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Abstract We aimed to investigate whether exosomes (Exo) affected chronic obstructive pulmonary disease (COPD) by influencing ferroptosis of bronchial epithelial cells (BECs) and the mechanisms involved. Here we took the peripheral blood samples of normal subjects and COPD patients, extracted and identified endothelial progenitor cells (EPCs) and EPC-Exo. An animal model of COPD was established. Then human BECs were taken and treated with cigarette smoke extract (CSE) for 24 h to construct a COPD cell model. Next, we screened differentially expressed ferroptosis-related genes in COPD patients by bioinformatics. Bioinformatics predicted the miRNA targeting PTGS2. Then, the mechanism of action of miR-26a-5p and Exo-miR-26a-5p was investigated in vitro. We successfully isolated and identified EPC and Exo. In vitro, EPC alleviated CSE-induced ferroptosis in BECs by transporting Exo. In vivo, Exo alleviated cigarette smoke-induced ferroptosis and airway remodeling in mice. Through further validation, we found that CSE-induced ferroptosis promoted the epithelial-mesenchymal transition (EMT) of BECs. Bioinformatics analysis and validation showed that PTGS2/PGE2 pathway affected CSE-induced ferroptosis in BECs. Meanwhile, miR-26a-5p targeting PTGS2 affected CSE-induced ferroptosis in BECs. Additionally, we found that miR-26a-5p affected CSE-induced BECs EMT. Exo-miR-26a-5p alleviated CSE-induced ferroptosis and EMT. In conclusion, EPC-exosomal miR-26a-5p improved airway remodeling in COPD by inhibiting ferroptosis of BECs via the PTGS2/PGE2 pathway.

BackgroundAn increasing number of studies have shown the association between traumatic events occurring in childhood and adolescence and post-traumatic stress disorder (PTSD). A gap remains in the literature on the epidemiology and influencing factors of traumatic events and post-traumatic stress disorder in communities in northern China. This study aimed to determine the prevalence of traumatic events and PTSD in communities in northern China, to explore the types of stressful traumatic events and the impact of these traumatic events on children and adolescents, and to investigate the effect of sociodemographic factors on PTSD.MethodsA cross-sectional survey study was conducted among 6,027 students (7–17 years old) from 6 cities in Liaoning Province, China. The sample consisted of 2,853 males (47.34%) and 3,174 females (52.66%). The Essen Trauma-Inventory for Children and Adolescents (ETI-CA) Scale was used. The ETI-CA has 5 sections, which include type of traumatic events, worst traumatic event, post-traumatic symptoms, onset, duration, burden of PTSD, and present difficulties in different areas of life. PTSD symptoms were assessed with 23 items in Part 3 of the ETI-CA.ResultsWe found that 2,068 (34.3%) of 6,027 participants experienced trauma events and 686 (33.2%) of 2,068 reported PTSD. Among trauma-exposed youth (2,068), the sudden death of close relatives (33.9%), serious accidents (20.9%), and parental divorce (15.5%) were reported as the worst traumatic events. Studies have shown that after exposure to stressful life events, more than 30% of people feel nervous or upset (39.8%), scared (33.4%), helpless (32.6%), and about 10% have headaches (15.5%), rapid heartbeat (13.3%), and dizziness (11.8%). Multivariable logistic regression analyses showed that students in middle school [OR = 1.29 (1.016, 1.637)], not a student leader [OR = 0.738 (0.618, 0.881)], and their parents in single marital status significantly predicted higher PTSD prevalence the remarried [OR = 0.474 (0.252, 0.893)], married [OR = 0.42 (0.227, 0.778)].ConclusionThe present study suggests the government to train psychological counselors in schools and communities to provide emotional and psychological support, as well as the school leaders and parents to elevate adolescents' psychological suzhi. Particularly, counseling and professional support should be given to those students whose parents are single.

BackgroundNon-alcoholic fatty liver disease (NAFLD), especially lean NAFLD is associated with an increased risk of atherosclerotic cardiovascular disease (CVD). It is not currently known which clinical phenotypes of NAFLD contribute most to individual subclinical atherosclerosis risk. We examined the relationship between body mass index (BMI), the metabolically healthy status, and subclinical atherosclerosis in the NAFLD population.MethodsData from asymptomatic NAFLD subjects who participated in a routine health check-up examination were collected. Participants were stratified by BMI (cutoff values: 24.0–27.9 kg/m2 for overweight and ≥28.0 kg/m2 for obesity) and metabolic status, which was defined by Adult Treatment Panel III criteria. Subclinical atherosclerosis was evaluated by brachial-ankle pulse wave velocity (baPWV) in 27,738 participants and by carotid plaque in 14,323 participants.ResultsWithin each BMI strata, metabolically unhealthy subjects had a significantly higher prevalence of subclinical atherosclerosis than metabolically healthy subjects, whereas fewer differences were observed across subjects within the same metabolic category. When BMI and metabolic status were assessed together, a metabolically unhealthy status was the main contributor to the association of clinical phenotypes with the subclinical atherosclerosis burden (all p

Abstract Background Previous studies, predominantly in Western individuals, have reported weight gain or weight loss are related to the increased depressive symptoms at all ages, but no study of depressive symptoms has examined its relation to actual (not just self-reported) weight changes in the middle-aged and older adults. Evidence of the relationship in older Asian individuals remains sparse. The study aimed to examine the relationship between weight changes and incidence of depressive symptoms in a nationally representative sample of community-dwelling older Asians. Method Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS), which included 17,284 adults aged 45 years. Participants were followed every two years using a face-to-face, computer-aided personal interview (CAPI) and structured questionnaire. We excluded participants with no follow-up data. The numbers of individuals who completed both the baseline and follow-up surveys were 3118 for the short-term (two years from 2011–2013) and the long-term (four years from 2011–2015). Additionally, to associate weight change with subsequent depressive symptoms, we also included 2472 participants without depressive symptom in 2013 and observed the incidence of depressive symptom in 2015 (subsequent term from 2013–2015). Finally, weight changes were classified as loss > -3%, stable-3–3%, gain3-6%, gain6-9%, and gain > 9%. Multivariable-adjusted cox regression in the study were used to assess the hazard ratios (HRs) of each weight change category. Results The incidence of depressive symptoms was 20.72% in the 2011–2013, 27.04% in the 2011–2015, and 23.02% in 2013–2015. Weight loss > 3% for all intervals was associated with higher depressive symptoms than stable weight during the 2011–2013 [1.305(1.031,1.651)] among the total populations. When stratified by sex, the results in males and females were different from those in the total population [females:1.389(0.997, 1.935); males:1.263(0.902, 1.767)]. Weight loss > 3% for intervals was associated with higher depressive symptoms than stable weight during the 2013–2015[1.643(1.140, 2.368)] among the males and its effect was also stronger for the total in 2011–2013. Moreover, there was no significant association between weight gain and incident depressive symptom, and no significant interaction effect in terms of the sex*weight changes. Conclusion Our findings could inform health promotion interventions to body-weight management aimed at improving the health of the middle-aged and older adults, particularly in the total people with short-term weight loss and males with subsequent term weight loss.

Abstract To quantitatively evaluate the impact of domestic aviation control measures on the spread of COVID-19 in China. The number of international flights from March to September 2019 simulated the number of flights from March to September 2020 without implementing aviation control measures. In addition, the proportion of asymptomatic persons and the delay in case reporting were adjusted to estimate the prevalence of each country during the same period and calculate the estimated imported cases. The estimated imported cases were assigned each day with weight, and the estimated daily reported cases were obtained based on the actual daily number of domestic cases in China. Effective Reproduction Number ( $$R_t$$ R t ) was calculated based on delayed distribution, Basic Reproductive Number ( $$R_0$$ R 0 ) distribution, and generation time distribution were reported in previous studies. Gaussian Process was used to estimate the effect of time-varying on $$R_t$$ R t , and the estimated $$R_t$$ R t was compared with the actual $$R_t$$ R t . The estimated imported cases increased significantly compared with the actual number of imported cases. The estimated imported cases were mainly concentrated in North America and Europe from March to April and gradually increased in many East Asian countries from May to September. The difference between predicted $$R_t$$ R t and actual $$R_t$$ R t was statistically significant. The estimated imported cases and the estimated $$R_t$$ R t have increased compared to the actual situation. This paper quantitatively proves that Chinese aviation control measures significantly suppress the COVID-19 epidemic, which is conducive to promoting and applying this measure.

