Bayesian network analysis of factors influencing type 2 diabetes, coronary heart disease, and their comorbidities.

OBJECTIVE: Bayesian network (BN) models were developed to explore the specific relationships between influencing factors and type 2 diabetes mellitus (T2DM), coronary heart disease (CAD), and their comorbidities. The aim was to predict disease occurrence and diagnose etiology using these models, thereby informing the development of effective prevention and control strategies for T2DM, CAD, and their comorbidities. METHOD: Employing a case-control design, the study compared individuals with T2DM, CAD, and their comorbidities (case group) with healthy counterparts (control group). Univariate and multivariate Logistic regression analyses were conducted to identify disease-influencing factors. The BN structure was learned using the Tabu search algorithm, with parameter estimation achieved through maximum likelihood estimation. The predictive performance of the BN model was assessed using the confusion matrix, and Netica software was utilized for visual prediction and diagnosis. RESULT: The study involved 3,824 participants, including 1,175 controls, 1,163 T2DM cases, 982 CAD cases, and 504 comorbidity cases. The BN model unveiled factors directly and indirectly impacting T2DM, such as age, region, education level, and family history (FH). Variables like exercise, LDL-C, TC, fruit, and sweet food intake exhibited direct effects, while smoking, alcohol consumption, occupation, heart rate, HDL-C, meat, and staple food intake had indirect effects. Similarly, for CAD, factors with direct and indirect effects included age, smoking, SBP, exercise, meat, and fruit intake, while sleeping time and heart rate showed direct effects. Regarding T2DM and CAD comorbidities, age, FBG, SBP, fruit, and sweet intake demonstrated both direct and indirect effects, whereas exercise and HDL-C exhibited direct effects, and region, education level, DBP, and TC showed indirect effects. CONCLUSION: The BN model constructed using the Tabu search algorithm showcased robust predictive performance, reliability, and applicability in forecasting disease probabilities for T2DM, CAD, and their comorbidities. These findings offer valuable insights for enhancing prevention and control strategies and exploring the application of BN in predicting and diagnosing chronic diseases.

P. gingivalis in oral-prostate axis exacerbates benign prostatic hyperplasia via IL-6/IL-6R pathway.

BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. There is increasing evidence that periodontitis increases the risk of BPH, but the specific mechanism remains unclear. This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis (P. gingivalis) in the development of BPH. METHODS: The subgingival plaque (Sp) and prostatic fluid (Pf) of patients with BPH concurrent periodontitis were extracted and cultured for 16S rDNA sequencing. Ligature-induced periodontitis, testosterone-induced BPH and the composite models in rats were established. The P. gingivalis and its toxic factor P. gingivalis lipopolysaccharide (P.g-LPS) were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate. P.g-LPS was used to construct the prostate cell infection model for mechanism exploration. RESULTS: P. gingivalis, Streptococcus oralis, Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Pf and Sp of patients with BPH concurrent periodontitis, and the average relative abundance of P. gingivalis was found to be the highest. P. gingivalis was detected in both Pf and Sp in 62.5% of patients. Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes. P. gingivalis and P.g-LPS infection could induce obvious hyperplasia of the prostate epithelium and stroma (epithelial thickness was 2.97- and 3.08-fold that of control group, respectively), and increase of collagen fibrosis (3.81- and 5.02-fold that of control group, respectively). P. gingivalis infection promoted prostate cell proliferation, inhibited apoptosis, and upregulated the expression of inflammatory cytokines interleukin-6 (IL-6; 4.47-fold), interleukin-6 receptor-α (IL-6Rα; 5.74-fold) and glycoprotein 130 (gp130; 4.47-fold) in prostatic tissue. P.g-LPS could significantly inhibit cell apoptosis, promote mitosis and proliferation of cells. P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex, which destroys the imbalance between proliferation and apoptosis of prostate cells, induces BPH. CONCLUSION: P. gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis. P. gingivalis infection can promote BPH, which may affect the progression of BPH via inflammation and the Akt signaling pathway.

Investigation of bioactive compounds and their correlation with the antioxidant capacity in different functional vinegars.

