vitamin D on ovarian cancer risk remain controversial. We aimed to assess these associations by using an updated meta-analysis. Five electronic databases (e.g. PubMed and Embase) were searched from inception to 24 December 2019. Pooled relative risks (RR) with 95 % CI were calculated. A total of twenty-nine case–control or cohort studies were included. For comparisons of the highest v. lowest intakes, higher whole milk intake was associated with increased ovarian cancer risk (RR 1·35; 95 % CI 1·15, 1·59), whereas decreased risks were observed for higher intakes of low-fat milk (RR 0·84; 95 % CI 0·73, 0·96), dietary Ca (RR 0·71; 95 % CI 0·60, 0·84) and dietary vitamin D (RR 0·80; 95 % CI 0·67, 0·95). Additionally, for every 100 g/d increment, increased ovarian cancer risks were found for total dairy products (RR 1·03; 95 % CI 1·01, 1·04) and for whole milk (RR 1·07; 95 % CI 1·03, 1·11); however, decreased risks were found for 100 g/d increased intakes of low-fat milk (RR 0·95; 95 % CI 0·91, 0·99), cheese (RR 0·87; 95 % CI 0·76, 0·98), dietary Ca (RR 0·96; 95 % CI 0·95, 0·98), total Ca (RR 0·98; 95 % CI 0·97, 0·99), dietary vitamin D (RR 0·92; 95 % CI 0·87, 0·97) and increased levels of circulating vitamin D (RR 0·84; 95 % CI 0·72, 0·97). These results show that whole milk intake might contribute to a higher ovarian cancer risk, whereas low-fat milk, dietary Ca and dietary vitamin D might reduce the risk.

To compare the clinical outcomes of intrauterine insemination (IUI) with or without ovulation induction (OI), IUI cycles from January 2008 to December 2017 in Zhoushan Maternity and Child Healthcare Hospital were included, consisting of 455 natural cycles and 536 OI cycles. The overall clinical pregnancy rate did not differ between the two groups (P0.05). Stratified by OI medications such as clomiphene (CC), human menopausal gonadotropin (HMG) and follicle stimulating hormone (FSH), the pregnancy rates in HMG, CC, CC+HMG, and FSH/FSH+HMG groups were 11.70%, 13.58%, 15.95%, and 13.46%, respectively, but the difference was not significant compared with natural cycles (P0.05). Stratified by infertility etiology, the pregnancy rate was significantly higher in stimulated cycles than natural cycles with ovulation disorders (P0.01) and unexplained factors (P0.01) while it was significantly lower regarding cervical factors (P0.01), endometriosis (P0.05), male factor (P0.01) and other female factors. There was no strong difference of pregnancy rate for biparental causes (P0.05). Stratified by age category, women over 35 had higher pregnancy rate in stimulated cycles compared with natural cycles (18.75 vs. 12.24%; P0.05), while women under 35 had no significant difference of pregnancy rate between the two groups (13.65 vs 13.05%; P0.05). However, there was no significant difference between each ovarian stimulation group and natural cycle group regardless of the infertility causes or age categories. To conclude, IUI-OI could achieve a higher overall pregnancy rate for women over 35 and infertile patients with ovulation disorders and unexplained factors.

Optoacoustic tomography (photoacoustic tomography) is an emerging imaging technology displaying great potential for medical diagnosis and preclinical research. Rationally designing activatable optoacoustic probes capable of diagnosing diseases and locating their foci can bring into full play the role of optoacoustic tomography (OAT) as a promising noninvasive imaging modality. Here we report two xanthene-based optoacoustic probes (C1X-OR1 and C2X-OR2) for temporospatial imaging of hepatic alkaline phosphatase (or β-galactosidase) for evaluating and locating drug-induced liver injury (or metastatic tumor). The probes rapidly respond to the disease-specific biomarkers by displaying red-shifted NIR absorption bands and generate prominent optoacoustic signals. Using multispectral optoacoustic tomography (MSOT), we can precisely localize the focus of drug-induced liver injury in mice using C1X-OR1, and the metastatic tumors using C2X-OR2. This work suggests that the activatable optoacoustic chromophores may potentially be applied for diagnosing and localizing disease foci, especially smaller and deeper ones., Optoacoustic tomography has great potential for medical diagnosis and preclinical research. Here they develop near infrared activatable xanthene-based optoacoustic probes for diagnosing and localizing drug-induced liver injury and metastasis in mouse models.

