MiR-9 promotes G-MDSC recruitment and tumor proliferation by targeting SOCS3 in breast cancer.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of cells that differentiate from myeloid cells, proliferate in cancer and inflammatory reactions, and mainly exert immunosuppressive functions. Nonetheless, the precise mechanisms that dictate both the accumulation and function of MDSCs remain only partially elucidated. In the course of our investigation, we observed a positive correlation between the content of MDSCs especially G-MDSCs and miR-9 level in the tumor tissues derived from miR-9 knockout MMTV-PyMT mice and 4T1 tumor-bearing mice with miR-9 overexpression. Combined with RNA-seq analysis, we identified SOCS2 and SOCS3 as direct targets of miR-9. Additionally, our research unveiled the pivotal role of the CCL5/CCR5 axis in orchestrating the chemotactic recruitment of G-MDSCs within the tumor microenvironment, a process that is enhanced by miR-9. These findings provide fresh insights into the molecular mechanisms governing the accumulation of MDSCs within the framework of breast cancer development.

Transforming growth factor-ß1 protects against white matter injury and reactive astrogliosis via the p38 MAPK pathway in rodent demyelinating model.

In central nervous system (CNS), demyelination is a pathological process featured with a loss of myelin sheaths around axons, which is responsible for the diseases of multiple sclerosis, neuromyelitis optica, and so on. Transforming growth factor-beta1 (TGF-ß1) is a multifunctional cytokine participating in abundant physiological and pathological processes in CNS. However, the effects of TGF-ß1 on CNS demyelinating disease and its underlying mechanisms are controversial and not well understood. Herein, we evaluated the protective potential of TGF-ß1 in a rodent demyelinating model established by lysophosphatidylcholine (LPC) injection. It was identified that supplement of TGF-ß1 evidently rescued the cognitive deficit and motor dysfunction in LPC modeling mice assessed by novel object recognition and balance beam behavioral tests. Besides, quantified by luxol fast blue staining, immunofluorescence, and western blot, administration of TGF-ß1 was found to significantly ameliorate the demyelinating lesion and reactive astrogliosis by suppressing p38 MAPK pathway. Mechanistically, the results of in vitro experiments indicated that treatment of TGF-ß1 could directly promote the differentiation and migration of cultured oligodendrocytes. Our study revealed that modulating TGF-ß1 activity might serve as a promising and innovative therapeutic strategy in CNS demyelinating diseases.

Analysis of the prevalence and clinical features of respiratory syncytial virus infection in a pediatric hospital in Zhejiang Province from 2019 to 2023.

The aim of this study was to investigate the epidemiological characteristics of respiratory syncytial virus (RSV) infections in children in Zhejiang from 2019 to 2023. Data from pediatric patients who visited the Children's Hospital of Zhejiang University School of Medicine for RSV infection between 2019 and 2023 were analyzed. Nasopharyngeal swabs were collected for RSV antigen detection, and relevant patient information was collected. Factors such as age were analyzed. A total of 673 094 specimens were included from 2019 to 2023, with a rate of positive specimens of 4.74% (31 929/673 094). The highest rate of positive specimens of 10.82%, was recorded in 2021, while the remaining years had a rate of approximately 3%-5%. In terms of seasonal prevalence characteristics, the rate of positive specimens in 2019, 2020, and 2022 peaked in the winter months at approximately 8% and decreased in the summer months, where the rate of positive specimens remained at approximately 0.5%. In contrast, summer is the peak period for RSV incidence in 2021 and 2023, with the rate of positive specimens being as high as 9%-12%. Based on the prevalence characteristics of gender and age, this study found that the detection rate of positive specimens was higher in boys than in girls in 2019-2023. In 2019-2022, among the different age groups, the highest rate of positive specimens was found in children aged 0 to <6 months, and it decreased with age. In 2023, the rate of positive specimens was above 8% in the 0 to <6 months, 6 to <12 months, and 1-2 years age groups, with the highest rate of positive specimens in the 1-2 years age group, and a gradual decrease in the rate of positive specimens with age for children over 3 years of age. Between 2019 and 2023, the epidemiological pattern of RSV changed. A summer peak was observed in 2021 and 2023.

Epidemiological and clinical characteristics of adenovirus-associated respiratory tract infection in children in Hangzhou, China, 2019-2024.

