Comparative efficacy and acceptability of different exercise patterns for reducing cardiovascular events in pre-diabetes: protocol for a systematic review and network meta-analysis of randomised controlled trials.

INTRODUCTION: Exercise has been used to reverse dysglycaemic states in patients with pre-diabetes. Systematic reviews show that exercise is an effective way to reduce the incidence of diabetes, but there is conflicting evidence for reducing the occurrence of cardiovascular events. Therefore, we present a systematic review and network meta-analysis protocol designed to compare the effectiveness of different forms of exercise in reducing cardiovascular events and their tolerability in different populations. METHODS AND ANALYSIS: We will include all randomised controlled trials and compare one exercise intervention to another. We will compare the following exercise patterns: standard endurance training, strength training, high-intensity interval training, mind-body exercise, and mixed strength and aerobic training. The primary outcomes are the occurrence of major cardiovascular events and the rate of patient attrition during the intervention. We will search major English and Chinese databases as well as trial registry websites for published and unpublished studies. All reference selection and data extraction will be conducted by at least two independent reviewers. We will conduct a random effects model to combine effect sizes and use the surface under the cumulative ranking curve and the mean ranks to rank the effectiveness of interventions. All data will be fitted at WinBUGS in a Bayesian framework and correlation graphs will be plotted using StataSE 14. We will also use the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework to evaluate the quality of evidence for the study results. ETHICS AND DISSEMINATION: This study does not involve a population-based intervention, and therefore, does not require ethical approval. We will publish the findings of this systematic review in a peer-reviewed scientific journal, and the dataset will be made available free of charge. The completed review will be disseminated electronically in print and on social media, where appropriate. PROSPERO REGISTRATION NUMBER: CRD42023422737.

Incidence, risk factors, and outcomes of acute liver injury in hospitalized adults with acute kidney injury: a large multicenter study.

BACKGROUND: Acute kidney injury (AKI) and acute liver injury (ALI) were associated with poor outcomes during hospitalization, respectively. However, the clinical outcome of AKI combined with ALI (AKI-ALI) remains unknown. The current study aimed to describe AKI-ALI's incidences, risk factors, and outcomes. METHODS: The study population included patients aged 18-99 years with enough serum creatinine and liver testing hospitalized at 19 medical centers throughout China between 2000 and 2021. AKI was defined by Kidney Disease Improving Global Outcomes and ALI was defined by the change of liver enzymes based on Asia Pacific Association of Study of Liver consensus guidelines. Cox proportional hazard model was used to identify risk factors for AKI-ALI, and a time-dependent Cox proportional hazard regression model was used to estimate the association between AKI-ALI and in-hospital mortality. RESULTS: Among the 18,461 patients with AKI, 1689 (9.1%) combined with ALI. Male patients or those who have used nonsteroidal anti-inflammatory drugs or vasopressors, and who have heart failure or shock, with higher AST or GGT values, were associated with an increased risk of AKI-ALI. Compared with AKI-nonALI, patients with AKI-ALI were at higher risk of in-hospitalized mortality (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.54, 2.00). In addition, a stronger association between AKI-ALI and in-hospital mortality was found in those with lower AKI grades (p for interaction = 0.037). CONCLUSIONS: ALI was not uncommon among patients with AKI, especially in patients who used vasopressors and had shock. This study highlights the association between AKI-ALI and a significantly increased risk of mortality. It suggests that dynamic monitoring of liver function is essential, particularly in patients with AST and GGT exceeding the normal upper limit, to improve the in-hospital prognosis of AKI patients.

Distinctive subgingival microbial signatures in older adults with different levels of cognitive function.