There are complex and diverse substances in traditional vinegars, some of which have been identified as biologically active factors, but the variety of functional compounds is currently restricted. In this study, it was aimed to determine the bioactive compounds in 10 typical functional vinegars. The findings shown that total flavonoids (0.21-7.19 mg rutin equivalent/mL), total phenolics (0.36-3.20 mg gallic acid equivalent/mL), and antioxidant activities (DPPH: 3.17-47.63 mmol trolox equivalent/L, ABTS: 6.85-178.29 mmol trolox equivalent/L) varied among different functional vinegars. In addition, the concentrations of the polysaccharides (1.17-44.87 mg glucose equivalent/mL) and total saponins (0.67-12.46 mg oleanic acid equivalent/mL) were determined, which might play key role for the function of tested vinegars. A total of 8 organic acids, 7 polyphenol compounds and 124 volatile compounds were measured and tentatively identified. The protocatechuic acid (4.81-485.72 mg/L), chlorogenic acid (2.69-7.52 mg/L), and epicatechin (1.18-97.42 mg/L) were important polyphenol compounds in the functional vinegars. Redundancy analysis indicated that tartaric acid, oxalic acid and chlorogenic acid were significantly positively correlated with antioxidant capacity. Various physiologically active ingredients including cyclo (Pro-Leu), cyclo (Phe-Pro), cyclo (Phe-Val), cyclo (Pro-Val), 1-monopalmitin and 1-eicosanol were firstly detected in functional vinegars. Principle component analysis revealed that volatiles profile of bergamot Monascus aromatic vinegar and Hengshun honey vinegar exhibited distinctive differences from other eight vinegar samples. Moreover, the partial least squares regression analysis demonstrated that 11 volatile compounds were positively correlated with the antioxidant activity of vinegars, which suggested these compounds might be important functional substances in tested vinegars. This study explored several new functionally active compounds in different functional vinegars, which could widen the knowledge of bioactive factor in vinegars and provide new ideas for further development of functional vinegar beverages.

Cannabidiol Inhibits Epithelial Ovarian Cancer: Role of Gut Microbiome.

Epithelial ovarian cancer is among the deadliest gynecological tumors worldwide. Clinical treatment usually consists of surgery and adjuvant chemo- and radiotherapies. Due to the high rate of recurrence and rapid development of drug resistance, the current focus of research is on finding effective natural products with minimal toxic side effects for treating epithelial ovarian tumors. Cannabidiol is among the most abundant cannabinoids and has a non-psychoactive effect compared to tetrahydrocannabinol, which is a key advantage for clinical application. Studies have shown that cannabidiol has antiproliferative, pro-apoptotic, cytotoxic, antiangiogenic, anti-inflammatory, and immunomodulatory properties. However, its therapeutic value for epithelial ovarian tumors remains unclear. This study aims to investigate the effects of cannabidiol on epithelial ovarian tumors and to elucidate the underlying mechanisms. The results showed that cannabidiol has a significant inhibitory effect on epithelial ovarian tumors. In vivo experiments demonstrated that cannabidiol could inhibit tumor growth by modulating the intestinal microbiome and increasing the abundance of beneficial bacteria. Western blot assays showed that cannabidiol bound to EGFR/AKT/MMPs proteins and suppressed EGFR/AKT/MMPs expression in a dose-dependent manner. Network pharmacology and molecular docking results suggested that cannabidiol could affect the EGFR/AKT/MMPs signaling pathway.

Soy Product Consumption and the Risk of Cancer: A Systematic Review and Meta-Analysis of Observational Studies.