Background Ectopic pregnancy (EP) is the main cause of maternal death during early pregnancy. Blastocyst transfer (BT) reduces EP rates compared with cleavage stage embryo transfer (ET), and frozen ET reduces EP rates compared with fresh ET. However, data comparing the EP rate of fresh BT and frozen BT are limited. The objective of this meta-analysis was to determine whether frozen BT decreases the EP rate compared with fresh BT. Materials and methods PUBMED, EMBASE, and Cochrane Library databases were searched for papers with no limitation on language and publication year. A systemic literature search identified 14 studies which met the inclusion criteria for further analysis. EP rate is our only outcome measure. All statistical analyses were carried out using RevMan software [version 5.3]. Random effects models were chosen to calculate the odds ratio (OR). Results Fourteen retrospective studies (n = 251,762 cycles) were finally analyzed, including 154,214 and 97,548 cycles undergoing fresh and frozen BT, respectively. Compared with fresh BT, the frozen BT was associated with an decrease in EP rate [OR = 1.79; 95% confidence interval (CI) = 1.37-2.34, heterogeneity was 71%], the EP rate was 1.74% (2683/154,214 pregnancies) for fresh BT and 0.97% (949/97,548 pregnancies) for frozen BT. The number of embryos transferred in subgroup analysis found that the incidence of EP in frozen BT is lower than fresh BT (OR = 1.62; 95% CI = 1.38-1.91), the EP rate was 1.2% (206/16,610 pregnancies) for one fresh BT and 0.8% (153/19,569 pregnancies) for one frozen BT, also the EP rate was 1.9% (78/4043 pregnancies) for two fresh BT and 1.1% (19/1790 pregnancies) for two frozen BT. Conclusions Our meta-analysis found that frozen BT was associated with an decrease in EP rate compared with fresh BT in IVF/ICSI patients. We also found that a single frozen BT is the better choice as a method to reduce the incidence of EP.

Background The mechanism of the long-lasting effect and the relationship between the long-lasting effect and the deqi sensation, which is the key of achieving the acupuncture effect, has not been well investigated. This trial focuses on investigating the possible central mechanism of the long-lasting effect influenced by the deqi sensation. Methods A randomized controlled functional brain imaging trial is currently being conducted in Sichuan, China. In total 105 functional dyspepsia (FD) patients will be allocated into three groups: an acupuncture with deqi group, an acupuncture without deqi group, and a wait-list group. This trial will include a 2-week baseline period, a 4-week treatment period, and a 4-week follow-up period. During the 4-week treatment, patients in two acupuncture groups will receive 20 sessions of acupuncture treatment with or without deqi. The Nepean Dyspepsia Index (NDI) and the short form Leeds Dyspepsia Questionnaire (SF-LDQ) will be used to evaluate the clinical efficacy of acupuncture treatment at baseline, the end of treatment, and the end of the follow-up. Functional magnetic resonance imaging (fMRI) scans will be performed to detect cerebral functional changes in 25 patients in each group at three time points mentioned above. The clinical data and fMRI data will be analyzed, respectively. Correlation analysis will be conducted to investigate the relationship between cerebral functional changes and symptom improvement. Discussion The results of this trial will allow us to compare the changes of acupuncture therapeutic effect at three time points (the baseline vs. the end of treatment vs. the end of follow-up), and investigate the potential central mechanism of the long-lasting effect influenced by acupuncture with deqi. This trial aims to re-identify the long-lasting effect of acupuncture and investigate its central mechanism, and to further explore the central influence of deqi sensation on the long-lasting effect. Trial registration Chinese Clinical Trial Registry, IDF: ChiCTR-IOR-15006523. Registered on 5 June 2015. Electronic supplementary material The online version of this article (10.1186/s13063-018-2742-0) contains supplementary material, which is available to authorized users.

