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Aurora kinases are emerging as key regulators of centrosome function, chromosome segregation and cytokinesis. We previously isolated Aurora-C (Aie1), a third type of Aurora kinase, in a screen for kinases expressed in mouse sperm and eggs. Currently, we know very little about the precise localization and function of Aurora-C. Immunofluorescence analysis of ectopically expressed GFP-Aurora-C has revealed that Aurora-C is a new member of the chromosomal passenger proteins localizing first to the centromeres and then to the central spindles during cytokinesis. In order to study the potential role of Aurora-C, we examined the effects of a kinase-deficient (KD) mutant (AurC-KD) in HeLa Tet-Off cells under tetracycline control. Our results showed that overexpression of AurC-KD causes defects in cell division and induces polyploidy and apoptosis. Interestingly, AurC-KD overexpression also inhibits centromere/kinetochore localization of Aurora-B, Bub1, and BubR1, reduces histone H3 phosphorylation, and disrupts the association of INCENP with Aurora-B. Together, our results showed that Aurora-C is a chromosomal passenger protein, which may serve as a key regulator in cell division. [ABSTRACT FROM AUTHOR]

Nuclear mitotic apparatus protein (NuMA), originally described as a nuclear protein, is an essential component in the formation and maintenance of mitotic spindle poles. In this study, we analyze the expression pattern and function of NuMA in mouse oocytes and early embryos. In germinal vesicle-stage oocytes, NuMA was detected both at the centrosome and in the nucleus. However, after nuclear maturation and extrusion of the first polar body, NuMA was concentrated at the broad meiotic spindle poles and at cytasters (centers of cytoplasmic microtubule asters) of mature metaphase II oocytes. Cold-induced depolymerization of microtubules appeared to disassociate NuMA foci from the cytoplasmic cytasters. During fertilization, NuMA was relocated into the re-formed male and female pronuclei. Microinjection of anti-NuMA antibody into 1 of 2 cells of 2-cell-stage embryos inhibited normal cell division. These results suggest that NuMA might play an important role in cell division during early embryonic mitosis. Copyright © 2004 National Science Council, ROC and S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a liver disease that is strongly associated with chronic low-grade inflammation. Stage 3 of MASLD is characterized by excessive formation of connective tissues, commonly referred to as liver fibrosis. Although numerous inflammatory markers have been identified and extensively studied, including the tumor necrosis factor-α and interleukin-6 have been studied [Byrne CD, Targher G. NAFLD: a multisystem disease. J Hepatol. 2015;62(1 Suppl):S47-64], the lymphocyte-to-high-density lipoprotein ratio (LHR) as a new biomarker that has not been sufficiently studied. This study aims to investigate the relationship between LHR levels and MASLD, determine its potential as a predictive marker for steatosis and fibrosis stages., Methods: This was a population-based study using data from 15,560 participants in the 2017-2020 National Health and Nutrition Examination Survey (NHANES) database. The study aimed to explore the relationship between LHR and MASLD. The disease progression was tracked by continuously measuring CAP and liver stiffness measurements. Participants who exhibited a median Controlled Attenuation Parameter (CAP) of 248 dB/m or higher were deemed to have hepatic steatosis. The LHR was calculated by dividing the lymphocyte count by the high-density lipoprotein cholesterol (HDL-C) level. Multivariate linear regression models were employed to explore the linear association between LHR and MASLD. Fitted smoothing curves and threshold effect analysis were employed to display nonlinear relationships. A two-part linear regression model was employed to estimate threshold effects. Subgroup analyses were conducted to determine the consistency of this association across various demographic groups., Results: A total of 6,950 adults aged 18 years and older were enrolled in the study, with an average age of 48.15 ± 17.10 years (49.14% male, 50.86% female). The adjusted multiple logistic regression analysis revealed a significant positive correlation between LHR and MASLD (OR: 1.64, 95% CI: 1.40-1.92). Using the complex two-piece linear regression model, we observed an inverted L-shaped association between LHR and CAP, suggesting a critical inflection point at -2.58. Subgroup analyses indicated a pronounced association of the LHR index with obese individuals (OR: 1.96, 95% CI: 1.66-2.32) and females (OR: 1.76, 95% CI: 1.25-2.46). There was no significant association between LHR and clinically significant fibrosis., Conclusion: The LHR index is positively correlated