Objective Musculoskeletal pain is having growing impacts worldwide with clinical challenge in pain management. The purpose of the present study is to investigate the preferences of orthopedic surgeons of China for using medicine in musculoskeletal pain. Methods A questionnaire was developed, including the following domains, personal information, medication preference for pain treatment, and perceptions of topical medicine. Ten participants were selected to confirm the consistency of questionnaire. A cross‐sectional survey was conducted in orthopedic physicians with different specialties in different regions of China via the online survey platform. The participants' survey results were analyzed one‐way and multi‐way using chi‐square test and logistic regression. Results The pre‐survey analysis results of 10 randomly selected investigators were a mean weighted kappa coefficient of 0.76 (range 0.61–0.89), which indicated the substantial consistency of the present questionnaire. A total of 1099 orthopedic surgeons (mean age, 41.67 ± 8.31 years) responded to our survey, most of whom were male (90.72%), and most of whom worked in level III hospitals (63.24%) and trained in modern medicine (71.43%). Most surgeons who participated in the survey had used topical analgesics in their clinical work (95.81%), and most preferred to use topical analgesics (39.50%) or a combination of oral analgesics (28.87%). Primary reasons for preferring topical analgesics were as follows: less adverse reactions (68.01%); ease of use (60.90%); and not interfering with other oral medications (49.60%). The preference for prescribing topical analgesics increased with the education level of the respondent, where statistically significant differences were seen (P

BackgroundIrreversible electroporation (IRE) is a novel local tumor ablation approach with the potential to stimulate an antitumor immune response. However, it is not effective in preventing distant metastasis in isolation. This study aimed to compare the potential of augmenting the antitumor immune response in patients with locally advanced pancreatic cancer (LAPC) who underwent IRE combined with chemotherapy and PD-1/PD-L1 blockade with those who underwent IRE combined with chemotherapy.MethodsA retrospective review was conducted on LAPC patients treated either with IRE in combination with chemotherapy and PD-1/PD-L1 blockade (group A) or with IRE with chemotherapy alone (group B) from July 2015 to June 2021. The primary outcomes were overall survival (OS) and progression-free survival (PFS), with immune responses and adverse events serving as secondary endpoints. Risk factors for OS and PFS were identified using univariate and multivariate analyses.ResultsA total of 103 patients were included in the final analysis, comprising 25 in group A and 78 in group B. The median duration of follow-up was 18.2 months (3.0–38.6 months). Group A patients demonstrated improved survival compared to group B (median OS: 23.6 vs. 19.4 months, p = 0.001; median PFS: 18.2 vs. 14.7 months, p = 0.022). The data suggest a robust immune response in group A, while adverse events related to the treatment were similar in both groups. The multivariate analysis identified the combination of IRE, chemotherapy, and PD-1/PD-L1 blockade as an independent prognostic factor for OS and PFS.ConclusionThe addition of PD-1/PD-L1 blockade to the regimen of IRE combined with chemotherapy enhanced antitumor immunity and extended survival in LAPC patients.

IntroductionMulberry bacterial wilt is a serious destructive soil-borne disease caused by a complex and diverse group of pathogenic bacteria. Given that the bacterial wilt has been reported to cause a serious damage to the yield and quality of mulberry, therefore, elucidation of its main pathogenic groups is essential in improving our understanding of this disease and for the development of its potential control measures.MethodsIn this study, combined metagenomic sequencing and culture-dependent approaches were used to investigate the microbiome of healthy and bacterial wilt mulberry samples.ResultsThe results showed that the healthy samples had higher bacterial diversity compared to the diseased samples. Meanwhile, the proportion of opportunistic pathogenic and drug-resistant bacterial flora represented by Acinetobacter in the diseased samples was increased, while the proportion of beneficial bacterial flora represented by Proteobacteria was decreased. Ralstonia solanacearum species complex (RSSC), Enterobacter cloacae complex (ECC), Klebsiella pneumoniae, K. quasipneumoniae, K. michiganensis, K. oxytoca, and P. ananatis emerged as the main pathogens of the mulberry bacterial wilt.DiscussionIn conclusion, this study provides a valuable reference for further focused research on the bacterial wilt of mulberry and other plants.

ObjectiveTo predict the optimal cut-off values for screening and predicting metabolic syndrome(MetS) in a middle-aged and elderly Chinese population using 13 obesity and lipid-related indicators, and to identify the most suitable predictors.MethodsThe data for this cross-sectional investigation came from the China Health and Retirement Longitudinal Study (CHARLS), including 9457 middle-aged and elderly people aged 45-98 years old. We examined 13 indicators, including waist circumference (WC), body mass index (BMI), waist-height ratio (WHtR), visceral adiposity index (VAI), a body shape index (ABSI), body roundness index (BRI), lipid accumulation product index (LAP), conicity index (CI), Chinese visceral adiposity index (CVAI), triglyceride-glucose index (TyG-index) and their combined indices (TyG-BMI, TyG-WC, TyG-WHtR). The receiver operating characteristic curve (ROC) was used to determine the usefulness of indicators for screening for MetS in the elderly and to determine their cut-off values, sensitivity, specificity, and area under the curve (AUC). Association analysis of 13 obesity-related indicators with MetS was performed using binary logistic regression analysis.ResultsA total of 9457 middle-aged and elderly Chinese were included in this study, and the overall prevalence of the study population was 41.87% according to the diagnostic criteria of NCEP ATP III. According to age and gender, the percentage of males diagnosed with MetS was 30.67% (45-54 years old: 30.95%, 55-64 years old: 41.02%, 65-74 years old: 21.19%, ≥ 75 years old: 6.84%). The percentage of females diagnosed with MetS was 51.38% (45-54 years old: 31.95%, 55-64 years old: 39.52%, 65-74 years old: 20.43%, ≥ 75 years old: 8.10%). The predictive power of Tyg-related parameters was more prominent in both sexes. In addition, LAP and CVAI are also good at predicting MetS. ABSI had a poor prediction ability.ConclusionsAmong the middle-aged and elderly population in China, after adjusting for confounding factors, all the indicators except ABSI had good predictive power. The predictive power of Tyg-related parameters was more prominent in both sexes. In addition, LAP and CVAI are also good at predicting MetS.

ObjectiveTo explore the correlation between baseline serum uric acid (SUA) and SUA changes with the incidence of type 2 diabetes mellitus (T2DM) among middle-aged and older individuals.MethodBinary logistic regression was used to calculate the odds ratio (ORs) and 95% confidence intervals (CIs) of the effects of baseline and changes in SUA on the incidence of T2DM. Stratified analysis was conducted based on sex, and the SUA levels were classified into four quartiles to assess the effect of baseline and relative changes in SUA on the incidence of T2DM. Furthermore, interaction analysis was performed between body mass index (BMI) and SUA, age and SUA, and sex and SUA.ResultsIn the cohort study, the highest quartiles of SUA were significantly correlated with an increased incidence of T2DM among females in model 1 [OR = 2.231 (1.631, 3.050)], model 2 [OR = 2.090 (1.523, 2.867)], model 3 [OR = 2.075 (1.511, 2.849)], and model 4 [OR = 1.707 (1.234, 2.362)]. The highest quartiles of SUA had a statistically significant effect on the incidence of T2DM among all participants in model 1 [OR = 1.601 (1.277, 2.008)], model 2 [OR = 1.519 (1.204, 1.915)], model 3 [OR = 1.597 (1.257, 2.027)], and model 4 [OR = 1.380 (1.083, 1.760)]. Regarding the relative change of SUA, the highest quantiles of SUA were significantly correlated with an increased incidence of T2DM among females in model 1 [OR = 1.409 (1.050, 1.890)], model 2 [OR = 1.433 (1.067, 1.926)], and model 3 [OR = 1.420 (1.056, 1.910)], and there was a statistically significant correlation with incident T2DM among all participants in model 4 [OR = 1.346 (1.079, 1.680)] after adjusting for all covariates. However, there was no significant correlation between baseline, relative, and absolute changes in SUA and the incidence of T2DM among males. The interaction analysis demonstrated that sex, BMI, and the relative changes in SUA had a combined effect on the incidence of T2DM, while age and the changes in SUA had a joint effect on the incidence of T2DM only in females.ConclusionThere was a positive association between SUA and the incidence of T2DM for all participants. However, significant sex differences in incidence were observed only in women, not men.

