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Introduction Geriatric assessment (GA) is widely used to detect vulnerability in older patients. As this process is time-consuming, prescreening tools have been developed to identify patients at risk for frailty. We aimed to assess whether the Geriatric 8 (G8) or the Korean Cancer Study Group Geriatric Score (KG-7) shows better performance in identifying patients who are in need of full GA. Materials and methods A consecutive series of patients aged ≥ 60 years with colorectal cancer were included. The sensitivity, specificity, predictive value, and 95% confidence intervals (95% CI) were calculated for the G8 and the KG-7 using the results of GA as the reference standard. ROC(Receiver Operating Characteristic) was used to evaluate the accuracy of the G8 and the KG-7. Results One hundred four patients were enrolled. A total of 40.4% of patients were frail according to GA, and 42.3% and 50.0% of patients were frail based on the G8 and the KG-7, respectively. The sensitivity and specificity of the G8 were 90.5% (95% CI: 77.4–97.3%) and 90.3% (95% CI: 80.1–96.4%), respectively. For the KG-7, the sensitivity and specificity were 83.3% (95% CI: 68.6–93.0%) and 72.6% (95% CI: 59.8–83.1%), respectively. Compared to the KG-7, the G8 had a higher predictive accuracy (AUC: (95% CI): 0.90 (0.83–0.95) vs. 0.78 (0.69–0.85); p Conclusion Both the G8 and the KG-7 showed a great ability to detect frailty in older patients with colorectal cancer. In this population, compared to the KG-7, the G8 had a better performance in identifying those in need of a full Geriatric Assessment.

Background The various types of ionising radiation and altered gravity in the space environment present a risk to humans during space missions. Changes in the space environment lead to skin diseases affecting the status of the aviators. Therefore, it is important to explore the molecular level changes in the skin during space missions. Aim Bioinformatics analysis of gene arrays from hair follicle tissue of 10 astronauts was performed to explore changes in gene expression. Methods First, STEM software was used to identify the expression patterns of hair follicle genes of astronauts among preflight, inflight and postflight. GO enrichment analysis was then performed to explore the gene functions within the module. Protein-protein interaction (PPI) network analysis was performed on skin-related genes. The transcriptional regulatory network within the module was constructed using the TRRUST database. The circadian rhythm-related genes within the module were screened using the MSigDB database. Results Based on differential expression analysis between the two groups, there were 327 differentially expressed genes after the astronauts entered space compared to preflight, and only 54 differentially expressed genes after returning to Earth. This outcome suggests that the expression of most genes can be recovered upon return to the ground, but there are a small number of genes the expression of which cannot be recovered in a short period of time. Based on time series analysis, 311 genes showed increased expression upon entry into space and decreased expression upon return to Earth. The genes in this expression pattern were associated with skin development, keratinocyte differentiation and cornification. 10 hub genes were identified for skin-related genes within the module. In addition, 9 transcription factors and 3 circadian genes were identified in the module. One hundred seventy-nine genes decreased in expression after entry into space and increased when returned to Earth. By reviewing the literature, we found that four genes, CSCD2, HP, CXCR1 and SSTR4, are associated with skin diseases. Conclusions Through bioinformatics analysis, we found that the space environment affects the differentiation of skin keratinocytes, leading to skin barrier damage and inflammatory responses, and this effect was decreased after return to Earth.

Purpose. To evaluate the association of near heterophoria with refraction and axial length (AL) in Chinese school children. Methods. This school-based cross-sectional study included 15,081 Chinese primary school children (grades 1–6) examined during 2017. Near heterophoria was measured at 33 cm using the Maddox rod and prism test. Noncycloplegic refraction and AL were also measured. A generalized additive model with a Gaussian link was used to determine the association of near heterophoria with refraction and AL. Analyses were adjusted for age to account for differences in the age distribution of the sample. Results. Overall, data were analyzed for 11,013 students ranging in age from 6 to 13 years. The most common type of near heterophoria was exophoria (64.96%), the proportion and value of which increased according to grade. Exophoria accounted for 62.53% (2,328/3,723), 65.03% (2,501/3,846), and 67.51% (2,325/3,444) of near heterophoria cases for grades 1-2, grades 3-4, and grades 5-6, respectively. Prism diopter (PD) values for near heterophoria in these grades were −6.30 ± 3.69, −6.81 ± 4.01, and −8.32 ± 5.12 PD, respectively. The average spherical equivalent (SE) in children with orthophoria was 0.23 D and 0.25 D lower than those in children with exophoria and esophoria, respectively ( P < 0.001 ). The mean AL in children with orthophoria was 0.11 mm shorter than that in children with either exophoria or esophoria ( P < 0.001 ). Near heterophoria exhibited a significant correlation with refraction and AL, irrespective of age. Conclusions. Exophoria represents the most common type of near heterophoria in children. Children with more severe near heterophoria, whether exophoria or esophoria, exhibited a higher degree of myopia and longer AL than those with relatively less severe near heterophoria. These results highlight the need for further, long-term investigation regarding the role of near heterophoria in visual development.

Introduction Magnetic resonance imaging (MRI) has shown the potential to improve the screening effectiveness among women with dense breasts. The introduction of fast abbreviated protocols (AP) makes MRI more feasible to be used in a general population. We aimed to investigate the cost-effectiveness of AP-MRI in women with dense breasts (heterogeneously/extremely dense) in a population-based screening program. Methods A previously validated model (SiMRiSc) was applied, with parameters updated for women with dense breasts. Breast density was assumed to decrease with increased age. The base scenarios included six biennial AP-MRI strategies, with biennial mammography from age 50–74 as reference. Fourteen alternative scenarios were performed by varying screening interval (triennial and quadrennial) and by applying a combined strategy of mammography and AP-MRI. A 3% discount rate for both costs and life years gained (LYG) was applied. Model robustness was evaluated using univariate and probabilistic sensitivity analyses. Results The six biennial AP-MRI strategies ranged from 132 to 562 LYG per 10,000 women, where more frequent application of AP-MRI was related to higher LYG. The optimal strategy was biennial AP-MRI screening from age 50–65 for only women with extremely dense breasts, producing an incremental cost-effectiveness ratio of € 18,201/LYG. At a threshold of € 20,000/LYG, the probability that the optimal strategy was cost-effective was 79%. Conclusion Population-based biennial breast cancer screening with AP-MRI from age 50–65 for women with extremely dense breasts might be a cost-effective alternative to mammography, but is not an option for women with heterogeneously dense breasts., Highlights • AP-MRI can be cost-effective for screening women with extremely dense breast. • The more frequent the use of AP-MRI, the more life years will be gained. • Biennial AP-MRI for women with extremely dense breast up to age 65 is optimal.