BACKGROUND: The association between soy product consumption and cancer risk varies among studies. Therefore, this comprehensive meta-analysis of observational studies examines the association between soy product consumption and total cancer risk. METHODS: This study was conducted following the PRISMA guidelines. Up to October 2023, all eligible published studies were searched through PubMed and Web of Science databases. RESULTS: A total of 52 studies on soy product consumption were included in this meta-analysis (17 cohort studies and 35 case-control studies). High consumption of total soy products (RR: 0.69; 95% CI: 0.60, 0.80), tofu (RR: 0.78; 95% CI: 0.70, 0.86), and soymilk (RR: 0.75; 95% CI: 0.60, 0.93) were associated with reduced total cancer risk. No association was found between high consumption of fermented soy products (RR: 1.18; 95% CI: 0.95, 1.47), non-fermented soy products (RR: 0.95; 95% CI: 0.77, 1.18), soy paste (RR: 1.00; 95% CI: 0.88, 1.14), miso soup (RR: 0.99; 95% CI: 0.87, 1.12), or natto (RR: 0.96; 95% CI: 0.82, 1.11) and cancer risk. A 54 g per day increment of total soy products reduced cancer risk by 11%, a 61 g per day increment of tofu reduced cancer risk by 12%, and a 23 g per day increment of soymilk reduced cancer risk by 28%, while none of the other soy products were associated with cancer risk. CONCLUSION: Our findings suggest that high total soy product consumption, especially soymilk and tofu, is associated with lower cancer risk. More prospective cohort studies are still needed to confirm the causal relationship between soy product consumption and cancer risk.

First-in-human study of GFH018, a small molecule inhibitor of transforming growth factor-ß receptor I inhibitor, in patients with advanced solid tumors.

BACKGROUND: Transforming growth factor-ß (TGF-ß) is a cytokine with multiple functions, including cell growth regulation, extracellular matrix production, angiogenesis homeostasis adjustment and et al. TGF-ß pathway activation promotes tumor metastasis/progression and mediates epithelial-mesenchymal transmission suppressing immunosurveillance in advanced tumors. GFH018, a small molecule inhibitor blocking TGF-ß signal transduction, inhibits the progression and/or metastasis of advanced cancers. This first-in-human study evaluated the safety, tolerability, pharmacokinetics (PK), and efficacy of GFH018 monotherapy in patients with advanced solid tumors. METHODS: This phase I, open-label, multicenter study used a modified 3+3 dose escalation and expansion design. Adult patients with advanced solid tumors failing the standard of care were enrolled. Starting at 5 mg, eight dose levels up to 85 mg were evaluated. Patients received GFH018 BID (14d-on/14d-off) starting on the 4th day after a single dose on cycle 1, day 1. Subsequent cycles were defined as 28 days. The study also explored the safety of 85 mg BID 7d-on/7d-off. Adverse events were graded using NCI criteria for adverse events (NCI-CTCAE v5.0). PK was analyzed using a noncompartmental method. Efficacy was evaluated using RECIST 1.1. Blood samples were collected for biomarker analysis. RESULTS: Fifty patients were enrolled and received at least one dose of GFH018. No dose-limiting toxicity occurred, and the maximum tolerated dose was not reached. Forty-three patients (86.0%) had at least one treatment-related adverse event (TRAE), and three patients (6.0%) had ≥ G3 TRAEs. The most common TRAEs (any grade/grade ≥3) were AST increased (18%/0%), proteinuria (14%/2%), anemia (14%/2%), and ALT increased (12%/0%). No significant cardiotoxicity or bleeding was observed. GFH018 PK was linear and dose-independent, with a mean half-life of 2.25-8.60 h from 5 - 85 mg. Nine patients (18.0%) achieved stable disease, and one patient with thymic carcinoma achieved tumor shrinkage, with the maximum target lesion decreased by 18.4%. Serum TGF-ß1 levels were not associated with clinical responses. The comprehensive recommended dose for Phase II was defined as 85 mg BID 14d-on/14d-off. CONCLUSIONS: GFH018 monotherapy presented a favorable safety profile without cardiac toxicity or bleeding. Modest efficacy warrants further studies, including combination strategies. TRIAL REGISTRATION: ClinicalTrial. gov ( https://www. CLINICALTRIALS: gov/ ), NCT05051241. Registered on 2021-09-02.

Luteolin: A promising multifunctional natural flavonoid for human diseases.