with MASLD among US adults. Therefore, LHR may be a robust marker for early screening, diagnosis, and monitoring of treatment efficacy in clinical practice., Competing Interests: Declarations. Ethics approval and consent to participate: In compliance with the Declaration of Helsinki, every NHANES protocol was approved by Ethics Review Board of National Center for Health Statistics. Every participant signed the informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Helicobacter pylori (H. pylori), a widely prevalent pathogen that can be cured through relatively simple medical methods, is thought to be potentially associated with the risk of cardiovascular diseases (CVD), although controversy remains. Currently, it is unclear whether the triglyceride-glucose index (TGI), a classic indicator of insulin resistance, influences the relationship between H. pylori infection and CVD. The present work explored the relationships between H. pylori seropositivity, the TGI and CVD, and the potential effect of TGI in this association., Methods: In this cross-sectional and cohort study, data from the National Health and Nutrition Examination Survey (NHANES) III (1988-1994) and NHANES (1999-2000) were used. The effects of the TGI, H. pylori seropositivity, and their interaction on the risk of CVD were assessed using logistic regression models. The hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause mortality (ACM) were calculated using the Cox proportional hazards model. Restricted cubic spline (RCS) curves were employed to investigate potential non-linear or linear relationships among the TGI, H. pylori seropositivity, occurrence of CVD, and ACM. Mediation analyses were employed to assess the potential effects of H. pylori seropositivity and TGI on the risk of CVD and mortality., Results: Of the 9,399 participants, 4,488 (47.75%) were H. pylori-immunoglobulin G (IgG)-positive, and 3,934 (41.86%) were diagnosed with CVD. In the general population, participants with a TGI ≥ 75th percentile who were positive for H. pylori-IgG antibody had the highest risk of developing CVD (odds ratio = 1.487; 95% CI: 1.088-2.033). Among patients with CVD, those with a TGI ≥ 75th percentile & positive for H. pylori-IgG antibody were at a higher ACM risk (HR = 1.227; 95% CI: 1.009-1.491). H. pylori exhibited a significant mediating effect on CVD occurrence (Pindir = 0.004) and mortality (Pindir = 0.004) via the TGI., Conclusions: H. pylori seropositivity may indirectly elevate the risk of CVD and mortality via the TGI. Combining the patient's H. pylori serological status with their TGI could enhance the predictive ability for CVD occurrence and related mortality. Therefore, the clinical practice of screening for and eradicating H. pylori in CVD patients may be anticipated., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: Approval of the use of NHANES was obtained from the Research Ethics Review Board of the National Center for Health Statistics. Written informed consent was provided by all subjects prior to participation. Consent for publication: Not applicable., (© 2024. The Author(s).)

Background: This aimed to elucidate the impact of stress hyperglycemia on early neurological deterioration (END) in patients with acute non-cardiogenic cerebral infarction who did not experience hemorrhagic transformation following intravenous thrombolysis to identify risk factors associated with END., Methods: This retrospective case-control study analyzed data from consecutive patients who received intravenous thrombolysis for acute ischemic stroke (AIS) without hemorrhagic transformation at the Stroke Center of The Fifth Affiliated Hospital of Sun Yat-sen University from January 2018 to February 2023. END was defined as an increase of more than 2 points on the National Institutes of Health Stroke Scale (NIHSS) within 7 days of admission., Results: A total of 250 patients (56 males, 22.4%) were included, with a mean age of 63.34 ± 12.90 years. Of them, 41 were classified into the END group and 209 into the non-END group. Stress hyperglycemia ratio (SHR) demonstrated a significant correlation with END (r=-0.003, P = 0.003). HbA1c (OR = 0.68, 95% CI: 0.481-0.921) and SHR (OR = 0.00, 95% CI: 0.0-0.051) were independently associated with END. Receiver-operating characteristic (ROC) curve analysis indicated that SHR had a sensitivity of 79.9%, specificity of 88.8%, and an area under the curve (AUC) of 0.857 for predicting END., Conclusions: SHR was significantly associated with END in patients with acute non-cardioembolic cerebral infarction who did not undergo hemorrhagic transformation after intravenous thrombolysis., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Committee of the Fifth Affiliated Hospital of Sun Yat-sen University(K557). The requirement for individual consent was waived by the committee owing to the