This study aimed to assess the impact of COVID-19 on the prevalence of adenovirus (AdV) infection in children. This study retrospectively analyzed the changes in the epidemiological and clinical features of AdV-associated respiratory infections in children in Hangzhou, China, between January 2019 and July 2024. A total of 771 316 samples were included in the study, and the positive rate was 6.10% (47 050/771 316). Among them, the positive rate of AdV infection was highest in 2019, reaching 11.29% (26 929/238 333), while the positive rates in the remaining years were between 2% and 9%. In terms of seasonal epidemic characteristics, the summer of 2019 was the peak of AdV incidence, with the positive rate peaking at around 16.95% (7275/45 268), followed by a gradual decline and a low-level epidemic in winter, with a positive rate of 8.79% (8094/92 060). However, during the period 2020-2024, the AdV epidemic season did not show any significant regularity. Gender analysis revealed that the positive rate of male patients was generally greater than that of female patients. In different age groups, the population susceptible to AdV changed before and after the epidemic. In the early and middle stages of the COVID-19 epidemic, the susceptible population was mainly 2-5 years old, whereas in the later stages of the epidemic, the susceptible population was 5-18 years old. In addition, the main clinical symptoms of AdV-positive children from 2019-2024 were respiratory tract symptoms and fever. In summary, the COVID-19 epidemic has had a certain impact on the prevalence of AdV. These findings provide an important basis and reference for the prevention and diagnosis of AdV, especially in the context of increasing age- and gender-specific public health strategies.

The effects of parental retirement on adult children's health: Evidence from China.

Using representative data from China, we examine the causal effects of parental retirement on the health of adult children. To do so, we adopt a fuzzy regression discontinuity design and exploit the mandatory retirement ages in China as cut-off points. We find no evidence that parental retirement has significant effects on the mental health, healthcare utilization, or risky health behaviors of adult children. However, paternal retirement and maternal retirement have different effects on adult children's Self-reported health (SRH). Paternal retirement has a significantly negative effect only on the SRH of sons, while maternal retirement does not induce such effects. Potential mechanisms of intergenerational transfer through which parental retirement might affect adult children's health are also explored.

The impact of health insurance on hypertension care: a household fixed effects study in India.

INTRODUCTION: Hypertension is highly prevalent in India, but the proportion of patients achieving blood pressure control remains low. Efforts have been made to expand health insurance coverage nationwide with the aim of improving overall healthcare access. It is critical to understand the role of health insurance coverage in improving hypertension care. METHODS: We used secondary data from the nationally representative sample of adults aged 15-49 years from the 2015-2016 National Family Health Survey (NFHS) in India. We defined the hypertension care cascade as four successive steps of (1) screened, (2) diagnosed, (3) treated, and (4) controlled, and operationalized these variables using blood pressure measurements and self-reports. We employed household fixed effect models that conceptually matched people with and without insurance within the household, to estimate the impact of insurance coverage on the likelihood of reaching each care cascade step, while controlling for a wide range of additional individual-level variables. RESULTS: In all 130,151 included individuals with hypertension, 20.4% reported having health insurance. For the insured hypertensive population, 79.8% (95% Confidence Interval: 79.3%-80.3%) were screened, 49.6% (49.0%-50.2%) diagnosed, 14.3% (13.9%-14.7%) treated, and 7.9% (7.6%-8.2%) controlled, marginally higher than the percentages for the uninsured 79.8% (79.5%-80.0%), 48.2% (47.9%-48.6%), 13.3% (13.1%-13.5%), and 7.5% (7.4%-7.7%) for each cascade step, respectively. From the household fixed effects model, health insurance did not show significant impact on the hypertension care cascade, with the estimated relative risks of health insurance 0.97 (0.93-1.02), 0.97 (0.91-1.03), 0.95 (0.77-1.30), and 0.97 (0.65-1.10) for each cascade step, respectively. We further performed stratified analyses by sociodemographic and behavioral risk factors and a sensitivity analysis with district fixed effects, all of which yielded results that confirmed the robustness of our main findings. CONCLUSIONS: Health insurance did not show significant impact on improving hypertension care cascade among young and middle-aged adults with hypertension in India. Innovative strategies for overcoming practical barriers to healthcare services in addition to improving financial access are needed to address the large unmet need for hypertension care.