BackgroundLittle is known on the association of types of grains with mortality and the moderating effect of lifestyle on this association. This study aims to evaluate the single or joint associations of types of grains and lifestyle with all-cause mortality among Chinese older adults.MethodsData were derived from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 1998 to 2018. Subjects aged ≥ 65 years were eligible. The types of grains included wheat, total rice, and coarse cereals. Lifestyle was derived using smoking, alcohol consumption, physical activity, and dietary pattern. All-cause mortality was the primary outcome.ResultsThis study included 30275 participants with a mean age 87 ± 11 years and documented 19261 deaths during a mean follow-up of 4.8 years. Compared to wheat, in those with healthy and intermediate lifestyle, total rice was associated with a 13% (HR: 0.87,95% CI0.80, 0.93) and 6% (HR: 0.94,95% CI0.90, 1.00) lower risk of mortality, respectively, and coarse cereals were associated with a 14% (HR: 0.86,95% CI0.74, 1.00) and 12% (HR: 0.88,95% CI0.79, 0.97) lower risk of mortality, respectively. Meanwhile, an increase per SD in intakes of wheat and coarse cereals was associated with a 10% (HR: 1.10,95% CI1.03, 1.18) and 25% (HR: 1.25,95% CI1.08, 1.44) higher mortality rate in those with healthy lifestyle, and a 13% (HR: 1.13,95% CI1.08, 1.19) and 29% (HR: 1.29,95% CI1.17, 1.44) higher mortality in females but not males. In addition, a U-shaped association of intake of total grains with all- cause mortality was observed (Pfor non-linearity = 0.002), and a J-shaped association of intake of total rice with all- cause mortality was observed (Pfor non-linearity = 0.003).ConclusionsSpecific types of grains and lifestyle were separately or jointly associated with all-cause mortality. Compared to wheat, total rice and coarse cereals were advanced grains for participants with a relatively healthy lifestyle. Intake of total rice was related to all-cause mortality in a dose–response manner. Therefore, a combination of intermediate intake of total rice and healthy lifestyle should be encouraged in older adults.

Background Resistance to conventional dose schemes and radiotoxicity of healthy tissue is a clinical challenge in the radiation therapy of large locally advanced drug-resistant gastrointestinal stromal tumor (LADR-GIST). This study aimed to assess the feasibility of using multi-shell Simultaneous Integrated Boost Intensity-Modulated modality (SIB-IMRT) strategy to provide a safe and effective escalation dose regimen for LADR-GIST. Methods 7 patients with LADR-GIST were selected in this study. The modified SIB-IMRT plans for all patients were generated by delivering different escalation-dose gradients to four ring shaped regions (shells) within the gross tumor volume (GTV). The doses of the central volume of the tumor (GTVcenter) were escalated up to 70–92.5 Gy (25 fractions), while the doses of planning target volume (PTV) and shell-1 were kept at 50.0 Gy. Based on different escalation-dose gradients, the modified SIB-IMRT plans were divided into four groups (SIB-IMRT groups). For comparison purposes, plans obtained by conventional IMRT technique (Con-IMRT) with 50 Gy (25 fractions) were also generated for all patients (Con-IMRT group). All plans were normalized to cover 95% of the PTV with the prescribed dose of 50.0 Gy. The equivalent uniform dose (EUD), relative equivalent uniform dose (rEUD), dose volume histogram (DVH), dose profile, conformity index (CI) and monitor unit (MU) were evaluated in five groups. The Friedman Test was performed to determine whether there were significant differences (P Results Compared with the Con-IMRT group, the EUD of GTV (EUDGTV) and rEUD of SIB-IMRT groups were improved when escalation-dose gradient was increased, and the improvement became significant when the escalation-dose gradient reached 20% of the prescription dose. The rEUD tended to be stable as the escalation-dose gradient went up to 25% of the prescription dose. There were no significant differences in CIs and DVH metrics for OARs between the Con-IMRT group and any SIB-IMRT group, but the significant differences were observed between the SIB10-IMRT group and the SIB25-IMRT group. For the SIB-IMRT groups, as the dose gradient became steeper in the dose profiles, the higher dose was mainly accumulated in the inner part of GTV accompanied with a higher MU. Conclusions The proposed multi-shell SIB-IMRT strategy is feasible in dosimetry for LADR-GIST and can acquire higher therapeutic gain without sacrifice of healthy tissues. It appears that the scheme of delivering 20% of the prescribed escalation-dose gradient to the target volume can provide satisfactory dose irradiation for LADR-GIST, and it should be evaluated in future clinical study.

BackgroundLipoid congenital adrenal hyperplasia (LCAH) is a rare and severe disorder that is caused by mutations in the steroidogenic acute regulatory protein (StAR). Non-classic LCAH is defined as late-onset glucocorticoid deficiency and even complete male external genitalia in 46,XY individuals. However, to date, few cases of non-classic LCAH have been reported.MethodsIt was attempted to describe the clinical characteristics of a male child with complete male external genitalia in terms of age of onset, adrenal function, and biochemical indicators. Previously reported cases were also reviewed to investigate the relationship of age of onset with enzymatic activity in non-classic LCAH.ResultsThe patient with complete male external genitalia was diagnosed with non-classic LCAH, in which the reason for his referral to a local hospital at the of age 1.25 years was progressive skin hyperpigmentation, and plasma adrenocorticotropic hormone (ACTH) level was elevated to higher than 1,250 pg/ml. The compound heterozygous mutations c.772C>T/c.562C>T in STAR gene were identified via genetic testing. The literature review resulted in identification of 47 patients with non-classic LCAH from 36 families. The mutational analysis showed that c.562C>T mutation was prevalent in patients with non-classic LCAH, accounting for 37.2% of the total mutant alleles, which could reflect the founder effect on the non-classic LCAH population. In total, 28 46,XY patients were reported, including 22 (78.5%) cases with complete male external genitalia and six (21.5%) cases with different degrees of hypospadias.ConclusionThe clinical phenotypes of non-classic LCAH are highly variable. Routine physical examination, laboratory measurement, genetic testing, and, importantly, enzymatic activity assay may facilitate the early diagnosis of non-classic LCAH. The age of primary adrenal insufficiency (PAI) onset may not be a diagnostic basis for non-classic LCAH, and enzymatic activity assay determination may be more effective.

Removal feasibility of Fe impurity form La metal by electron beam melting (EBM) was analyzed, the removal mechanism was discussed, and the verification experiments were carried out in this study. The research results indicate that, the evaporation coefficient of Fe in La metal is 35–175 at 1800–3000 K, and Fe impurity can be removed by EBM; the removal efficiency of Fe impurity is improved with the increasing EBM power, the Fe concentration is significantly decreased from 1482 to 0.1 μg/g under 50 kW and 2400 s; the reaction of Fe removal by EBM follows the first-order rate law, and Fe impurity is removed by evaporation as a single atom; transport from the La melt to the liquid boundary layer of the Fe atom is rate-controlling step in the EBM when the EBM power is 30–50 kW.