retrospective nature of the study. All procedures performed in this study involving human participants were in accordance with the ethical standards of The Fifth Affiliated Hospital of Sun Yat-Sen University committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Competing of interests: All authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: The relationship between ozone (O 3 ) exposure and blood pressure (BP) remains inconclusive. Given the scarcity of Chinese epidemiological data, more research on this association is of paramount importance, particularly among middle-aged and older Chinese populations., Methods: This study involved 10,875 participants (median age: 60.0 years) in Xiamen, China, from 2013 to 2019, with 34,939 repeated BP measurements. Air pollutant exposure data, including O 3 , particulate matter, nitrogen dioxide, sulfur dioxide, and carbon monoxide were derived from China High Air Pollutants and High-resolution Air Quality Reanalysis datasets using a k-nearest neighbor algorithm. The relationship between mixed air pollutant exposure and BP was evaluated using Bayesian kernel machine regression model. The effects of daily-specific O 3 exposure on BP were assessed by distributed lag models integrated into a linear mixed-effects framework. The mediating role of total cholesterol (TC), serum total bilirubin (STB), triglyceride (TG), and low-density lipoprotein (LDL) were examined using multilevel mediation analysis with a fully adjusted model., Results: Mixed air pollutant exposure was positively correlated with BP, with O 3 being a predominant contributor exhibiting an inverse effect. O 3 exposure had immediate effects on pulse pressure (PP), while systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) showed delayed responses, with 3-, 14-, and 8-day lags, respectively. During the study period of up to 30 days, each 10 μg/m 3 increase in maximum daily 8-h average O 3 concentration was associated with reductions in SBP (β =  - 1.176 mm Hg), DBP (- 0.237 mm Hg), PP (β =  - 0.973 mm Hg), and MAP (β =  - 0.544 mm Hg). Stronger correlations were observed in the older participants (aged ≥ 65 years), overweight/obese individuals, smokers and alcohol consumers, and those with hypertension or type 2 diabetes mellitus. STB and LDL mediated these effects, while TC and TG played mitigating roles., Conclusions: Short-term O 3 exposure is negatively associated with BP in middle-aged and older Chinese individuals. The findings provide preliminary evidence for the impact of O 3 exposure on BP regulation and underscore the urgent need to reassess public health policies in response to O 3 pollution., Competing Interests: Declarations. Ethics approval and consent to participate: All procedures were approved by the Medical Ethics Committee of the School of Medicine, Xiamen University (Approval Number: XDYX202208H04). All participants provided written informed consent at recruitment. Participants voluntarily joined the study and were free to withdraw at any time. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The efforts of early psychosis intervention programmes can be impeded by difficulties in maintaining the engagement of service users. As disengagement is often an autonomous decision made by service users, the main aim of this study was to gain insight into the reasons for service user disengagement through qualitative interviews with the service users themselves, and caregivers as proxies or secondary informants., Methods: Participants recruited for the study were enrolled in the Early Psychosis Intervention Programme in Singapore for at least a year, aged 21 and above, able to communicate in English, and had disengaged for at least three months. The recruitment and interview processes were conducted independently for service user and caregiver participants. Potential participants were invited to a face-to-face semi-structured interview over video call or in-person. Each interview spanned one to two hours, and comprised five phases - icebreaker, exploration of the participant's experience with EPIP before deciding to disengage, discussion of reasons for disengagement, exploration of the post-disengagement experience, and feedback and suggestions for EPIP. Recruitment aimed to conclude after 10-15 participants were interviewed for both service user and caregiver groups, with the expectation that data sufficiency would be reached with no new themes being generated., Results: Ultimately, 12 service user and 12 caregiver participants were recruited. There were six pairs of service user and caregiver dyads, where the caregivers interviewed were caring for service users also enrolled in the study. Valuable qualitative insights were gathered, including the type of disengagement, medication compliance during disengagement, the decision-making process behind disengaging, and