AIM: To examine association between subgingival microbial signatures and levels of cognitive impairment in older adults. MATERIALS AND METHODS: We analysed subgingival plaque samples and 16S ribosomal RNA sequences for microbiota among 165 participants (normal controls [NCs]: 40, subjective cognitive decline [SCD]: 40, mild cognitive impairment [MCI]: 49 and dementia: 36). RESULTS: The bacterial richness was lower among individuals with worse cognitive function, and subgingival microbial communities differed significantly among the four groups. Declining cognitive function was associated with decreasing relative abundance of genera Capnocytophaga, Saccharibacteria_genera_incertae_sedis, Lautropia and Granulicatella, and increasing abundance of genus Porphyromonas. Moreover, there were differentially abundant genera among the groups. Random forest model based on subgingival microbiota could distinguish between cognitive impairment and NC (AUC = 0.933, 95% confidence interval 0.873-0.992). Significant correlations were observed between oral microbiota and sex, Montreal Cognitive Assessment (MoCA) score and Mini-Mental State Examination score. Partial correlation analysis showed that Leptotrichia and Burkholderia were closely negatively associated with the MoCA score after adjusting for multiple covariates. Gene function was not significantly different between SCD and NC groups, whereas three homozygous genes were altered in MCI patients and two in dementia patients. CONCLUSIONS: This is the first study to demonstrate an association between the composition, function and metabolic pathways of subgingival microbiota and different levels of cognitive function among older individuals. Future cohort studies should assess its diagnostic usefulness for cognitive impairment.

Comprehensive proteogenomic characterization of rare kidney tumors.

Non-clear cell renal cell carcinomas (non-ccRCCs) encompass diverse malignant and benign tumors. Refinement of differential diagnosis biomarkers, markers for early prognosis of aggressive disease, and therapeutic targets to complement immunotherapy are current clinical needs. Multi-omics analyses of 48 non-ccRCCs compared with 103 ccRCCs reveal proteogenomic, phosphorylation, glycosylation, and metabolic aberrations in RCC subtypes. RCCs with high genome instability display overexpression of IGF2BP3 and PYCR1. Integration of single-cell and bulk transcriptome data predicts diverse cell-of-origin and clarifies RCC subtype-specific proteogenomic signatures. Expression of biomarkers MAPRE3, ADGRF5, and GPNMB differentiates renal oncocytoma from chromophobe RCC, and PIGR and SOSTDC1 distinguish papillary RCC from MTSCC. This study expands our knowledge of proteogenomic signatures, biomarkers, and potential therapeutic targets in non-ccRCC.

Investigating the association between inflammation mediated by mushroom consumption and mild cognitive impairment in Chinese older adults.

Background: Chronic inflammatory stimulation is a major risk factor for mild cognitive impairment. Mushroom consumption and inflammatory factors may play an important role in the pathogenesis of mild cognitive impairment. Additionally, consuming mushrooms can reduce the levels of inflammatory cytokines and preserve cognitive function. Therefore, this study aimed to investigate the relationship between mushroom consumption and serum inflammatory cytokines and mild cognitive impairment (MCI). Methods: Binary logistic regression was used to determine the relationship between mushroom consumption and MCI in 550 participants. Subsequently, mediation analysis was used to analyze the relationship between mushroom consumption, inflammatory factors, and the Montreal Cognitive assessment (MoCA) score in 248 participants. Results: Mushroom consumption was associated with MCI (odds ratio = 0.623, 95% confidence interval = 0.542-0.715, P < 0.001). The association between mushroom intake and MCI was mediated by interleukin-6 (IL-6) and hypersensitive C-reactive protein (hs-CRP), and the MoCA score was 12.76% and 47.59%, respectively. Conclusion: A high intake of mushrooms was associated with a low risk of MCI. Serum inflammatory factors including IL-6 and hs-CRP play a partial mediating role between mushroom intake and the MoCA score, and the underlying mechanism needs to be further explored.

CDK12 Loss Promotes Prostate Cancer Development While Exposing Vulnerabilities to Paralog-Based Synthetic Lethality.

