Risk factors for peripheral artery disease and diabetic peripheral neuropathy among patients with type 2 diabetes.

AIMS: To investigate the prevalence of peripheral artery disease (PAD) and diabetic peripheral neuropathy (DPN) and the associated risk factors among Chinese patients with type 2 diabetes mellitus. METHODS: A cross-sectional study was conducted using data between November 1, 2018, and December 31, 2022. PAD was defined as ABI ≤ 0.9. DPN diagnosis involved specialized physician assessments using questionnaires and vibration perception threshold tests. Logistic regression analysis was used to identify related factors. We also evaluated the association between the clustering of risk factors and disease incidence. RESULTS: The study population comprised 13,315 patients (mean age: 63.3 years). 4.9 % of the patients had PAD and 43.9 % had DPN. Multivariate regression analysis revealed advanced age, smoking, hypertension, coronary heart disease, dyslipidemia, elevated HbA1c, and uric acid levels as independent risk factors for PAD. For DPN, independent risk factors included advanced age, female gender, hypertension, coronary heart disease, elevated total cholesterol, triglycerides, lipoprotein(a), fasting plasma glucose, HbA1c, alkaline phosphatase, cystatin C, albumin-to-creatinine ratio, and elevated homocysteine levels, whereas apolipoprotein A was a protective factor. The clustering of risk factors was prevalent and associated with higher disease risk. CONCLUSIONS: Our study contributed to identifying high-risk individuals and improving lower limb health among diabetic individuals.

High-Performance Artificial Ligament Made from Helical Polyester Fibers Wrapped with Aligned Carbon Nanotube Sheets.

Repairing high-load connective tissues, such as ligaments, by surgically implanting artificial grafts after injury is challenging because they lack biointegration with host bones for stable interfaces. Herein, a high-performance helical composite fiber (HCF) ligament by wrapping aligned carbon nanotube (CNT) sheets around polyester fibers is proposed. Anterior cruciate ligament (ACL) reconstruction surgery shows that HCF grafts could induce effective bone regeneration, thus allowing the narrowing of bone tunnel defects. Such repair of the bone tunnel is in strong contrast to the tunnel enlargement of more than 50% for commercial artificial ligaments made from bare polyester fibers. Rats reconstructed with this HCF ligament show normal jumping, walking, and running without limping. This work allows bone regeneration in vivo through a one-step surgery without seeding cells or transforming growth factors, thereby opening an avenue for high-performance artificial tissues.

Metabolic reprogramming and epigenetic modifications in cancer: from the impacts and mechanisms to the treatment potential.

Metabolic reprogramming and epigenetic modifications are hallmarks of cancer cells. In cancer cells, metabolic pathway activity varies during tumorigenesis and cancer progression, indicating regulated metabolic plasticity. Metabolic changes are often closely related to epigenetic changes, such as alterations in the expression or activity of epigenetically modified enzymes, which may exert a direct or an indirect influence on cellular metabolism. Therefore, exploring the mechanisms underlying epigenetic modifications regulating the reprogramming of tumor cell metabolism is important for further understanding tumor pathogenesis. Here, we mainly focus on the latest studies on epigenetic modifications related to cancer cell metabolism regulations, including changes in glucose, lipid and amino acid metabolism in the cancer context, and then emphasize the mechanisms related to tumor cell epigenetic modifications. Specifically, we discuss the role played by DNA methylation, chromatin remodeling, noncoding RNAs and histone lactylation in tumor growth and progression. Finally, we summarize the prospects of potential cancer therapeutic strategies based on metabolic reprogramming and epigenetic changes in tumor cells.

Association of Systemic Immune Inflammation Index with All-Cause, Cardiovascular Disease, and Cancer-Related Mortality in Patients with Cardiovascular Disease: A Cross-Sectional Study.