Mechanism studies have suggested that carotenoids may benefit bone health due to their antioxidant properties, but epidemiological data on their effects on risk of hip fracture are sparse.To explore the relationships between dietary total and specific carotenoids and the risk of hip fracture in a middle-aged and elderly Chinese population.A case-control study of 1070 patients with hip fractures (diagnosed within 2 weeks) aged 55-80 years and 1070 age- (within 3 years) and gender-matched controls was conducted in Guangdong, China between 2009 and 2015. Information on dietary carotenoid intake was assessed using a 79-item food frequency questionnaire administered in face-to-face interviews, and general information was collected using structured questionnaires. The univariate and multivariate conditional logistic regression models were applied to analyze the associations.Higher intakes of both total and some specific carotenoids (including β-carotene, β-cryptoxanthin and lutein/zeaxanthin) were significantly associated with a lower risk of hip fracture (all p trends0.01). Compared with the lowest quartile of carotenoids, the multivariate-adjusted odds ratios and 95% confidential intervals of the highest quartile were 0.44 (0.29, 0.68) (total carotenoids), 0.50 (0.29, 0.69) (β-carotene), 0.55 (0.38, 0.80) (β-cryptoxanthin) and 0.40 (0.27, 0.59) (lutein/zeaxanthin), respectively. There were no statistically significant associations between α-carotene and lycopene intakes and hip fracture risk after adjustment for various confounding variables.These results suggest that the consumption of carotenoids may be protective against hip fracture in middle-aged and elderly Chinese adults.

Background Exposure to per- and polyfluoroalkyl substances (PFAS) during pregnancy has been suggested to be associated with adverse pregnancy and birth outcomes; however, the findings have been inconsistent. We aimed to conduct a systematic review and meta-analysis to provide an overview of these associations. Methods The online databases PubMed, EMBASE and Web of Science were searched comprehensively for eligible studies from inception to February 2021. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using random- or fixed-effects models, and dose-response meta-analyses were also conducted when possible. Findings A total of 29 studies (32,905 participants) were included. The pooled results demonstrated that perfluorooctane sulfonate (PFOS) exposure during pregnancy was linearly associated with increased preterm birth risk (pooled OR per 1-ng/ml increase: 1.01, 95% CIs: 1.00–1.02, P = 0.009) and perfluorononanoate (PFNA) and perfluorooctanoate (PFOA) exposure showed inverted U-shaped associations with preterm birth risk (P values for the nonlinear trend: 0.025 and 0.030). Positive associations were also observed for exposure to perfluorodecanoate (PFDA) and miscarriage (pooled OR per 1-ng/ml increase: 1.87, 95% CIs: 1.15–3.03) and PFOS and preeclampsia (pooled OR per 1-log increase: 1.27, 95% CIs: 1.06–1.51), whereas exposure to perfluoroundecanoate (PFUnDA) was inversely associated with preeclampsia risk (pooled OR per 1-log increase: 0.81, 95% CIs: 0.71–0.93). Based on individual evidence, detrimental effects were observed between PFDA exposure and small for gestational age and between PFOA and PFOS and intrauterine growth restriction. No significant associations were found between pregnancy PFAS exposure and other adverse pregnancy outcomes (i.e., gestational diabetes mellitus, pregnancy-induced hypertension, low birth weight, and large and small for gestational age). Interpretation Our findings indicated that PFOS, PFOA and PFNA exposure during pregnancy might be associated with increased preterm birth risk and that PFAS exposure might be associated with the risk of miscarriage and preeclampsia. Due to the limited evidence obtained for most associations, additional studies are required to confirm these findings.

To better understand the olfactory mechanisms in the oriental armyworm Mythimna separate, one of the most serious pests of cereals, an antennal transcriptome was constructed in this study. A total of 130 olfactory related transcripts were identified. These transcripts were predicted to encode 32 odorant-binding proteins (OBPs), 16 chemosensory proteins (CSPs), 71 olfactory receptors (ORs), 8 ionotropic receptors (IRs), 1 gustatory receptor (GR) and 2 sensory neuron membrane proteins (SNMPs). Q-PCR analysis of the temporal expression profiles of seven OBPs in different tissues indicated that, except for MsepOBP19 which was highly expressed in the wings of 0-day-old adult and MsepOBP20 which was low expressed in all tissues, other tested MsepOBPs were significantly more highly expressed in the antenna than in the head (antenna excluded), thorax, abdomen, legs and wings. The expression levels of MsepOBPs were diverse in different life stages (differed on eclosion days). MsepOBP5 exhibited female-biased expression in 0- and 5-day-old adult, while no gender bias in 1- and 3-day-old adult was detected and similar expression profiles were found for MsepOBP7, 20, 24 and 26. In addition, we found that although the expression of MsepOBP22 was female biased in 0- and 5-day-old adult, in the 3-day-old adult it was male-biased. Our findings established a foundation for future studies of the functions of olfactory proteins in M. separata.