Non–small-cell lung cancer (NSCLC) is one of the most fatal malignant tumors harmful to human health. Previous studies report that Platycodin D (PD) exhibits anti-tumor effects in multiple human cancers, including NSCLC, but the underlying mechanisms are largely unknown. Accumulating evidence indicates that non-coding RNAs (ncRNAs) participate in NSCLC disease progression, but the link between PD and the ncRNAs in NSCLC is poorly elucidated. Here, we used whole transcriptome sequencing to systematically investigate the RNAs-associated regulatory network in the PD treating NSCLC cell lines. A total of 942 significantly dysregulated RNAs were obtained. Among those, five circRNAs and six IncRNAs were rigorously selected via database and in vitro validation. In addition, the functional enrichment study of differentially expressed mRNAs, single nucleotide polymorphisms (SNPs) within PD-related mRNA structures, and the interaction between PD and mRNA-related proteins were analyzed through gene set enrichment analysis (GSEA), structural variant analysis, and molecular docking, respectively. With further in vitro validation, the results show that PD inhibits cell proliferation, arrests the cell cycle, and induces cell apoptosis through targeting BCL2-related proteins. We hope these data can provide a full concept of PD-related molecular changes, leading to a new treatment for NSCLC.

We aimed to quantitatively summarise the health economic evaluation evidence of prevention and control programs addressing COVID-19 globally.We did a systematic review and meta-analysis to assess the economic and health benefit of interventions for COVID-19. We searched PubMed, Embase, Web of Science, and Cochrane Library of economic evaluation from December 31, 2019, to March 22, 2022, to identify relevant literature. Meta-analyses were done using random-effects models to estimate pooled incremental net benefit (INB). Heterogeneity was assessed using IOf 16 860 studies identified, 85 articles were included in the systematic review, and 25 articles (10 studies about non-pharmacological interventions (NPIs), five studies about vaccinations and 10 studies about treatments) were included in the meta-analysis. The pooled INB of NPIs, vaccinations, and treatments were $1378.10 (95% CI = $1079.62, $1676.59), $254.80 (95% CI = $169.84, $339.77) and $4115.11 (95% CI = $1631.09, $6599.14), respectively. Sensitivity analyses showed similar findings.NPIs, vaccinations, and treatments are all cost-effective in combating the COVID-19 pandemic. However, evidence was mostly from high-income and middle-income countries. Further studies from lower-income countries are needed.

The family of Poly(A)-binding proteins (PABPs) regulates the stability and translation of messenger RNAs (mRNAs). Here we reported that the three members of PABPs, including PABPC1, PABPC3 and PABPC4, were identified as novel substrates for MKRN3, whose deletion or loss-of-function mutations were genetically associated with human central precocious puberty (CPP). MKRN3-mediated ubiquitination was found to attenuate the binding of PABPs to the poly(A) tails of mRNA, which led to shortened poly(A) tail-length of GNRH1 mRNA and compromised the formation of translation initiation complex (TIC). Recently, we have shown that MKRN3 epigenetically regulates the transcription of GNRH1 through conjugating poly-Ub chains onto methyl-DNA bind protein 3 (MBD3). Therefore, MKRN3-mediated ubiquitin signalling could control both transcriptional and post-transcriptional switches of mammalian puberty initiation. While identifying MKRN3 as a novel tissue-specific translational regulator, our work also provided new mechanistic insights into the etiology of MKRN3 dysfunction-associated human CPP.

The museum is gradually deepening the "people-oriented" design concept, and the interaction between the audience and the exhibits has attracted wide attention. This article classifies the physical display and virtual display of museum costumes, expounds the visual style of costume display from the perspective of the physical field, and then uses the Shanghai Textile and Clothing Museum as the experimental base to extract the factors that affect the audience's interactive experience through interviews, and construct an evaluation of the interactive experience Indicators, using T test to obtain experimental results, and comparing and analyzing the difference between physical display and virtual display of clothing under interactive experience from the perspective of psychological field, and then discussing the design principles of museum clothing display.

Objective to examine the association between different patterns of impaired lung function with the incident risk of dementia and magnetic resonance imaging (MRI)-based brain structural features. Methods in UK Biobank, a total of 308,534 dementia-free participants with valid lung function measures (forced expiratory volume in 1 s [FEV1] and forced vital capacity [FVC]) were included. Association was assessed using Cox proportional hazards regression model. Furthermore, the association between impaired lung function and brain MRI biomarkers related to cognitive function was analysed among 30,159 participants. Results during a median follow-up of 12.6 years, 3,607 incident all-cause dementia cases were recorded. Restrictive impairment (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.27–1.60) and obstructive impairment (HR, 1.28; 95% CI, 1.15–1.42) were associated with higher risk of all-cause dementia. The restricted cubic splines indicated FEV1% predicted and FVC % predicted had reversed J-shaped associations with dementia. Participants with impaired lung function have higher risks of all-cause dementia across all apolipoprotein E (APOE) risk categories, whereas associations were stronger among those of low APOE risk (P for interaction = 0.034). In addition, restrictive and obstructive impairment were linked to lower total (β: −0.075, SE: 0.021, Pfdr = 0.002; β: −0.033, SE: 0.017, Pfdr = 0.069) and frontoparietal grey matter volumes, higher white matter hyperintensity, poorer white matter integrity, lower hippocampus (β: –0.066, SE: 0.024, Pfdr = 0.017; β: –0.051, SE: 0.019, Pfdr = 0.019) and other subcortical volumes. Conclusions participants with restrictive and obstructive impairments had a higher risk of dementia. Brain MRI indices further supported adverse effects and provided insight into potential pathophysiology biomarkers.

