Roles of serum uric acid on the association between arsenic exposure and incident metabolic syndrome in an older Chinese population.

Growing evidences showed that heavy metals exposure may be associated with metabolic diseases. Nevertheless, the mechanism underlying arsenic (As) exposure and metabolic syndrome (MetS) risk has not been fully elucidated. So we aimed to prospectively investigate the role of serum uric acid (SUA) on the association between blood As exposure and incident MetS. A sample of 1045 older participants in a community in China was analyzed. We determined As at baseline and SUA concentration at follow-up in the Yiwu Elderly Cohort. MetS events were defined according to the criteria of the International Diabetes Federation (IDF). Generalized linear model with log-binominal regression model was applied to estimate the association of As with incident MetS. To investigate the role of SUA in the association between As and MetS, a mediation analysis was conducted. In the fully adjusted log-binominal model, per interquartile range increment of As, the risk of MetS increased 1.25-fold. Compared with the lowest quartile of As, the adjusted relative risk (RR) of MetS in the highest quartile was 1.42 (95% confidence interval, CI: 1.03, 2.00). Additionally, blood As was positively associated with SUA, while SUA had significant association with MetS risk. Further mediation analysis demonstrated that the association of As and MetS risk was mediated by SUA, with the proportion of 15.7%. Our study found higher As was remarkably associated with the elevated risk of MetS in the Chinese older adults population. Mediation analysis indicated that SUA might be a mediator in the association between As exposure and MetS.

Schnurri-3 inhibition rescues skeletal fragility and vascular skeletal stem cell niche pathology in the OIM model of osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a disorder of low bone mass and increased fracture risk due to a range of genetic variants that prominently include mutations in genes encoding type I collagen. While it is well known that OI reflects defects in the activity of bone-forming osteoblasts, it is currently unclear whether OI also reflects defects in the many other cell types comprising bone, including defects in skeletal vascular endothelium or the skeletal stem cell populations that give rise to osteoblasts and whether correcting these broader defects could have therapeutic utility. Here, we find that numbers of skeletal stem cells (SSCs) and skeletal arterial endothelial cells (AECs) are augmented in Col1a2oim/oim mice, a well-studied animal model of moderate to severe OI, suggesting that disruption of a vascular SSC niche is a feature of OI pathogenesis. Moreover, crossing Col1a2oim/oim mice to mice lacking a negative regulator of skeletal angiogenesis and bone formation, Schnurri 3 (SHN3), not only corrected the SSC and AEC phenotypes but moreover robustly corrected the bone mass and spontaneous fracture phenotypes. As this finding suggested a strong therapeutic utility of SHN3 inhibition for the treatment of OI, a bone-targeting AAV was used to mediate Shn3 knockdown, rescuing the Col1a2oim/oim phenotype and providing therapeutic proof-of-concept for targeting SHN3 for the treatment of OI. Overall, this work both provides proof-of-concept for inhibition of the SHN3 pathway and more broadly addressing defects in the stem/osteoprogenitor niche as is a strategy to treat OI.

Predicting Continuous Locomotion Modes via Multidimensional Feature Learning from sEMG.

Walking-assistive devices require adaptive control methods to ensure smooth transitions between various modes of locomotion. For this purpose, detecting human locomotion modes (e.g., level walking or stair ascent) in advance is crucial for improving the intelligence and transparency of such robotic systems. This study proposes Deep-STF, a unified end-to-end deep learning model designed for integrated feature extraction in spatial, temporal, and frequency dimensions from surface electromyography (sEMG) signals. Our model enables accurate and robust continuous prediction of nine locomotion modes and 15 transitions at varying prediction time intervals, ranging from 100 to 500 ms. Experimental results showcased Deep-STP's cutting-edge prediction performance across diverse locomotion modes and transitions, relying solely on sEMG data. When forecasting 100 ms ahead, Deep-STF achieved an improved average prediction accuracy of 96.60%, outperforming seven benchmark models. Even with an extended 500ms prediction horizon, the accuracy only marginally decreased to 93.22%. The averaged stable prediction times for detecting next upcoming transitions spanned from 31.47 to 371.58 ms across the 100-500 ms time advances. Although the prediction accuracy of the trained Deep-STF initially dropped to 71.12% when tested on four new terrains, it achieved a satisfactory accuracy of 92.51% after fine-tuning with just 5 trials and further improved to 96.27% with 15 calibration trials. These results demonstrate the remarkable prediction ability and adaptability of Deep-STF, showing great potential for integration with walking-assistive devices and leading to smoother, more intuitive user interactions.