Objective: Our research was designed to investigate the relationship between systemic immune inflammation (SII) index and all-cause, cardiovascular disease (CVD), and cancer-related mortality in patients with CVD. Methods: We used the National Health and Nutrition Examination Survey data from 1999 to 2018 to conduct this study. The association between SII index and all-cause, CVD, and cancer-related mortality in patients with CVD was examined using restricted cubic splines (RCS), Cox proportional hazard models, and subgroup analysis, respectively. CVD was defined as a composite of five outcomes of CVD, including coronary heart disease (CHD), congestive heart failure (CHF), angina pectoris, myocardial infarction, and stroke. Additionally, the link between SII index and all-cause, CVD, and cancer-related mortality in patients with a composite of five outcomes of CVD was also explored. Results: In total, 5329 participants were included. The RCS also showed a U-curve correlation between SII index and the all-cause, CVD, and cancer-related mortality in patients with CVD. As compared with the individuals with lowest quartile of SII index, hazard ratios with 95% confidence intervals for all-cause, CVD, and cancer-related mortality across the quartiles were (1.202 (0.981, 1.474), 1.184 (0.967, 1.450), and 1.365 (1.115, 1.672)), (1.116 (0.815, 1.527), 1.017 (0.740, 1.398), and 1.220 (0.891, 1.670)), and (1.202 (0.981, 1.474), 1.184 (0.967, 1.450), and 1.365 (1.115, 1.672)), respectively, in the full-adjusted model. The SII index also had a U-shaped relationship with all-cause, CVD, and cancer-related mortality in patients with CHD, angina, and myocardial infarction. Additionally, the U-shaped relationship between SII index and all-cause, and cancer-related mortality also exists in CHF, and stroke. However, there was a positive linear correlation between SII index and CVD mortality in patients with CHF, and stroke. Conclusion: In the United States general population, the correlation between SII index and all-cause, CVD, and cancer-related mortality showed a U-shaped curve in patients with CVD.

Specific Spleen-Accumulated NIR-II Fluorescent Probe for Imaging-Guided Splenic Operation.

Spleen is a large immune organ in the body. Splenic operations such as splenectomy and intrasplenic injection are of paramount importance for immunological research and splenic diseases. Fluorescence imaging can vastly simplify these operations, but a specific spleen-targeting probe is still unavailable. Herein, the first specific spleen-accumulated fluorescent probe, VIX-S is reported, which fluoresces at 1064 nm and is highly stable. Systematic studies reveal the superior targeting and imaging performance of VIX-S for the spleen in both nude and haired mice. In vivo imaging indicates that the probe can image the morphology of spleen with a signal-background ratio of at least two-fold higher than that of the liver. Moreover, the application of VIX-S in imaging-guided splenic operation, including splenic injury and intrasplenic injection, is demonstrated, which may provide a practice tool for spleen research in the animal model.

Exosomal cargos-mediated metabolic reprogramming in tumor microenvironment.

Metabolic reprogramming is one of the hallmarks of cancer. As nutrients are scarce in the tumor microenvironment (TME), tumor cells adopt multiple metabolic adaptations to meet their growth requirements. Metabolic reprogramming is not only present in tumor cells, but exosomal cargos mediates intercellular communication between tumor cells and non-tumor cells in the TME, inducing metabolic remodeling to create an outpost of microvascular enrichment and immune escape. Here, we highlight the composition and characteristics of TME, meanwhile summarize the components of exosomal cargos and their corresponding sorting mode. Functionally, these exosomal cargos-mediated metabolic reprogramming improves the "soil" for tumor growth and metastasis. Moreover, we discuss the abnormal tumor metabolism targeted by exosomal cargos and its potential antitumor therapy. In conclusion, this review updates the current role of exosomal cargos in TME metabolic reprogramming and enriches the future application scenarios of exosomes.

The role of tripartite motif-containing 28 in cancer progression and its therapeutic potentials.

Tripartite motif-containing 28 (TRIM28) belongs to tripartite motif (TRIM) family. TRIM28 not only binds and degrades its downstream target, but also acts as a transcription co-factor to inhibit gene expression. More and more studies have shown that TRIM28 plays a vital role in tumor genesis and progression. Here, we reviewed the role of TRIM28 in tumor proliferation, migration, invasion and cell death. Moreover, we also summarized the important role of TRIM28 in tumor stemness sustainability and immune regulation. Because of the importance of TRIM28 in tumors, TIRM28 may be a candidate target for anti-tumor therapy and play an important role in tumor diagnosis and treatment in the future.