Grazing disturbance can change the structure of plant rhizosphere microbial communities and thereby alter the feedback to promote plant growth or induce plant defenses. However, little is known about how such changes occur and vary under different grazing pressures or the roles of root metabolites in altering the composition of rhizosphere microbial communities. In this study, the effects of different grazing pressures on the composition of microbial communities were investigated, and the mechanisms by which different grazing pressures changed rhizosphere microbiomes were explored with metabolomics. Grazing changed composition, functions, and co-expression networks of microbial communities. Under light grazing (LG), some saprophytic fungi, such as Lentinus sp., Ramichloridium sp., Ascobolus sp. and Hyphoderma sp., were significantly enriched, whereas under heavy grazing (HG), potentially beneficial rhizobacteria, such as Stenotrophomonas sp., Microbacterium sp., and Lysobacter sp., were significantly enriched. The beneficial mycorrhizal fungus Schizothecium sp. was significantly enriched in both LG and HG. Moreover, all enriched beneficial microorganisms were positively correlated with root metabolites, including amino acids (AAs), short-chain organic acids (SCOAs), and alkaloids. This suggests that these significantly enriched rhizosphere microbial changes may be caused by these differential root metabolites. Under LG, it is inferred that root metabolites, especially AAs such as L-Histidine, may regulate specific saprophytic fungi to participate in material transformations and the energy cycle and promote plant growth. Furthermore, to help alleviate the stress of HG and improve plant defenses, it is inferred that the root system actively regulates the synthesis of these root metabolites such as AAs, SCOAs, and alkaloids under grazing interference, and then secretes them to promote the growth of some specific plant growth-promoting rhizobacteria and fungi. To summarize, grasses can regulate beneficial microorganisms by changing root metabolites composition, and the response strategies vary under different grazing pressure in typical grassland ecosystems.

BackgroundRemnant cholesterol (RC) and chronic kidney disease (CKD) have not been definitively linked in individuals with different characteristics. This study aims to investigate the relationship between serum RC level and CKD and examine possible effect modifiers in Chinese patients with hypertension.MethodsOur study is based on the Chinese H-type Hypertension Project, which is an observational registry study conducted in real-world settings. The outcome was CKD, defined as an estimated glomerular filtration rate of less than 60 ml/min·1.73 m2. Multivariate logistic regression and smooth curve fitting were used to analyze the association between RC and CKD. Subgroup analyses were subsequently conducted to examine the effects of other variables.ResultsThe mean age of the 13,024 patients with hypertension at baseline was 63.8 ± 9.4 years, and 46.8% were male. A conspicuous linear positive association was observed between RC level and CKD (per SD increment; odds ratio [OR], 1.15; 95% confidence interval [CI], 1.08–1.23). Compared with the lowest quartile group of RC, the risk of CKD was 53% higher (OR, 1.53; 95% CI, 1.26–1.86) in the highest quartile group. Furthermore, a stronger positive association between RC level and CKD was found among participants with a higher body mass index (BMI

ObjectiveDepressive symptom is a serious mental illness often accompanied by physical and emotional problems. The prevalence of depressive symptom in older adults has become an increasingly important public health priority. Our study used cardiometabolic indicators to predict depressive symptom in middle-aged and older adults in China.MethodsThe data came from the China Health and Retirement Longitudinal Study 2011 (CHARLS2011), which was a cross-sectional study. The analytic sample included 8,942 participants aged 45 years or above. The study evaluated the relationship between cardiometabolic indicators and depression by measuring 13 indicators, including body mass index (BMI), waist circumference, waist-height ratio (WHtR), conicity index, visceral adiposity index (VAI), Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP), a body shape index (ABSI), body roundness index (BRI), triglyceride glucose index (TyG-index) and its correlation index (TyG-BMI, TyG-waist circumference, TyG-WHtR). Binary logistic regression analysis was used to examine the association between thirteen cardiometabolic indicators and depressive symptom. In addition, the receiver operating characteristic (ROC) curve analysis and area under curve (AUC) were used to evaluate the predictive anthropometric index and to determine the optimum cut-off value.ResultsThe study included 8,942 participants, of whom 4,146 (46.37%) and 4,796 (53.63%) were male and female. The prevalence of depressive symptom in mid-aged and older adults in China was 41.12% in males and 55.05% in females. The results revealed that BMI [AUC = 0.440, 95%CI: 0.422–0.457], waist circumference [AUC = 0.443, 95%CI: 0.425–0.460], WHtR [AUC = 0.459, 95%CI: 0.441–0.476], LAP [AUC = 0.455, 95%CI: 0.437–0.472], BRI [AUC = 0.459, 95%CI: 0.441–0.476], CVAI [AUC = 0.449, 95%CI: 0.432–0.467], TyG-BMI [AUC = 0.447, 95%CI: 0.429–0.465], and TyG-waist circumference [AUC =0.452, 95%CI: 0.434–0.470] were weak predictors of depressive symptom (p

Abstract Background Nursing students are experiencing complex learning environments and will experience complex work environments in future clinical work, which lead to emotional problems easily. However, one’s beliefs about controlling their emotions portend a series of vital psychological outcomes. So, it is especially important to search for suitable tools to assess the emotion and regulation beliefs of nursing students and give timely intervention to improve their physical and mental health. This study aimed to translate the American version of the Emotion and Regulation Beliefs Scale (ERBS) into Chinese, revise the original scale and form a simplified version, and assess the reliability and validity of the brief Chinese version in nursing students. Methods The study adopted a cross-sectional design and the multistage sampling design. The ERBS was translated into Chinese, and the reliability and validity of the Chinese version were tested in 980 nursing students. Results The content validity index was 0.920. Exploratory factor analysis supported a three-factor model for the Chinese version of Brief-ERBS, and confirmatory factor analysis indicated that the model fit the Brief-ERBS well. Furthermore, the three-factors model was obtained by using exploratory factor analysis, explaining 51.023% variance, and the communalities of the items ranged from 0.359 to 0.680. With modified confirmatory factor analysis, the fit indices were chi-square/degree of freedom (CMIN/DF) = 4.092, goodness of fit index (GFI) = 0.949, adjusted goodness of fit index (AGFI) = 0.927, comparative fit index (CFI) = 0.913, incremental fit index (IFI) = 0.914, Tucker Lewis index (TLI) = 0.908, root-mean-square error of approximation (RMSEA) = 0.061. The two-tailed independent samples t-test showed the scores of the top (50%) and low (50%) groups reached the level of significance (P

Appropriate grazing pressure and fertilizer application of nitrogen (N) and phosphorus (P) are effective measures to increase grassland productivity. In this study, we report on the interactive effects of grazing intensity and fertilizer application on soil properties, enzyme characteristics, and soil bacterial community compositions. The experiment was set up in a typical grassland in Xilingol, Inner Mongolia, and had 12 treatments (CC, CN, CP, CNP, LC, LN, LP, LNP, HC, HN, HP, and HNP). These consisted of three grazing intensity levels crossed with four fertilizer application treatments: no fertilizer, N fertilizer, P fertilizer addition alone, and both N and P fertilizers addition, subjected to field sampling and laboratory analysis. The results showed that soil alkaline hydrolysis nitrogen was increased by 15 and 13.6% in LN over LC in the 0–10 and 10–20 cm soil depth layers, respectively. Soil available P was 135.6% higher in LP than in LC at 0–10 cm but similar between LP and LC at 10–20 cm. Soil urease activity rose by 46.8 and 39.3% in 0–10 cm soil and was augmented by 63.1 and 60.3% in 10–20 cm soil of LN and LP relative to LC, respectively. Soil catalase (CAT) activity was decreased in response to LNP by 29.4, 23.5, and 26.5% vis-à-vis LC, LN, and LP in the 0–10 cm layer. Soil CAT activity also decreased in 0–20 cm layer for HN and HNP in comparison with HP. The relative abundance of Actinobacteria increased by 38.1 and 45.0% in HC over that in CC and LC, respectively, in 0–10 cm soil; compared with LC, it increased by 35.8 and 21.7% in LN and LNP, respectively. The relative abundance of Proteobacteria was increased in LNP versus LC in 0–10 cm soil. Overall, fertilizer application coupled with a light grazing intensity promoted key soil properties and the relative abundance of a dominant bacterial phylum.