Changing Reimbursement Criteria on Anti-VEGF Treatment Patterns Among Wet Age-Related Macular Degeneration and Diabetic Macular Edema Patients: An Interrupted Time Series Analysis.

BACKGROUND: To evaluate the impact of reimbursement criteria change on the utilization pattern of anti-vascular endothelial growth factor (anti-VEGF) among patients with wet age-related macular degeneration (wAMD) and diabetic macular edema (DME) separately in Taiwan. METHODS: An interrupted time series analysis (ITSA) was performed using Taiwan's National Health Insurance (NHI) database, and patients with wAMD or DME diagnosis at the first injection of anti-VEGF agents was identified from 2011 to 2019. The outcome of interest was treatment gaps between injections of anti-VEGF. This outcome was retrieved quarterly, and the study period was divided into three phases in wAMD (two criteria changed in August 2014 [intervention] and December 2016 [intervention]) and two phases in DME (three consecutive criteria changed in 2016 [intervention]). Segmented regression models adjusted for autocorrelation were used to estimate the change in level and the change in slope of the treatment gaps between each anti-VEGF injection. RESULTS: The treatment gaps between each anti-VEGF injection decreased from 2011 to 2019. The cancellation of the annual three needles limitation was associated with significantly shortened treatment gaps between the third and fourth needles (wAMD change in level: -228 days [95% CI -282, -173], DME change in level: -110 days [95% CI -141, -79]). The treatment gap between the fifth and sixth needles revealed a similar pattern but without significant change in DME patients. Other treatment gaps revealed considerable change in slopes in accordance with criteria changes. CONCLUSION: This is the first nationwide study using ITSA to demonstrate the impact of reimbursement policy on treatment gaps between each anti-VEGF injection. After canceling the annual limitation, we found that the treatment gaps significantly decreased among wAMD and DME patients. The shortened treatment gaps might further link to better visual outcomes according to previous studies. The different impacts from criteria changes can assist future policy shaping. Future studies were warranted to explore whether such changes are associated with the benefits of visual effects.

Metformin alleviates cryoinjuries in porcine oocytes by reducing membrane fluidity through the suppression of mitochondrial activity.

Plasma membrane damage in vitrified oocytes is closely linked to mitochondrial dysfunction. However, the mechanism underlying mitochondria-regulated membrane stability is not elucidated. A growing body of evidence indicates that mitochondrial activity plays a pivotal role in cell adaptation. Since mitochondria work at a higher temperature than the constant external temperature of the cell, we hypothesize that suppressing mitochondrial activity would protect oocytes from extreme stimuli during vitrification. Here we show that metformin suppresses mitochondrial activity by reducing mitochondrial temperature. In addition, metformin affects the developmental potential of oocytes and improves the survival rate after vitrification. Transmission electron microscopy results show that mitochondrial abnormalities are markedly reduced in vitrified oocytes pretreated with metformin. Moreover, we find that metformin transiently inhibits mitochondrial activity. Interestingly, metformin pretreatment decreases cell membrane fluidity after vitrification. Furthermore, transcriptome results demonstrate that metformin pretreatment modulates the expression levels of genes involved in fatty acid elongation process, which is further verified by the increased long-chain saturated fatty acid contents in metformin-pretreated vitrified oocytes by lipidomic profile analysis. In summary, our study indicates that metformin alleviates cryoinjuries by reducing membrane fluidity via mitochondrial activity regulation.

Piperidine-based ionic liquid additive with electrostatic shielding and redox activity enabling advanced lithium-oxygen batteries.

Here, we propose a piperidine-based ionic liquid additive. The electrostatic shielding effect of the piperidine cation (PP13+) effectively inhibits the growth of lithium dendrites. Simultaneously, the redox activity of the bromine anion synergistically reduces the overpotential. This approach significantly improves the cycling performance of lithium-oxygen batteries.

Multi-trajectories in different domains of social supports and subjective motoric cognitive risk syndrome: a 16-year group-based multi-trajectory analysis.