Natural products are closely associated with human health. Luteolin (LUT), a flavonoid polyphenolic compound, is widely found in fruits, vegetables, flowers, and herbs. It is noteworthy that LUT exhibits a variety of beneficial pharmacological properties and holds significant potential for clinical applications, particularly in antitumor, anti-convulsion, diabetes control, anti-inflammatory, neuroprotection, anti-oxidation, anti-cardiovascular, and other aspects. The potential mechanism of action has been partially elucidated, including the mediation of NF-κB, toll-like receptor, MAPK, Wnt/ß-catenin, PI3K/Akt, AMPK/mTOR, and Nrf-2, among others. The review that aimed to comprehensively consolidate essential information on natural sources, pharmacological effects, therapeutic and preventive potential, as well as potential mechanisms of LUT. The objective is to establish a theoretical basis for the continued development and application of LUT.

Cortactin controls bone homeostasis through regulating the differentiation of osteoblasts and osteoclasts.

Cortactin, a cytoskeletal protein and substrate of src kinase, is implicated in tumor aggressiveness. However, its role in bone cell differentiation remains unknown. The current study revealed that cortactin was upregulated during osteoblast and adipocyte differentiation. Functional experiments demonstrated that cortactin promoted the differentiation of mesenchymal stem/progenitor cells into osteogenic and adipogenic lineages. Mechanistically, cortactin was able to stabilize the protein level of mechanistic target of rapamycin kinase (mTOR), leading to the activation of mTOR signaling. In-depth investigation revealed that cortactin could bind with casitas B lineage lymphoma-c (c-CBL) and counteract the function of c-CBL, a known E3 ubiquitin ligase responsible for the proteasomal degradation of mTOR. Silencing c-Cbl alleviated the impaired differentiation of osteoblasts and adipocytes caused by cortactin siRNA, while silencing mTOR mitigated the stimulation of osteoblast and adipocyte differentiation induced by cortactin overexpression. Notably, transplantation of cortactin-silenced bone marrow stromal cells (BMSCs) into the marrow of mice led to a reduction in trabecular bone mass, accompanied by a decrease in osteoblasts and an increase in osteoclasts. Furthermore, cortactin-silenced BMSCs expressed higher levels of RANKL than control BMSCs did, and promoted osteoclast differentiation when cocultured with bone marrow-derived osteoclast precursor cells. This study provides evidence that cortactin favors osteoblast differentiation by counteracting the c-CBL-induced degradation of mTOR and inhibits osteoclast differentiation by downregulating the expression of RANKL. It also suggests that maintaining an appropriate level of cortactin expression may be advantageous for maintaining bone homeostasis.

Medial sural artery perforator free flap versus radial forearm free flap in oral cavity reconstruction and donor site morbidity.

OBJECTIVE: Radial Forearm Free flap (RFFF) is widely used in head and neck reconstruction, yet its donor site defect remains a significant drawback. The Medial Sural Artery Perforator Free Flap (MSAPFF) is considered an alternative flap to RFFF. This study aims to comprehensively analyze their characteristics, outcomes, and their impact on patient quality of life. METHODS: All patients who underwent oral cavity reconstruction using RFFF and MSAPFF between February 2017 and April 2023 were included in this study. Flap characteristics, outcomes and post-operative complications were recorded and compared. Subjective donor site morbidity, aesthetic and functional results, and quality of life were also analyzed. RESULTS: The study included 76 patients: 37 underwent reconstruction with RFFF, and 39 with MSAPFF. There was no significance difference between the RFFF and MSAPFF regarding the success rate (97.2% vs 97.4%), flap size (4.8 × 8.8 cm2 vs 5 × 9.8 cm2), hospital of stay (15.5 days vs 13.5 days) and recipient site complications (P > 0.05). However, MSAPFF showed larger flap thickness (P = 0.001), smaller arterial caliber (P = 0.008), shorter pedicle length (P = 0.001), and longer harvesting time (P < 0.001). No significant difference was observed between the pre-and postoperative ranges of wrist and ankle movements or in recipient site complications. MSAPFF showed a significant difference in donor site morbidity (P < 0.05). CONCLUSION: The MSAPFF is an excellent alternative to the RFFF for repairing oral cavity defects, with additional advantage of a well-hidden scar on the posterior calf, a larger flap thickness, accepted pedicle length and arterial caliber. However, one should consider the harvesting time and surgical skills required in comparison to the RFFF. CLINICAL RELEVANCE: The study highlights the importance of the MSAPFF as an alternative option for RFFF with less donor site morbidity and high success rate in oral cavity reconstruction and improved patient Quality of life after ablative surgery.