Knowledge and trust of mothers regarding childhood vaccination in Rwanda.

INTRODUCTION: Knowledge and trust are some of the contributing factors to vaccine acceptance(VA) and Vaccine hesitancy (VH) is one of the top threats to global health. A significant drop in childhood vaccination has been observed in recent years. One important reason that influences mothers' choice to either postpone or avoid children's vaccinations is knowledge and trust in childhood vaccines. This study aimed to assess mothers' knowledge and trust on vaccination of their children, and to examine the association between vaccination knowledge and selected socio-demographic factors. METHODS: A cross-sectional survey was conducted from January 2022 to March 2022 to assess the knowledge and trust of mothers regarding childhood vaccination. Data was collected with self-administered questionnaires. Multivariable logistic regression analysis was employed to assess factors associated with childhood vaccine knowledge and trust. RESULTS: Of the 2,126 Rwandan parents who participated in the study, the proportions with good knowledge of - and good trust in childhood vaccination were 95.5% and 91.4%, respectively. The popular sources of information about childhood vaccination were health care professionals (91.8%) and mass media (28.9%). Multinomial logistic regression analysis showed that good knowledge of - and trust in childhood vaccination were associated with the relationship with child(ren), education, occupation, and monthly income. The Multinomial logistic regression also revealed that the determinants of good knowledge of - and trust in childhood vaccination were; caregiver (p = 4.0 × 10-4, adjusted Odds Ratio (aOR); 1.7, 95%C.I; 1.3 - 2.3), no formal educational status (p = 3.3 × 10-2, aOR; 1.7, 95%C.I; 1.0 - 3.0), the unemployed occupational status (p = 2.4 × 10-2, aOR; 1.2, 95%C.I; 1.0 - 1.4), and persons on more than $401 per month (p = 2.0 × 10-4, aOR; 3.5, 95%C.I; 1.8 - 6.8). CONCLUSION: The majority of parents in Rwanda had both good knowledge of-and good trust regarding childhood vaccination. Public health strategies to promote vaccination, education programmes as well as improved communication tools between health care professionals/traditional leaders/religious leaders and parents need to be considered to achieve favourable vaccination attitudes and practices for all parents in Rwanda.

The acceptance of COVID-19 vaccines in Rwanda: a cross-sectional study.

The first reported case of Coronavirus Disease 2019 (COVID-19) in Rwanda occurred on March 14 2020. By the end of July 2024, a total of 133,518 individuals had tested positive for the infection, resulting in 1,468 deaths and 132,039 had fully recovered. The success of COVID-19 elimination in Rwanda hinges on the public's level of acceptance of the COVID-19 vaccination. Although COVID-19 is no longer a pandemic anymore, the World Health Organisation recommends countries vaccinate their populations to protect them from COVID-19 and its variants. Globally, COVID-19 has affected 704,753,890 people, caused 7,010,681 deaths and 675,619,811 have recovered. This study aimed to assess the acceptability of COVID-19 vaccines among adults aged 18 years and above in Rwanda. A cross-sectional study was conducted from January to March 2022 to determine the associations between COVID-19 vaccine acceptance (VA) with respondents' characteristics, using logistic regression analysis. This study enrolled 2,126 respondents with a mean age of 31 years, the majority of whom were females (82.2%), 51.4% had completed primary education, and 78.7% were married. Most respondents recognized the importance of COVID-19 vaccination for both personal health and community well-being. The study found a high rate of COVID-19 vaccine acceptance, with 91.6% of respondents expressing VA and an overall VA rate of 98.2%. Having a relationship with the child(ren) was the only characteristic associated with COVID-19 vaccine acceptance (p; 3.2 × 10- 3, OR; 2.9, 95% C.I; 1.4-5.9). In conclusion, the study found a high rate of COVID-19 vaccine acceptance among adults in Rwanda, with COVID-19 associated with having a relationship with the child(ren). The study recommends the need for mass educational campaigns and awareness-raising efforts to understand of COVID-19 vaccines.

Economic burden of patients with leading cancers in China: a cost-of-illness study.