IntroductionHematologic toxicity (HT) is a joint adverse event after CAR-T cells infusion. Some patients experience prolonged hematologic toxicity (PHT), which is challenging to treat.MethodsWe collected clinical data from patients with relapsed refractory B-ALL treated with CD19 CAR-T cells. Patients with PHT who did not respond to erythropoietin, platelet receptor agonists, transfusion, or G-CSF and eventually received low-dose prednisone therapy were included in the analysis. We retrospectively analyzed the efficacy and safety of low-dose prednisone on PHT.ResultsAmong 109 patients treated with CD19 CAR-T cells, 78.9% (86/109) of patients were evaluated as PHT. Of these, 15 patients had persistent hematological toxicity after infusion (12 were grade 3/4 cytopenia, 12 were trilineage cytopenia and 3 were bilineage cytopenia), 2 developed cytopenia without apparent cause after D28. The initial prednisone dose was 0.5 mg/kg/day, and the median response time was 21 days (7-40 days). The recovery rate of blood count was 100%, and the complete recovery rate ranged from 60% to 66.67%. Especially exciting was that HT recurred in 6 patients after stopping prednisone. They were relieved again after the administration of prednisone. The median follow-up time was 14.97 months (4.1-31.2 months). Twelve-month duration of PFS and OS rates were 58.8% (±11.9%) and 64.7% (±11.6%). We did not observe any other side effects of prednisone apart from drug-controllable hyperglycemia and hypertension.DiscussionWe suggest that low-dose prednisone is a beneficial and tolerable therapy for PHT after CAR-T cells. The trials have been registered at www.chictr.org.cn as ChiCTR-ONN-16009862 (November 14, 2016) and ChiCTR1800015164 (March 11, 2018).

Abstract Angiopoietin-like-4 (ANGPTL4), a secreted glycoprotein that is mainly known as a regulator in lipid metabolism, now, is also indicated to be involved in the regulation of cancer progression and metastasis. However, little is known about not only biological functions, but also underlying mechanism of ANGPTL4 in the progression of osteosarcoma (OS). Here, we discovered that ANGPTL4 is downregulated in OS, and is associated with branched-chain amino acid (BCAA) metabolism. The BCAAs (valine, leucine, and isoleucine) are essential amino acids that play an important role in metabolic regulation. Aberrant BCAA metabolism is also found in various cancers and is associated with tumor progression, including proliferation, invasion, and metastasis. In this study, we indicated that the negative relation between the expression of ANGPTL4 and BCAA catabolism in OS samples and cell lines. The knockdown of ANGPTL4 in OS cells resulted in the accumulation of BCAAs, which in turn activated the mTOR signaling pathway, enhancing OS cell proliferation. Thus, reduced expression of ANGPTL4 is associated with the progression of OS. Taken together, our results demonstrated that the ANGPTL4/BCAA/mTOR axis is an important pathway in OS progression and may be a potential therapeutic target to slow OS progression.

Abstract Background Transforming growth factor (TGF) is a cytokine that acts on the proliferation, migration, differentiation, and apoptosis of cells and the accumulation of extracellular matrix components. Very few studies have precisely evaluated the concentration of TGF-β in the aqueous humour (AH) of diabetic and cataract (DMC) eyes due to the low expression of proteins in the AH or other reasons. The concentrations of TGF-β1, -β2, and -β3 in the AH of the DMC group were compared with those of the age-related cataract (ARC) group. Methods We collected AH and lens epithelium samples from 33 DMC patients and 36 ARC patients. Luminex liquid suspension chip detection was applied to detect the concentration of TGF-β1, -β2, and -β3 in the AH samples. The expression of TGFB1/2/3 in lens epithelium samples was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Results The concentrations of TGF-β1 and TGF-β2 in AH samples of DMC eyes were higher than those of ARC eyes. The differences in TGF-β1 and TGF-β2 between the two groups were statistically significant (P value = 0.001 for TGF-β1, P value = 0.023 for TGF-β2). The difference of the correlation between TGF-β1 and glycosylated haemoglobin was significant (P value = 0.011, and Pearson correlation coefficient = 0.306). The difference of the correlation between TGF-β2 and glycosylated haemoglobin was significant (P value = 0.026, and Pearson correlation coefficient = 0.269). The mRNA expression levels of TGFB1 and TGFB2 were upregulated in DMC epithelium samples compared with ARC epithelium samples. The differences in TGFB1 and TGFB2 between the two groups were statistically significant (P value for TGFB1 = 0.041, P value for TGFB2 = 0.021). Conclusions The concentrations of TGF-β1 and TGF-β2 in AH samples were significantly higher in DMC eyes than in ARC eyes. The higher the glycosylated haemoglobin was, the higher the concentrations of TGF-β1 and -β2 were. The mRNA expression of TGFB1 and TGFB2 was significantly upregulated in DMC epithelial samples compared with ARC epithelial samples, suggesting the proinflammatory status of the anterior chamber of DMC eyes.

Abstract Aims Intralesional curettage is a commonly used treatment for primary bone tumors. However, local recurrence of tumors after curettage remains a major challenge. Questions (1) Is blood pressure related to local recurrence after intralesional curettage for benign or intermediate bone tumors? (2) What’s the impact of tourniquet usage on the risk of recurrence from high blood pressure? Methods This retrospective study evaluated patients receiving intralesional curettage for primary bone tumors from January 2011 to January 2015. A total of 411 patients with a minimum five-year follow-up were included for analysis. Demographic and disease-related variables were first assessed in univariable analyses for local recurrence risk. When a yielded p-value was 5 cm: OR, 3.58; 95% CI, 1.38–9.33; p = 0.009); anatomical site (proximal femur: OR, 2.49; 95% CI, 1.21–5.15; p = 0.014; proximal humerus: OR, 3.34; 95% CI, 1.61–6.92; p = 0.001); and preoperative mean arterial pressure (> 110 mmHg: OR, 2.61; 95% CI, 1.20–5.67; P = 0.015). In subgroup analyses, after adjusting for age, tumor type, lesion size, and anatomical site, tourniquet use modified the preoperative mean arterial pressure - recurrence relationship: when tourniquet was not used, preoperative mean arterial pressure predicted local recurrence (95–110 mmHg, 4.13, 1.42–12.03, p = 0.009; > 110 mmHg, 28.06, 5.27–149.30, p 0.05). Conclusions A high preoperative blood pressure was related to local recurrence after intralesional curettage for primary bone tumors in our study. Tourniquet usage and controlling blood pressure might be beneficial for reducing local recurrence in patients scheduled to receive intralesional curettage for primary bone tumor treatment. Level of evidence Level IV, hypothesis-generating study.