BackgroundIn the patient-specific quality assurance (QA), DVH is a critical clinically relevant parameter that is finally used to determine the safety and effectiveness of radiotherapy. However, a consensus on DVH-based action levels has not been reached yet. The aim of this study is to explore reasonable DVH-based action levels and optimal DVH metrics in detecting systematic MLC errors for cervical cancer RapidArc plans.MethodsIn this study, a total of 148 cervical cancer RapidArc plans were selected and measured with COMPASS 3D dosimetry system. Firstly, the patient-specific QA results of 110 RapidArc plans were retrospectively reviewed. Then, DVH-based action limits (AL) and tolerance limits (TL) were obtained by statistical process control. Secondly, systematic MLC errors were introduced in 20 RapidArc plans, generating 380 modified plans. Then, the dose difference (%DE) in DVH metrics between modified plans and original plans was extracted from measurement results. After that, the linear regression model was used to investigate the detection limits of DVH-based action levels between %DE and systematic MLC errors. Finally, a total of 180 test plans (including 162 error-introduced plans and 18 original plans) were prepared for validation. The error detection rate of DVH-based action levels was compared in different DVH metrics of 180 test plans.ResultsA linear correlation was found between systematic MLC errors and %DE in all DVH metrics. Based on linear regression model, the systematic MLC errors between -0.94 mm and 0.88 mm could be caught by the TL of PTV95 ([-1.54%, 1.51%]), and the systematic MLC errors between -1.00 mm and 0.80 mm could also be caught by the TL of PTVmean ([-2.06%, 0.38%]). In the validation, for original plans, PTV95 showed the minimum error detection rate of 5.56%. For error-introduced plans with systematic MLC errors more than 1mm, PTVmean showed the maximum error detection rate of 88.89%, and then was followed by PTV95 (86.67%). All the TL of DVH metrics showed a poor error detection rate in identifying error-induced plans with systematic MLC errors less than 1mm.ConclusionIn 3D quality assurance of cervical cancer RapidArc plans, process-based tolerance limits showed greater advantages in distinguishing plans introduced with systematic MLC errors more than 1mm, and reasonable DVH-based action levels can be acquired through statistical process control. During DVH-based verification, main focus should be on the DVH metrics of target volume. OARs in low-dose regions were found to have a relatively higher dose sensitivity to smaller systematic MLC errors, but may be accompanied with higher false error detection rate.

In this paper, the purification of lanthanum was studied by using zone-refining technology. The equilibrium distribution coefficient of impurities was calculated using a liquidus slope method to reveal impurities’ distribution properties. Meanwhile, the analysis of impurities’ concentration distribution for Fe and Si has been investigated based on the SPIM model. The calculated findings based on SPIM were found to be in good agreement with the experimental results. In addition, the influence of the zone-refining rate and the number of passes on the purification of lanthanum were studied. It was found that after ten times of zone refining with a zone-refining rate of 5 mm/min, the contents of Fe and Si impurities in metal decreased to 4 and 2 ppm, respectively.

BackgroundThe gut microbiome is important for host nutrition and metabolism. Whether the gut microbiome under normal diet regulate human height remains to be addressed. Our study explored the possible relationship between gut microbiota, its metabolic products and the pathogenesis of idiopathic short stature disease (ISS) by comparing the gut microbiota between children with ISS and of normal height, and also the short-chain fatty acids (SCFAs) produced by the gut microbiota.MethodsThe subjects of this study were 32 prepubescent children aged 4-8 years. The fecal microbial structure of the subjects was analyzed by 16S rRNA high-throughput sequencing technology. The concentrations of SCFAs in feces were determined by gas chromatography-mass spectrometry.ResultsThe richness of gut microbiota in ISS group was decreased, and the composition of gut microbiota was significantly different between ISS group and control group. The relative abundance of nine species including family Ruminococcaceae and genera Faecalibacterium and Eubacterium, in ISS group was significantly lower than that in control group (PParabacteroides and genus Clostridium, in ISS group was significantly higher than that in control group (PFaecalibacterium and Eubacterium was positively correlated with the standard deviation score of height. Furthermore, the concentrations of total SCFAs and butyrate were positively correlated with serum insulin-like growth factor 1 (IGF-1)-SDS. Disease prediction model constructed based on the bacteria who abundance differed between healthy children and ISS children exhibited high diagnostic value (AUC: 0.88).ConclusionsThe composition of gut microbiota and the change in its metabolite levels may be related to ISS pathogenesis. Strains with increased or decreased specificity could be used as biomarkers to diagnose ISS.

BACKGROUND Identifying patients at high risk of diabetic kidney disease (DKD) helps improve clinical outcome. PURPOSE To establish a model for predicting DKD. DATA SOURCES The derivation cohort was from a meta-analysis. The validation cohort was from a Chinese cohort. STUDY SELECTION Cohort studies that reported risk factors of DKD with their corresponding risk ratios (RRs) in patients with type 2 diabetes were selected. All patients had estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio (UACR) DATA EXTRACTION Risk factors and their corresponding RRs were extracted. Only risk factors with statistical significance were included in our DKD risk prediction model. DATA SYNTHESIS Twenty cohorts including 41,271 patients with type 2 diabetes were included in our meta-analysis. Age, BMI, smoking, diabetic retinopathy, hemoglobin A1c, systolic blood pressure, HDL cholesterol, triglycerides, UACR, and eGFR were statistically significant. All these risk factors were included in the model except eGFR because of the significant heterogeneity among studies. All risk factors were scored according to their weightings, and the highest score was 37.0. The model was validated in an external cohort with a median follow-up of 2.9 years. A cutoff value of 16 was selected with a sensitivity of 0.847 and a specificity of 0.677. LIMITATIONS There was huge heterogeneity among studies involving eGFR. More evidence is needed to power it as a risk factor of DKD. CONCLUSIONS The DKD risk prediction model consisting of nine risk factors established in this study is a simple tool for detecting patients at high risk of DKD.

Central precocious puberty (CPP) refers to a human syndrome of early puberty initiation with characteristic increase in hypothalamic production and release of gonadotropin-releasing hormone (GnRH). Previously, loss-of-function mutations in human MKRN3, encoding a putative E3 ubiquitin ligase, were found to contribute to about 30% of cases of familial CPP. MKRN3 was thereby suggested to serve as a ‘brake’ of mammalian puberty onset, but the underlying mechanisms remain as yet unknown. Here, we report that genetic ablation of Mkrn3 did accelerate mouse puberty onset with increased production of hypothalamic GnRH1. MKRN3 interacts with and ubiquitinates MBD3, which epigenetically silences GNRH1 through disrupting the MBD3 binding to the GNRH1 promoter and recruitment of DNA demethylase TET2. Our findings have thus delineated a molecular mechanism through which the MKRN3–MBD3 axis controls the epigenetic switch in the onset of mammalian puberty.

Terpene synthase (TPS) is related to the production of aromatic substances, but there are few studies on the impact of abiotic stress on TPS and its molecular mechanism, especially in peaches. This study found that salt resistance and abscisic acid (ABA) sensitivity of transgenic tomatoes were enhanced by overexpression of PpTPS1. Moreover, it was found that PpTPS1 interacted with and antagonized the expression of the bZIP transcription factor ABA INSENSITIVE 5 (PpABI5), which is thought to play an important role in salt suitability. In addition, PpTCP1, PpTCP13, and PpTCP15 were found to activate the expression of PpTPS1 by yeast one-hybrid (Y1H) and dual-luciferase assays, and they could also be induced by ABA. In summary, PpTPS1 may be involved in the ABA signaling regulatory pathway and play an important role in salt acclimation, providing a new reference gene for the improvement of salt resistance in peaches.