Fenton-ultrasound treatment of corn stalks enhances humification during composting by stimulating the inheritance and synthesis of polyphenolic compounds-preliminary evidence from a laboratory trial.

The impact of Fenton-ultrasound treatment on the production of polyphenols and humic acid (HA) during corn stalk composting was investigated by analyzing the potential for microbial assimilation of polysaccharides in corn stalks to generate polyphenols using a13C-glucose tracer. The results showed that Fenton-ultrasound treatment promoted the decomposition of lignocellulose and increased the HA content, degree of polymerization (DP), and humification index (HI). The primary factor could be attributed to Fenton-ultrasound treatment-induced enhanced the abundance of lignocellulose-degrading microorganisms, as Firmicutes, Actinobacteria phylum and Aspergillis genus, which serve as the primary driving forces behind polyphenol and HA formation. Additionally, the utilization of a13C isotope tracer revealed that corn stalk polysaccharide decomposition products can be assimilated by microbes and subsequently secrete polyphenolic compounds. This study highlights the potential of microbial activity to generate phenolic compounds, offering a theoretical basis for increasing polyphenol production and promoting HA formation during composting.

Extraction, purification, structural characteristics, biological activities, and applications of polysaccharides from the genus Lilium: A review.

The genus Lilium (Lilium) has been widely used in East Asia for over 2000 years due to its rich nutritional and medicinal value, serving as both food and medicinal ingredient. Polysaccharides, as one of the most important bioactive components in Lilium, offer various health benefits. Recently, polysaccharides from Lilium plants have garnered significant attention from researchers due to their diverse biological properties including immunomodulatory, anti-oxidant, anti-diabetic, anti-tumor, anti-bacterial, anti-aging and anti-radiation effects. However, the limited comprehensive understanding of polysaccharides from Lilium plants has hindered their development and utilization. This review focuses on the extraction, purification, structural characteristics, biological activities, structure-activity relationships, applications, and relevant bibliometrics of polysaccharides from Lilium plants. Additionally, it delves into the potential development and future research directions. The aim of this article is to provide a comprehensive understanding of polysaccharides from Lilium plants and to serve as a basis for further research and development as therapeutic agents and multifunctional biomaterials.

25-Hydroxycholesterol regulates lysosome AMP kinase activation and metabolic reprogramming to educate immunosuppressive macrophages.

Macrophages are critical to turn noninflamed "cold tumors" into inflamed "hot tumors". Emerging evidence indicates abnormal cholesterol metabolites in the tumor microenvironment (TME) with unclear function. Here, we uncovered the inducible expression of cholesterol-25-hydroxylase (Ch25h) by interleukin-4 (IL-4) and interleukin-13 (IL-13) via the transcription factor STAT6, causing 25-hydroxycholesterol (25HC) accumulation. scRNA-seq analysis confirmed that CH25Hhi subsets were enriched in immunosuppressive macrophage subsets and correlated to lower survival rates in pan-cancers. Targeting CH25H abrogated macrophage immunosuppressive function to enhance infiltrating T cell numbers and activation, which synergized with anti-PD-1 to improve anti-tumor efficacy. Mechanically, lysosome-accumulated 25HC competed with cholesterol for GPR155 binding to inhibit the kinase mTORC1, leading to AMPKα activation and metabolic reprogramming. AMPKα also phosphorylated STAT6 Ser564 to enhance STAT6 activation and ARG1 production. Together, we propose CH25H as an immunometabolic checkpoint, which manipulates macrophage fate to reshape CD8+ T cell surveillance and anti-tumor response.

Re-exploration of immunotherapy targeting EMT of hepatocellular carcinoma: Starting from the NF-κB pathway.