ObjectiveMetabolic syndrome is a common condition among middle-aged and elderly people. Recent studies have reported the association between obesity- and lipid-related indices and metabolic syndrome, but whether those conditions could predict metabolic syndrome is still inconsistent in a few longitudinal studies. In our study, we aimed to predict metabolic syndrome by obesity- and lipid-related indices in middle-aged and elderly Chinese adults.MethodA national cohort study that consisted of 3,640 adults (≥45 years) was conducted. A total of 13 obesity- and lipid-related indices, including body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), conicity index (CI), visceral adiposity index (VAI), Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP), a body shape index (ABSI), body roundness index (BRI), and triglyceride glucose index (TyG-index) and its correlation index (TyG-BMI, TyG-WC, and TyG-WHtR), were recorded. Metabolic syndrome (MetS) was defined based on the criteria of the National Cholesterol Education Program Adult Treatment Panel III (2005). Participants were categorized into two groups according to the different sex. Binary logistic regression analyses were used to evaluate the associations between the 13 obesity- and lipid-related indices and MetS. Receiver operating characteristic (ROC) curve studies were used to identify the best predictor of MetS.ResultsA total of 13 obesity- and lipid-related indices were independently associated with MetS risk, even after adjustment for age, sex, educational status, marital status, current residence, history of drinking, history of smoking, taking activities, having regular exercises, and chronic diseases. The ROC analysis revealed that the 12 obesity- and lipid-related indices included in the study were able to discriminate MetS [area under the ROC curves (AUC > 0.6, P < 0.05)] and ABSI was not able to discriminate MetS [area under the ROC curves (AUC < 0.6, P > 0.05)]. The AUC of TyG-BMI was the highest in men, and that of CVAI was the highest in women. The cutoff values for men and women were 187.919 and 86.785, respectively. The AUCs of TyG-BMI, CVAI, TyG-WC, LAP, TyG-WHtR, BMI, WC, WHtR, BRI, VAI, TyG index, CI, and ABSI were 0.755, 0.752, 0.749, 0.745, 0.735, 0.732, 0.730, 0.710, 0.710, 0.674, 0.646, 0.622, and 0.537 for men, respectively. The AUCs of CVAI, LAP, TyG-WC, TyG-WHtR, TyG-BMI, WC, WHtR, BRI, BMI, VAI, TyG-index, CI, and ABSI were 0.687, 0.674, 0.674, 0.663, 0.656, 0.654, 0.645, 0.645, 0.638, 0.632, 0.607, 0.596, and 0.543 for women, respectively. The AUC value for WHtR was equal to that for BRI in predicting MetS. The AUC value for LAP was equal to that for TyG-WC in predicting MetS for women.ConclusionAmong middle-aged and older adults, all obesity- and lipid-related indices, except ABSI, were able to predict MetS. In addition, in men, TyG-BMI is the best indicator to indicate MetS, and in women, CVAI is considered the best hand to indicate MetS. At the same time, TyG-BMI, TyG-WC, and TyG-WHtR performed better than BMI, WC, and WHtR in predicting MetS in both men and women. Therefore, the lipid-related index outperforms the obesity-related index in predicting MetS. In addition to CVAI, LAP showed a good predictive correlation, even more closely than lipid-related factors in predicting MetS in women. It is worth noting that ABSI performed poorly, was not statistically significant in either men or women, and was not predictive of MetS.

Soil organic carbon (SOC) and soil inorganic carbon (SIC) has important effects on soil physical, chemical and biological properties. They play an important role in coordinating the relationship between soil water and air, increasing soil water holding capacity and improving plant productivity. In this study, a boosted regression trees (BRT) model was developed to map the spatial distribution carbon stocks in the semi-arid region of Northeast China in 1990 and 2015. During the two periods, 10-fold cross-validation technology was used to test the performance and uncertainty of BRT model. In order to construct the model, 9 environmental variables (derived from climate, topography and biology) and 173 (1990) and 223 (2015) topsoil (0–30 cm) samples were used. The comparison between estimated and observed data shows that the RMSE of SOC and SIC stocks were 0.53 kgm−2 and 0.19 kgm−2 in 1990, and 0.65 kgm−2 and 0.20 kgm−2 in 2015, respectively. Elevation, normalized difference vegetation index, mean annual precipitation and Landsat band 3 were identifies as critical environmental factors for simulating the spatial distribution of SOC, accounting for 76.6 % and 70.3 % of the total relative importance in 1990 and 2015, respectively. Mean annual precipitation, mean annual temperature and topographic wetness index were the critical environmental factors for simulating the spatial variation of SIC during the two periods. Land use change also played an important role in the spatial variability of SOC and SIC stocks. In the past 25 years, soil carbon stocks decreased from 6.2 kg m−2 in 1990 to 5.9 kg m−2 in 2015. The spatial distribution pattern of SOC was high in northeastern area and low in southwestern area during the two periods, while the spatial distribution pattern of SIC was opposite to that of SOC stocks. The mapped soil carbon stock distribution is fundamental to future study of soil carbon cycle and regional carbon balance in semi-arid regions.

ObjectivePrevious studies have reported that navigation systems can improve clinical outcomes of intramedullary nailing (IMN) for patients with intertrochanteric fractures. However, information is lacking regarding the relationship between the costs of navigated systems and clinical outcomes. The present research aimed to evaluate the cost-effectiveness of navigated IMN as compared with traditional freehand IMN for patients with intertrochanteric fractures.MethodsA Markov decision model with a 5-year time horizon was constructed to investigate the costs, clinical outcomes and incremental cost-effectiveness ratio (ICER) of navigated IMN for a 70-year-old patient with an intertrochanteric fracture in mainland China. The costs [Chinese Yuan (¥)], health utilities (quality-adjusted life-years, QALYs) and transition probabilities were obtained from published studies. The willingness-to-pay threshold for ICER was set at ¥1,40,000/QALY following the Chinese gross domestic product in 2020. Three institutional surgical volumes were used to determine the average navigation-related costs per patient: low volume (100 cases), medium volume (200 cases) and high volume (300 cases).ResultsInstitutes at which 300, 200 and 100 cases of navigated IMN were performed per year showed an ICER of ¥43,149/QALY, ¥76,132.5/QALY and ¥1,75,083/QALY, respectively. Navigated IMN would achieve cost-effectiveness at institutes with an annual volume of more than 125 cases.ConclusionsOur analysis demonstrated that the navigated IMN could be cost-effective for patients with inter-trochanteric fracture as compared to traditional freehand IMN. However, the cost-effectiveness was more likely to be achieved at institutes with a higher surgical volume.

Abstract Glycosylation is an important modification of membrane proteins that results in functional changes in many cellular activities, from cell-cell recognition to regulatory signaling. Fucosyltransferase 8 (FUT8) is the sole enzyme responsible for core fucosylation, and aberrant fucosylation by dysregulated expression of fucosyltransferases is responsible for the growth of various types of carcinomas. However, the function of FUT8 in the progress of osteosarcoma (OS) has not been reported. In this study, we found that FUT8 is expressed at lower levels in patients with OS and in human OS cell lines such as MNNG/HOS, U2OS, and 143B, suggesting that attenuated expression of FUT8 is involved in the growth and progression of OS. Mechanistically, FUT8 affects the survival strategy of OS by modifying core-fucosylation levels of TNF receptors (TNFRs). Lower fucosylation of TNFRs activates the non-canonical NF-κB signaling pathway, and in turn, decreases mitochondria-dependent apoptosis in OS cells. Together, our results point to FUT8 being a negative regulator of OS that enhances OS-cell apoptosis and suggests a novel therapeutic strategy for treating OS.

Abstract Background The determination of systemic inflammatory markers is one of the important directions to study the pathogenesis of asthma and improve the diagnosis of asthma. Current studies have found that the 14-3-3 protein family subtypes interact with target proteins to participate in the pathogenesis of a variety of immune inflammatory diseases. However, studies on serum tyrosine3-monooxygenase/tryptophan5-monooxygenase activation protein β (14-3-3β) in asthma are scarce. This study aimed to assess the clinical significance of 14-3-3β in asthmatic patients. Methods We recruited 54 asthmatic patients with acute exacerbation and 50 asthmatic patients with chronic persistent. The normal control group included 54 healthy individuals. Clinical characteristics, clinical indicators [fractional expiratory nitric oxide (FeNO), eosinophil count, forced vital capacity (FVC), percent of predicted FVC (FVC% predicted), forced expiratory volume in one second (FEV1), percent of predicted FEV1 (FEV1% predicted), the ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC) and serum 14-3-3β levels were measured to compare among each group. Spearman’s rank correlation coefficient was used to evaluate the correlation between 14-3-3β and clinical indicators. Finally, Receiver-operating characteristic (ROC) curves analysis was used to determine the sensitivity and specificity of 14-3-3β. Results Our results showed that median (interquartile range) of serum 14-3-3β concentration (ng/mL) in acute exacerbation group of asthma (41.18 [33.06–51.76]) was much higher than that in normal control group (24.99 [17.43–29.91]; P