Biallelic loss of cyclin-dependent kinase 12 (CDK12) defines a unique molecular subtype of metastatic castration-resistant prostate cancer (mCRPC). It remains unclear, however, whether CDK12 loss per se is sufficient to drive prostate cancer development-either alone, or in the context of other genetic alterations-and whether CDK12-mutant tumors exhibit sensitivity to specific pharmacotherapies. Here, we demonstrate that tissue-specific Cdk12 ablation is sufficient to induce preneoplastic lesions and robust T cell infiltration in the mouse prostate. Allograft-based CRISPR screening demonstrated that Cdk12 loss is positively associated with Trp53 inactivation but negatively associated with Pten inactivation-akin to what is observed in human mCRPC. Consistent with this, ablation of Cdk12 in prostate organoids with concurrent Trp53 loss promotes their proliferation and ability to form tumors in mice, while Cdk12 knockout in the Pten-null prostate cancer mouse model abrogates tumor growth. Bigenic Cdk12 and Trp53 loss allografts represent a new syngeneic model for the study of androgen receptor (AR)-positive, luminal prostate cancer. Notably, Cdk12/Trp53 loss prostate tumors are sensitive to immune checkpoint blockade. Cdk12-null organoids (either with or without Trp53 co-ablation) and patient-derived xenografts from tumors with CDK12 inactivation are highly sensitive to inhibition or degradation of its paralog kinase, CDK13. Together, these data identify CDK12 as a bona fide tumor suppressor gene with impact on tumor progression and lends support to paralog-based synthetic lethality as a promising strategy for treating CDK12-mutant mCRPC.

Targeting PIKfyve-driven lipid homeostasis as a metabolic vulnerability in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) subsists in a nutrient-deregulated microenvironment, making it particularly susceptible to treatments that interfere with cancer metabolism12. For example, PDAC utilizes and is dependent on high levels of autophagy and other lysosomal processes3-5. Although targeting these pathways has shown potential in preclinical studies, progress has been hampered by the challenge of identifying and characterizing favorable targets for drug development6. Here, we characterize PIKfyve, a lipid kinase integral to lysosomal functioning7, as a novel and targetable vulnerability in PDAC. In human patient and murine PDAC samples, we discovered that PIKFYVE is overexpressed in PDAC cells compared to adjacent normal cells. Employing a genetically engineered mouse model, we established the essential role of PIKfyve in PDAC progression. Further, through comprehensive metabolic analyses, we found that PIKfyve inhibition obligated PDAC to upregulate de novo lipid synthesis, a relationship previously undescribed. PIKfyve inhibition triggered a distinct lipogenic gene expression and metabolic program, creating a dependency on de novo lipid metabolism pathways, by upregulating genes such as FASN and ACACA. In PDAC, the KRAS-MAPK signaling pathway is a primary driver of de novo lipid synthesis, specifically enhancing FASN and ACACA levels. Accordingly, the simultaneous targeting of PIKfyve and KRAS-MAPK resulted in the elimination of tumor burden in a syngeneic orthotopic model and tumor regression in a xenograft model of PDAC. Taken together, these studies suggest that disrupting lipid metabolism through PIKfyve inhibition induces synthetic lethality in conjunction with KRAS-MAPK-directed therapies for PDAC.

Effects of the seedling tray overlapping for seed emergence mode on emergence characteristics and growth of rice seedlings.

Seedling mode plays a crucial role in the rice production process, as it significantly affects the growth and development of seedlings. Among the various seedling modes, the seedling tray overlapping for seed emergence mode (STOSE mode) has been demonstrated to be effective in enhancing seedling quality. However, the impact of this mode on the germination and growth of seeds with varying plumpness remains uncertain. To investigate the effect of the STOSE mode on seedling emergence characteristics, growth uniformity, and nutrient uptake of seeds with varying plumpness levels, we conducted a study using super early rice Zhongzao 39 (ZZ39) as the test material. The seeds were categorized into three groups: plumped, mixed, and unplumped. The results indicated that the STOSE mode significantly improved the seedling rate for all types of seeds in comparison to the seedling tray nonoverlapping for seed emergence mode (TSR mode). Notably, the unplumped seeds exhibited the most pronounced enhancement effect. The soluble sugar content of the seeds increased significantly after 2 days of sowing under the STOSE mode, whereas the starch content exhibited a significant decrease. Furthermore, the STOSE mode outperformed the TSR mode in several aspects including seedling growth uniformity, aboveground dry matter mass, root traits, and nutrient uptake. Overall, the STOSE mode not only promoted the germination and growth of plumped and mixed seeds but also had a more pronounced impact on unplumped seeds.

p300/CBP degradation is required to disable the active AR enhanceosome in prostate cancer.