To summarize the clinical characteristics, genetics and follow-up data of four children with thyroid hormone resistance (RTH) syndrome and review the related literatures.The clinical data of the four children diagnosed with RTH syndrome in our hospital from 2018 to 2020 were retrospectively analyzed. Next-generation sequencing of the candidate genes related to thyroid diseases was performed using the blood collected from all the children and their parents who signed an informed consent. Then, relevant cases were retrieved on medical literature databases for analysis and summary.Among the four cases, three cases of goiter; two cases of tachycardia, palpitations, personality change, hyperactivity, weight loss; one case of academic performance decline, and no hearing and vision loss were observed. Laboratory thyroid function tests indicated a mild increase in free triiodothyronine and with or without increased free thyroxine levels. Thyroid-stimulating hormone (TSH) levels were normal or slightly elevated, but thyrotropin receptor autoantibodies were negative. Octreotide inhibition test showed that the TSH levels of all the children decreased by more than 50% compared with the basal value (the genes of four cases were positive). However, magnetic resonance imaging of the pituitary gland showed no abnormalities. Related gene detection in the children and their families showed that four cases hadThe clinical manifestations of pediatric RTH syndrome vary, and the diagnosis mainly depends on thyroid function tests. Heterozygous mutations in THRB are overall rare, even if with the advanced development of next-generation sequencing, not all the children with RTH syndrome have mutations. Furthermore, octreotide inhibition tests cannot be used as a diagnostic criterion to distinguish RTH syndrome from pituitary tumors in children.

Background Glucocorticoids (GCs) are commonly used to treat autoimmune diseases and malignancies in children and adolescents. Growth retardation is a common adverse effect of GC treatment in pediatric patients. Accumulating evidence indicates that non-coding RNAs (ncRNAs) are involved in the pathogenesis of glucocorticoid-induced growth retardation (GIGR), but the roles of specific ncRNAs in growth remain largely unknown. Methods In this study, 2-week-old male Sprague-Dawley rats had been treated with 2 mg/kg/d of dexamethasone for 7 or 14 days, after which the growth plate tissues were collected for high-throughput RNA sequencing to identify differentially expressed mRNAs, lncRNAs, circRNAs, and miRNAs in GIGR rats. Results Transcriptomic analysis identified 1,718 mRNAs, 896 lncRNAs, 60 circRNAs, and 72 miRNAs with different expression levels in the 7d group. In the 14d group, 1,515 mRNAs, 880 lncRNAs, 46 circRNAs, and 55 miRNAs with differential expression were identified. Four mRNAs and four miRNAs that may be closely associated with the development of GIGR were further validated by real-time quantitative fluorescence PCR. Function enrichment analysis indicated that the PI3K-Akt signaling pathway, NF-kappa B signaling pathway, and TGF-β signaling pathway participated in the development of the GIGR. Moreover, the constructed ceRNA networks suggested that several miRNAs (including miR-140-3p and miR-127-3p) might play an important role in the pathogenesis of GIGR. Conclusions These results provide new insights and important clues for exploring the molecular mechanisms underlying GIGR.

Erbium metal with purity ≥ 99% was cold rolled to 30%, 40%, 50%, and 60% deformations and the Er metal of 60% deformation was annealed at different temperatures for 1 h. The effect of cold rolling deformation and annealing on the microstructure and texture evolution of Er metal was investigated by XRD, EBSD, Microhardness tester, and OM. P is the orientation index, which is used to judge the preferred orientation. The research results showed that grains were broken and refined gradually with increasing deformation, the average grain size was 3.37 µm, and the orientation distribution was uniform for 60% deformation; deformation twins appeared in the grain when the deformation was less than 40%, which contributed to the generation of (0001) plane orientation. Comparing with the initial state, the (011−0) plane orientation gradually weakened and the (111−0) plane orientation had a trend of further strengthening with the increasing deformation; the (1−21−0) plane orientation remained unchanged, but there was a gradual weakening trend when the deformation was greater than 50%. For 60% deformation of Er metal, the deformed microstructure was replaced by fine equiaxed grains with the increasing annealing temperature, and the high-performance Er metal with fine and uniform equiaxed grains can be obtained under annealing at 740 °C for 1 h.

Background and Objective: Few studies have explored the relationship between malnutrition measured by the Geriatric Nutritional Risk Index (GNRI) and cognitive performance. This study aimed to investigate the association of malnutrition with cognitive function in the Chinese population.Methods: It was a prospective longitudinal study and used three waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) data in 2011–2012, 2014, and 2017–2018. Participants aged 60 years or older without mental illness and cerebrovascular diseases were eligible. The GNRI was used to assess nutritional status as follows: normal nutrition (a GNRI > 98), mild malnutrition (92 ≤ a GNRI ≤ 98), and moderate-to-severe malnutrition (a GNRI < 92). Cognitive performance was evaluated by the Mini-Mental State Examination (MMSE) scores. The relationship between the GNRI and cognitive function was analyzed using a linear mixed-effects model.Results: A total of 1,632 subjects were analyzed, including 741 males and 891 females. Of these, 65.0, 19.4, and 15.6% of subjects were at normal nutritional status, mild, and moderate-to-severe malnutrition, respectively. After adjusting for potential confounders, participants under mild and moderate-to-severe malnutrition status have a lower MMSE score [β (95% CI): –0.95 (–1.60, –0.25) and –1.39 (–2.21, –0.57), respectively], compared with those having normal nutrition. Also, there was a linear trend in the association of malnutrition risk with cognitive function in the total population [β (95% CI): –0.74 (–1.13, –0.35)]. However, a significant association of malnutrition with cognitive function was observed only among illiterate females aged above 90 years.Conclusion: This study suggested that there was a significant relationship between the GNRI and cognitive function in the Chinese elderly. Furthermore, subjects with more serious malnutrition have a worse cognitive function, especially in the oldest illiterate females. Clinicians should put more emphasis on assessing the nutritional and cognitive status of the elderly to timely intervene and prevent cognitive impairment.

Background: Central precocious puberty (CPP) is one of the most common and complex problems in clinical pediatric endocrinology practice. Mutation of the MKRN3 gene can cause familial CPP.Methods and Results: Here we reported a Chinese patient bearing a novel MKRN3 mutation (c.G277A/p.Gly93Ser) and showing the CPP phenotype. Functional studies found that this mutation of MKRN3 attenuated its autoubiquitination, degradation, and inhibition on the transcriptional activity of GNRH1, KISS1, and TAC3 promoters.Conclusion: MKRN3 (Gly93Ser) is a loss-of-function mutation, which attenuates the inhibition on GnRH1-related signaling, suggesting that this mutant can lead to central precocious puberty.