Although femoral neck fractures in young patients are rare and their complications are well-documented, there is a paucity of data on patient-reported outcomes for this population. The purpose of this study was to describe the quality of life and the effect of clinical complications on the outcomes of young patients with femoral neck fractures in a Chinese cohort. In this prospective observational cohort study, patients aged 18 to 55 years admitted to one of three participating trauma hospitals in China for treatment of a femoral neck fracture were recruited. The primary outcome was the patient's health-related quality of life using the Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey at 1 year after injury. Associations between the primary outcome and potential predictors were explored with univariate and multivariate regression analysis. One hundred seven patients (mean age, 44 years) completed 1-year follow-up. Nearly all patients were treated with closed reduction and screw fixation. Nine cases of nonunion, 7 cases of malunion, and 11 cases of osteonecrosis were identified. The mean SF-36 Physical Component Score was 48.6 ± 8.5, and the mean Mental Component Score was 51.0 ± 7.4. Fracture displacement, quality of reduction, and nonunion were associated with a poor Physical Component Score outcome. Our results demonstrate that the quality of life for patients after closed reduction and screw fixation of femoral neck fractures is similar to that of the general population, particularly when complications of nonunion and malunion are avoided. Level I.

Migraine is a common neurological disease with a high prevalence and unsatisfactory treatment options. The specific pathophysiological mechanisms of migraine remain unclear, which restricts the development of effective treatments for this prevalent disorder. The aims of this study were to 1) compare the spontaneous brain activity differences between Migraine without Aura (MwoA) patients and healthy controls (HCs), using amplitude of low-frequency fluctuations (ALFF) calculation method, and 2) explore how an effective treatment (verum acupuncture) could modulate the ALFF of MwoA patients. One hundred MwoA patients and forty-six matched HCs were recruited. Patients were randomized to four weeks' verum acupuncture, sham acupuncture, and waiting list groups. Patients had resting state BOLD-fMRI scan before and after treatment, while HCs only had resting state BOLD-fMRI scan at baseline. Headache intensity, headache frequency, self-rating anxiety and self-rating depression were used for clinical efficacy evaluation. Compared with HCs, MwoA patients showed increased ALFF in posterior insula and putamen/caudate, and reduced ALFF in rostral ventromedial medulla (RVM)/trigeminocervical complex (TCC). After longitudinal verum acupuncture treatment, the decreased ALFF of the RVM/TCC was normalized in migraine patients. Verum acupuncture and sham acupuncture have different modulation effects on ALFF of RVM/TCC in migraine patients. Our results suggest that impairment of the homeostasis of the trigeminovascular nociceptive pathway is involved in the neural pathophysiology of migraines. Effective treatments, such as verum acupuncture, could help to restore this imbalance., Highlights • Impairment of the homeostasis of the brainstem activity is involved in the neural pathophysiology of migraines. • Effective treatments, such as verum acupuncture, could help to normalise the abnormal brainstem activity in migraines. • Verum and sham acupuncture have different modulation effects on the abnormal brainstem activity in migraines.

