A national study exploring the association between triglyceride-glucose index and risk of hyperuricemia events in adults with hypertension.

Background: The triglyceride-glucose (TyG) index has been recommended as a practical surrogate of insulin resistance (IR). However, the association between the TyG index and hyperuricemia among adults with hypertension remains to be elucidated. Methods: We included and analyzed 3134 HTN patients and 4233 non-HTN participants from the cross-sectional 2013-2018 U.S. National Health and Nutrition Examination Surveys (NHANES). Multivariable logistic regression and restricted cubic splines (RCS) were used to explore the association between the TyG index and hyperuricemia. Stratifed analyses were performed to assess the association in populations with different subgroups of hypertension. Results: The prevalence of hyperuricemia was higher in HTN patients (28.00 %) than in non-HTN participants (12.47 %). The multivariable logistic regression showed that the TyG index was significantly associated with hyperuricemia. After multivariable adjustment, higher TyG index levels were found to be associated with a higher prevalence of hyperuricemia in HTN patients (OR: 2.39, 95 % CI: 1.37-4.17, Ptrend < 0.001) and non-HTN participants (OR: 2.61, 95 % CI: 1.45-4.69, Ptrend < 0.001). Restricted cubic spline regression showed linearity of the associations between the TyG index and hyperuricemia (p-nonlinear > 0.05). In the subgroup analysis suggested that the positive association seemed to be strong among male, alcohol use, and diabetes group (P for interaction < 0.05). Conclusions: TyG index, a practical surrogate of IR, was linearly and positively associated with hyperuricemia in HTN and non-HTN participants. Proactive measures are needed to prevent the comorbidity of IR-driven hyperuricemia in the future.

Social integration and utilization of national basic public health services among China's internal migrants with chronic diseases: A structural equation modelling approach.

Internal migrants with chronic diseases (IMCDs) are a specific subgroup of the internal migrants, but few studies have focused on health service utilization among this group. Social integration is an essential element in the maintenance of health and well-being in migrants. However, the measurement of social integration remains inconsistent. This study aimed to measure social integration more comprehensively and evaluate the association between social integration and National Basic Public Health Services (NBPHS) utilization among IMCDs in China, thereby providing theoretical support for health promotion among IMCDs. The data of this study were obtained from the China Migrants Dynamic Survey (CMDS) in 2017. A total of 9272 internal migrants who self-reported hypertension and/or type 2 diabetes were included in the analysis. Four factors were extracted through exploratory factor analysis to measure the social integration of IMCDs: psychological identity, community involvement, social security, and sociocultural adaptation. The results show the IMCDs underutilized NBPHS, with 26.80 % stating that they have not used any of the services in the NBPHS. We confirmed the positive association between social integration and NBPHS use among IMCDs. The social integration of IMCDs in developed regions was relatively worse than in developing regions, further exacerbating the underutilization of NBPHS in developed regions. Therefore, targeted government measures and supportive policies are necessary, especially in developed regions, to encourage IMCDs to participate in social organizations and community activities and stimulate their active participation in the NBPHS.

Predictive value of machine learning on fracture risk in osteoporosis: a systematic review and meta-analysis.

OBJECTIVES: Early identification of fracture risk in patients with osteoporosis is essential. Machine learning (ML) has emerged as a promising technique to predict the risk, whereas its predictive performance remains controversial. Therefore, we conducted this systematic review and meta-analysis to explore the predictive efficiency of ML for the risk of fracture in patients with osteoporosis. METHODS: Relevant studies were retrieved from four databases (PubMed, Embase, Cochrane Library and Web of Science) until 31 May 2023. A meta-analysis of the C-index was performed using a random-effects model, while a bivariate mixed-effects model was used for the meta-analysis of sensitivity and specificity. In addition, subgroup analysis was performed according to the types of ML models and fracture sites. RESULTS: Fifty-three studies were included in our meta-analysis, involving 15 209 268 patients, 86 prediction models specifically developed for the osteoporosis population and 41 validation sets. The most commonly used predictors in these models encompassed age, BMI, past fracture history, bone mineral density T-score, history of falls, BMD, radiomics data, weight, height, gender and other chronic diseases. Overall, the pooled C-index of ML was 0.75 (95% CI: 0.72, 0.78) and 0.75 (95% CI: 0.71, 0.78) in the training set and validation set, respectively; the pooled sensitivity was 0.79 (95% CI: 0.72, 0.84) and 0.76 (95% CI: 0.80, 0.81) in the training set and validation set, respectively; and the pooled specificity was 0.81 (95% CI: 0.75, 0.86) and 0.83 (95% CI: 0.72, 0.90) in the training set and validation set, respectively. CONCLUSIONS: ML has a favourable predictive performance for fracture risk in patients with osteoporosis. However, most current studies lack external validation. Thus, external validation is required to verify the reliability of ML models. PROSPERO REGISTRATION NUMBER: CRD42022346896.