BACKGROUND: To decrease the burden of breast cancer (BC), the Chinese government recently introduced biennial mammography screening for women aged 45-70 years. In this study, we assess the effectiveness and cost-effectiveness of implementing this programme in urban China using a micro-simulation model.METHODS: The 'Simulation Model on radiation Risk and breast cancer Screening' (SiMRiSc) was applied, with parameters updated based on available data for the Chinese population. The base scenario was biennial mammography screening for women aged 45-70 years, and this was compared to a reference population with no screening. Seven alternative scenarios were then simulated by varying the screening intervals and participant ages. This analysis was conducted from a societal perspective. The discounted incremental cost-effectiveness ratio (ICER) was compared to a threshold of triple the gross domestic product (GDP) per life years gained (LYG), which was 30 785 USD/LYG. Univariate sensitivity analyses were conducted to evaluate model robustness. In addition, a budget impact analysis was performed by comparing biennial screening with no screening at a time horizon of 10 years.RESULTS: Compared with no screening, the base scenario was cost-effective in urban China, giving a discounted average cost-effectiveness ratio (ACER) of 17 309 USD/LYG. The model was most sensitive to the cost of mammography per screen, followed by mean size of self-detected tumours, mammographic breast density and the cumulative lifetime risk of BC. The efficient frontier showed that at a threshold of 30 785 USD/LYG, the base scenario was the optimal scenario with a discounted ICER of 25 261 USD/LYG. Over 10 years, screening would incur a net cost of almost 38.1 million USD for a city with 1 million citizens.CONCLUSION: Compared to no screening, biennial mammography screening for women aged from 45-70 is cost-effective in urban China.

Necroptosis is a recently defined type of programmed cell death with the specific signaling cascade of receptor-interacting protein 1 (RIPK1) and RIPK3 complex to activate the executor MLKL. However, the pathophysiological roles of necroptosis are largely unexplored. Here, we report that fungus triggers myeloid cell necroptosis and this type of cell death contributes to host defense against the pathogen infection. Candida albicans as well as its sensor Dectin-1 activation strongly induced necroptosis in myeloid cells through the RIPK1-RIPK3-MLKL cascade. CARD9, a key adaptor in Dectin-1 signaling, was identified to bridge the RIPK1 and RIPK3 complex-mediated necroptosis pathway. RIPK1 and RIPK3 also potentiated Dectin-1-induced MLKL-independent inflammatory response. Both the MLKL-dependent and MLKL-independent pathways were required for host defense against C. albicans infection. Thus, our study demonstrates a new type of host defense system against fungal infection.

OBJECTIVE This study aimed to examine the associations of BMI and waist circumference with all-cause mortality in a general adult population from the China Health and Nutrition Survey. METHODS Based on the World Health Organization recommendations, the general adult population was divided into underweight (BMI

Lanthanum fluoride (LaF3) thin films were deposited on the Ge substrate using the molybdenum boat evaporation method. The effect of films’ oxygen impurity on the infrared optical properties has been investigated for the first time in this report. With the increase in oxygen content in the films, the F content decreases, and the O/F ratio decreases from 0.160 to 0.055. XRD patterns reveal that the presence of O impurity destroys the crystal structure integrity of the LaF3 films and leads to the intensification of infrared absorption. The average transmittance decreases from 58.1% to 52.2%, and the peak transmittance decreases from 59.9% to 54.5%. Additionally, the refractive index and extinction coefficient of LaF3 films with different oxygen content are obtained by fitting the transmittance test data. The results show that the refractive index and extinction coefficient of the films in 8–12 μm increase with the increase in oxygen content, the average refractive index increases from 1.339 to 1.478, and the extinction coefficient increases from 0.001 to 0.030. In this paper, the influence of oxygen impurity in the LaF3 film on its infrared optical properties is revealed, which lays a theoretical foundation for the development of high-performance LaF3 infrared antireflective film.

Background: Central precocious puberty (CPP) is one of the most common and complex problems in clinical pediatric endocrinology practice. Mutation of the MKRN3 gene can cause familial CPP. Methods and Results: Here we reported a Chinese patient bearing a novel MKRN3 mutation (c.G277A/p.Gly93Ser) and showing the CPP phenotype. Functional studies found that this mutation of MKRN3 attenuated its autoubiquitination, degradation, and inhibition on the transcriptional activity of GNRH1, KISS1, and TAC3 promoters. Conclusion: MKRN3 (Gly93Ser) is a loss-of-function mutation, which attenuates the inhibition on GnRH1-related signaling, suggesting that this mutant can lead to central precocious puberty.

Neurofibromatosis type 1 (NF1) is a common genetic disorder characterized by cafe’-au-lait spots, skinfold freckles, the formation of neurofibromas, skeletal dysplasia, vascular dysplasia, and an increased risk of malignant tumors. In this study, two Chinese NF1 children troubled with bone lesions or hypertension were reported. A de novo NF1 mutation (c.4925T > A/p.V1642E) and a maternally inherited NF1 mutation (c.4883T > A/p.L1628∗) were identified by molecular sequence. According to the ACMG/AMP guidelines, the c.4925T > A was classified as variants of uncertain significance (VOUS) while the c.4883T > A mutation was identified as likely Pathogenic. Further study found that these two NF1 mutants had lost their function to inhibit the Ras/Erk signaling and the proliferation of cells, which could interpretate some phenotypes of these two NF1 patients. We also observed these two NF1 mutants displayed decreased protein stability with increased ubiquitination levels compared with that of wild-type NF1.

Background Neurofibromatosis type 1 is an autosomal dominant inherited disease and caused by NF1 gene mutation. Its clinical manifestations include multiple cafe´‐au lait (CAL) spots, skinfold freckling, neurofibroma, bone dysplasia, learning disabilities, and an increased risk of malignancy. Methods and Results Here, we reported a Chinese patient bearing with a novel NF1 mutation (c.2064delGGATGCAGCGG/p.Gly672AsnfsTer24) and complaining mainly about bone phenotype. Functional studies found that this novel mutation caused the damage of NF1 mRNA and protein levels, and lost the inhibition on Ras/Erk signaling. Conclusion A novel mutation in NF1 gene was identified and in vitro functional studies were performed, which provided a potential molecular mechanism to explain the bone maldevelopment of patients with neurofibromatosis type 1., A Chinese patient bearing with a novel NF1 mutation is involved in this study. The present complaint of this patient is bone phenotype including short stature and scoliosis. Functional studies confirm that this novel mutant could active Ras/Erk signaling and perhaps further inhibit the development of osteoblasts (OBLs), which provide a potential molecular mechanism to explain the bone maldevelopment of patients with neurofibromatosis type 1.