circumstances surrounding re-engagement. A total of five categories each with subthemes were identified from the reasons for service user disengagement - individual factors, stigma, progression, treatment factors, and external factors., Conclusions: There is a need to narrow down urgent areas of attention, aligning the study themes with established risk factors so that feasible solutions can be developed and appropriate care models can be adopted, to minimise adverse outcomes related to disengagement. It is important to keep an open mind to understand what personal recovery means to the individual service user, so that treatment goals can be better harmonised., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the National Health Group’s (NHG) Domain Specific Review Board (DSRB Ref. No.: 2020 − 00857). Written informed consent was obtained from all participants prior to enrolment in the study. All procedures were conducted in accordance with the Declaration of Helsinki. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown cause. N6-methyladenosine (m6A) is the most common mRNA modification and participates in various immune processes such as interferon production and immune cell regulation. However, the role of m6A in dysregulated immune response of SLE remains unknown., Methods: PBMCs from SLE patients were collected to compare the m6A modification profile by methylated RNA immunoprecipitation sequencing (MeRIP-seq). Interferon regulatory factor 4 (IRF4) was identified by combination with MeRIP-seq and RNA-Seq. IRF4 and methyltransferase 3 (METTL3) were detected using qRT-PCR and WB. Clinical significance of IRF4 in SLE patients was explored subsequently. IRF4 expression in B cell subsets of female MRL/lpr mice was detected by flow cytometry. Adeno-associated viruses (AAV) including AAV9-METTL3-OE and/or AAV9-IRF4-sh were treated with female MRL/lpr mice. Autoantibody levels and kidney injury were tested by ELISA, pathological staining, and immunofluorescence. m6A level of IRF4 was detected by MeRIP-qPCR. The downstream effectors of IRF4 contributing to renal pathology were explored by RNA-seq and verified by qRT-PCR., Results: m6A methylation features were obviously aberrant in SLE patients, and IRF4 was the upregulated gene modified by m6A. METTL3 and IRF4 expressions were elevated in SLE patients and kidney of MRL/lpr mice. Clinical analysis indicated that SLE patients with high IRF4 level were more prone to kidney damage. IRF4 expression was especially increased in plasma cells of MRL/lpr mice. METTL3 induced renal IRF4 expression, plasma creatinine, ANA and urine ALB levels, IgG and C3 deposition, and renal damage and plasma cell infiltration were aggravated in MRL/lpr mice. However, IRF4 depletion could partially reduce METTL3-induced kidney damage. Meanwhile, m6A level of IRF4 elevated with METTL3 overexpression. Also, the expression of Cxcl1, Bcl3, and Fos mRNA were significantly reduced after knockdown of IRF4, which were mainly involved in TNF signaling pathway., Conclusions: Our study confirmed that upregulated METTL3 promoting IRF4 expression in an m6A-dependent manner, thus causing plasma cell infiltration-mediated kidney damage of SLE. This provides new evidence for the role of m6A in SLE kidney injury., (© 2024. The Author(s).)

Atherosclerosis (AS) poses a significant threat to human life and health. However, conventional antiatherogenic medications exhibit insufficient targeting precision and restricted therapeutic effectiveness. Moreover, during the progression of AS, macrophages undergo polarization toward the proinflammatory M1 phenotype and generate reactive oxygen species (ROS) to accelerate the occurrence of inflammatory storms, and ingest excess lipids to form foam cells by inhibiting cholesterol efflux. In our study, we developed a macrophage membrane-functionalized hollow mesoporous manganese dioxide nanomedicine (Col@HMnO 2 -MM). This nanomedicine has the ability to evade immune cell phagocytosis, enables prolonged circulation within the body, targets the inflammatory site of AS for effective drug release, and alleviates the inflammatory storm at the AS site by eliminating ROS. Furthermore, Col@HMnO 2 -MM has the ability to generate oxygen autonomously by breaking down surplus hydrogen peroxide generated at the inflammatory AS site, thereby reducing the hypoxic microenvironment of the plaque by downregulating hypoxia-inducible factor (HIF-1α), which in turn enhances cholesterol efflux to inhibit foam cell formation. In an APOE -/- mouse model, Col@HMnO 2 -MM significantly reduced inflammatory factor levels, lipid storage, and plaque formation without significant long-term toxicity. In summary, this synergistic treatment significantly improved the effectiveness of nanomedicine and may offer a novel strategy for precise AS therapy., (© 2024. The Author(s).)