OBJECTIVE: The aim of this study was to examine the longitudinal relationships between the trajectories of distinct subtypes of various domains of social supports and risk of subjective motoric cognitive risk (MCR) syndrome. DESIGN: Longitudinal cohort study. SETTING AND PARTICIPANTS: 2,279 participants in the Taiwan Longitudinal Study on Aging (TLSA) between 1999 and 2011. METHOD: A group-based multi-trajectory modeling (GBMTM) was implemented to identify distinct trajectory subtypes within various social support domains, encompassing social networks, emotional support, instrumental support, as well as working and economic status. Logistic regression models were then utilized to evaluate the associations between these trajectory subtypes and the risk of subjective MCR. RESULTS: Among 2,279 participants, GBMTM identified four distinct trajectory subtypes: "low social support" (n = 371), "medium social support " (n = 862), "high social support" (n = 292), and "high social support with employment" (n = 754). The incidence rates of subjective MCR for these groups were 9.4%, 9.0%, 4.1%, and 0.8%, respectively. After adjusting for age, sex, education level, and comorbidities, both "low social support" (adjusted odds ratio (aOR) 4.07, 95% CI [1.60-10.34]) and "medium social support" (aOR 3.10, 95% CI [1.26-7.66]) were significantly associated with an increased risk of subjective MCR compared to the "high social support with employment" group. CONCLUSIONS AND IMPLICATIONS: The current study demonstrates that social support significantly reduces the risk of subjective MCR, with lower support levels correlating to higher risk, necessitating further intervention studies to confirm the link between social support and risk of subjective MCR.

Concomitant use of antidepressants and benzodiazepines during pregnancy and associated risk of congenital malformations: a population-based cohort study in Taiwan.

BACKGROUND: Despite the frequent co-administration of antidepressants and benzodiazepines, the association between such concomitant use during pregnancy and the risk of congenital malformations remains inadequately explored. This study aims to examine the association between concomitant use of antidepressants and benzodiazepines during the first trimester and organ-specific congenital malformations. METHODS: We conducted a population-based cohort study using Taiwan's National Birth Certificate Application database, the Maternal and Child Health database, and Taiwan's National Health Insurance database. Pregnant people aged 15-50 years with singleton births between Jan 1, 2004, and Dec 31, 2018, were included. Use of antidepressants and benzodiazepines was defined as at least one prescription during the first trimester, and concomitant use was defined as the overlapping prescription of both drugs with an overlapping prescription period. The primary outcomes were overall congenital malformations and eight organ-specific malformations, consisting of the nervous system, heart, respiratory system, oral cleft, digestive system, urinary system, genital system, and limb malformations. Logistic regression models with propensity score fine stratification weighting approach were used to control for measured confounders. Analyses controlling for confounding by indication and sibling comparison analyses were done to address unmeasured confounders. No individuals with lived experience participated in the research or writing process. FINDINGS: The cohort included 2 634 021 singleton pregnancies, and 8599 (0·3%) individuals were concomitant users of antidepressants and benzodiazepines during the first trimester (mean age at delivery was 31·8 years [SD 5·2] for pregnancies with exposure to antidepressants and benzodiazepines vs 30·7 years [SD 4·9] for pregnancies without exposure). All study participants were female, and information about ethnicity was not available. Absolute risk of overall malformations was 3·81 per 100 pregnancies with exposure, compared with 2·87 per 100 pregnancies without exposure. The propensity score-weighted odds ratios (weighted ORs) did not suggest an increased risk for overall malformations (weighted OR 1·10, 95% CI 0·94-1·28), heart defects (1·01, 0·83-1·23), or any of the other organ-specific malformations, except for digestive system malformations, for which the weighted OR remained statistically significant after adjustment (1·63, 1·06-2·51). The absence of an increased risk for overall congenital malformations associated with concomitant use of antidepressants and benzodiazepines was supported by the analyses controlling for confounding by indication and sibling-matched comparisons. INTERPRETATION: The findings of this study suggest that the concomitant use of antidepressants and benzodiazepines during the first trimester is not associated with a substantial increase in risk for most malformation subtypes. However, considering other potential adverse effects of using both medications concomitantly, a thorough assessment of the risks and benefits is crucial for clinical decision making. FUNDING: National Science and Technology Council.