Previous studies have reported that high-dose supplementation of n-3 polyunsaturated fatty acids (PUFAs) may reduce the risk of metabolic diseases, but there is limited evidence of an effect on body fat. We examined the associations of erythrocyte n-3 PUFAs with body fat and fat distribution in a general population consuming a normal diet.This community-based cross-sectional study included 3075 Chinese (68% women, 40-75 years) recruited between 2008 and 2013. We collected general information and measured anthropometric indices; erythrocyte n-3 PUFAs (including α-C18:3, C20:5, C22:5 and C22:6) by gas-chromatography, and fat mass (FM) and %FM at the total body (TB), android (A) and gynoid (G) regions by dual-energy X-ray absorptiometry (DXA).Both minimally and maximally adjusted models showed dose-dependent inverse associations of total and individual levels of erythrocyte n-3 PUFAs (except C20:5 n-3[EPA]) with adiposity indices. In the full model, the mean differences between quartiles 4 and 1 of total n-3 PUFAs were -1.60% (BMI), -4.06% (TB FM), -5.38% (A FM), -2.05% (G FM), -2.05% (TB %FM), -3.39% (A %FM) and -2.50% (% A/G); the ORs (95% CI) of %FM-derived obesity (≥25% for men, ≥35% for women) for the highest (vs. lowest) quartile were 0.70 (0.57, 0.86) for total n-3 PUFAs and 0.71 (0.58, 0.87), 0.96(0.78, 1.18), 0.82(0.67, 1.00), 0.66 (0.54, 0.81) for α-C18:3/C20:5/C22:5/C22:6 n-3, respectively. The favourable associations were more pronounced for the DXA-derived FM indices, measurements at the android region and for C22:6 n-3. No significant associations between C20:5 n-3 and the adiposity indices were observed.Higher levels of circulating n-3 PUFAs were dose-dependently associated with better profiles of body fat and fat distribution, particularly in the abdominal regions in this population.

With the increasing incidence of premature ovarian failure (POF) seriously threaten the women's health. Whether cryptotanshinone decreased the granulosa cell apoptosis to improve the POF would be explored. POF mice were conducted with intraperitoneal injection of cyclophosphamide and then treated with cryptotanshinone. The body weight and ovarian weight were recorded. The estrus was detected by vaginal smears. The pathological changes of ovarian were observed with hematoxylin and eosin staining. ELISA assay analyzed the levels of LH, FSH, AMH, E2 and AzpAB in mice serum. The expression of Bcl-2, Bax, KI67 and PCNA in ovarian tissues was detected by Western blot analysis and KI67 expression was also determined by immunohistochemistry. The body weight and ovarian weight were decreased and the pathological results of ovarian were worsen in POF mice. The estrus was decreased in POF mice. The levels of LH, FSH and AzpAB were increased and the levels of AMH and E2 were decreased in POF mice serum. The expression of Bcl-2, KI67 and PCNA was decreased and Bax expression was increased in ovarian tissues of POF mice. Those changes affected by cyclophosphamide could be reversed by cryptotanshinone. Cryptotanshinone could decrease the granulosa cell apoptosis to restore ovarian function.

Background Patients suffering from acute kidney injury (AKI) were associated with impaired sodium and potassium homeostasis. We aimed to investigate how admission serum sodium and potassium independently and jointly modified adverse clinical outcomes among AKI patients. Methods Patient data were extracted from the Multiparameter Intelligent Monitoring in Intensive Care Database III. Participants were categorized into three groups according to admission serum sodium and potassium, and the cut-off values were determined using smooth curve fitting. The primary outcome was 90-day mortality in the intensive care unit (ICU). Cox proportional hazards models were used to evaluate the prognostic effects of admission serum sodium and potassium levels. Results We included 13,621 ICU patients with AKI (mean age: 65.3 years; males: 55.4%). The middle category of admission serum sodium and potassium levels were 136.0–144.9 mmol/L and 3.7–4.7 mmol/L through fitting smooth curve. In multivariable Cox models, compared with the middle category, patients with hyponatremia or hypernatremia were associated with excess mortality and the HRs and its 95%CIs were 1.38 (1.27, 1.50) and 1.56 (1.36, 1.79), and patients with either hypokalemia or hyperkalemia were associated with excess mortality and the hazard ratios (HRs) and its 95% confidential intervals (95% CIs) were 1.12 (1.02, 1.24) and 1.25 (1.14, 1.36), respectively. Significant interactions were observed between admission serum sodium and potassium levels (P interaction = 0.001), with a higher serum potassium level associated with increased risk of 90-day mortality among patients with hyponatremia, whereas the effects of higher sodium level on prognostic effects of potassium were subtle. Conclusions Admission serum sodium and potassium were associated with survival in a U-shaped pattern among patients with AKI, and hyperkalemia predict a worse clinical outcome among patients with hyponatremia. Electronic supplementary material The online version of this article (10.1186/s12882-019-1505-9) contains supplementary material, which is available to authorized users.