The association between the Short Physical Performance Battery and longitudinal trajectories of depressive symptoms among Chinese older adults.

BACKGROUND: In this study, the long-term trajectories of depressive symptoms in a 7-year prospective survey cohort of Chinese older adults were explored. Additionally, the study examined whether there was an independent association between scores on the Short Physical Performance Battery (SPPB) and the different trajectories of depressive symptoms. METHODS: A total of 2177 elderly individuals had their depressive symptoms assessed based on the Center for Epidemiological Studies-Depression (CES-D) scale in the years 2011, 2013, 2015, and 2018. In addition, their demographic characteristics, chronic diseases, and lifestyle factors were also assessed. The trajectories of depressive symptoms were analysed using the group-based trajectories analysis model. Furthermore, the relationship between the objectively measured SPPB scores and the long-term trajectory of depressive symptoms was explored using multinomial logistic regression. RESULTS: The group-based trajectory analysis model categorized the trajectories of depressive symptoms across four waves into four groups: persistent low depressive symptoms, increasing depressive symptoms, decreased depressive symptoms, and persistent high depressive symptoms. After controlling for confounding factors, it was observed that a higher baseline SPPB score was associated with an increased likelihood of persistent high depressive symptoms, OR (95% CI) = 0.724 (0.644, 0.814), for the persistent high depressive symptoms versus the persistent low depressive symptoms. CONCLUSIONS: Low levels of SPPB score are associated with persistent high depressive symptoms in older adults. Conversely, improving physical performance as measured by the SPPB can help reduce the risk of major depressive disorder and persistent depressive disorder in the elderly.

Construction of predictive model for osteoporosis related factors among postmenopausal women on the basis of logistic regression and Bayesian network.

Osteoporosis is a prevalent chronic disease that often goes unnoticed in postmenopausal women. Early identification of risk factors for osteoporosis in postmenopausal women is essential. This study aimed to develop predictive models for osteoporosis-related factors among postmenopausal women in the U.S. and explore the influencing factors. In this cross-sectional study, we included 4417 postmenopausal women from the NHANES (2009-2010, 2013-2014, and 2017-2020). Through multiple regression analysis, we found that age, minutes of sedentary activity, prednisone or cortisone usage, arthritis, bone loss around teeth, and trouble sleeping were risk factors for osteoporosis after menopause. Conversely, height, BMI, and age at the last menstrual period were identified as protective factors. The findings from the Bayesian network analysis indicated that several factors influenced osteoporosis, including age, BMI, bone loss around teeth, prednisone or cortisone usage, arthritis, and age at the last menstrual period. On the other hand, minutes of sedentary activity and height might have indirect effects, while trouble sleeping may not have a significant impact. Both logistic regression and Bayesian network models demonstrated good predictive capabilities in predicting osteoporosis among postmenopausal women. In addition, Bayesian networks offer a more intuitive depiction of the intricate network risk mechanism between diseases and factors.

Transcriptomic landscape of GC-2spd(ts) cell in response to the downregulation of piR-1207/2107.

Spermatogenesis is a highly orchestrated dynamic developmental process, during which piRNAs play an indispensable role. Our previous studies have confirmed that the levels of piR-1207 and piR-2107 were significantly decreased in spermatozoa and seminal plasma of patients with asthenozoospermia, compared with the fertile controls. In order to explore the function of piR-1207 and piR-2107 in human spermatogenesis and their potential regulatory downstream genes, we examined the transcriptomic landscape in mouse spermatocyte cell line GC-2spd(ts) transfected with anti-piR-1207 and anti-piR-2107 by RNA sequencing. The result showed that 86 and 75 differential expression genes (DEGs) in anti-piR-1207 and anti-piR-2107 group, respectively. Among the DEGs, three genes including Pbp2, Pde3a and Cage1 were identified as potential key genes playing important roles in mediating sperm motility and morphology in anti-piR-1207 or anti-piR-2107 transfected transcriptomic response. Next, the expression levels of Pbp2, Pde3a and Cage1 were confirmed by qRT-PCR. These results showed that Pbp2, Pde3a and Cage1 may serve as the potential regulatory genes of piR-1207 or piR-2107. In summary, piR-1207 and piR-2107 might have an implication in modulating the process of spermatogenesis through regulating the expression of potential genes.