BACKGROUND: China accounts for 24% of newly diagnosed cancer cases and 30% of cancer-related deaths worldwide. Comprehensive analyses of the economic burden on patients across different cancer treatment phases, based on empirical data, are lacking. This study aims to estimate the financial burden borne by patients and analyze the cost compositions of the leading cancers with the highest number of new cases in China. METHODS: This cross-sectional cost-of-illness study analyzed patients diagnosed with lung, breast, colorectal, esophageal, liver, or gastric cancer, identified through electronic health records (EHRs) from 84 hospitals across 17 provinces in China. Patients completed any one of the initial treatment phase, follow-up phase, and relapse/metastasis phase were recruited by trained attending physicians through a stratified sampling procedure to ensure enough cases for each cancer progression stage and cancer treatment phase. Direct and indirect costs by treatment phase were collected from the EHRs and self-reported surveys. We estimated per case cost for each type of cancer, and employed subgroup analyses and multiple linear regression models to explore cost drivers. RESULTS: We recruited a total of 13,745 cancer patients across three treatment phases. The relapse/metastasis phase incurred the highest per case costs, varying from $8,890 to $14,572, while the follow-up phase was the least costly, ranging from $1,840 to $4,431. Being in the relapse/metastasis phase and having an advanced clinical stage of cancer at diagnosis were associated with significantly higher cost, while patients with low socioeconomic status borne lower costs. CONCLUSIONS: There were substantial financial burden on patients with six leading cancers in China. Health policymakers should emphasize comprehensive healthcare coverage for marginalized populations such as the uninsured, less educated, and those living in underdeveloped regions.

"Not Only a Matter of Personal Interest"-Vaccination Narratives and the Model of Moral Motives in China and Germany.

Understanding vaccination decision-making processes is vital for guiding vaccine promotion within pandemic contexts and for routine immunization efforts. Vaccine-related attitudes influencing individual decision-making can be affected by broader cultural and normative contexts. We conducted 73 qualitative interviews with adults in China (n = 40) and Germany (n = 33) between December 2020 and April 2021 to understand COVID-19 vaccination intentions and preferences, and we analyzed transcripts using a five-step framework approach. During early analysis, we identified moral considerations in line with the tenets of the Model of Moral Motives (MMM) as a recurrent theme in the data. The MMM guided further analysis steps, particularly with its distinction between motives that are proscriptive (focus on avoiding harm by inhibiting "bad" behavior) and prescriptive (focus on actively seeking positive outcomes). Proscriptive vaccination arguments that compelled vaccination in our data included avoiding negative attention, being a law-abiding citizen, preventing harm to others, and protecting one's country. Prescriptive motives focused on self-efficacious behavior such as protecting the health of oneself and others via widespread but voluntary vaccination, prioritizing elderly and predisposed individuals for vaccination, and favoring a fair and equitable distribution of vaccines at the global level. In the interviews in China, both lines of arguments emerged, with a general tendency toward more proscriptive reasoning; interviews conducted in Germany tended to reflect more prescriptive motives. We encourage research and vaccine promotion practice to reflect moral considerations when aiming to understand public health preventive behavior and when developing tailored health promotion campaigns.

Association of triglyceride-glucose index trajectory and frailty in urban older residents: evidence from the 10-year follow-up in a cohort study.

BACKGROUND: Frailty is an age-related geriatric syndrome that leads to a series of clinically negative events. A better understanding of the factors associated with frailty assists in preventing its progression. The triglyceride-glucose (TyG) index, a simple alternative index of insulin resistance, has not yet been proven to be associated with frailty. The present study aimed to investigate the association between the TyG index and its trajectory with frailty from a cross-sectional, retrospective and prospective level based on an ongoing cohort. METHODS: This longitudinal study included 1,866 older residents from the "Fujian prospective aging cohort" (ChiCTR 2,000,032,949). The TyG index was calculated as ln [fasting triglyceride (mg/dL) ╳ fasting plasma glucose (mg/dL)/2] and group-based trajectory model (GBTM) was applied to identify the trajectory of TyG index. The association between different trajectory groups of TyG index with frailty risk were estimated using multinomial logistic regression analysis. RESULTS: In the cross-sectional analysis, the highest quartile of the TyG index was associated with an increased risk of frailty (TyG index Q4 vs. Q1, OR = 1.50, 95% CI 1.00-2.25, P = 0.048). Restricted cubic splines demonstrated an increasing trend for TyG index and frailty risk. During a follow-up of ten years, three distinct trajectories of the TyG index were identified: low-stable (n = 697, 38.3%), moderate-stable (n = 910, 50.0%) and high-stable (n = 214, 11.7%). Compared with those in the stable-low group of TyG index trajectory, the ORs (95% CI) of prefrailty and frailty risk were 1.79 (95% CI 1.11-2.88) and 2.17 (95% CI 1.01-3.88) for the high-stable group, respectively (P = 0.017 and P = 0.038). In the subgroup analysis, the association of the high-stable trajectory of TyG and frailty status were only observed in subjects with BMI ≥ 24 kg/m2. Prospectively, the highest quartile of the TyG index was associated with a 2.09-fold significantly increased risk of one-year ADL/IADL decline (P = 0.045). CONCLUSIONS: The present study suggests a potential role for a high and sustainable level of TyG index in the risk of frailty. The trajectories of the TyG index can help to identify older individuals at a higher risk of frailty who deserve primitive preventive and therapeutic approaches.