Prostate cancer is an exemplar of an enhancer-binding transcription factor-driven disease. The androgen receptor (AR) enhanceosome complex comprised of chromatin and epigenetic coregulators assembles at enhancer elements to drive disease progression. The paralog lysine acetyltransferases p300 and CBP deposit histone marks that are associated with enhancer activation. Here, we demonstrate that p300/CBP are determinant cofactors of the active AR enhanceosome in prostate cancer. Histone H2B N-terminus multisite lysine acetylation (H2BNTac), which was exclusively reliant on p300/CBP catalytic function, marked active enhancers and was notably elevated in prostate cancer lesions relative to the adjacent benign epithelia. Degradation of p300/CBP rapidly depleted acetylation marks associated with the active AR enhanceosome, which was only partially phenocopied by inhibition of their reader bromodomains. Notably, H2BNTac was effectively abrogated only upon p300/CBP degradation, which led to a stronger suppression of p300/CBP-dependent oncogenic gene programs relative to bromodomain inhibition. In vivo experiments using a novel, orally active p300/CBP proteolysis targeting chimera (PROTAC) degrader (CBPD-409) showed that p300/CBP degradation potently inhibited tumor growth in preclinical models of castration-resistant prostate cancer and synergized with AR antagonists. While mouse p300/CBP orthologs were effectively degraded in host tissues, prolonged treatment with the PROTAC degrader was well tolerated with no significant signs of toxicity. Taken together, our study highlights the pivotal role of p300/CBP in maintaining the active AR enhanceosome and demonstrates how target degradation may have functionally distinct effects relative to target inhibition, thus supporting the development of p300/CBP degraders for the treatment of advanced prostate cancer.

Bone marrow CD8+ Trm cells induced by IL-15 and CD16+ monocytes contribute to HSPC destruction in human severe aplastic anemia.

Idiopathic severe aplastic anemia (SAA) is a disease of bone marrow failure caused by T-cell-induced destruction of hematopoietic stem and progenitor cells (HSPCs), however the mechanism remains unclear. We performed single-cell RNA sequencing of PBMCs and BMMCs from SAA patients and healthy donors and identified a CD8+ T cell subset with a tissue residency phenotype (Trm) in bone marrow that exhibit high IFN-γ and FasL expression and have a higher ability to induce apoptosis in HSPCs in vitro through FasL expression. CD8+ Trm cells were induced by IL-15 presented by IL-15Rα on monocytes, especially CD16+ monocytes, which were increased in SAA patients. CD16+ monocytes contributed to IL-15-induced CD38+CXCR6+ pre-Trm differentiation into CD8+ Trm cells, which can be inhibited by the CD38 inhibitor 78c. Our results demonstrate that IL-15-induced CD8+ Trm cells are pathogenic cells that mediate HSPC destruction in SAA patients and are therapeutic targets for future treatments.

Development and Validation of an 18-Gene Urine Test for High-Grade Prostate Cancer.