TFAP2A is involved in neuropathic pain by regulating Grin1 expression in glial cells of the dorsal root ganglion.

Neuropathic pain is a highly prevalent and refractory condition, yet its mechanism remains poorly understood. While NR1, the essential subunit of NMDA receptors, has long been recognized for its pivotal role in nociceptive transmission, its involvement in presynaptic stimulation is incompletely elucidated. Transcription factors can regulate the expression of both pro-nociceptive and analgesic factors. Our study shows that transcription factor TFAP2A was up-regulated in the dorsal root ganglion (DRG) neurons, satellite glial cells (SGCs), and Schwann cells following spinal nerve ligation (SNL). Intrathecal injection of siRNA targeting Tfap2a immediately or 7 days after SNL effectively alleviated SNL-induced pain hypersensitivity and reduced Tfap2a expression levels. Bioinformatics analysis revealed that TFAP2A may regulate the expression of the Grin1 gene, which encodes NR1. Dual-luciferase reporter assays confirmed TFAP2A's positive regulation of Grin1 expression. Notably, both Tfap2a and Grin1 were expressed in the primary SGCs and upregulated by lipopolysaccharides. The expression of Grin1 was also down-regulated in the DRG following Tfap2a knockdown. Furthermore, intrathecal injection of siRNA targeting Grin1 immediately or 7 days post-SNL effectively alleviated SNL-induced mechanical allodynia and thermal hyperalgesia. Finally, intrathecal Tfap2a siRNA alleviated SNL-induced neuronal hypersensitivity, and incubation of primary SGCs with Tfap2a siRNA decreased NMDA-induced upregulation of proinflammatory cytokines. Collectively, our study reveals the role of TFAP2A-Grin1 in regulating neuropathic pain in peripheral glia, offering a new strategy for the development of novel analgesics.

Uses of antiseizure medication among pregnant women with epilepsy and risk of adverse obstetric outcomes: A group-based trajectory analysis.

OBJECTIVE: This study was undertaken to examine the association between different patterns of antiseizure medication (ASM) use during pregnancy and adverse obstetric outcomes (preterm birth, low birth weight [LBW], and small for gestational age [SGA]). METHODS: This retrospective cohort study used the Birth Certificate Application and National Health Insurance data in Taiwan (January 1, 2004 through December 31, 2018). We retrieved weekly ASM among pregnant women with epilepsy who were prepregnancy chronic users and used group-based trajectory modeling to identify distinct patterns of use. Logistic regressions were adopted to examine the association between patterns of ASM use and risk of preterm birth, LBW, and SGA. In addition, we revealed postnatal ASM utilization pattern among these prepregnancy chronic users as an exploratory study. RESULTS: Of 2175 pregnant women with epilepsy, we identified four patterns of ASM use during pregnancy: frequent and continuous (64.87%), frequent but discontinuous (7.08%), intermittent (19.72%), and intermittent and discontinuous users (8.32%). Compared to frequent and continuous users, the adjusted odds ratios for preterm birth in frequent but discontinuous, intermittent, and intermittent and discontinuous users were .83 (95% confidence interval [CI] = .47-1.48), .71 (95% CI = .47-1.05), and .88 (95% CI = .52-1.49), respectively. Similar results were observed for LBW and SGA. In the exploratory study, we found that most of our study subjects maintained the same patterns before and after delivery. SIGNIFICANCE: After considering duration and timing of exposure, our study did not find an association between four distinct patterns of ASM use and adverse obstetric outcomes among women with epilepsy. The findings suggested that optimal seizure control could be received for pregnant women with epilepsy after evaluating the risks and benefits.

A new magnetic resonance imaging-based PUMCH classification system for congenital cervical malformations: devising a standardised diagnosis pathway.