Intraoperative crystalloid-colloid infusion ratio associated with the development of early surgical complications after ileal pouch-anal anastomosis in ulcerative colitis: a multicenter long-term follow-up study.

BACKGROUND: Intraoperative intravenous fluid administration proves to be associated with surgical patients' postoperative outcomes. Few studies reported the relationship between intraoperative crystalloid-colloid infusion ratio and early surgical complications after ileal pouch-anal anastomosis (IPAA) in ulcerative colitis (UC). METHODS: Data on patients with underwent IPAA from January 2008 to March 2022 at our three inflammatory bowel disease (IBD) surgery centers were retrospectively collected. Intraoperative anesthetic data were recorded and later evaluated by our team anesthesiologist. RESULTS: A total of 140 eligible patients with a median follow-up time of 6.0 years [interquartile range (IQR): 2.0-8.0] were enrolled. Among all enrolled patients, 34 (24.3%) developed early surgical complications after IPAA. Greater blood loss and lower crystalloid-colloid infusion ratio were observed in patients with early surgical complications. Crystalloid-colloid infusion ratio < 2 and blood loss ≥ 200 ml had the most significant area under the receiver-operating characteristic curve (AUC) of 0.664 and 0.674 in predicting early surgical complications. Crystalloid-colloid infusion ratio < 2 [odds ratio (OR), 2.571; 95% confidence intervals (CI), 1.067-6.195, p = 0.035] and blood loss ≥ 200 ml (OR, 3.165; 95% CI, 1.288-7.777, p = 0.012) were independent risk factors for the development of early post-IPAA complications. CONCLUSION: Intraoperative crystalloid-colloid infusion ratio < 2 and blood loss volume over 200 ml during IPAA contribute to the occurrence of early surgical complications. Early attentions and necessary interventions are warranted to avoid these risk factors during the IPAA surgery in order to prevent the development of early surgical complications.

Rac1 promotes the reprogramming of glucose metabolism and the growth of colon cancer cells through upregulating SOX9.

Metabolic reprogramming is the survival rule of tumor cells, and tumor cells can meet their high metabolic requirements by changing the energy metabolism mode. Metabolic reprogramming of tumor cells is an important biochemical basis of tumor malignant phenotypes. Ras-related C3 botulinum toxin substrate 1 (Rac1) is abnormally expressed in a variety of tumors and plays an important role in the proliferation, invasion, and migration of tumor cells. However, the role of Rac1 in tumor metabolic reprogramming is still unclear. Herein, we revealed that Rac1 was highly expressed in colon cancer tissues and cell lines. Rac1 promotes the proliferation, migration, and invasion of colon cancer cells by upregulating SOX9, which as a transcription factor can directly bind to the promoters of HK2 and G6PD genes and regulate their transcriptional activity. Rac1 upregulates the expression of SOX9 through the PI3K/AKT signaling pathway. Moreover, Rac1 can promote glycolysis and the activation of the pentose phosphate pathway in colon cancer cells by mediating the axis of SOX9/HK2/G6PD. These findings reveal novel regulatory axes involving Rac1/SOX9/HK2/G6PD in the development and progression of colon cancer, providing novel promising therapeutic targets.

LPLUNC1 reduces glycolysis in nasopharyngeal carcinoma cells through the PHB1-p53/c-Myc axis.

Cancer cells prefer glycolysis to support their proliferation. Our previous studies have shown that the long palate, lung, and nasal epithelial cell clone 1 (LPLUNC1) can upregulate prohibitin 1 (PHB1) expression to inhibit the proliferation of nasopharyngeal carcinoma (NPC) cells. Given that PHB1 is an important regulator of cell energy metabolism, we explored whether and how LPLUNC1 regulated glucose glycolysis in NPC cells. LPLUNC1 or PHB1 overexpression decreased glycolysis and increased oxidative phosphorylation (OXPHOS)-related protein expression in NPC cells, promoting phosphorylated PHB1 nuclear translocation through 14-3-3σ. LPLUNC1 overexpression also increased p53 but decreased c-Myc expression in NPC cells, which were crucial for the decrease in glycolysis and increase in OXPHOS-related protein expression induced by LPLUNC1 overexpression. Finally, we found that treatment with all-trans retinoic acid (ATRA) reduced the viability and clonogenicity of NPC cells, decreased glycolysis, and increased OXPHOS-related protein expression by enhancing LPLUNC1 expression in NPC cells. Therefore, the LPLUNC1-PHB1-p53/c-Myc axis decreased glycolysis in NPC cells, and ATRA upregulated LPLUNC1 expression, ATRA maybe a promising drug for the treatment of NPC.