Psychotherapy for advanced cancer patients: A meta-analysis of the quality of life and survival assessments.

OBJECTIVES: A meta-analysis has explored the effect of psychotherapy on the quality of life (QOL) but has not explored the effect on advanced cancer patients' survival, which is highly debated. Therefore, we consider the survival days and QOL as the primary outcomes in our analysis. METHODS: Eligible studies were collected from four databases (PubMed, Embase, Cochrane Library, and Web of Science) until February 20, 2021. The pooled effect sizes were presented as weighted mean difference (WMD) or relative risk (RR) with 95% confidence intervals (CIs). Publication bias was evaluated by Egger's test, and I2 statistics was used to assess the heterogeneity. RESULTS: Thirty-three studies were finally included, containing 2,159 patients in the psychotherapy group and 2,170 patients in the control group. McGill Quality of Life Questionnaire (MQOL) and European Organization for Research and Treatment of Cancer Quality of Life-C15-Palliative (EORTC-QLQ-C15-Pal) supported that QOL of the psychotherapy group was significantly higher than that of the control group, and WMD value was 0.42 (95% CI: 0.12-0.71) and 17.26 (95% CI: 11.08-23.44), respectively. No significant difference was observed between the two groups regarding to the survival time (WMD: 17.85, 95% CI: -8.79, 44.49, P = 0.189). Moreover, the levels of anxiety, depression, confusion, pain, and suffering were lowered in psychotherapy group (all P < 0.05). SIGNIFICANCE OF RESULTS: Psychotherapy could improve the QOL of advanced cancer patients but not affect the survival time.

Decreased piRNAs in Infertile Semen Are Related to Downregulation of Sperm MitoPLD Expression.

Currently, the molecular mechanisms underlining male infertility are still poorly understood. Our previous study has demonstrated that PIWI-interacting RNAs (piRNAs) are downregulated in seminal plasma of infertile patients and can serve as molecular biomarkers for male infertility. However, the source and mechanism for the dysregulation of piRNAs remain obscure. In this study, we found that exosomes are present in high concentrations in human seminal plasma and confirmed that piRNAs are predominantly present in the exosomal fraction of seminal plasma. Moreover, we showed that piRNAs were significantly decreased in exosomes of asthenozoospermia patients compared with normozoospermic men. By systematically screening piRNA profiles in sperms of normozoospermic men and asthenozoospermia patients, we found that piRNAs were parallelly reduced during infertility. At last, we investigated the expression of some proteins that are essential for piRNAs biogenesis in sperms and therefore identified a tight correlation between the levels of spermatozoa piRNA and MitoPLD protein, suggesting that the loss-of-function of MitoPLD could cause a severe defect of piRNA accumulation in sperms. In summary, this study identified a parallel reduction of piRNAs and MitoPLD protein in sperms of asthenozoospermia patients, which may provide pathophysiological clues about sperm motility.

NFIB functions as an oncogene in estrogen receptor-positive breast cancer and is regulated by miR-205-5p.

Nuclear factor I/B(NFIB) is a prominent transcription factor that plays a critical role in cancer progression. In this study, we found that the protein level of NFIB was significantly upregulated in estrogen receptor (ER) positive breast cancer tissues compared to matched adjacent noncancerous tissues while the NFIB mRNA expression level was not obviously dysregulated. Similarly, ER-positive breast cancer cell line, MCF7 express a high protein level of NFIB, while the mRNA level is not significantly upregulated. The function assays indicated that NFIB promoted MCF-7 cell cycle progression, cell proliferation and suppressed apoptosis in vitro. Furthermore, we explored the molecular mechanisms of NFIB as a target gene of miR-205-5p. Finally, we found that miR-205-5p was significantly downregulated in ER -positive breast cancer, and had the opposite eff ;ects on breast cancer cells compared with NFIB. Taken together, this study highlighted the molecular mechanisms of NFIB as an oncogene in ER-positive breast cancer, which was negatively regulated by miR-205-5p in breast cancer.

Dynamic core crosslinked camptothecin prodrug micelles with reduction sensitivity and boronic acid-mediated enhanced endocytosis: An intelligent tumor-targeted delivery nanoplatform.