OBJECTIVES: To develop an innovative magnetic resonance imaging (MRI)-based PUMCH (Peking Union Medical College Hospital) classification system aimed at standardising the diagnosis of congenital cervical malformations (CCMs) by identifying their distinctive MRI features. METHODS: Seventy-nine consecutive patients with CCM underwent pre-treatment pelvic MRI; three experienced gynaecological radiologists retrospectively analysed these images. Qualitative assessments included Rock et al's classification; PUMCH classification; haematometra; cervical signal features; ovarian endometriosis; haematosalpinx; and uterine, vaginal, urinary, and musculoskeletal malformations. Quantitative assessments involved the uterine volume, sagittal cervical length, and maximum ovarian cross-sectional area. The surgical treatment types were also recorded. Statistical methods were used to incorporate differences in clinical features and surgical methods into our classification. RESULTS: Morphologically, CCMs were categorised into three types: type I (53%) was characterised by the presence of a cervix with visible cervical canals; type II (23%) featured an existing cervix with concealed cervical canals; and type III (24%) indicated cervical aplasia, which involves a blind end in the lower part of the uterine corpus. Haematometra was significantly more prevalent in patients with type I CCM than in those with type II (p < 0.001). There were three cervical signal patterns: no signal (27%), no evident layer differentiation (21%), and multi-layer differentiation with haematocele (52%). Most patients (94%) had complete vaginal atresia. Type I CCM patients had a higher likelihood of regaining normal uterovaginal anatomy compared to types II and III. CONCLUSIONS: Our proposed PUMCH classification system has a high potential for enhancing the efficiency of clinical diagnosis among patients with CCM. CRITICAL RELEVANCE STATEMENT: The proposed new PUMCH classification promised to elevate the conventional diagnostic trajectory for congenital cervical malformations, offering a valuable framework to refine the selection and planning of surgical interventions, thereby enhancing overall clinical efficacy. KEY POINTS: Effective classification of congenital cervical malformations is desirable to optimise the diagnostic process. We presented a PUMCH classification of congenital cervical malformations using pelvic MRI. The new classification significantly aids clinical triage for congenital cervical malformations.

Ct-based diagnosis of sarcopenia as a prognostic factor for postoperative mortality after elective open-heart surgery in older patients: a cohort-based systematic review and meta-analysis.

Background: Cardiac open-heart surgery, which usually involves thoracotomy and cardiopulmonary bypass, is associated with a high incidence of postoperative mortality and adverse events. In recent years, sarcopenia, as a common condition in older patients, has been associated with an increased incidence of adverse prognosis. Methods: We conducted a search of databases including PubMed, Embase, and Cochrane, with the search date up to January 1, 2024, to identify all studies related to elective cardiac open-heart surgery in older patients. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence. Results: A total of 12 cohort studies were included in this meta-analysis for analysis. This meta-analysis revealed that patients with sarcopenia had a higher risk of postoperative mortality. Furthermore, the total length of hospital stay and ICU stay were longer after surgery. Moreover, there was a higher number of patients requiring further healthcare after discharge. Regarding postoperative complications, sarcopenia patients had an increased risk of developing renal failure and stroke. Conclusion: Sarcopenia served as a tool to identify high-risk older patients undergoing elective cardiac open-heart surgery. By identifying this risk factor early on, healthcare professionals took targeted steps to improve perioperative function and made informed clinical decisions.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023426026.

Safety and efficacy of baricitinib in steroid-resistant or relapsed immune thrombocytopenia: An open-label pilot study.

Patients with steroid-resistant or relapsed immune thrombocytopenia (ITP) suffer increased bleeding risk and impaired quality of life. Baricitinib, an oral Janus-associated kinases (JAK) inhibitor, could alleviate both innate and adaptive immune disorders without inducing thrombocytopenia in several autoimmune diseases. Accordingly, an open-label, single-arm, phase 2 trial (NCT05446831) was initiated to explore the safety and efficacy of baricitinib in ITP. Eligible patients were adults with primary ITP who were refractory to corticosteroids and at least one subsequent treatment, and had platelet counts below 30 × 109/L at enrolment. Participants received baricitinib 4 mg daily for 6 months. The primary endpoint was durable response at the 6-month follow-up. A total of 35 patients were enrolled. Durable response was achieved in 20 patients (57.1%, 95% confidence interval, 39.9 to 74.4), and initial response in 23 (65.7%) patients. For patients responding to baricitinib, the median time to response was 12 (IQR 6-20) days, and the median peak platelet count was 94 (IQR 72-128) × 109/L. Among the 27 patients undergoing extend observation, 12 (44.4%) remained responsive for a median duration of approximately 20 weeks after baricitinib discontinuation. Adverse events were reported in 11 (31.4%) patients, including infections in 6 (17.1%) patients during the treatment period. Treatment discontinuation due to an adverse event was reported in 2 (5.7%) patients. Evidence from this pilot study suggested that baricitinib might be a novel candidate for the armamentarium of ITP-modifying agents. Future studies are warranted to validate the safety, efficacy, and optimal dosing of baricitinib in patients with ITP.