Importance: Benefits of prostate cancer (PCa) screening with prostate-specific antigen (PSA) alone are largely offset by excess negative biopsies and overdetection of indolent cancers resulting from the poor specificity of PSA for high-grade PCa (ie, grade group [GG] 2 or greater). Objective: To develop a multiplex urinary panel for high-grade PCa and validate its external performance relative to current guideline-endorsed biomarkers. Design, Setting, and Participants: RNA sequencing analysis of 58 724 genes identified 54 markers of PCa, including 17 markers uniquely overexpressed by high-grade cancers. Gene expression and clinical factors were modeled in a new urinary test for high-grade PCa (MyProstateScore 2.0 [MPS2]). Optimal models were developed in parallel without prostate volume (MPS2) and with prostate volume (MPS2+). The locked models underwent blinded external validation in a prospective National Cancer Institute trial cohort. Data were collected from January 2008 to December 2020, and data were analyzed from November 2022 to November 2023. Exposure: Protocolized blood and urine collection and transrectal ultrasound-guided systematic prostate biopsy. Main Outcomes and Measures: Multiple biomarker tests were assessed in the validation cohort, including serum PSA alone, the Prostate Cancer Prevention Trial risk calculator, and the Prostate Health Index (PHI) as well as derived multiplex 2-gene and 3-gene models, the original 2-gene MPS test, and the 18-gene MPS2 models. Under a testing approach with 95% sensitivity for PCa of GG 2 or greater, measures of diagnostic accuracy and clinical consequences of testing were calculated. Cancers of GG 3 or greater were assessed secondarily. Results: Of 761 men included in the development cohort, the median (IQR) age was 63 (58-68) years, and the median (IQR) PSA level was 5.6 (4.6-7.2) ng/mL; of 743 men included in the validation cohort, the median (IQR) age was 62 (57-68) years, and the median (IQR) PSA level was 5.6 (4.1-8.0) ng/mL. In the validation cohort, 151 (20.3%) had high-grade PCa on biopsy. Area under the receiver operating characteristic curve values were 0.60 using PSA alone, 0.66 using the risk calculator, 0.77 using PHI, 0.76 using the derived multiplex 2-gene model, 0.72 using the derived multiplex 3-gene model, and 0.74 using the original MPS model compared with 0.81 using the MPS2 model and 0.82 using the MPS2+ model. At 95% sensitivity, the MPS2 model would have reduced unnecessary biopsies performed in the initial biopsy population (range for other tests, 15% to 30%; range for MPS2, 35% to 42%) and repeat biopsy population (range for other tests, 9% to 21%; range for MPS2, 46% to 51%). Across pertinent subgroups, the MPS2 models had negative predictive values of 95% to 99% for cancers of GG 2 or greater and of 99% for cancers of GG 3 or greater. Conclusions and Relevance: In this study, a new 18-gene PCa test had higher diagnostic accuracy for high-grade PCa relative to existing biomarker tests. Clinically, use of this test would have meaningfully reduced unnecessary biopsies performed while maintaining highly sensitive detection of high-grade cancers. These data support use of this new PCa biomarker test in patients with elevated PSA levels to reduce the potential harms of PCa screening while preserving its long-term benefits.

Intercropping improves maize yield and nitrogen uptake by regulating nitrogen transformation and functional microbial abundance in rhizosphere soil.

Intercropping-driven changes in nitrogen (N)-acquiring microbial genomes and functional expression regulate soil N availability and plant N uptake. However, present data seem to be limited to a specific community, obscuring the viewpoint of entire N-acquiring microbiomes and functions. Taking maize intercropped with legumes (peanut and soybean) and non-legumes (gingelly and sweet potato) as models, we studied the effects of intercropping on N transformations and N-acquiring microbiomes in rhizosphere soil across four maize growth stages. Meanwhile, we compiled promising strategies such as random forest analysis and structural equation model for the exploitation of the associations between microbe-driven N dynamics and soil-plant N trade-offs and maize productivity. Compared with monoculture, maize intercropping significantly increased the denitrification rate of rhizosphere soils across four maize growth stages, net N mineralization in the elongation and flowering stages, and the nitrification rate in the seedling and mature stages. The abundance of most N-acquiring microbial populations was influenced significantly by intercropping patterns and maize growth stages. Soil available N components (NH4+-N, NO3--N, and dissolved organic N content) showed a highly direct effect on plant N uptake, which mainly mediated by N transformations (denitrification rate) and N-acquiring populations (amoB, nirK3, and hzsB genes). Overall, the adaptation of N-acquiring microbiomes to changing rhizosphere micro-environments caused by intercropping patterns and maize development could promote soil N transformations and dynamics to meet demand of maize for N nutrient. This would offer another unique perspective to manage the benefits of the highly N-effective and production-effective intercropping ecosystems.