Nerve growth factor (NGF) can promote the development, differentiation and regeneration of neurons. Recently, in order to efficiently produce human NGF (hNGF) drugs with better efficacy, we created transgenic mice expressing hNGF specifically in their salivary glands, and purified highly active hNGF protein from their saliva. Some studies reported that the NGF secretion in mouse saliva is affected by gender and age. Here, in order to select hNGF transgenic mice with high NGF secretion for saliva collection and hNGF purification, we divided transgenic mice into 4 groups, including 28-day-old young males and females, 63-day-old adult males and females. We compared their saliva volume, total salivary protein amount, salivary mNGF protein amount and salivary hNGF protein amount. The results showed that the saliva volume as well as amounts of total salivary protein, salivary mNGF protein and salivary hNGF protein secreted by 63-day-old transgenic mice were significantly higher than those secreted by sex-match 28-day-old transgenic mice, and the salivary hNGF protein amount secreted by male transgenic mice at the age of 63 days was significantly higher than that of female transgenic mice at the same age; Among 4 groups of mice, 63-day-old male transgenic mice secreted the highest salivary hNGF content, which was about 46 times higher than that secreted by the 28-day-old female transgenic mice. Therefore, 63-day-old male transgenic mice should be selected for saliva collection and hNGF purification.神经生长因子 (Nerve growth factor，NGF) 是一种能促进神经元发育、分化、再生的蛋白。为高效生产药效更佳的人源NGF (hNGF) 药物，最近，笔者实验室构建出唾液腺特异表达hNGF 的转基因小鼠，并从该转基因小鼠唾液中纯化获得具有高生物学活性的hNGF 蛋白。为了选择性别和日龄最适宜的转hNGF 基因小鼠用于收集纯化hNGF蛋白，文中比较了28 日龄 (性成熟前) 雄性、雌性，63 日龄 (性成熟后) 雄性、雌性转hNGF 基因小鼠，共4 组转hNGF 基因小鼠分泌的唾液量、唾液总蛋白量、唾液鼠源NGF (mNGF) 蛋白量和唾液hNGF 蛋白量等指标。结果显示，63 日龄的转hNGF 基因小鼠分泌的唾液量、唾液总蛋白量、唾液mNGF 蛋白量和唾液hNGF 蛋白量显著高于28 日龄同一性别的转hNGF 基因小鼠，且63 日龄的雄性转hNGF 基因小鼠分泌的唾液hNGF 蛋白量显著高于同一日龄的雌性转hNGF 基因小鼠；在4 组小鼠中，63 日龄的雄性转hNGF 基因小鼠分泌的唾液hNGF 含量最高，比28 日龄雌性转hNGF 基因小鼠高出约46 倍，最适宜用于收集唾液并从中纯化hNGF。.

Dihydroberberine (DHB), a hydrogenated derivative of berberine (BBR), has been firstly identified in Phellodendri Chinese Cortex (PC) by HPLC-ESI-MS/MS. Nowadays most researches on PC focus on its main components like BBR, however, the role of its naturally-occurring derivatives remains poorly defined heretofore. The present work aimed to comparatively evaluate the in vivo anti-inflammatory properties and mechanisms of DHB and BBR in three typical inflammatory murine models. The results showed that DHB effectively mitigated acetic acid-induced vascular permeability, xylene-elicited ear edema and carrageenan-caused paw edema. Meanwhile, DHB markedly attenuated the inflammatory cell infiltration in pathological sections of ears and paws. DHB was also observed to significantly decrease the production and mRNA expression levels of IL-6, IL-1β, TNF-α, NO (iNOS) and PGE2 (COX-2), increase the release of IL-10, and inhibit the activation of NF-κB and MAPK signaling pathways. The anti-inflammatory effect of DHB was weaker than that of BBR. The results might further contribute to unraveling the pharmacodynamic basis of PC and support its ethnomedical use in the treatment of inflammatory diseases. DHB possesses good potential to be further developed into a promising anti-inflammatory alternative, and can serve as a lead template for novel anti-inflammatory candidate.