Medical students' preferences for asynchronous online or face-to-face learning strategies in learning gross anatomy and neuroanatomy during the COVID-19 pandemic.

Gross anatomy and neuroanatomy are fundamental subjects in medical education. However, learning different anatomical terms and understanding the complexity of the subjects are often challenging for medical students. At National Taiwan University, the 2020-2021 cohort adopted a face-to-face (F2F) learning strategy for gross anatomy and neuroanatomy lecture and laboratory courses until May 17, 2021. After the aforementioned date, the same cohort learned the rest of the gross anatomy and neuroanatomy courses via asynchronous online learning. This study aimed to evaluate the benefits of and students' preferences for F2F and asynchronous online learning strategies in learning gross anatomy and neuroanatomy. A survey with closed-ended and open-ended questions was used to quantitatively and qualitatively explore medical students' learning preferences for two teaching strategies in gross anatomy and neuroanatomy. The results identified different learning preferences among students in learning gross anatomy and neuroanatomy-satisfied with both learning strategies, satisfied with only F2F learning strategy, satisfied with only asynchronous online learning strategy, and satisfied with neither learning strategy. The survey results with closed-ended and open-ended questions showed that medical students preferred F2F learning for anatomical laboratory courses but favored asynchronous online learning for neuroanatomical laboratory courses. In addition, medical students considered peer discussion more critical in learning gross anatomy than neuroanatomy. These findings provide valuable information about medical students' preference for gross anatomy and neuroanatomy courses, which anatomy teachers can consider when planning to enhance their curriculum in the future.

Co-Invasion of Congeneric Invasive Plants Adopts Different Strategies Depending on Their Origins.

Plant communities may be co-invaded by invasive plants, sometimes even by congeneric invasive plants (CIPs). Despite the growing understanding of co-invasion in the environment, little is known about how CIP interactions and mechanisms regulate co-invasion. Darwin's naturalisation conundrum predicts that the coexistence of closely related species is difficult due to their structural and behavioural similarities. Nevertheless, communities containing closely related species are more susceptible to being invaded because close relatives may favour similar environments; therefore, this hypothesis should be followed in the co-invasion of CIPs. To explore whether the phylogenetic relatedness and origins of invasive species to CIPs can promote or hinder co-invasion, we conducted a controlled interaction and soil-legacy greenhouse experiment to quantify the growth response of invasive plants and their congeners. We consistently found that CIPs of identical origin were more likely to co-invade compared to CIPs of distinct origins. CIPs of distinct origins exhibited an antagonistic effect on co-invasion by allelopathy. Invasive plant-conditioned soil was more conducive to the growth of CIPs of identical origin than CIPs of distinct origins. Our results revealed the different effects of invader-invader phylogenetic relatedness on co-invader success and impact, suggesting the operation of different mechanisms across co-invasion.

Intratumoral microbiome is associated with gastric cancer prognosis and therapy efficacy.

The role of the intratumoral microbiome in gastric cancer (GC) has not been comprehensively assessed. Here, we explored the relationship between the microbial community and GC prognosis and therapy efficacy. Several cancer-associated microbial characteristics were identified, including increased α-diversity, differential ß-diversity, and decreased Helicobacter pylori abundance. After adjusting for clinical features, prognostic analysis revealed 2 phyla, 14 genera, and 5 species associated with the overall survival of patients with GC. Additionally, 2 phyla, 14 genera, and 6 species were associated with adjuvant chemotherapy (ACT) efficacy in patients with stage II - III GC. Furthermore, we classified GC microbiome structures into three microbial subtypes (MS1, MS2 and MS3) with distinguishing features. The MS1 subtype exhibited high immune activity and enrichment of microbiota related to immunotherapy and butyric acid-producing, as well as potential benefits in immunotherapy. MS2 featured the highest α-diversity and activation of the TFF pathway, MS3 was characterized by epithelial-mesenchymal transition and was associated with poor prognosis and reduced ACT efficacy. Collectively, the results of this study provide valuable insights into the microbial characteristics associated with GC prognosis and therapy efficacy.