Increased co-expression of ICOS and PD-1 predicts poor overall survival in patients with acute myeloid leukemia.

BACKGROUND: Inducible co-stimulatory factor (ICOS) has a dual role: activating cytotoxic T cells against tumors or exacerbating immunosuppression of regulatory T cells (Tregs) to participate in immune evasion. However, the correlation between ICOS and its co-expression with inhibitory immune checkpoints (IICs) and prognosis in acute myeloid leukemia (AML) is little known. METHODS: The prognostic importance of ICOS and IICs in 62 bone marrow (BM) samples of de novo AML patients from our clinical center (GZFPH) was explored and then the RNA sequencing data of 155 AML patients from the Cancer Genome Atlas (TCGA) database was used for validation. RESULTS: In both GZFPH and TCGA cohorts, high expression of ICOS was significantly associated with poor overall survival (OS) in patients with AML (P < 0.05). Importantly, co-expression of ICOS and PD-1, PD-L1, PD-L2, CTLA-4, and LAG-3 predicted poor OS in AML; among them, ICOS/PD-1 was the optimal combination of immune checkpoints (ICs). The co-expression of ICOS and PD-1 was correlated with poor OS in non-acute promyelocytic leukemia (non-APL) patients following chemotherapy. Additionally, ICOS/PD-1 was an independent OS-predicting factor (P < 0.05). Notably, a nomogram model was constructed by combining ICOS/PD-1, age, European Leukemia Net (ELN) risk stratification, and therapy to visually and personalized predict the 1-, 3-, and 5-year OS of patients with non-APL. CONCLUSION: Increased expression of ICOS predicted poor outcomes, and ICOS/PD-1 was the optimal combination of ICs to predict outcomes in patients with AML, which might be a potential immune biomarker for designing novel AML therapy.

NSD2 is a requisite subunit of the AR/FOXA1 neo-enhanceosome in promoting prostate tumorigenesis.

The androgen receptor (AR) is a ligand-responsive transcription factor that binds at enhancers to drive terminal differentiation of the prostatic luminal epithelia. By contrast, in tumors originating from these cells, AR chromatin occupancy is extensively reprogrammed to drive hyper-proliferative, metastatic, or therapy-resistant phenotypes, the molecular mechanisms of which remain poorly understood. Here, we show that the tumor-specific enhancer circuitry of AR is critically reliant on the activity of Nuclear Receptor Binding SET Domain Protein 2 (NSD2), a histone 3 lysine 36 di-methyltransferase. NSD2 expression is abnormally gained in prostate cancer cells and its functional inhibition impairs AR trans-activation potential through partial off-loading from over 40,000 genomic sites, which is greater than 65% of the AR tumor cistrome. The NSD2-dependent AR sites distinctly harbor a chimeric AR-half motif juxtaposed to a FOXA1 element. Similar chimeric motifs of AR are absent at the NSD2-independent AR enhancers and instead contain the canonical palindromic motifs. Meta-analyses of AR cistromes from patient tumors uncovered chimeric AR motifs to exclusively participate in tumor-specific enhancer circuitries, with a minimal role in the physiological activity of AR. Accordingly, NSD2 inactivation attenuated hallmark cancer phenotypes that were fully reinstated upon exogenous NSD2 re-expression. Inactivation of NSD2 also engendered increased dependency on its paralog NSD1, which independently maintained AR and MYC hyper-transcriptional programs in cancer cells. Concordantly, a dual NSD1/2 PROTAC degrader, called LLC0150, was preferentially cytotoxic in AR-dependent prostate cancer as well as NSD2-altered hematologic malignancies. Altogether, we identify NSD2 as a novel subunit of the AR neo-enhanceosome that wires prostate cancer gene expression programs, positioning NSD1/2 as viable paralog co-targets in advanced prostate cancer.

Knowledge, attitude, and practice toward tuberculosis prevention and management among household contacts in Suzhou Hospital, Jiangsu province, China.