Abstract Background Malnutrition in early life may affect health in later life. The associations between malnutrition and serum uric acid (SUA) and hypertension were inconsistent. The present study aimed to investigate the individual and combined association between famine exposure and serum uric acid and hypertension in middle-aged and older Chinese. Methods Data were selected from the China Health and Retirement Longitudinal Study (CHARLS) Wave2011. The analytic sample included 9368 individuals aged 45 to 90. Differences between baseline characteristics and famine exposure/SUA level were evaluated using the Chi-square test, t-test, and F-test. Then, the differences in the prevalence of hypertension between characteristic groups was also estimated by the Chi-square and t-test. Finally, multivariable-adjusted logistic regression models examined association of famine exposure and serum uric acid with odds of prevalence of hypertension. Results A total of 9368 individuals were enrolled in the study, 4366 (46.61%) and 5002 (53.39%) were male and female, respectively. Among males, 459 (10.51%) had been exposed to the Chinese famine during the fetal stage, whereas 1760 (40.31%) and 1645 (37.68%) had been exposed to the famine during childhood and adolescence/adult stage, respectively. Among females, 635 (12.69%) had been exposed to the Chinese famine during the fetal stage, whereas 1988 (39.74%) and 1569 (31.37%) had been exposed to the famine during childhood and adolescence/adult stage, respectively. Regarding the participants with SUA level measurements, 290 (6.64%) reported having Hyperuricemia (HUA) in males and 234 (4.68%) in the females. Furthermore, 1357 (31.08%) reported having hypertension in male and 1619 (32.37%) in the female. In multivariable-adjusted model, famine exposure and serum uric acid were associated with prevalence of hypertension independently in total populations [(1) Model fourd, fatal exposed group vs non-exposed group: 1.25 (95% CI 1.03, 1.52); childhood-exposed group vs non-exposed group:1.60 (95% CI 1.37, 1.87); adolescence/adult exposed group vs non-exposed group: 2.87 (95% CI 2.44, 3.37), P for trend

ObjectiveThe pandemic of COVID-19 continues to challenge people's health worldwide. In the second year of the pandemic, adherence to COVID-19 preventive behavior is key to continuing efforts to overcome the epidemic. This study aims to assess the COVID-19-related knowledge, attitude, and prevention behavior (KAP) and electronic health literacy (eHealth literacy) among Anhui residents in China.MethodsFrom January 30 to March 27, 2021, the cross-sectional study was performed among Anhui residents in China, including 16 cities. An online survey was adopted to assess KAP regarding COVID-19, and eHealth, involving a total of 2,122 citizens. Following informed consent, residents were recruited by convenience sampling. Frequencies and proportions were calculated. Additionally, Mann–Whitney U tests were used to analyze the variables. Independent predictors of preventive behavior of COVID-19 were ascertained using a multivariable logistic regression model.ResultResidents demonstrated good knowledge, positive attitudes, acceptable practices, and good eHealth literacy. Online news and WeChat are the main health information resources. Citizens who had good knowledge, a positive attitude, good eHealth, and did not participate in the online lectures or training COVID-19 were more likely to take preventive measures. Those with poor health, who were male, did not have family members working in health care facilities, and did not work in a face-to-face environment were less likely to take precautions. Compared with a master's degree and above, participants with middle school education level and below took preventive behavior sometimes. Residents who browse the COVID-19 webpage

Abstract Purpose Malignant pleural effusion (MPE) is an adverse prognostic factor in patients with osteoblastic osteosarcoma; however, the cellular contexts of MPE are largely unknown. Experimental design We performed single‐cell RNA‐sequencing (scRNA‐seq) on 27 260 cells from seven MPE samples and 91 186 cells from eight osteosarcoma tissues, including one recurrent, one lung metastasis and six primary tumour (PT) samples, to characterize their tumour microenvironment. Results Thirteen main cell groups were identified in osteosarcoma tumour and MPE samples. Immune cells dominate the cellular contexts in MPE with more T/NK cells and less osteoclasts compared to PT samples. Of T/NK cells, CD8+GNLY+, CD8+KLRC2+ T cells and FCGR3A+NK cells were enriched in MPE but CD4+FOXP3+ Tregs were enriched in PT samples. Naïve IGHD+ B and immune regulatory IGHA1+ B cells were largely identified in MPE, whereas bone metabolism‐related CLEC11A+ B cells were significantly enriched in osteosarcoma PT. M2‐type TAMs, including CLEC11A_TAM, C1QC_TAM and Prolif_TAMs, among myeloid cells were enriched in PT, which may suppress cytotoxicity activities of T cells through multiple ligand–receptor interactions. Mature LAMP3+ DCs were transformed from CD1C+ DC and CLEC9A+ DC sub‐clusters when exposure to tumour alloantigens, which may improve T cell cytotoxicity activities on tumour cells under anti‐PD‐L1 treatments. In further, immune cells from MPE usually present up‐regulated glycolysis and down‐regulated oxidative phosphorylation and riboflavin metabolism activities compared to those in PT samples. Conclusions Our study provided a novel cellular atlas of MPE and PT in patients with advanced osteosarcoma, which may provide potential therapeutic targets in the future.

Background: The prevalence of Type 1 Diabetes is increasing in pediatrics and diabetes education plays one of the most important role in the management of diabetes, especially in children. However, the related evidence concerned diabetes education is rare in children and adolescents. Therefore, we aimed to investigate the status of diabetes education in hospital, which could help us know the reality of diabetes education. Methods: We choose a nurse who is mainly responsible for diabetes education and management in each hospital to fill out the questionnaire. Overall, 98 nurses were enrolled from tertiary children's specialized hospitals and pediatric wards of general tertiary hospitals from Jan 2018 to Dec 2019. Results: Of 98 nurses enrolled, 61 (63.3%) nurses from 98 hospitals responded, 39 (63.9%) of them received specialized training in diabetes. There were no differences in education characteristics among regions of China. There were 26(42.6%) hospitals have a full-time nurse for diabetes education or nurses with endocrinology training increased with the number of cases/year (P=0.02 and P=0.009). The use of game-based education, knowledge assessment at discharge did not vary among hospital volumes, and the presence of a psychiatrist (P=0.41, P=0.65, and P=0.85, respectively). Diet management education is the most common (23.0%) difficulty in children diabetes education. Conclusion: The level of diabetes education in children and adolescents varied among hospitals, but not among regions in China. There was a lack of resources provided for children and adolescents diabetes education in terms of training and specialized services.

Numerous in vitro and in vivo studies have shown that curcumin primarily activates apoptotic pathways in cancer cells and inhibits cancer progression by modulating various molecular targets. In this study, we utilized reverse docking servers to predict 444 human proteins that may potentially be targeted by curcumin. Then, high-throughput assays were conducted by using RNA-seq technology on curcumin-treated MCF-7 (human breast cancer ER (+)) and MDA-MB-231 (human breast cancer ER(-)/TNBC) cancer cell lines. Enrichment analysis identified seven and eight significantly down-regulated signaling pathways in these two cell lines, where the enriched genes were used to construct protein–protein interaction networks. From these networks, the MCODE algorithm screened out 42 hub targets, which are core genes of the RTK-(PI3K-AKT)/(MEK/ERK1/2) crosstalk network. Genetic alteration and expression patterns of hub targets of curcumin may be closely related to the overall pathogenesis and prognosis of breast cancer. MAPKAPK3, AKT3, CDK5, IGF1R, and MAPK11 are potential prognostic markers and therapeutic targets of curcumin in patients with triple-negative breast cancer. Molecular docking and transcriptomic results confirmed that curcumin can inhibit these high-scoring targets at the protein level. Additionally, these targets can act as self-feedback factors, relying on the cascading repressive effects in the network to limit their own transcription at the mRNA level. In conclusion, the integration of transcriptomic and molecular docking approaches enables the rapid identification of dual or multiple inhibitory targets of curcumin in breast cancer. Our study provides the potential elucidation of the anti-cancer mechanism of curcumin.

Localization is one of the essential problems in internet of things (IoT) and wireless sensor network (WSN) applications. However, most traditional range-free localization algorithms cannot fulfill the practical demand for high localization accuracy. Therefore, a localization algorithm based on an enhanced flower pollination algorithm (FPA) with Gaussian perturbation (EFPA-G) and the DV-Hop method is proposed.FPA is widely applied, but premature convergence still cannot be avoided. How to balance its global exploration and local exploitation capabilities still remains an outstanding problem. Therefore, the following improvement schemes are introduced. A search strategy based on Gaussian perturbation is proposed to solve the imbalance between the global exploration and local exploitation search capabilities. Meanwhile, to fully exploit the variability of population information, an enhanced strategy is proposed based on optimal individual and Lévy flight. Finally, in the experiments with 26 benchmark functions and WSN simulations, the former verifies that the proposed algorithm outperforms other state-of-the-art algorithms in terms of convergence and search capability. In the simulation experiment, the best value for the normalized mean squared error obtained by the most advanced algorithm, RACS, is 20.2650%, and the best value for the mean distance error is 5.07E+00. However, EFPA-G reached 19.5182% and 4.88E+00, respectively. It is superior to existing algorithms in terms of positioning, accuracy, and robustness.