The function of prohibitins in mitochondria and the clinical potentials.

Prohibitins (PHBs) are a class of highly evolutionarily conserved proteins that widely distribute in prokaryotes and eukaryotes. PHBs function in cell growth and proliferation or differentiation, regulating metabolism and signaling pathways. PHBs have different subcellular localization in eukaryotes, but they are mainly located in mitochondria. In the mitochondria, PHBs stabilize the structure of the mitochondrial membrane and regulate mitochondrial autophagy, mitochondrial dynamics, mitochondrial biogenesis and quality control, and mitochondrial unfolded protein response. PHBs has shown to be associated with many diseases, such as mitochondria diseases, cancers, infectious diseases, and so on. Some molecule targets of PHBs can interfere with the occurrence and development of diseases. Therefore, this review clarifies the functions of PHBs in mitochondria, and provides a summary of the potential values in clinics.

The lncRNA MIAT regulates CPT-1a mediated cardiac hypertrophy through m6A RNA methylation reading protein Ythdf2.

Pathological cardiac hypertrophy is a key contributor in heart failure (HF). Long non-coding RNAs (lncRNAs) and N6-methyladenosine (m6A) modification play a vital role in cardiac hypertrophy respectively. Nevertheless, the interaction between lncRNA and m6A methylase in cardiac hypertrophy is scarcely reported. Here, we constructed a cardiac hypertrophy mouse model by transverse aortic constriction (TAC) surgery and H9c2 cell model by stimulating with AngII. We found that lncRNA MIAT mRNA level, and m6A RNA methylation reading protein Ythdf2 mRNA and protein levels, were significantly increased in the cardiac hypertrophy model both in vivo and vitro. MIAT or Ythdf2 overexpression aggravated cardiac hypertrophy, and vice versa. Through bioinformatics prediction, western blotting, FISH, RNA pull-down, and RIP, we found that MIAT bound to Ythdf2 and regulated its expression. Furthermore, we discovered that Ythdf2 function was a downstream of MIAT in cardiac hypertrophy. Finally, we found that MIAT was a necessary regulator of cardiac hypertrophy due to its regulation of the Ythdf2/PPARα/CPT-1a axis. This study indicated a new hypertrophic signaling pathway: MIAT/Ythdf2/PPARα/CPT-1a. The results provided a new understanding of the MIAT and m6A RNA methylation reading protein, Ythdf2, function and mechanism in cardiac hypertrophy and highlighted the potential therapeutic benefits in the heart.

Endothelial MEKK3-KLF2/4 signaling integrates inflammatory and hemodynamic signals during definitive hematopoiesis.

The hematopoietic stem cells (HSCs) that produce blood for the lifetime of an animal arise from RUNX1+ hemogenic endothelial cells (HECs) in the embryonic vasculature through a process of endothelial-to-hematopoietic transition (EHT). Studies have identified inflammatory mediators and fluid shear forces as critical environmental stimuli for EHT, raising the question of how such diverse inputs are integrated to drive HEC specification. Endothelial cell MEKK3-KLF2/4 signaling can be activated by both fluid shear forces and inflammatory mediators, and it plays roles in cardiovascular development and disease that have been linked to both stimuli. Here we demonstrate that MEKK3 and KLF2/4 are required in endothelial cells for the specification of RUNX1+ HECs in both the yolk sac and dorsal aorta of the mouse embryo and for their transition to intraaortic hematopoietic cluster (IAHC) cells. The inflammatory mediators lipopolysaccharide and interferon-γ increase RUNX1+ HECs in an MEKK3-dependent manner. Maternal administration of catecholamines that stimulate embryo cardiac function and accelerate yolk sac vascular remodeling increases EHT by wild-type but not MEKK3-deficient endothelium. These findings identify MEKK-KLF2/4 signaling as an essential pathway for EHT and provide a molecular basis for the integration of diverse environmental inputs, such as inflammatory mediators and hemodynamic forces, during definitive hematopoiesis.