Hepatocellular carcinoma (HCC) is the fifth most common malignancies worldwide, and its high morbidity and mortality have brought a heavy burden to the global public health system. Due to the concealment of its onset, the limitation of treatment, the acquisition of multi-drug resistance and radiation resistance, the treatment of HCC cannot achieve satisfactory results. Epithelial mesenchymal transformation (EMT) is a key process that induces progression, distant metastasis, and therapeutic resistance to a variety of malignant tumors, including HCC. Therefore, targeting EMT has become a promising tumor immunotherapy method for HCC. The NF-κB pathway is a key regulatory pathway for EMT. Targeting this pathway has shown potential to inhibit HCC infiltration, invasion, distant metastasis, and therapeutic resistance. At present, there are still some controversies about this pathway and new ideas of combined therapy, which need to be further explored. This article reviews the progress of immunotherapy in improving EMT development in HCC cells by exploring the mechanism of regulating EMT.

Ultrasound manifestations and clinical analysis of 50 cases of heterotopic pregnancy.

OBJECTIVE: To investigate the value of ultrasonography in the diagnosis of heterotopic pregnancy and the follow-up. METHODS: A retrospective analysis of 50 cases of clinically diagnosed heterotopic pregnancy in our hospital was performed, the clinical characteristics and ultrasonographic manifestations of the patients were summarized, the reasons for initial ultrasound missed diagnosis and misdiagnosis were analyzed, and the pregnancy outcomes were followed up. RESULTS: Among the 50 cases, the initial ultrasound diagnoses of intrauterine pregnancy were all gestational sac type, 32 cases of ectopic pregnancy were located in the fallopian tube, and 10 cases were located in the uterine horn, 1 case at cervix, and 1 case at caesarean section scar. Forty-one cases were consistent with surgery and/or pathology, representing initial ultrasound diagnosis coincidence rate of about 82%. Six cases were missed in the initial ultrasound examination (12%), and three cases were misdiagnosed (6%). The maximum diameter of the intrauterine gestational sac was 9-48 mm, the average was about 24.90 ± 9.56 mm, the maximum diameter of the ectopic pregnancy gestational sac or mass was 11-63 mm, and the average was about 31.45 ± 13.82 mm (p < 0.05). Intrauterine pregnancy outcomes were followed up, 45 patients with complete data and 5 patients were lost to follow-up. The follow-up rate was about 90%. CONCLUSION: Combining the patient's medical history and clinical characteristics can reduce missed diagnosis and misdiagnosis of heterotopic pregnancy. Ultrasonography has important value in the assessment of intrauterine pregnancy growth and development, and the integrity of maternal uterus.

Primary nasopharyngeal carcinoma with cerebrospinal fluid EBV positivity: A case report and mini literature review.

Background: To summarize the diagnosis and treatment of a patient with nasopharyngeal carcinoma and cerebrospinal fluid (CSF) Epstein-Barr virus (EBV) positivity (determined by next-generation sequencing), review the relevant literature, and explore the significance of EBV presence in the CSF of patients with nasopharyngeal carcinoma. Methods: A patient presenting with headache as the initial symptom was diagnosed with nasopharyngeal carcinoma and admitted to the Eighth Medical Center of Chinese PLA General Hospital on March 3, 2021. Available databases were screened for reports on nasopharyngeal carcinoma with EBV-positive CSF and analyzed. The patients' general information, initial symptoms, treatment, and prognosis were subsequently evaluated. Results: EBV-positive CSF is commonly observed in patients with recurrent nasopharyngeal carcinoma. However, no reports of EBV-positive CSF in patients with primary nasopharyngeal carcinoma have been published to date. Conclusion: The presence of EBV in the CSF of patients with recurrent nasopharyngeal carcinoma is indicative of a poor prognosis. Thus, newly diagnosed nasopharyngeal carcinoma patients should undergo a lumbar puncture as soon as possible to have their CSF tested for EBV. Such a measure would promptly predict the prognosis and facilitate the development of a personalized treatment strategy.