Background: The COVID-19 pandemic is an unprecedented global crisis and has a profound impact on health-care systems, society and economy. The cost-effectiveness of different interventions for the prevention and control of COVID-19 remains debated. We aimed to quantitatively summarize the health economic evaluation evidence of prevention and control programs addressing COVID-19 globally. Methods: We did a systematic review and meta-analysis to assess the economic and health benefit of interventions of COVID-19. We searched PubMed, Embase, Web of Science and Cochrane Library of economic evaluation from 31 December, 2019 to 13 July, 2021 to identify relevant literatures. Two researchers screened titles and abstracts, extracted data from full-text articles, and did quality assessment by the Consolidated Health Economic Evaluation Reporting Standards checklist. Meta-analyses were done using random-effects models to estimate pooled incremental net benefit (INB). Heterogeneity was assessed using I^2 statistics, and publication bias was assessed by Egger’s test. This study is registered with PROSPERO, CRD42021267475.Findings Of 15542 studies identified, 50 articles were included in the systematic review, and 17 articles (9 studies about non-pharmacological interventions (NPIs), 4 studies about vaccinations and 4 studies about treatments) were included in the meta-analysis. The pooled INB of NPIs, vaccinations and treatments were $972·05 (95% CI $772·52 to $1171·59), $295·18 (95% CI $209·58 to $380·77) and $14854·90 (95% CI $1783·60 to $27926·20), respectively. The pooled INBs in subgroups of screening, and suppression were $2390·89 (95% CI $1932·92 to $2848·85) and $2156·00 (95% CI $1114·40 to $3197·59). Sensitivity analyses showed similar findings. Interpretation: NPIs, vaccinations and treatments are all cost-effective in combating COVID-19 pandemic. However, evidence almost from high-income and middle-income countries, further studies from lower-income countries are needed. Funding: National Natural Science Foundation of China (No. 71910107004, 91746205, 72122001, 71934002). Declaration of Interest: The authors declare no competing interests.

The zone refining technology is considered to be one of the most effective means of purifying lanthanum. However, it is tough to obtain the temperature distribution of the molten region through experimental methods. In this study, finite element analysis was used to establish the zone refining simulation model, and the impurity distribution of lanthanum after purification was investigated experimentally. Good agreement between the simulated and experimental results was obtained. The effects of the current and the frequency on the temperature distribution and the width of the region were studied using the simulation model. Through the zone refining experiment, the impurity distributions under different widths of molten region were revealed. Finally, the influence of molten region width on the limiting distribution was calculated by solving the limiting distribution equation.

Objectives: To evaluate the cost-effectiveness of community-based Atrial fibrillation (AF) screening by 12-lead electrocardiogram (ECG) in Chinese healthcare setting.Methods: A Markov state transition model was used to simulate the costs and effects on a 55/65/75-year-old cohort under routine care and AF screening by 12-lead ECG. The circle length was 1 year, and people were simulated until 90 years old. The cost-effectiveness analysis was perform using a societal perspective. Transition probability, costs, and utility data were derived from open dataset and published literature. One-way and probabilistic sensitivity analyses were performed to exam the uncertainty of the results. Results: Annual AF screening in 65/75-year-old cohort was highly cost-effective with the incremental cost-effectiveness ratio (ICER) Chinese Yuan Renminbi (CNY) 64147/49736 per quality-adjusted life year (QALY) gained. Annual AF screening in 65/75-year-old cohort was associated with 535/492 prevented ischemic strokes and 174/163 more intracerebral hemorrhages, and the anticoagulation rate increased from the assumed 10% on routine care to 61.5%. Probabilistic sensitivity analysis indicated that these two strategies have 55% and 78% chances of being cost-effective at a willingness-to-pay (WTP) threshold of 1× gross domestic product per capita of China in 2019, US $10635 QALY.Conclusion: Annual community-based screening of population aged 65 years and older in China is likely to be cost-effective at conventional willingness-to-pay thresholds to reduce the unnecessary burden of strokes.

ObjectiveCatch-up growth (CUG) in small for gestational age (SGA) leads to increased risk of metabolic syndrome and cardiovascular diseases in adults. It remains unclear if microbiota could play an important role in CUG-SGA independent of genetic or nutritional factors. The present study explored the role of gut microbiota in, and its association with, metabolic disorders during CUG-SGA.MethodsAn SGA rat model was established by restricting food intake during pregnancy, and the rats were divided into catch-up growth (CUG-SGA) and non-catch-up growth (NCUG-SGA) groups based on body weight and length at the fourth postnatal week. High-throughput sequencing of 16S rRNA was conducted to detect the diversity and composition of the gut microbiota. Fecal short-chain fatty acids (SCFAs) were detected by gas chromatography-mass spectrometry. Transcriptome sequencing of liver tissue was performed and verified using real-time PCR. Concentrations of insulin and total cholesterol were determined using enzyme-linked immunosorbent assay.ResultsThe composition of gut microbiota in CUG-SGA rats differed from that of NCUG-SGA rats, with reduced abundance of Lactobacillus in the CUG-SGA group. The decrease in Lactobacillus was significantly associated with increased body weight and upregulated insulin and total cholesterol levels. Five SCFAs and two branched chain fatty acids were significantly higher in the CUG-SGA group than in the NCUG-SGA group. Additionally, SCFAs were positively associated with clinical indices such as weight, body mass index, insulin, and total cholesterol. Transcriptomic data revealed that insulin-like growth factor-2 expression was significantly decreased in CUG-SGA rats and was associated with a decrease in Lactobacillus bacteria.ConclusionLactobacillus and SCFAs were associated with the metabolic disorders during CUG in SGA. Gut microbiome may play a certain role on metabolic disorders during catch-up growth in small-for-gestational-age.

OBJECTIVE: To evaluate the efficacy and safety of the third-generation aromatase inhibitor letrozole in the treatment of McCune-Albright syndrome (MAS) girls with peripheral precocious puberty. METHODS: Twenty-one MAS girls with peripheral precocious puberty treated in Pediatrics Department of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from March 2012 to June 2017 were enrolled in the study. Patients presented with repeated vaginal bleeding, premature breast enlargement, café-au-lait spots or dysplasia of bone fibers, and low levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH); and the congenital adrenal hyperplasia, estrogen-producing tumors, and exogenous estrogen intake were excluded. Letrozole were administrated at a dose of 0.5-2 mg·m (-2)·d (-1) for 6 to 12 months. The patients were observed for changes in breast staging, vaginal bleeding, sex hormone levels, liver function and bone age changes, and changes in uterine and ovarian volume. RESULTS: After treatment, bone age/chronological age (BA/CA)was decreased from 1.23±0.30 to 1.11±0.18 ( P < 0.01); the predicted adult height (PAH) increased from (156.2±5.9)cm to (158.4±2.1)cm after treatment ( P < 0.05); the vaginal bleeding was reduced and the estradiol level decreased, while the teststosterone level and the uterus showed no significant increase, and no adverse reactions such as ovarian torsion and abnormal liver function were observed. CONCLUSION: Precocious puberty is one of the most common endocrine manifestations in MAS. Our findings suggest that letrozole may be an effective and safe therapy to precocious puberty in girls with McCune-Albright Syndrome.