Exosomal miR-205-5p enhances angiogenesis and nasopharyngeal carcinoma metastasis by targeting desmocollin-2.

The aim of this study was to investigate whether and how exosomal miR-205-5p regulated angiogenesis and nasopharyngeal carcinoma (NPC) metastasis. We found that up-regulated serum exosomal miR-205-5p levels were associated with NPC progression and worse overall survival of NPC patients. miR-205-5p over-expression significantly increased tube formation, wound healing, migration and invasion of NPC cells, and lung metastasis of NPC tumors, whereas miR-205-5p inhibition had opposite effects. Exosomal miR-205-5p from NPC cells promoted the migration, tube formation, and microvessel density (MVD) of HUVECs in vitro and in vivo. Furthermore, bioinformatics-, luciferase reporter-, and biotinylated miR-205-5p-based pull-down assays indicated that miR-205-5p directly bound to the 3' UTR of desmocollin-2 (DSC2). Exosomal miR-205-5p targeted DSC2 to enhance the EGFR/ERK signaling and MMP2/MMP9 expression, promoting angiogenesis and NPC metastasis, which was abrogated by DSC2 over-expression. Finally, the levels of miR-205-5p transcripts were positively correlated with MVD but negatively with DSC2 expression in NPC tissues, and patients with miR-205high/DSC2low NPC had worse overall survival. In conclusion, exosomal miR-205-5p promotes angiogenesis and NPC metastasis by targeting DSC2 to enhance EGFR/ERK signaling and MMP expression. This exosomal/miR-205-5p/EGFR/ERK axis may be a new therapeutic target for intervention of NPC metastasis.

The POU2F1-ALDOA axis promotes the proliferation and chemoresistance of colon cancer cells by enhancing glycolysis and the pentose phosphate pathway activity.

Cancer metabolic reprogramming enhances its malignant behaviors and drug resistance, which is regulated by POU domain transcription factors. This study explored the effect of POU domain class 2 transcription factor 1 (POU2F1) on metabolic reprogramming in colon cancer. The POU2F1 expression was analyzed in GEO dataset, TCGA cohorts and human colon cancer tissues by bioinformatics and immunohistochemistry. The effects of altered POU2F1 expression on proliferation, glucose metabolism and oxaliplatin sensitivity of colon cancer cells were tested. The impacts of POU2F1 on aldolase A (ALDOA) expression and malignant behaviors of colon cancer cells were examined. We found that up-regulated POU2F1 expression was associated with worse prognosis and oxaliplatin resistance in colon cancer. POU2F1 enhanced the proliferation, aerobic glycolysis and the pentose phosphate pathway (PPP) activity, but reduced oxidative stress and apoptosis in colon cancer cells, dependent on up-regulating ALDOA expression. Mechanistically, POU2F1 directly bound to the ALDOA promoter to enhance the ALDOA promoter activity in colon cancer cells. Moreover, activation of the POU2F1-ALDOA axis decreased the sensitivity to oxaliplatin in colon cancer cells. These data indicate that the POU2F1-ALDOA axis promotes the progression and oxaliplatin resistance by enhancing metabolic reprogramming in colon cancer. Our findings suggest that the POU2F1-ALDOA axis may be new therapeutic targets to overcome oxaliplatin resistance in colon cancer.

Research Progress on N6-adenosylate Methylation RNA Modification in Heart Failure Remodeling.