Background: China is among the 10 high-burden tuberculosis (TB) countries in the world; thus, investigation and management of household contacts is an essential part of TB prevention strategy. Objective: To explore the knowledge, attitude, and practice (KAP) toward TB prevention and management among household contacts of TB patients. Methods: This cross-sectional study enrolled household contacts in Suzhou Hospital of Integrated Traditional Chinese and Western Medicine between September 2022 and January 2023; KAP and demographic characteristics were assessed with the self-designed questionnaire and analyzed by multivariate logistic regression. Results: A total of 503 participants were included; of them, 280 (55.78%) were female, and 303, (60.36%) aged ≥45 years. The KAP scores were 6.24 ± 2.20 (possible range: 0-12), 18.69 ± 2.80 (possible range: 0-36), and 20.37 ± 5.15 (possible range: 0-36), respectively. Suburban (OR = 0.18, 95% CI: 0.04-0.79, p = 0.023) and rural (OR = 0.12, 95% CI: 0.03-0.57, p = 0.008) were independently associated with knowledge. Positive attitude (OR = 7.03, 95% CI: 2.92-16.96, p < 0.001), education (high school or technical secondary school, OR = 4.91, 95% CI: 1.63-14.73, p = 0.005; college and above, OR = 14.94, 95% CI: 3.51-63.58, p < 0.001), and shorter disease duration (3-6 months, OR = 0.40, 95% CI: 0.18-0.90, p = 0.026) were independently associated with better practice scores. Conclusion: Household contacts of TB patients demonstrated insufficient knowledge, unfavorable attitude, and suboptimal practice toward TB prevention and management. Tailored interventions are needed to ensure information accessibility, especially for individuals living in suburban and rural areas.

Current understanding of children's head shape and its impact on health: a cross-sectional study among pediatric medical staff in China.

Background: Head shape problems are common in infancy and early childhood, and thus their early identification and management can benefit the health of children. This study aimed to investigate pediatric healthcare professionals' existing knowledge of children's head shape abnormalities and their associated effects in China, providing guidelines for future clinical interventions, training, and interdisciplinary collaboration. Methods: We conducted a survey among pediatric medical staff, encompassing various age groups, genders, hospitals, and professional levels. The electronic questionnaire queried respondents' basic information, knowledge pertaining to head shape issues, diagnosis and treatment approaches, and the clinical development status of head shape problems. All surveys and data collection were conducted anonymously. Results: A total of 214 valid questionnaires were collected. Differences in the level of understanding among medical staff regarding head shape issues were observed. Medical staff in tertiary care facilities showed the highest proficiency in diagnosing and treating positional plagiocephaly and cranial asymmetry (P<0.05), while those in primary care facilities exhibited the lowest competency in diagnosing head shape abnormalities (P<0.05). Most medical staff had a partial understanding of specific aspects of head shape issues, such as identifying high-risk individuals (n=144, 67.29%), making diagnoses (n=176, 82.24%), and understanding the consequences (n=151, 70.56%), with no significant differences across medical facilities of various levels. Additionally, 99.07% (n=212) of the medical staff believed that head shape measurements should be included as a routine component of pediatric physical examinations, and 75.23% (n=161) incorporate head shape assessment as part of their routine physical examination. Furthermore, 91.12% (n=195) of the medical staff received consultations on children's head shape issues, with a higher prevalence in secondary and tertiary care facilities. Finally, 93.97% (n=201) of the participants expressed the need for further education and knowledge on pediatric head shape, with no significant differences across medical facilities of various levels. Conclusions: There is a limited understanding among medical personnel in China regarding children's head shape issues. Therefore, it is imperative to enhance training and educational initiatives for medical staff in China, with the goal of enhancing their awareness and knowledge regarding children's head shape problems.

Improvement of Salivary EGF Levels and Serum Inflammatory Factors in Patients with Recurrent Oral Ulcers Treated with Shuanghuanglian Oral Solution.