Background: The growth and yield of pepper, a typical temperature-loving vegetable, are limited by low-temperature environments. Using low-temperature sensitive 'Hangjiao No. 4' (Capsicum annuum L.) as experimental material, this study analyzed the changes in plant growth and photosynthesis under different treatments: normal control (NT), low-temperature stress alone (LT), low-temperature stress in strigolactone pretreated plants (SL_LT), and low-temperature stress in strigolactone biosynthesis inhibitor pretreated plants (Tis_LT)., Results: SL pretreatment increased the net photosynthetic rate (Pn) and PSII actual photochemical efficiency (φPSII), reducing the inhibition of LT on the growth of pepper by 17.44% (dry weight of shoot). Due to promoting the accumulation of carotenoids, such as lutein, and the de-epoxidation of the xanthophyll cycle [(Z + A)/(Z + A + V)] by strigolactone after long-term low-temperature stress (120 h), non-photochemical quenching (NPQ) of pepper was increased to reduce the excess excitation energy [(1-qP)/NPQ] and the photoinhibition degree (Fv/Fm) of pepper seedlings under long-term low-temperature stress was alleviated. Twelve cDNA libraries were constructed from pepper leaves by transcriptome sequencing. There were 8776 differentially expressed genes (DEGs), including 4473 (51.0%) upregulated and 4303 (49.0%) downregulated genes. Gene ontology pathway annotation showed that based on LT, the DEGs of SL_LT and Tis_LT were significantly enriched in the cellular component, which is mainly related to the photosystem and thylakoids. Further analysis of the porphyrin and chlorophyll biosynthesis, carotenoid biosynthesis, photosynthesis-antenna protein, and photosynthetic metabolic pathways and the Calvin cycle under low-temperature stress highlighted 18, 15, 21, 29, and 31 DEGs for further study, which were almost all highly expressed under SL_LT treatment and moderately expressed under LT treatment, whereas Tis_LT showed low expression., Conclusion: The positive regulatory effect of SLs on the low-temperature tolerance of pepper seedlings was confirmed. This study provided new insights for the development of temperature-tolerant pepper lines through breeding programs., (© 2024. The Author(s).)

Background: The consequences of trace element exposure on cognitive function in elderly adults have been recognized as primarily attributed to the inflammatory response. It is noteworthy that diet can either exacerbate or reduce the inflammatory response. Despite this, there have been limited studies about the effects of diet on the relationship between trace element exposure and cognitive function., Methods: A cross-sectional study utilized data from the 2011-2014 NHANES survey to explore the association between trace element exposure and cognitive function in elderly adults. The study enrolled 1726 participants, and generalized linear regression model (GLM), Bayesian kernel machine regression model (BKMR), weighted quantile sum regression (WQS), and quantile g-computation regression analysis (Qg-comp) were conducted to assess the impact of five trace elements (lead, cadmium, mercury, manganese, and selenium) in blood on cognitive function under the anti-inflammatory and pro-inflammatory diet., Results: The GLM analysis showed a positive correlation between selenium (Se) and both the instant recall test (IRT) and digit symbol substitution test (DSST) (β = 2.06, 95% CI: 0.70 ~ 3.41; and β = 6.41, 95% CI: 2.35 ~ 10.46, respectively). In contrast, cadmium (Cd) was negatively associated with DSST (β = -1.17, 95% CI: -2.13~ -0.22), and lead (Pb) was negatively associated with IRT (β = -0.47, 95% CI: -0.82~ -0.11). For the animal fluency test (AFT), the highest quartile of manganese (Mn) was negatively associated with the lowest quartile (β = -0.72, 95% CI: -1.34~-0.10), while mercury (Hg) showed no significant associations with cognitive function tests. Subgroup analysis revealed the effects of Cd on IRT and DSST and Se on DSST under the pro-inflammatory diet. Furthermore, The BKMR analysis showed an inverted U-shaped curve with the negative impact of trace element mixtures and DSST and a linearly negative trend with IRT in the pro-inflammatory diet. Among them, Cd was emphasized as the most potent risk factor, and Se was the most vital protective factor for IRT and DSST in WQS and Qg-comp analysis., Conclusions: The study suggests that a high-quality diet might alleviate the adverse effects of Cd on IRT and DSST. High Se levels were also associated with better IRT and DSST scores in the pro-inflammatory diet. These findings provide valuable insights into the connection between diet, trace element exposure, and cognitive function in elderly adults., (© 2024. The Author(s).)