The features of high-risk human papillomavirus infection in different female genital sites and impacts on HPV-based cervical cancer screening.

BACKGROUND: The causal role of high-risk Human papillomavirus (HR-HPV) in the pathogenesis of anogenital cancers is well established. In contrast, information on HR-HPV distribution of continuous anatomic sites within the female genital tract is limited, and the impact of sample type on the clinical performance in HPV-based cervical cancer screening warrants investigation. METHODS: A total of 2,646 Chinese women were enrolled in the study from May 2006 to April 2007. We analyzed the infection features by infection status and pathological diagnoses of 489 women with complete HR-HPV type and viral load data on the cervix, upper vagina, lower vagina, and perineum samples. Additionally, we assessed the clinical performance for detecting high-grade cervical intraepithelial neoplasia of grade two or worse (≥ CIN2) among these four types of samples. RESULTS: HR-HPV positivity rate was lower in the cervix (51.53%) and perineum (55.83%), higher in the upper (65.64%) and lower vagina (64.42%), and increased with the severity of cervical histological lesions (all P<0.001). Single infection was more dominant than multiple infections at each anatomic site of the female genital tract. The proportion of single HR-HPV infection decreased successively from the cervix (67.05%) to the perineum (50.00%) (Ptrend=0.019) in cervical intraepithelial neoplasia grade 1 (CIN1) and was higher in samples of the cervix (85.11%) and perineum (72.34%) in ≥ CIN2. In addition, the highest viral load was observed in the cervix compared to the other three sites. The overall agreement of the cervical and perineum samples was 79.35% and increased continuously from normal (76.55%) to ≥ CIN2 (91.49%). As for the detection of ≥ CIN2, the sensitivity was 100.00%, 97.87%, 95.74%, and 91.49% for the cervix, upper vagina, lower vagina, and perineum samples, respectively. CONCLUSIONS: Single HR-HPV infection predominated throughout the female genital tract, but the viral load was lower compared to multiple HR-HPV infections. Despite the decreasing viral load from cervix to perineum, the clinical performance for detecting ≥ CIN2 of the perineum sample was comparable to that of the cervix.

Deliberation, context, emotion and trust - understanding the dynamics of adults' COVID-19 vaccination decisions in Germany.

BACKGROUND: Willingness to vaccinate against coronavirus disease 2019 (COVID-19), which is vital to successful vaccination campaigns, is wavering and suboptimal. In Germany, quantitative research highlighted concerns regarding the safety and efficacy of COVID-19 vaccines as barriers to uptake, but qualitative insights regarding individuals' decisions about COVID-19 vaccines and how personal perceptions reflect or refute existing behavioral theories are lacking. METHODS: To identify how individuals make COVID-19 vaccination decisions within real-life contexts, we conducted 33 semi-structured, in-depth qualitative interviews with individuals in Germany between March and April 2021 using maximum variation sampling, focusing on perceptions of COVID-19 vaccines. Analysis, informed by a framework approach, began in the field via debriefings and was amplified upon the conclusion of data collection. RESULTS: Four interconnected themes (deliberation, context, emotion, trust) shaped respondents' decisions about vaccination. Personal deliberation regarding benefits and risks of vaccines and perceptions of the broader social and political context sparked a spectrum of emotions that underpinned vaccination decisions. Trust in science and researchers emerged as a powerful protective factor facilitating the decision to get vaccinated even amidst a rapidly changing context and disconcerting information. CONCLUSIONS: Our findings add to ongoing debates about the breadth of vaccination decisions by highlighting how respondents are influenced by their perceptions of the political context and the emotional heft of their decisions. The role of cognitive evaluation, context, and emotions mirrors other decision-making frameworks, particularly the Risk as Feelings Theory. We extend on the elements of this theory by highlighting trust as a protective factor when making decisions particularly in highly uncertain contexts. Success of vaccination campaigns, more important than ever as new variants of COVID-19 emerge, is interwoven with an ability to bolster trust in science. Communicating public-health decisions and information about vaccines transparently without instilling fear offers promising chances to strengthen public trust in COVID-19 vaccines. TRIAL REGISTRATION: German Clinical Trials Register ( DRKS00024505 ).