Effect of ultrasound-guided injection of botulinum toxin type A into shoulder joint cavity on shoulder pain in poststroke patients: study protocol for a randomized controlled trial.

BACKGROUND: Hemiplegic shoulder pain (HSP) is a common complication after stroke. It severely affects the recovery of upper limb motor function. Early shoulder pain in hemiplegic patients is mainly neuropathic caused by central nerve injury or neuroplasticity. Commonly used corticosteroid injections in the shoulder joint can reduce shoulder pain; however, the side effects also include soft tissue degeneration or increased tendon fragility, and the long-term effects remain controversial. Botulinum toxin injections are relatively new and are thought to block the transmission of pain receptors in the shoulder joint cavity and inhibit the production of neuropathogenic substances to reduce neurogenic inflammation. Some studies suggest that the shoulder pain of hemiplegia after stroke is caused by changes in the central system related to shoulder joint pain, and persistent pain may induce the reorganization of the cortical sensory center or motor center. However, there is no conclusive evidence as to whether or not the amelioration of pain by botulinum toxin affects brain function. In previous studies of botulinum toxin versus glucocorticoids (triamcinolone acetonide injection) in the treatment of shoulder pain, there is a lack of observation of differences in changes in brain function. As the content of previous assessments of pain improvement was predominantly subjective, objective quantitative assessment indicators were lacking. Functional near-infrared imaging (fNIRS) can remedy this problem. METHODS: This study protocol is designed for a double-blind, randomized controlled clinical trial of patients with post-stroke HSP without biceps longus tenosynovitis or acromion bursitis. Seventy-eight patients will be randomly assigned to either the botulinum toxin type A or glucocorticoid group. At baseline, patients in each group will receive shoulder cavity injections of either botulinum toxin or glucocorticoids and will be followed for 1 and 4 weeks. The primary outcome is change in shoulder pain on the visual analog scale (VAS). The secondary outcome is the assessment of changes in oxyhemoglobin levels in the corresponding brain regions by fNIRS imaging, shoulder flexion, external rotation range of motion, upper extremity Fugl-Meyer, and modified Ashworth score. DISCUSSION: Ultrasound-guided botulinum toxin type A shoulder joint cavity injections may provide evidence of pain improvement in patients with HSP. The results of this trial are also help to analyze the correlation between changes in shoulder pain and changes in cerebral hemodynamics and shoulder joint motor function. TRIAL REGISTRATION: Chinese clinical Trial Registry, ChiCTR2300070132. Registered 03 April 2023, https://www.chictr.org.cn/showproj.html?proj=193722 .

Prescription Patterns and Predisposing Factors of Benzodiazepine and Z-Hypnotic Use During Pregnancy: A Nationwide Cohort Study.

PURPOSE: The use of benzodiazepines and Z-hypnotics during pregnancy has raised significant concerns in recent years. However, there are limited data that capture the prescription patterns and predisposing factors in use of these drugs, particularly among women who have been long-term users of benzodiazepines and Z-hypnotics before pregnancy. METHODS: This population-based cohort study comprised 2 930 988 pregnancies between 2004 and 2018 in Taiwan. Women who were dispensed benzodiazepines or Z-hypnotics during pregnancy were identified and further stratified into groups based on their status before pregnancy: long-term users (with a supply of more than 180 days within a year), short-term users (with a supply of less than 180 days within a year), and nonusers. Trends in the use of benzodiazepines or Z-hypnotics and concomitant use with antidepressants or opioids were assessed. Logistic regression models were utilized to identify factors associated with use of these drugs during pregnancy, and interrupted time series analyses (ITSA) were employed to evaluate utilization patterns of these drugs across different pregnancy-related periods. RESULTS: The overall prevalence of benzodiazepine and Z-hypnotic use was 3.5% during pregnancy. Among prepregnancy long-term users, an upward trend was observed. The concomitant use of antidepressants or opioids among exposed women increased threefold (from 8.6% to 23.1%) and sixfold (from 0.3% to 1.7%) from 2004 to 2018, respectively. Women with unhealthy lifestyle behaviors, such as alcohol abuse (OR 2.48; 95% CI, 2.02-3.03), drug abuse (OR 10.34; 95% CI, 8.46-12.64), and tobacco use (OR 2.19; 95% CI, 1.96-2.45), as well as those with psychiatric disorders like anxiety (OR 6.99; 95% CI, 6.77-7.22), insomnia (OR 15.99; 95% CI, 15.55-16.45), depression (OR 9.43; 95% CI, 9.07-9.80), and schizophrenia (OR 21.08; 95% CI, 18.76-23.69), and higher healthcare utilization, were more likely to use benzodiazepines or Z-hypnotics during pregnancy. ITSA revealed a sudden decrease in use of benzodiazepines and Z-hypnotics after recognition of pregnancy (level change -0.55 percentage point; 95% CI, -0.59 to -0.51). In contrast, exposures to benzodiazepines and Z-hypnotics increased significantly after delivery (level change 0.12 percentage point; 95% CI, 0.09 to 0.16). CONCLUSIONS: In this cohort study, an increased trend of benzodiazepine and Z-hypnotic use during pregnancy among prepregnancy long-term users, as well as concomitant use with antidepressants or opioids were found. The findings have highlighted the existence of various risk factors associated with the use of these drugs during pregnancy. Utilization patterns varied across different stages of pregnancy, highlighting the need for prescription guidelines and educational services for women using these drugs during pregnancy.