Background: Osteoporosis results from decreased bone mass and disturbed bone structure. Human bone marrow mesenchymal stem cells (hBMSCs) demonstrate robust osteogenic differentiation, a critical process for bone formation. This research was designed to examine the functions of LINC01133 in osteogenic differentiation., Methods: Differentially expressed lncRNAs affecting osteogenic differentiation in hBMSCs were identified from the GEO database. A total of 74 osteoporosis patients and 70 controls were enrolled. hBMSCs were stimulated to undergo osteogenic differentiation using an osteogenic differentiation medium (OM). RT-qPCR was performed to evaluate LINC01133 levels and osteogenesis-related genes such as osteocalcin, osteopontin, and RUNX2. An alkaline phosphates (ALP) activity assay was conducted to assess osteogenic differentiation. Cell apoptosis was detected using flow cytometry. Dual luciferase reporter assay and RIP assay were employed to investigate the association between miR-214-3p and LINC01133 or CTNNB1. Loss or gain of function assays were conducted to elucidate the impact of LINC01133 and miR-214-3p on osteogenic differentiation of hBMSCs., Results: LINC01133 and CTNNB1 expression decreased in osteoporotic patients but increased in OM-cultured hBMSCs, whereas miR-214-3p showed an opposite trend. Depletion of LINC01133 suppressed the expression of genes associated with bone formation and ALP activity triggered by OM in hBMSCs, leading to increased cell apoptosis. Nevertheless, this suppression was partially counteracted by the reduced miR-214-3p levels. Mechanistically, LINC01133 and CTNNB1 were identified as direct targets of miR-214-3p., Conclusions: Our study highlights the role of LINC01133 in positively regulating CTNNB1 expression by inhibiting miR-214-3p, thereby promoting osteogenic differentiation of BMSCs. These findings may provide valuable insights into bone regeneration in osteoporosis., (© 2024. The Author(s).)

Background: Many studies have demonstrated the association between intestinal microbiota and joint diseases. The "gut-joint axis" also has potential roles in chikungunya virus (CHIKV) infection. Pro-inflammatory arthritis after CHIKV infection might disrupt host homeostasis and lead to dysbacteriosis. This study investigated the characteristics of fecal and gut microbiota, intestinal metabolites, and the changes in gene regulation of intestinal tissues after CHIKV infection using multi-omics analysis to explore the involvement of gut microbiota in the pathogenesis of CHIKV infection., Results: CHIKV infection increases the systemic burden of inflammation in the GI system of infected animals. Moreover, infection-induced alterations in GI microbiota and metabolites may be indirectly involved in the modulation of GI and bone inflammation after CHIKV infection, including the modulation of inflammasomes and interleukin-17 inflammatory cytokine levels., Conclusion: Our results suggest that the GI tract and its microbes are involved in the modulation of CHIKV infection, which could serve as an indicator for the adjuvant treatment of CHIKV infection. Video Abstract., (© 2024. The Author(s).)

Background: Neutral Lipid Storage Disease with Myopathy (NLSDM) is a rare lipid metabolism disorder caused by PNPLA2 gene mutations. Clinical manifestations are heterogeneous, and diagnosis is often delayed, usually gaining patients' attention due to the increased risk of cardiomyopathy., Case Presentation: We herein report a 36-year-old Asian male presenting with progressive limb weakness, muscle atrophy of limbs and trunk, dysarthria, and heart failure. Electromyography indicated myogenic changes, and muscle biopsy results revealed characteristics of lipid storage myopathy. Genetic analysis of PNPLA2 revealed two heterozygous mutations: c.757 + 1G > T (chr11-823588, splice-5) on intron 6 and c.919delG (chr11-823854, p.A307Pfs*13) on exon 7. The patient improved limb strength, and dysarthria disappeared after the Medium Chain Fatty Acids diet., Conclusions: In conclusion, we report for the first time that the two heterozygous mutations PNPLA2 c.919delG and c.757 + 1G > T together induced NLSDM, which was confirmed by muscle biopsy., (© 2024. The Author(s).)