Variation in the Proportion of Adults in Need of Blood Pressure-Lowering Medications by Hypertension Care Guideline in Low- and Middle-Income Countries: A Cross-Sectional Study of 1 037 215 Individuals From 50 Nationally Representative Surveys.

BACKGROUND: Current hypertension guidelines vary substantially in their definition of who should be offered blood pressure-lowering medications. Understanding the effect of guideline choice on the proportion of adults who require treatment is crucial for planning and scaling up hypertension care in low- and middle-income countries. METHODS: We extracted cross-sectional data on age, sex, blood pressure, hypertension treatment and diagnosis status, smoking, and body mass index for adults 30 to 70 years of age from nationally representative surveys in 50 low- and middle-income countries (N = 1 037 215). We aimed to determine the effect of hypertension guideline choice on the proportion of adults in need of blood pressure-lowering medications. We considered 4 hypertension guidelines: the 2017 American College of Cardiology/American Heart Association guideline, the commonly used 140/90 mm Hg threshold, the 2016 World Health Organization HEARTS guideline, and the 2019 UK National Institute for Health and Care Excellence guideline. RESULTS: The proportion of adults in need of blood pressure-lowering medications was highest under the American College of Cardiology/American Heart Association, followed by the 140/90 mm Hg, National Institute for Health and Care Excellence, and World Health Organization guidelines (American College of Cardiology/American Heart Association: women, 27.7% [95% CI, 27.2-28.2], men, 35.0% [95% CI, 34.4-35.7]; 140/90 mm Hg: women, 26.1% [95% CI, 25.5-26.6], men, 31.2% [95% CI, 30.6-31.9]; National Institute for Health and Care Excellence: women, 11.8% [95% CI, 11.4-12.1], men, 15.7% [95% CI, 15.3-16.2]; World Health Organization: women, 9.2% [95% CI, 8.9-9.5], men, 11.0% [95% CI, 10.6-11.4]). Individuals who were unaware that they have hypertension were the primary contributor to differences in the proportion needing treatment under different guideline criteria. Differences in the proportion needing blood pressure-lowering medications were largest in the oldest (65-69 years) age group (American College of Cardiology/American Heart Association: women, 60.2% [95% CI, 58.8-61.6], men, 70.1% [95% CI, 68.8-71.3]; World Health Organization: women, 20.1% [95% CI, 18.8-21.3], men, 24.1.0% [95% CI, 22.3-25.9]). For both women and men and across all guidelines, countries in the European and Eastern Mediterranean regions had the highest proportion of adults in need of blood pressure-lowering medicines, whereas the South and Central Americas had the lowest. CONCLUSIONS: There was substantial variation in the proportion of adults in need of blood pressure-lowering medications depending on which hypertension guideline was used. Given the great implications of this choice for health system capacity, policy makers will need to carefully consider which guideline they should adopt when scaling up hypertension care in their country.

Transforming growth factor-ß1 protects against LPC-induced cognitive deficit by attenuating pyroptosis of microglia via NF-κB/ERK1/2 pathways.