The physicochemical properties of camptothecin (CPT) limit its clinical application. To maximize drug efficacy, a novel intelligent prodrug delivery nanoplatform with a tumor microenvironment-cleavable core crosslinking strategy was proposed based on a phenylboronic acid (PBA) modified polyethylene glycol (PEG)-polyglutamic acid (PGlu) polymer with disulfide-bonded CPT, called PBA-PEG-P(Glu-co-GlussCPT). The fabricated nanoplatform was a spherical micelle that could withstand dilution and carry a large number of therapeutic molecules to the tumor tissues, thereby minimizing premature drug release. Moreover, the nanoplatform release 6.2 ± 0.62, 12.4 ± 1.8, 46.7 ± 0.33, and 79.2 ± 1.58% of CPT after incubation in 0.02, 1, 5, and 10 mM dithiothreitol for 24 h, respectively, exhibiting good reduction-sensitivity. Moreover, the nanoplatform exhibited significant antiproliferative activity against tumor cells. In addition, with PBA modification, the nanoplatform demonstrated enhanced endocytosis efficiency. This prodrug nanoplatform also exhibited significant in vivo antitumor efficacy on both murine and human hepatoma xenograft models, without showing significant systemic toxicity but demonstrating good biocompatibility. In other words, this novel intelligent prodrug delivery nanoplatform with tumor microenvironment-cleavable core crosslinking strategy and active targeting strategy based on prodrug polymer PBA-PEG-P(Glu-co-GlussCPT) demonstrated multiple functions and significant potential for antitumor drug delivery.

Bioinspired nanoplatform for enhanced delivery efficiency of doxorubicin into nucleus with fast endocytosis, lysosomal pH-triggered drug release, and reduced efflux.

A novel bioinspired nanoplatform capable of fast endocytosis, lysosomal pH-triggered drug release, and reduced drug efflux based on PBA-PEG-b-P(Glu-co-GluDA) copolymer was developed in this study. The synthesized copolymer could facilitate doxorubicin encapsulation with relatively high drug-loading content and efficiency. Inspired by mussel byssal threads, a core crosslinking strategy based on the coordination between catechol and ferric ions was introduced to improve the stability of nanomicelles and realize lysosomal pH-controlled drug release. This nanoplatform could maintain integrity even after being dissolved in a good solvent, demonstrating its the potential to withstand infinite dilution of plasma after intravenous injection. Moreover, this nanoplatform demonstrated lysosomal pH-triggered drug release, and the cumulative release amount of doxorubicin under a simulated lysosomal condition was 13 times higher than that under a simulated plasma condition. Moreover, as a result of the high binding capacity between phenylboronic acid (PBA) and sialic acid on the surface of human hepatoma cell line (HepG2), the fast and enhanced endocytosis in addition to lysosomal pH-triggered release property and significantly low efflux, this nanoplatform exhibits improved delivery efficiency of doxorubicin into the nucleus and notably outstanding antiproliferative effects compared with doxorubicin. Furthermore, the PBA modification remarkably increased the mean fluorescence intensity of this nanoplatform endocytosed by HepG2 cells to twice that of doxorubicin after one hour of incubation. The nanoplatform exhibited an inhibition rate of 70% against tumor growth. Thus, this novel nanoplatform based on PBA-PEG-b-P(Glu-co-GluDA) copolymer displayed multifunctionality and exhibited great potential as an intelligent nanoplatform for antitumor drug delivery.

Rod-Shaped Micelles Based on PHF- g-(PCL-PEG) with pH-Triggered Doxorubicin Release and Enhanced Cellular Uptake.

A biodegradable brush-type copolymer PHF- g-(PCL-PEG) based on a cleavable polyacetal backbone and biodegradable side chain modified with polyethylene glycol (PEG) was synthesized in this paper. This particular structure was directional to facilitate the formation of spherical or rod-shaped micelles. Flow cytometry showed that rod-shaped micelles displayed enhanced cellular uptake compared to spherical micelles. Rod-shaped micelles were selected to investigate their drug delivery abilities in detail. In vitro experiments verified the pH-triggered drug release of DOX-loaded micelles, and the release rate of doxorubicin (DOX) was 77% at pH 5.0 and 26% at pH 7.4. In drug-release kinetic analysis, a double-exponential model achieved the best fit. The copolymer appeared to be almost nontoxic, while the DOX-loaded micelles showed equivalent cytotoxicity compared to DOX at high concentration. The endocytosis of DOX-loaded micelles was two times that of DOX. Our findings suggest that the pH-sensitive brush type copolymer could be a possible carrier in drug delivery.