Human trophoblastic cell surface antigen 2 (Trop2) is a glycoprotein, a cellular marker of trophoblastic and stem cells, and a calcium signaling transducer involved in several signaling pathways, leading to the proliferation, invasion, and metastasis of tumors. It is expressed at a low level in normal epithelial cells, but at a high level in many tumors, making it an ideal target for cancer therapy. According to previous literature, Trop2 is broadly expressed in all breast cancer subtypes, especially in triple negative breast cancer (TNBC). Several clinical trials have demonstrated the effectiveness of Trop2-targeted therapy in breast cancer. Sacituzumab govitecan (SG) is a Trop2-targeted antibody-drug conjugate (ADC) that has been approved for the treatment of metastatic TNBC and hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer. This article reviews the structure and function of Trop2, several major Trop2-targeted ADCs, other appealing novel Trop2-targeted agents and relevant clinical trials to provide a landscape of how Trop2-targeted treatments will develop in the future., (© 2024. The Author(s).)

Background: For patients with rectal cancer, the utilization of temporary ileostomy (TI) has proven effective in minimizing the occurrence of severe complications post-surgery, such as anastomotic leaks; however, some patients are unable to reverse in time or even develop a permanent stoma (PS). We aimed to determine the preoperative predictors associated with TS failure and develop and validate appropriate predictive models to improve patients' quality of life., Methods: This research included 403 patients with rectal cancer who underwent temporary ileostomies between January 2017 and December 2021. All patients were randomly divided into either the developmental (70%) or validation (30%) group. The independent risk factors for PS were determined using univariate and multivariate logistic regression analyses. Subsequently, a nomogram was constructed, and the prediction probability was estimated by calculating the area under the curve (AUC) using receiver operating characteristic (ROC) analysis. A calibration plot was used to evaluate the nomogram calibration., Results: Of the 403 enrolled patients, 282 were randomized into the developmental group, 121 into the validation group, and 58 (14.39%) had a PS. The development group consisted of 282 patients, of whom 39 (13.81%) had a PS. The validation group consisted of 121 patients, of whom, 19 (15.70%) had a PS; 37 related factors were analyzed in the study. Multivariate logistic regression analysis demonstrated significant associations between the occurrence of PS and various factors in this patient cohort, including tumor location (OR = 6.631, P = 0.005), tumor markers (OR = 2.309, P = 0.035), American Society of Anesthesiologists (ASA) score (OR = 4.784, P = 0.004), T4 stage (OR = 2.880, P = 0.036), lymph node metastasis (OR = 4.566, P = 0.001), and distant metastasis (OR = 4.478, P = 0.036). Furthermore, a preoperative nomogram was constructed based on these data and subsequently validated in an independent validation group., Conclusion: We identified six independent preoperative risk factors associated with PS following rectal cancer resection and developed a validated nomogram with an area under the ROC curve of 0.7758, which can assist surgeons in formulating better surgical options, such as colostomy, for patients at high risk of PS., (© 2024. The Author(s).)

Objective: We aimed to compare the clinical efficacy of inverted triangular cannulated compression screws combined with Gotfried positive or negative buttress reduction in the healing of femoral neck fractures., Methods: Between October 2017 and March 2021, 55 patients with femoral neck fractures underwent treatment using inverted triangular cannulated compression screws combined with Gotfried positive or negative buttress reduction. Among these patients, 29 received inverted triangular cannulated compression screws combined with Gotfried positive buttress reduction treatment. This group consisted of 16 males and 13 females, with an average age of 43.45 ± 8.23 years. Additionally, 26 patients received inverted triangular cannulated compression nails combined with Gotfried negative buttress reduction treatment. This group included 14 males and 12 females, with an average age of 41.96 ± 8.69 years. Postsurgery, various measurements were taken, including the degree of shortening of the femoral neck, degree of bone nonunion, degree of fixation failure, degree of ischemic necrosis of the femoral head, and Harris score of the hip joint., Results: All patients were followed up for a minimum of 18 months. The group that underwent treatment with an inverted triangular cannulated compression screw combined with Gotfried positive buttress reduction did not experience any cases of bone nonunion, fixation failure, or ischemic necrosis of the femoral head. In the group that received treatment with inverted triangle cannulated compression screws combined with Gotfried negative buttress reduction, there was one case of bone nonunion, three cases of early fixation failure, and one case of ischemic necrosis. Ultimately, five patients (19.23% of the total) underwent joint replacement surgery. The average shortening lengths in the vertical plane were 4.07 ± 1.98 mm and 8.08 ± 3.54 mm, respectively. In the horizontal plane, the average shortening lengths were 3.90 ± 1.57 mm and 7.77 ± 3.31 mm, respectively. At the last follow-up, the group that received Gotfried positive buttress reduction had a greater Harris hip joint score., Conclusion: The success rate of combining inverted triangular cannulated compression screws with Gotfried positive buttress reduction surgery is relatively high. This surgical approach effectively prevents femoral neck shortening and improves hip joint function. Moreover, it is crucial to avoid negative buttress reduction when managing femoral neck fractures., (© 2024. The Author(s).)