BACKGROUND: Demyelinating diseases in central nervous system (CNS) are a group of diseases characterized by myelin damage or myelin loss. Transforming growth factor beta1 (TGF-ß1) is widely recognized as an anti-inflammatory cytokine, which can be produced by both glial and neuronal cells in CNS. However, the effects of TGF-ß1 on demyelinating diseases and its underlying mechanisms have not been well investigated. METHODS: A demyelinating mouse model using two-point injection of lysophosphatidylcholine (LPC) to the corpus callosum in vivo was established. Exogenous TGF-ß1 was delivered to the lesion via brain stereotactic injection. LFB staining, immunofluorescence, and Western blot were applied to examine the severity of demyelination and pyroptosis process in microglia. Morris water maze test was used to assess the cognitive abilities of experimental mice. Furthermore, lipopolysaccharide (LPS) was applied to induce pyroptosis in primary cultured microglia in vitro, to explore potential molecular mechanism. RESULTS: The degree of demyelination in LPC-modeling mice was found improved with supplement of TGF-ß1. Besides, TGF-ß1 treatment evidently ameliorated the activated proinflammatory pyroptosis of microglia, with downregulated levels of the key pyroptosis effector Gasdermin D (GSDMD), inflammasomes, and cleaved-IL-1ß, which effectively attenuated neuroinflammation in vivo. Evaluated by behavioral tests, the cognitive deficit in LPC-modeling mice was found mitigated with application of TGF-ß1. Mechanistically, TGF-ß1 could reverse pyroptosis-like morphology in LPS-stimulated primary cultured microglia observed by scanning electron microscopy, as well as decrease the protein levels of cleaved-GSDMD, inflammasomes, and cleaved-IL-1ß. Activation of ERK1/2 and NF-κB pathways largely abolished the protective effects of TGF-ß1, which indicated that TGF-ß1 alleviated the pyroptosis possibly via regulating NF-κB/ERK1/2 signal pathways. CONCLUSIONS: Our studies demonstrated TGF-ß1 notably relieved the demyelinating injury and cognitive disorder in LPC-modeling mice, by attenuating the inflammatory pyroptosis of microglia via ERK1/2 and NF-κB pathways. Targeting TGF-ß1 activity might serve as a promising therapeutic strategy in demyelinating diseases.

Concordance between the BD Onclarity and Roche cobas assays for detection of HPV DNA in a Chinese population.

As cervical cancer screening shifts from cytology to human papillomavirus (HPV) testing, a major issue involves validating more HPV tests. In recent years, some HPV tests are used for clinical performance verification in China. The purpose of this study was to explore whether the BD Onclarity (Becton, Dickinson and Company)HPV assay differs from the Roche cobas (Roche Molecular Systems)HPV assay, as determined using 944 cervical samples, including 588 with sequencing results. In the nucleic acid assay accuracy verification, the assays showed excellent concordance for detection of HPV16 (κ = 0.93, 95% confidence interval [CI]: 0.89-0.97) and HPV18 (κ = 0.90, 95% CI: 0.83-0.97), and very good concordance for the 12 other high-risk types (HPV31/33/35/39/45/51/52/56/58/59/66/68, κ = 0.79, 95% CI: 0.75-0.83). The overall agreement for HPV DNA detection between Onclarity and cobas was very good (κ = 0.7755). No difference for ≥CIN2 sensitivity was observed between Onclarity and cobas (both 96.5%), whereas the ≥CIN2 specificity for detection of Onclarity (16.6%, 95% CI: 13.7-19.9) was higher than that of cobas (11.5%, 95% CI: 9.1-14.5). Onclarity exhibited comparable screening performance and triage efficiency compared to cobas in the detection of cervical disease in Chinese women.

Probiotics for the Treatment of Gastric Diseases.

Common gastric diseases include chronic gastritis, gastric ulcers and gastric cancer. The etiology of gastric diseases is complicated, including genetics, diet, excessive smoking and drinking, environmental factors, and bacterial infections. As live microorganisms, probiotics can confer health benefits to the host. At present, probiotics have been widely used in the preparation of foods, health products, and medicines. Due to their positive effects in improving diarrhea, constipation, alleviating allergies, enhancing immunity, and maintaining intestinal homeostasis, studies worldwide have focused on whether probiotics also provide therapeutic effects on gastric diseases. Thus, this review summarizes the possible mechanism of probiotics in the treatment of gastric diseases and provides a reference for expanding not only their application but also that of other microecological agents.

OutbreakFlow: Model-based Bayesian inference of disease outbreak dynamics with invertible neural networks and its application to the COVID-19 pandemics in Germany.