Diabetes is characterized by dysfunction and loss of beta-cells, and promoting beta-cell survival is of therapeutic interest. Here the authors show that Large-tumor suppressor 2 (LATS2), a core component of the Hippo signaling pathway, induces beta-cell failure through mTORC1 hyperactivation and autophagic flux suppression.

Given the fragmentation of public opinion dissemination and the lag of network users’ cognition, the paper analyzes public opinion dissemination with incomplete information, which can provide reference for us to control and guide the spread of public opinion. Based on the derivative and secondary radiation of public opinion dissemination with incomplete information, the Susceptible-Susceptible-Infected-Recovered-Recovered-Infected (SSIRR-I) model is proposed. Given the interaction between users, the Deffuant opinion dynamics model and evolutionary game theory are introduced to simulate the public opinion game between dissemination and immune nodes. Finally, the numerical simulation and results analysis are given. The results reveal that the rate of opinion convergence significantly affects disseminating public opinion, which is positively correlated with the promotion effect of the dissemination node and negatively correlated with the suppression effect of the immune node of public opinion dissemination. Derivative and secondary radiations have different effects on public opinion dissemination in the early stage, but promote public opinion dissemination in the later stage. The dominant immune nodes have an apparent inhibitory effect on the spread of public opinion; nevertheless, they cannot block the dissemination of public opinion.

Mycoplasma hyopneumoniae is the etiological agent of swine enzootic pneumonia (EP), which resulting in considerable economic losses in pig farming globally. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is a major tool for gene expression studies. However, no internal reference genes for normalization of RT-qPCR data of M. hyopneumoniae have been reported. The aim of this study was to screen the most stable genes for RT-qPCR analysis in M. hyopneumoniae under different conditions. Therefore, a total of 13 candidate internal reference genes (rpoC, Lipo, sgaB, oppB, hypo621, oppF, gyrB, uvrA, P146, prfA, proS, gatB, and hypo499) of M. hyopneumoniae filtered according to the reported quantitative proteomic analysis and the 16S rRNA internal reference gene frequently used in other bacteria were selected for RT-qPCR analysis. The mRNAs from different virulence strains (168, 168 L, J, NJ, and LH) at five different growth phases were extracted. The corresponding cycle threshold (Ct) values of the 25 reverse transcribed cDNAs using the 14 candidate genes were determined. Different internal reference genes or combinations were then screened for expression stability analysis using various statistical tools and algorithms, including geNorm, BestKeeper, and NormFinder software, to ensure the reliability of the analysis. Through further comprehensive evaluation of the RefFinder software, it is concluded that the gatB gene was the most suitable internal reference gene for samples of the different virulence strains in different growth phases for M. hyopneumoniae, followed by prfA, hypo499, and gyrB.

Abstract In recent years, carbon dots (CDs), including carbon nanodots, carbonized polymer dots, carbon quantum dots, and graphene quantum dots have attracted a mounting interest as readily accessible, nontoxic, and relatively inexpensive carbon‐based nanomaterials. Yet, despite intense research for a number of years, a unifying picture is still lacking to clarify the exact definition, clear chemical structure, and unique optical properties of this family of nanomaterials. In this review, we systematically summarize the recent development of CDs from molecular design to related properties of excited states as well as their applications in optoelectronic devices and biology. We point out the current challenges, including exploring precise synthesis, clarifying the structure‐property relationship, and regulating singlet and triplet states of fluorescence, phosphorescence, and delayed fluorescence. Moreover, the structural optimization of optoelectronic devices, tumor targeting mechanism, selective imaging, and drug delivery of CDs are also highlighted. We hope that the information provided in this review will inspire more exciting research on CDs from a brand‐new perspective and promote practical application of CDs in multiple directions of current and future research.

BackgroundPatients with lung adenocarcinoma (LUAD) exhibit significant heterogeneity in therapeutic responses and overall survival (OS). In recent years, accumulating research has uncovered the critical roles of hypoxia in a variety of solid tumors, but its role in LUAD is not currently fully elucidated. This study aims to discover novel insights into the mechanistic and therapeutic implications of the hypoxia genes in LUAD cancers by exploring the potential association between hypoxia and LUAD.MethodsFour machine learning approaches were implemented to screen out potential hypoxia-related genes for the prognosis of LUAD based on gene expression profile of LUAD samples obtained from The Cancer Genome Atlas (TCGA), then validated by six cohorts of validation datasets. The risk score derived from the hypoxia-related genes was proven to be an independent factor by using the univariate and multivariate Cox regression analyses and Kaplan–Meier survival analyses. Hypoxia-related mechanisms based on tumor mutational burden (TMB), the immune activity, and therapeutic value were also performed to adequately dig deeper into the clinical value of hypoxia-related genes. Finally, the expression level of hypoxia genes was validated at protein level and clinical samples from LUAD patients at transcript levels.ResultsAll patients in TCGA and GEO-LUAD group were distinctly stratified into low- and high-risk groups based on the risk score. Survival analyses demonstrated that our risk score could serve as a powerful and independent risk factor for OS, and the nomogram also exhibited high accuracy. LUAD patients in high-risk group presented worse OS, lower TMB, and lower immune activity. We found that the model is highly sensitive to immune features. Moreover, we revealed that the hypoxia-related genes had potential therapeutic value for LUAD patients based on the drug sensitivity and chemotherapeutic response prediction. The protein and gene expression levels of 10 selected hypoxia gene also showed significant difference between LUAD tumors tissues and normal tissues. The validation experiment showed that the gene transcript levels of most of their genes were consistent with the levels of their translated proteins.ConclusionsOur study might contribute to the optimization of risk stratification for survival and personalized management of LUAD patients by using the hypoxia genes, which will provide a valuable resource that will guide both mechanistic and therapeutic implications of the hypoxia genes in LUAD cancers.

ABSTRACT Mycoplasma hyorhinis is a widespread pathogen in pig farms worldwide. Although the majority of M. hyorhinis-colonized pigs have no apparent clinical disease, the pathogen can induce diseases such as polyserositis, arthritis, and eustachitis in some cases. To explore the mechanisms for the occurrence of these diseases, we challenged 4 groups of Bama miniature pigs with M. hyorhinis isolated from pigs without clinical symptoms (non-clinical origin [NCO] strain) or with typical clinical symptoms (clinical origin [CO] strain) and investigated the impacts of different strains and inoculation routes (intranasal [IN], intravenous [IV] + intraperitoneal [IP], and IV+IP+IN) on disease induction. Another group of pigs was set as a negative control. Pigs inoculated with the CO strain through a combined intravenous and intraperitoneal (IV+IP) route showed a significant decrease in average daily weight gain (ADWG), serious joint swelling, and lameness compared with the pigs in the negative-control group. Furthermore, this group developed moderate-to-severe pericarditis, pleuritis, peritonitis, and arthritis, as well as high levels of IgG and IgM antibodies. Pigs inoculated IV+IP with the NCO strain developed less marked clinical, pathological changes and a weaker specific antibody response compared with the pigs inoculated with the CO strain. The challenging results of the NCO strain via different routes (IV+IP, IV+IP+IN, and IN) indicated that the combined route (IV+IP) induced the most serious disease compared to the other inoculation routes. Intranasal inoculation induced a smaller decrease in ADWG without obvious polyserositis or arthritis. These data suggest that differences in both strain virulence and inoculation route affect the consequences of M. hyorhinis infection. IMPORTANCE Mycoplasma hyorhinis is a widespread pathogen in pig farms worldwide. The mechanisms or conditions that lead to the occurrence of disease in M. hyorhinis-infected pigs are still unknown. The objective of this study was to evaluate the impact of differences in the virulence of strain and the inoculation route on the consequences of M. hyorhinis infection.