Cardiovascular disease (CVD) is the major cause of disability-adjusted life years (DALY) and death globally. The most common internal modification of mRNA is N6-adenosylate methylation (m6A). Recently, a growing number of studies have been devoted to researching cardiac remodeling mechanisms, especially m6A RNA methylation, revealing a connection between m6A and cardiovascular diseases. This review summarized the current understanding regarding m6A and elucidated the dynamic modifications of writers, erasers, and readers. Furthermore, we highlighted m6A RNA methylation related to cardiac remodeling and summarized its potential mechanisms. Finally, we discussed the potential of m6A RNA methylation in the treatment of cardiac remodeling.

Upregulation of wild-type p53 by small molecule-induced elevation of NQO1 in non-small cell lung cancer cells.

The tumor suppressor p53 is usually inactivated by somatic mutations in malignant neoplasms, and its reactivation represents an attractive therapeutic strategy for cancers. Here, we reported that a new quinolone compound RYL-687 significantly inhibited non-small cell lung cancer (NSCLC) cells which express wild type (wt) p53, in contract to its much weaker cytotoxicity on cells with mutant p53. RYL-687 upregulated p53 in cells with wt but not mutant p53, and ectopic expression of wt p53 significantly enhanced the anti-NSCLC activity of this compound. RYL-687 induced production of reactive oxygen species (ROS) and upregulation of Nrf2, leading to an elevation of the NAD(P)H:quinoneoxidoreductase-1 (NQO1) that can protect p53 by inhibiting its degradation by 20S proteasome. RYL-687 bound NQO1, facilitating the physical interaction between NQO1 and p53. NQO1 was required for RYL-687-induced p53 accumulation, because silencing of NQO1 by specific siRNA or an NQO1 inhibitor uridine, drastically suppressed RYL-687-induced p53 upregulation. Moreover, a RYL-687-related prodrug significantly inhibited tumor growth in NOD-SCID mice inoculated with NSCLC cells and in a wt p53-NSCLC patient-derived xenograft mouse model. These data indicate that targeting NQO1 is a rational strategy to reactivate p53, and RYL-687 as a p53 stabilizer bears therapeutic potentials in NSCLCs with wt p53.

Exploration of the value of progesterone and progesterone/estradiol ratio on the hCG trigger day in predicting pregnancy outcomes of PCOS patients undergoing IVF/ICSI: a retrospective cohort study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder with the disorders of estrogen(E2) and progesterone(P) secretion. The purpose of this study was to evaluate the association between the progesterone level or progesterone/estradiol(P/E2) ratio on human chorionic gonadotropin (hCG) trigger day and the outcome of in vitro fertilization in PCOS patients and explore the value of progesterone and P/E2 ratio for predicting the clinical pregnancy. METHODS: The clinical data of 1254 PCOS patients who satisfied the inclusion criteria were retrospectively analyzed, including baseline characteristics such as age, body mass index, basal sex hormone levels, et al., as well as ovarian stimulation data and clinic outcome. RESULTS: The number of follicles larger than 14 mm in diameter (P < 0.001) and retrieved oocytes (P < 0.001) was greater in the high progesterone group (progesterone ≥ 0.92 ng/mL). In the high P/E2 group(P/E2 ratio ≥ 0.3), the number of follicles larger than 14 mm in diameter (P < 0.001) and retrieved oocytes (P < 0.001), as well as the rate of high-quality embryos (P = 0.040) were significantly decreased. In ultralong GnRH agonist protocol, the implantation rate(P < 0.001), hCG positive rate (P < 0.001), clinical pregnancy rate (P < 0.001) and live birth rate (P < 0.001) were all significantly higher than long GnRH agonist protocol and GnRH antagonist protocol. The clinical pregnancy rate of high progesterone group was significantly lower than that of low progesterone group in ultralong GnRH agonist (P = 0.008). The progesterone level could be used as an indicator to predict the positive clinical pregnancy (long GnRH agonist: P = 0.001; ultralong GnRH agonist: P < 0.001) except in cycles using GnRH antagonist (P = 0.169). In the ultralong GnRH agonist, the value of progesterone level in the prediction of clinical pregnancy was significantly higher than that of the P/E2 ratio (P = 0.021). CONCLUSIONS: In PCOS patients, the progesterone level is associated with clinical pregnancy rate while P/E2 ratio is not. In subgroup analysis using three different COS protocols, a significant association between progesterone level and clinical pregnancy rate can be observed in the long GnRH agonist protocol and ultralong GnRH agonist protocol. The progesterone level is significantly better than the P/E2 ratio in predicting the pregnancy outcome of PCOS patients, especially in ultralong GnRH agonist cycles.