SMRT sequencing of a full-length transcriptome reveals cold induced alternative splicing in Vitis amurensis root.

Alternative splicing enhances diversity at the transcriptional and protein levels that widely involved in plant response to biotic and abiotic stresses. V. amurensis is an extremely cold-tolerant wild grape variety, however, studies on alternative splicing (AS) in amur grape at low temperatures are currently poorly understood. In this study, we analyzed full-length transcriptome and RNA seq data at 0, 2, and 24 h after cold stress in V. amurensis roots. Following quality control and correction, 221,170 high-quality full-length non-concatemer (FLNC) reads were identified. A total of 16,181 loci and 30,733 isoforms were identified. These included 22,868 novel isoforms from annotated genes and 2815 isoforms from 2389 novel genes. Among the distinguished novel isoforms, 673 Long non-coding RNAs (LncRNAs) and 18,164 novel isoforms open reading frame (ORF) region were found. A total of 2958 genes produced 8797 AS events, of which 189 genes were involved in the low-temperature response. Twelve transcription factors show AS during cold treatment and VaMYB108 was selected for initial exploration. Two transcripts, Chr05.63.1 (VaMYB108short) and Chr05.63.2 (VaMYB108normal) of VaMYB108, display up-regulated expression after cold treatment in amur grape roots and are both localized in the nucleus. Only VaMYB108normal exhibits transcriptional activation activity. Overexpression of either VaMYB108short or VaMYB108normal in grape roots leads to increased expression of the other transcript and both increased chilling resistance of amur grape roots. The results improve and supplement the genome annotations and provide insights for further investigation into AS mechanisms during cold stress in V. amurensis.

Zinc hexacyanoferrate/g-C3N4 nanocomposites with enhanced photothermal and photodynamic properties for rapid sterilization and wound healing.

Photoactivated therapy has gradually emerged as a promising and rapid method for combating bacteria, aimed at overcoming the emergence of drug-resistant strains resulting from the inappropriate use of antibiotics and the subsequent health risks. In this work, we report the facile fabrication of Zn3[Fe(CN)6]/g-C3N4 nanocomposites (denoted as ZHF/g-C3N4) through the in-situ loading of zinc hexacyanoferrate nanospheres onto two-dimensional g-C3N4 sheets using a simple metal-organic frameworks construction method. The ZHF/g-C3N4 nanocomposite exhibits enhanced antibacterial activity through the synergistic combination of the excellent photothermal properties of ZHF and the photodynamic capabilities of g-C3N4. Under dual-light irradiation (420 nm + 808 nm NIR), the nanocomposites achieve remarkable bactericidal efficacy, eliminating 99.98% of Escherichia coli and 99.87% of Staphylococcus aureus within 10 minutes. Furthermore, in vivo animal experiments have demonstrated the outstanding capacity of the composite in promoting infected wound healing, achieving a remarkable wound closure rate of 99.22% after a 10-day treatment period. This study emphasizes the potential of the ZHF/g-C3N4 nanocomposite in effective antimicrobial applications, expanding the scope of synergistic photothermal/photodynamic therapy strategies.