Background Celecoxib is frequently prescribed to treat knee osteoarthritis (KOA), but how celecoxib influences the activity of the central nervous system to alleviate chronic pain remains unclear. Methods One hundred eight patients with KOA will be enrolled in this study. Patients will be allocated randomly to three groups: the celecoxib group, the placebo group, and the waiting list group. The patients in the celecoxib group will orally take celecoxib 200 mg once daily and the patients in placebo group with placebo 200 mg every day for 2 weeks. Functional magnetic resonance imaging scan will be performed on all patients at baseline and the end of interventions to detect the cerebral activity changes. The short form of McGill pain questionnaire and the Visual Analog Scale will be used as the primary endpoints to evaluate the improvement of knee pain. The secondary endpoints include the Western Ontario and McMaster osteoarthritis index (WOMAC), the Attention Test Scale, the Pain Assessment of Sphygmomanometer, the Self-rating Anxiety Scale, the Self-rating Depression Scale, and 12-Item Short Form Health Survey (SF-12). Discussion The results will investigate the influence of celecoxib treatment on cerebral activity of patients with KOA and the possible relationship between the cerebral activity changes and improvement of clinical variables so as to explore the central mechanism of celecoxib in treating knee pain. Trial registration ChiCTR-IOR-17012365. Registered on August 14, 2017. Electronic supplementary material The online version of this article (10.1186/s13063-018-3111-8) contains supplementary material, which is available to authorized users.

The envelope protein of Zika virus (ZIKV) exists as a dimer on the mature viral surface and is an attractive antiviral target because it mediates viral entry. However, recombinant soluble wild-type ZIKV envelope (wtZE) might preferentially exist as monomer (monZE). Recently, it has been shown that the A264C substitution could promote formation of dimeric ZIKV envelope protein (ZE(A264C)), requiring further characterization of purified ZE(A264C) for its potential applications in vaccine development. We also noted that ZE(A264C), connected by disulfide bond, might be different from the noncovalent native envelope dimer on the virion surface. Because the antibody Fc fragment exists as dimer and is widely used for fusion protein construction, here we fused wtZE to human immunoglobulin G1 (IgG1) Fc fragment (ZE-Fc) for noncovalent wtZE dimerization. Using a multistep purification procedure, we separated dimeric ZE(A264C) and ZE-Fc, revealing that they both exhibit typical β-sheet–rich secondary structures and stabilities similar to those of monZE. The binding activities of monZE, ZE(A264C), and ZE-Fc to neutralizing antibodies targeting different epitopes indicated that ZE(A264C) and ZE-Fc could better mimic the native dimeric status, especially in terms of the formation of tertiary and quaternary epitopes. Both ZE(A264C) and ZE-Fc recognize a ZIKV-sensitive cell line as does monZE, indicating that the two constructs are still functional. Furthermore, a murine immunization assay disclose that ZE(A264C) and ZE-Fc elicit more neutralizing antibody responses than monZE does. These results suggest that the two immunogen candidates ZE(A264C) and ZE-Fc have potential utility for neutralizing antibody selection and vaccine design against ZIKV.

Objective: There has been growing body of literatures showing that chronic inflammation might play an important role in cancer development. This meta-analysis aimed to assess the association between the dietary inflammation index (DII) score and gynecological cancers. Methods: A systematic search of PubMed, EMBASE and Web of Science up until October 20, 2018 was carried out to retrieve all related cohort and case-control studies. The summary risk assessments were pooled using random-effects models. The dose-response relationship was estimated by linear relationship model. Results: Twelve case-control studies (10,774 cases/15,958 controls) and six prospective cohort studies (330,363 participants/23,133 incident cases) were included in this meta-analysis. The pooled adjusted relative risk (RR) of gynecological cancers for the highest DII category compared to the lowest category was 1.38, (95% confidence intervals [CIs], 1.21-1.56, p

Aims This study aims to investigate the resting-state functional connectivity (rs-fc) of the right frontoparietal network (rFPN) between migraineurs and healthy controls (HCs) in order to determine how the rFPN rs-fc can be modulated by effective treatment. Methods One hundred patients and 46 matched HCs were recruited. Migraineurs were randomized to verum acupuncture, sham acupuncture, and waiting list groups. Resting-state functional magnetic resonance imaging data were collected before and after longitudinal treatments. Independent component analysis was applied in the data analysis. Results We found that migraineurs showed decreased rs-fc between the rFPN and bilateral precuneus compared with HCs. After treatments (real and sham), rFPN rs-fc with the precuneus was significantly reduced. This reduction was associated with headache intensity relief. In order to explore the role of the precuneus in acupuncture modulation, we performed a seed-based rs-fc analysis using the precuneus as a seed and found that the precuneus rs-fc with the bilateral rostral anterior cingulate cortex/medial prefrontal cortex, ventral striatum, and dorsolateral prefrontal cortex was significantly enhanced after treatment. Conclusion Our results suggest that migraineurs are associated with abnormal rFPN rs-fc. An effective treatment, such as acupuncture, may relieve symptoms by strengthening the cognitive adaptation/coping process. Elucidation of the adaptation/coping mechanisms may open up a new window for migraine management.