The abnormal level of HSP70 is related to Treg/Th17 imbalance in PCOS patients.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a disease with chronic nonspecific low-grade inflammation. The imbalance of immune cells exists in PCOS. Several studies have found that heat shock protein 70 (HSP70) may be involved in the immunological pathogenesis of PCOS, but the relationship between HSP70 and Regulatory T cell (Treg)/T helper cell 17(Th17) ratio remains unclear. This study aims to explore the correlation between HSP70 and Treg/Th17 ratio and to provide evidence for the role of HSP70 in the immunological etiology of PCOS. RESULTS: There was no significant difference in age and body mass index (BMI) between the two groups. The concentrations of basal estradiol (E2), basal follicle-stimulating hormone (FSH) did not show a significant difference between the two groups. The concentrations of basal luteinizing hormone (LH) (P < 0.01), testosterone (T) (P < 0.01), glucose (P < 0.001) and insulin (P < 0.001) in PCOS patients were significantly higher than those in the control group. The protein levels of HSP70 were significantly higher in serum in the PCOS group (P < 0.001). The percentage of Treg cells was significantly lower (P < 0.01), while the percentage of the Th17 cells of the PCOS group was significantly higher than that of the control group (P < 0.05). The ratio of Treg/Th17 in the PCOS group was significantly lower (P < 0.001). The concentrations of Interleukin (IL)-6, IL-17, and IL-23 were significantly higher, while the levels of IL-10 and Transforming growth factor-ß (TGF-ß) were significantly lower in the PCOS group (P < 0.001). Spearman rank correlation analysis showed a strong negative correlation of serum HSP70 levels with Treg/Th17 ratio, IL-10, and TGF-ß levels. In contrast, HSP70 levels were significantly positively correlated with IL-6, IL-17, IL-23, LH, insulin, and glucose levels. CONCLUSION: The abnormal level of HSP70 is correlated with Treg/Th17 imbalance and corresponding cytokines, which indicates that HSP70 may play an important role in PCOS immunologic pathogenesis.

It's Time to Add Electrocardiography and Echocardiography to CVD Risk Prediction Models: Results from a Prospective Cohort Study.

OBJECTIVE: To develop and validate a new prediction model for the general population based on a large panel of both traditional and novel factors in cardiovascular disease (CVD). DESIGN AND SETTING: We used a prospective cohort in the Northeast China Rural Cardiovascular Health Study (NCRCHS). PARTICIPANTS: A total of 11,956 participants aged ≥35 years were recruited between 2012 and 2013, using a multistage, randomly stratified, cluster-sampling scheme. In 2015 and 2017, the participants were invited to join the follow-up study for incident cardiovascular events. The loss to follow-up number was 351. At the study's end, we obtained the CVD outcome events for 10,349 participants. PRIMARY AND SECONDARY OUTCOME MEASURES: The prediction model was developed using demographic factors, blood biochemical indicators, electrocardiographic (ECG) characteristics, and echocardiography indicators collected at baseline (Model 1). Framingham-related variables, namely age, sex, smoking, total and high-density lipoprotein cholesterol and diabetes status were used to construct the traditional model (Model 2). RESULTS: For the observed population (n = 10,349), the median follow-up time was 4.66 years. The total incidence of CVD was 1.1%/year, including stroke (n = 342) and coronary heart disease (n = 175). The results of Model 1 indicated that in addition to the traditional risk factors, QT interval (p < 0.001), aortic root diameter (p < 0.001), and ventricular septal thickness (p < 0.001) were predictive factors for CVD. Decision curve analysis (DCA) showed that the net benefit with Model 1 was higher than that of Model 2. CONCLUSION: QT interval from electrocardiography and aortic root diameter and ventricular septal thickness from echocardiography should be included in the CVD risk prediction models.