Background A colorectal cancer screening programme (CCSP) was implemented from 2012 to 2017 in Tianjin, China. Residents with a positive faecal immunochemical test (FIT) or positive self-reported symptom questionnaire (SRSQ) were recommended to undergo colonoscopy. The objective was to investigate the potential factors associated with nonadherence to colonoscopy among a risk-increased population. Methods Data were obtained from the CCSP database, and 199,522 residents with positive FIT or positive SRSQ during two screening rounds (2012–2017) were included in the analysis. Logistic regression analysis was performed to assess the association between nonadherence to colonoscopy and potential predictors. Results A total of 152,870 (76.6%) individuals did not undergo colonoscopy after positive FIT or positive SRSQ. Residents with positive SRSQ but without positive FIT were more likely not to undergo colonoscopy (negative FIT: OR, 2.35; 95% CI, 2.29–2.41, no FIT: OR, 1.27; 95% CI, 1.24–1.31). Patients without a cancer history were less likely to undergo colonoscopy even if they received risk-increased reports based on the SRSQ. Conclusion In the CCSP, seventy-seven percent of the risk-increased population did not undergo colonoscopy. FIT should be recommended since positive FIT results are related to improved adherence to colonoscopy. Residents with negative FIT but positive SRSQ should be informed of the potential cancer risk to ensure adherence to colonoscopy.

Background The occurrence of multiple endocrine neoplasia type 2B (MEN2B) in Asians is very rare. In particular, patients with intractable constipation as the main clinical manifestation are even rarer. Atypical clinical manifestations are likely to lead to a diagnostic delay. In this report, we described a case of a delayed diagnosis of MEN2B, and the first clinical manifestation was intractable constipation. Case presentation A female teenager had suffered from intractable constipation since infancy. Because the colonoscopy and biopsy results from local hospitals did not confirm the presence of congenital megacolon, the girl had been followed up at a local clinic for a long time. The diagnosis was not confirmed until thyroid masses were found in the Pediatric Department of Shanghai Ruijin Hospital when she was 12 years old. According to our detailed evaluation, she suffered from Hirschsprung disease (HD), growth retardation, medullary thyroid carcinoma (MTC) and mucosal neuroma due to a mutation in the RET gene. Thus, the diagnosis of MEN2B was confirmed. Afterward, the girl underwent several surgeries and was still being followed up before the article was published. Conclusion MEN2B has atypical clinical symptoms in the early stage. Refractory constipation may be the only clinical manifestation that lasts for several years. Therefore, we recommend that early screening and gene sequencing should be performed for patients with severe constipation due to HD to determine the cause of the disease and to improve the survival outcome.

Background Stroke has become the leading cause of death in China. This study aimed to assess the age-period-cohort (APC) effects on the long-term trends of type-specific stroke morbidity and mortality in China between 1993 and 2017.Methods and Results:The data were obtained from the Global Burden of Disease 2017 (GBD 2017) and were analyzed with the age-period-cohort framework. The net drifts of mortality were below 0 (hemorrhagic stroke [HS]: males: -1.620%, females: -3.531%; ischemic stroke [IS]: males: -1.041%, females: -3.002%), and the local drift values were below 0 in all age groups and for both genders. The net drifts of HS incidence were below 0 (males: -1.412%, females: -2.688%), while those of IS were above 0 (males: 1.425%, females: 1.117%). Period effect of mortality showed similar monotonic downward patterns for both genders, with a faster decrease for females than for males. Period effect of incidence showed a declined trend of incidence for HS, but an elevated trend for IS in both genders. After controlling for age and period effects, cohort effects on incidence found a monotonic decline trend for HS, while for IS, an elevated trend was found at first to peak during the 1950-1970 s, then declined steadily afterwards. Cohort effects on mortality showed a monotonic declined trend. Conclusions By using Age-Period-Cohort (APC) analysis, a disparity between HS and IS was identified. Different prevention and control strategies should be used depending on the subtypes of stroke.

Background The impact of socioeconomic developments on stroke incidence and mortality must be understood to target prevention strategies appropriately. We assessed the secular trends in stroke incidence and mortality in China based on data from the Global Burden of Disease Study 2016. Methods Trends of stroke incidence and mortality of China was described in different categories of age, sex and stroke type using the GBD study database. Also a comparative study was conducted between China and Japan, U.S. to find reasonable references for development. Secular trends in incidence and mortality (per 100,000 population) were assessed for stroke, including ischemic and hemorrhagic stroke from 1990 to 2016. Population pyramid was used to illustrate changes in age- and sex-specific incidence and mortality rates. Results During the study period, stroke incidence in China increased from 204.52 to 403.08 and mortality increased from 122.09 to 130.94; the corresponding age-standardized rates changed from 335.63 to 353.70 and from 231.28 to 132.84, respectively. Among those aged 15–49 and 50–69 years, the incidence rates of ischemic stroke and hemorrhagic stroke both tended to increase, whereas the mortality rates tended to decline in all age groups. The incidence and mortality were highest among those aged ≥70 years. Compared with the U.S. and Japan, age-standardized rates of incidence and mortality were higher in China. Conclusions Although the incidence of stroke has increased in China, overall mortality has decreased. A priority of stroke prevention and control strategies will transition from reducing mortality to controlling the incidence in at-risk populations.

Additional file 11: Figure S3. Hierarchical clustering of cucumber gene expression profiles under heat treatment. A, Hierarchical cluster of expressed cucumber genes in 9 samples. In the color panels, each transverse line represents a single gene and the color of the line indicates the expression level of the gene relative to the mean center in a specific sample: red, high expression; green, low expression level. B, The hierarchical clustering on the gene expression matrix, using the Pearson correlation coefficient as a proxy of similarity between transcriptomes. HT0h = heat treatment for 0 h (hours), HT3h = heat treatment for 3 h, HT6h = heat treatment for 6 h.

Additional file 2: Figure S2. The number of WRKY genes mapped on every chromosome according to cucumber genome v1.0 (previous study) and v3.0 (this study).

Additional file 5: Table S3. List of WRKY domain sequences of WRKY IIa proteins.