Objective: Recurrent oral ulcer (ROU) is a common oral mucosal disease with recurrent ulcerative lesions. Shuanghuanglian Oral liquid is a traditional Chinese medicine preparation widely used to treat oral ulcers. This study aimed to explore the effect of Shuanghuanglian oral liquid on the epidermal growth factor (EGF) level in saliva and serum inflammatory factors in patients with recurrent oral ulcers to provide a certain reference for clinical treatment. Methods: A retrospective analysis of 90 ROU patients from 2018 to 2021 was divided into an observation group (n=45) and a control group (n=45). All patients were recruited from Kunming Stomatological Hospital North Downtown Campus. The control group used a mouthwash containing chlorhexidine, while the observation group used the same mouthwash with an additional topical application of Shuanghuanglian. The EGF level in saliva, serum inflammatory factor, clinical efficacy, pain and quality of life scores, recurrence rate, and incidence of adverse reactions were observed in the two groups. Results: After treatment, EGF (RR 0.41, 95%CI 0.15-0.73, P < .001), tumor necrosis factor-α (TNF-α) (RR 0.68, 95%CI 0.53-0.77, P = .003), interleukin-10 (IL-10) (RR 0.64, 95%CI 0.48-0.75, P < .001), and C-reactive protein (CRP) (RR 0.52, 95%CI 0.35-0.65, P < .001) in observation group were significantly lower than those in the control group; The total effective rate of the observation group was significantly higher than that of the control group (RR 0.85, 95%CI 0.44-0.95, P = .02); Visual analogue scale (VAS) (RR 0.48, 95%CI 0.35-0.68, P < .001) and Oral Health Rating Scale (OHIP-4) scores (RR 0.61, 95%CI 0.47-0.84, P < .001)of observation group were significantly lower than those of control group after treatment; The incidence of total adverse reactions (RR 0.73, 95%CI 0.61-0.86, P = .011) and the recurrence rate at 6 months after treatment in the observation group were significantly lower than those in the control group (RR 0.78, 95%CI 0.69-0.91, P = .015). Conclusion: Shuanghuanglian oral liquid has a remarkable effect on patients with ROU by reducing the levels of EGF and inflammatory factors in patients, reducing the pain degree of patients, improving the oral health of patients, improving the quality of life of patients, and reducing the incidence of adverse reactions and the recurrence rate of patients to a certain extent.

Effects of message framing and risk perception on health communication for optimum cardiovascular disease primary prevention: a protocol for a multicenter randomized controlled study.

Background: Although several guidelines for cardiovascular disease (CVD) management have highlighted the significance of primary prevention, the execution and adherence to lifestyle modifications and preventive medication interventions are insufficient in everyday clinical practice. The utilization of effective risk communication can assist individuals in shaping their perception of CVD risk, motivating them to make lifestyle changes, and increasing their willingness to engage with preventive medication, ultimately reducing their CVD risks and potential future events. However, there is limited evidence available regarding the optimal format and content of CVD risk communication. Objective: The pilot study aims to elucidate the most effective risk communication strategy, utilizing message framing (gain-framed, loss-framed, or no-framed), for distinct subgroups of risk perception (under-perceived, over-perceived, and correctly-perceived CVD risk) through a multi-center randomized controlled trial design. Methods: A multi-center 3 × 3 factorial, observer-blinded experimental design was conducted. The participants will be assigned into three message-framing arms randomly in a 1:1:1 ratio and will receive an 8-week intervention online. Participants are aged 20-80 years old and have a 10-year risk of absolute CVD risk of at least 5% (moderate risk or above). We plan to enroll 240 participants based on the sample calculation. The primary outcome is the CVD prevention behaviors and CVD absolute risk value. Data collection will occur at baseline, post-intervention, and 3-month follow-up. Discussion: This experimental study will expect to determine the optimal matching strategy between risk perception subgroups and risk information format, and it has the potential to offer health providers in community or clinic settings a dependable and efficient health communication information template for conducting CVD risk management.Clinical trial registration: https://www.chictr.org.cn/bin/project/edit?pid=207811, ChiCTR2300076337.