Multimorbidity and mortality among older patients with coronary heart disease in Shenzhen, China.

BACKGROUND: The current understanding of the magnitude and consequences of multimorbidity in Chinese older adults with coronary heart disease (CHD) is insufficient. We aimed to assess the association and population-attributable fractions (PAFs) between multimorbidity and mortality among hospitalized older patients who were diagnosed with CHD in Shenzhen, China. METHODS: We conducted a retrospective cohort study of older Chinese patients (aged ≥ 65 years) who were diagnosed with CHD. Cox proportional hazards models were used to estimate the associations between multimorbidity and all-cause and cardiovascular disease (CVD) mortality. We also calculated the PAFs. RESULTS: The study comprised 76,455 older hospitalized patients who were diagnosed with CHD between January 1, 2016, and August 31, 2022. Among them, 70,217 (91.9%) had multimorbidity, defined as the presence of at least one of the predefined 14 chronic conditions. Those with cancer, hemorrhagic stroke and chronic liver disease had the worst overall death risk, with adjusted HRs (95% CIs) of 4.05 (3.77, 4.38), 2.22 (1.94, 2.53), and 1.85 (1.63, 2.11), respectively. For CVD mortality, the highest risk was observed for hemorrhagic stroke, ischemic stroke, and chronic kidney disease; the corresponding adjusted HRs (95% CIs) were 3.24 (2.77, 3.79), 1.91 (1.79, 2.04), and 1.81 (1.64, 1.99), respectively. All-cause mortality was mostly attributable to cancer, heart failure and ischemic stroke, with PAFs of 11.8, 10.2, and 9.1, respectively. As for CVD mortality, the leading PAFs were heart failure, ischemic stroke and diabetes; the corresponding PAFs were 18.0, 15.7, and 6.1, respectively. CONCLUSIONS: Multimorbidity was common and had a significant impact on mortality among older patients with CHD in Shenzhen, China. Cancer, heart failure, ischemic stroke and diabetes are the primary contributors to PAFs. Therefore, prioritizing improved treatment and management of these comorbidities is essential for the survival prognosis of CHD patients from a holistic public health perspective.

ST14 interacts with TMEFF1 and is a predictor of poor prognosis in ovarian cancer.

TMEFF1 is a new protein involved in the physiological functions of the central nervous system, and we previously reported TMEFF1 can promote ovarian cancer. ST14 was determined to be involved in the processes of epidermal differentiation, epithelial cell integrity, and vascular endothelial cell migration, etc. The relationship between ST14 and TMEFF1 in the ovary remains unknown. In this study, we detected the expression of ST14 and TMEFF1 in 130 different ovarian cancer tissues through immunohistochemistry. We determined ST14 and TMEFF1 were highly expressed in ovarian cancer, indicating a higher degree of tumor malignancy and a worse prognosis. Tissues significantly expressing ST14 also highly expressed TMEFF1, and the expression of the two proteins was positively correlated. Consistently, immunofluorescence double staining demonstrated the co-localization of ST14 and TMEFF1 in the same region, and immunoprecipitation confirmed the interaction between ST14 and TMEFF1. TMEFF1 expression was also reduced after knocking down ST14 through Western blot. MTT, wound healing and Transwell assays results determined that knockdown of ST14 inhibited proliferation, migration and invasion of ovarian cancer cells in vitro, but the inhibitory effect was restored after adding TMEFF1 exogenous protein. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways analysis showed that ST14 and its related genes were enriched in the processes of epithelial formation, intercellular adhesion, protein localization, and mitosis regulation. We also clarified the kinase, microRNA, and transcription factor target networks and the impact of genetic mutations on prognosis. Overall, high expression of ST14 and TMEFF1 in ovarian cancer predicts higher tumor malignancy and a worse prognosis. ST14 and TMEFF1 co-localize and interact with each other in ovarian cancer. ST14 can regulate TMEFF1 expression to promote proliferation, migration and invasion of ovarian cancer cells. We speculate that the relationship between ST14 and TMEFF1 in ovarian cancer could become a potential target for anti-cancer therapy.