Mathematical models in epidemiology are an indispensable tool to determine the dynamics and important characteristics of infectious diseases. Apart from their scientific merit, these models are often used to inform political decisions and interventional measures during an ongoing outbreak. However, reliably inferring the epidemical dynamics by connecting complex models to real data is still hard and requires either laborious manual parameter fitting or expensive optimization methods which have to be repeated from scratch for every application of a given model. In this work, we address this problem with a novel combination of epidemiological modeling with specialized neural networks. Our approach entails two computational phases: In an initial training phase, a mathematical model describing the epidemic is used as a coach for a neural network, which acquires global knowledge about the full range of possible disease dynamics. In the subsequent inference phase, the trained neural network processes the observed data of an actual outbreak and infers the parameters of the model in order to realistically reproduce the observed dynamics and reliably predict future progression. With its flexible framework, our simulation-based approach is applicable to a variety of epidemiological models. Moreover, since our method is fully Bayesian, it is designed to incorporate all available prior knowledge about plausible parameter values and returns complete joint posterior distributions over these parameters. Application of our method to the early Covid-19 outbreak phase in Germany demonstrates that we are able to obtain reliable probabilistic estimates for important disease characteristics, such as generation time, fraction of undetected infections, likelihood of transmission before symptom onset, and reporting delays using a very moderate amount of real-world observations.

The impact of retirement on inpatient healthcare utilization in Guangzhou, China: a regression discontinuity analysis of 189,031 health insurance claims.

BACKGROUND: Previous studies suggest that retirement, a major life event, affects overall healthcare utilization. We examine, the effects of retirement on inpatient healthcare utilization, including effect heterogeneity by gender, disease category, and type of health service. METHODS: We used routine health insurance claims data (N = 87,087) spanning the period 2021 - September 2013 from the Urban Employee Basic Medical Insurance (UEBMI), a mandatory social health insurance for working and retired employees in urban China. We applied a non-parametric fuzzy regression discontinuity design using the statutory retirement age in urban China as an exogenous instrument to measure the causal effect of retirement on six measures of inpatient healthcare utilization. RESULTS: Retirement reduced total hospital costs (-84.71 Chinese Yuan (CNY), 95% confidence interval (CI) -172.03 - 2.61), shortened length of hospital stays (-44.59, 95% CI -70.50 - -18.68), and increased hospital readmissions (0.06, 95% CI 0.00 - 0.12) and primary hospital visits (0.06, 95% CI 0.02 - 0.09) among women. Retirement did not significantly change inpatient healthcare utilization among men. The retirement effects among women varied by disease category. Specifically, retirement substantially increased hospitalizations for non-communicable diseases (NCDs), yet had only modest or no effect on hospitalizations for communicable diseases or injuries. Retirement effects among women also varied by the type of services. For relatively inexpensive services, such as nonoperative treatment, there were surges in the extensive margin (hospital readmission). For relatively expensive and invasive services, such as surgeries, retirement reduced the intensive margin (out-of-pocket expenditures and length of stay). CONCLUSIONS: Retirement decreases overall use of inpatient healthcare for women. The examination on the disease-related heterogeneous effects helps with the introduction and implementation of integrated healthcare delivery and appropriate incentive schemes to encourage better use of healthcare resources among older adults.

Trends of overweight and obesity among preschool children from 2013 to 2018: a cross-sectional study in Rhine-Neckar County and the City of Heidelberg, Germany.

BACKGROUND: Early childhood overweight and obesity is a growing public health concern worldwide. Few recent studies have addressed how time trends varied by sociodemographic characteristics at the regional level using large and high-quality data. This study determines how time trends vary in the prevalence of early childhood overweight and obesity by age, gender, and migration background at the regional level. METHODS: We used a Kernel-density curve to describe the BMI distribution, and evaluated the trends of overweight and obesity by age, gender, and migration background using logistic regression. RESULTS: Mean BMI and the overall prevalence of overweight and obesity increased among preschool children aged 4-6 years in the Rhine-Neckar County and the City of Heidelberg. After adjusting for age, sex, and migration background, trends of overweight significantly increased only among male children in the age 5 year group with migration background (P < 0.05), and an upward trend of obesity was observed only among male children in the age 5 year group and female children in the age 6 year group with migration background (P < 0.05). CONCLUSIONS: BMI distribution as well as general prevalence of overweight and obesity are still increasing among preschool children. Children with migration backgrounds, particularly male children in the age 5 year groups and female children in the age 6 year group should be prioritized. Health promotion strategies for children with migration backgrounds will help address this challenge.