Abstract Background Relevant studies focusing on epidemiological of profiles hypertensive disorders of pregnancy from global data that report the cause-specific prevalence and trends of hypertensive disorders of pregnancy at global, regional and national levels from 1990 to 2019 by age and sociodemographic index are still limited. Methods For hypertensive disorders of pregnancy, point prevalence, annual incidence, and years lived with disability numbers and age standardized rates per 100,000 population were compared at regional and national levels by age and sociodemographic index using data from the global Burden of Disease 2019 Study, covering populations from 204 countries and territories. Estimates are reported with uncertainty intervals to exhibit the changing trends during a specific period. Results The incidence of hypertensive disorders of pregnancy increased from 16.30 million to 18.08 million globally, with a total increase of 10.92 % from 1990 to 2019. The age-standardized incidence rate decreased, with an estimated annual percent change of -0.68 (95 % confidence interval [CI] -0.49 to -0.86). The number of deaths due to hypertensive disorders of pregnancy was approximately 27.83 thousand in 2019, representing a 30.05 % decrease from 1990. Based on the incidence and prevalence, the number of deaths and years lived with disability were highest in the group aged 25–29 years, followed by the groups aged 30–34 and 20–24 years, while the lowest estimated incidence rate was observed in the group aged 25–29 years and higher incidence rates were observed in the youngest and oldest groups. Positive associations between incidence rates and the sociodemographic index and human development index were found for all countries and regions in 2019. Age-standardized incidence rates were higher in countries/regions with lower sociodemographic indices and human development indices. Conclusions Our study provides a comprehensive overview of the global burden of hypertensive disorders of pregnancy. The death and incidence rates are decreasing in most countries and all regions except for those with low sociodemographic and human development indexes. This difference is mainly due to the increasing attention to prenatal examinations and health education. Further investigations should focus on forecasting the global disease burden of specific hypertensive disorders of pregnancy and modifiable risk factors.

Abstract Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs, targeted therapeutic drugs have become mainstream cancer treatments. Since the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration (FDA) in 2001, an increasing number of small-molecule targeted drugs have been developed for the treatment of malignancies. By December 2020, 89 small-molecule targeted antitumor drugs have been approved by the US FDA and the National Medical Products Administration (NMPA) of China. Despite great progress, small-molecule targeted anti-cancer drugs still face many challenges, such as a low response rate and drug resistance. To better promote the development of targeted anti-cancer drugs, we conducted a comprehensive review of small-molecule targeted anti-cancer drugs according to the target classification. We present all the approved drugs as well as important drug candidates in clinical trials for each target, discuss the current challenges, and provide insights and perspectives for the research and development of anti-cancer drugs.

Objective: Hepatocyte nuclear factor 4α (HNF4A) has been demonstrated to be an oncogene in gastric cancer (GC). However, the roles of different HNF4A isoforms derived from the 2 different promoters (P1 and P2) and the underlying mechanisms remain obscure. Methods: The expression and prognostic values of P1- and P2-HNF4A were evaluated in The Cancer Genome Atlas (TCGA) databases and GC tissues. Then, functional assays of P1- and P2-HNF4A were conducted both in vivo and in vitro. High-throughput RNA-seq was employed to profile downstream pathways in P1- and P2-HNF4A-overexpressing GC cells. The expression and gene regulation network of the candidate target genes identified by RNA-seq were characterized based on data mining and functional assays. Results: HNF4A amplification was a key characteristic of GC in TCGA databases, especially for the intestinal type and early stage. Moreover, P1-HNF4A expression was significantly higher in tumor tissues than in adjacent non-tumor tissues (P < 0.05), but no significant differences were found in P2-HNF4A expression (P > 0.05). High P1-HNF4A expression indicated poor prognoses in GC patients (P < 0.01). Furthermore, P1-HNF4A overexpression significantly promoted SGC7901 and BGC823 cell proliferation, invasion and migration in vitro (P < 0.01). Murine xenograft experiments showed that P1-HNF4A overexpression promoted tumor growth (P < 0.05). Mechanistically, RNA-seq showed that the cytokine-cytokine receptor interactions pathway was mostly enriched in P1-HNF4A-overexpressing GC cells. Finally, chemokine (C-C motif) ligand 15 was identified as a direct target of P1-HNF4A in GC tissues. Conclusions: P1-HNF4A was the main oncogene during GC progression. The cytokine-cytokine receptor interaction pathway played a pivotal role and may be a promising therapeutic target.

Osteosarcomas are difficult to treat and have a limited response to immunotherapy. Here, the authors analyse osteosarcomas at the single-cell level, and identify both the transdifferentiation of malignant cells and an array of immune cells that could have implications for metastasis and immunotherapy.

Objective We investigated the moderation/mediation between the age of menarche and obesity parameters in predicting blood pressure (BP) in middle-aged and elderly Chinese.Design Our study is a population-based cross-sectional study.Setting Participants in this study came from the China Health and Retirement Longitudinal Study (CHARLS).Participants The analytical sample included 4513 participants aged 45–96 years.Main outcome measurements Data were selected from the CHARLS, a cross-sectional study. Between-group differences were evaluated using χ2, t-test and one-way analysis of variance. The trend of related variables by characteristics was also tested using contrast analysis, as appropriate. Then, correlations between characteristics, moderator, mediator, and independent and dependent variables were used by Spearman’s correlation test and Pearson’s correlation test. Finally, the mediation analysis was performed by model 4 in PROCESS V3.3 macro for SSPSS, and moderation analysis was used by model 1 for assessment. All covariates were adjusted in the moderation or mediation models.Results In the correlation analysis, body mass index (BMI) and waist circle (WC) level were positively correlated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP) in women (BMI and DBP: r=0.221, p

ObjectivePrefrailty and frailty are two common conditions among older individuals. Recent studies have reported the association between frailty and depressive symptoms, but whether those conditions could predict depressive symptoms is still inconsistent in a few longitudinal studies. In our study, we aimed to estimate the cross-sectional and longitudinal associations between frailty and incident depressive symptoms in a nationally representative sample of community-dwelling middle-aged and older Chinese adults.MethodData were obtained from the China Health and Retirement Longitudinal Study (CHARLS), which included 17,284 adults aged ≥ 45 years. Participants were followed every two years using a face-to-face, computer-aided personal interview (CAPI) and structured questionnaire. We excluded participants with no follow-up data. The numbers of individuals who completed the baseline surveys were 2,579 and follow-up surveys were 839 for the short-term (2 years from 2011 to 2013) and 788 for the long-term (4 years from 2011 to 2015). In addition, Frailty was measured by the Fried criteria and depressive symptoms were estimated by the Chinese version of the Center for Epidemiologic Studies-Depression scale (CES-D). Logistic regression was used to analyze the odds ratio (OR), and 95% confidence interval (CI) for the cross-sectional associations of frailty and its components with depressive symptoms in the participants at baseline. Cox proportional hazards analysis was conducted using the hazard ratio (HR), and 95% confidence interval (CI) for the prospective associations of baseline frailty and pre-frailty and its component in the participants without depressive symptoms at baseline.ResultsAt baseline, 57.93% of participants had depressive symptoms and 55.84% had pre-frail and 11.63% had frailty. In the cross-sectional analysis, both pre-frailty (OR = 5.293, 95%CI 4.363–6.422) and frailty (OR = 16.025, 95%CI 10.948–23.457) were associated with depressive symptoms. In the longitudinal analysis, frailty [HR = 1.395 (0.966–2.013)] and pre-frailty [HR = 2.458 (0.933, 6.479)] were not significantly associated with incident depressive symptoms in a full-adjusted model among participants free of baseline depressive symptoms during the short-term. However, frailty [HR = 1.397 (1.017, 1.920)] and pre-frailty [HR = 2.992 (1.210, 7.397)] were significantly associated with incident depressive symptoms during the short term. In the components of frailty, slowness [HR = 1.597 (1.078, 2.366)] was associated with an increased risk of depressive symptoms onset during the short-term. Weakness [HR = 2.08 (1.055, 4.104)] and exhaustion [HR = 1.928 (1.297, 2.867)] were associated with increased risk of depressive symptoms onset during the short-term.ConclusionAmong the middle-aged and older adults, frailty, pre-frailty did not predict depressive symptoms during 2 years of follow-up, when accounting for the potential confounders, slowness considered alone predicted depressive symptoms. Additionally, frailty, pre-frailty predicted depressive symptoms during 4 years of follow-up, when accounting for the potential confounders, weakness and exhaustion considered alone predicted depressive symptoms.