Pogostone, a chemical constituent of patchouli oil, has been confirmed to possess favorable anti-inflammatory property. In the present study, we investigated the possible anti-photoaging potential of pogostone and the underlying mechanism against UV-induced skin damage in mice. The macroscopic and histopathological lesions were significantly ameliorated by pretreatment of pogostone as compared to the VC group. Furthermore, topical application of pogostone markedly increased the activities of the antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and observably decreased malonaldehyde (MDA) level. Analysis of inflammatory cytokines showed obvious down-regulation of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) in the pogostone groups. In addition, pogostone pretreatment evidently inhibited the abnormal expression of matrix metalloproteinases (MMP-1 and MMP-3). Taken together, pogostone exhibited prominent photo-protective activity mainly by its antioxidative and anti-inflammatory properties, promising it as an effective alternative pharmaceutical therapy for photoaging.

Currently drug-induced liver injury (DILI) has become a major and challenging public health issue in terms of medicine development and clinical therapy. The level of γ-glutamyl transpeptidase (GGT) has long been regarded as a preclinical/clinical biomarker for prediction of DILI. Herein, we report a two-photon fluorescent sensor for tracking GGT level changes resulted from DILI in vivo. The sensor was prepared by linking a glutamic acid to a dicyanomethylene-4H-pyran (DCM) derivative; and the presence of GGT cleaves γ-glutamyl amide group from the sensor and thereby restores the fluorescence emission (at 635 nm) of DCM moiety under femtosecond pulses at 800 nm. This two-photon sensor exhibits superior sensing performance such as red emission, high photostability and low detection limit (∼0.057 U/L). On a two-photon microscope, the sensor shows a bright red fluorescence in GGT-overexpressing A2780 cells; and it can fluorescently respond to the GGT generated in the liver of zebrafishes as a result of clinical drug (phenytoin) treatment. These findings demonstrate that a commonly-used clinical drug phenytoin can cause remarkable elevation in GGT level in liver, and this sensor may be useful as a marker to detect clinical drug-induced organ damages.

Abhydrolase domain containing 5 gene (ABHD5), also known as comparative gene identification 58 (CGI-58), is a member of the α/β-hydrolase family as a protein cofactor of ATGL stimulating its triacylglycerol hydrolase activity. In this study, we aim to characterize the expression and variations of ABHD5 and to study their functions in chicken fat metabolism. We compared the ABHD5 expression level in various tissues and under different nutrition conditions, identified the variations of ABHD5, and associated them with production traits in an F2 resource population of chickens. Overexpression analysis with two different genotypes and siRNA interfering analysis of ABHD5 were performed in chicken preadipocytes. Chicken ABDH5 was expressed widely and most predominantly in adipose tissue. Five SNPs of the ABHD5 gene were identified and genotyped in the F2 resource population. The c.490C T SNP was associated with subcutaneous fat thickness (P0.01), carcass weight (P0.05), body weight (P0.05), shank diameter (P0.05), and shank length (P0.05). The c.423T C SNP was also associated with chicken body weight (P0.05) and shank diameter (P0.05). In chicken preadipocytes, overexpression of wild type ABDH5 did not affect the mRNA level of ATGL (adipose triglyceride lipase) but markedly decreased (P0.05) the TG (triglyceride) content of the cell, whereas overexpression of mutation type ABHD5 did not affect either ATGL expression or TG content of the cell. The expression of ATGL and TG content of the cell were decreased (P0.05) after ABHD5 knockdown in preadipocytes. The mRNA level of ABHD5 was regulated by both feeding and fasting, and by consumption of a high fat diet. It was increased greatly by fasting (P0.05) and was returned to control levels after re-feeding in the adipose tissues, and down-regulated in abdominal fat (P0.05) and the liver (P0.01) of chickens with a high fat diet. These results suggest that expression and variations of ABHD5 may affect fat metabolism through regulating the activity of ATGL in chickens.