Objectives: The purpose of this study was to investigate the preferred modes of transportation to the hospital among patients with acute stroke and acute myocardial infarction (AMI), as well as to identify the factors that influence the utilization of ambulances., Methods: We conducted a cross-sectional study, including patients who were diagnosed with acute stroke and AMI, at the people's hospital of Zhongjiang, from September 30th, 2022 to August 30th, 2023. All patients were divided into emergency medical service (EMS)-activation group and self-transportation group. Chi-square and t-tests were utilized to discern differences between groups at baseline. To screen relevant variables, we employed the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis using R package glmnet. Subsequently, we performed a logistic regression analysis to identify predictors of EMS activation according the results of LASSO regression., Results: we collected 929 valid questionnaires. 26.16% of the patients required the services of EMS. 90.9% of individuals have not received any formal first aid education. 42.1% of them reported that they had no understanding of cardiovascular and cerebrovascular diseases. Diagnosed as AMI (OR 0.22, 95%CI 0.06 to 0.88) or acute cerebral infarction (OR 0.26, 0.10 to 0.68), the distance between the patient and the nearest 120 network hospital when the patient had these symptoms (OR 0.97, 0.94 to 0.99), the patient's son or daughter was there when the patient was symptomatic (OR 0.58, 0.37 to 0.94), the patient (OR 0.19, 0.05 to 0.72) and the patient's partner (wife or husband) (OR 0.36, 0.16 to 0.85) had decided that the patient needed further medical help, Among patients who did not seek immediate help after symptom onset, thinking that the symptoms will disappear spontaneously (OR 0.34, 0.13 to 0.92) or not wanting to disturb others (OR 0.06, 0.01 to 0.66) or believing that they are not important symptoms (OR 0.15, 0.05 to 0.42) were factors independently associated with less ambulance use. Age (OR 1.02, 1.00 to 1.04), Stroke patients have experienced symptoms of disturbance of consciousness or convulsions (OR 2.99, 1.72 to 5.2) were independent factors associated with increased ambulance use., Conclusion: There is still ambulance underutilization among patients with acute stroke and AMI in county territory of China. Moreover, it is needed to raise the level of first aid education and awareness about EMS. Additionally, private clinic doctors and the public should gain adequate understanding of the severity of acute stroke and AMI, as well as their common symptoms, the crucial importance of prompt medical intervention. Finally, we propose that all township hospitals should be integrated into the 120 emergency networks and equipped with emergency first aid capabilities, pre-hospital care, and transportation abilities., (© 2024. The Author(s).)

Background: Therapeutic options for early-stage hepatocellular carcinoma (HCC) in individual patients can be limited by tumor and location, liver dysfunction and comorbidities. Many patients with early-stage HCC do not receive curative-intent therapies. Stereotactic ablative body radiotherapy (SABR) has emerged as an effective, non-invasive HCC treatment option, however, randomized evidence for SABR in the first line setting is lacking., Methods: Trans-Tasman Radiation Oncology Group (TROG) 21.07 SOCRATES-HCC is a phase II, prospective, randomised trial comparing SABR to other current standard of care therapies for patients with a solitary HCC ≤ 8 cm, ineligible for surgical resection or transplantation. The study is divided into 2 cohorts. Cohort 1 will compromise 118 patients with tumors ≤ 3 cm eligible for thermal ablation randomly assigned (1:1 ratio) to thermal ablation or SABR. Cohort 2 will comprise 100 patients with tumors > 3 cm up to 8 cm in size, or tumors ≤ 3 cm ineligible for thermal ablation, randomly assigned (1:1 ratio) to SABR or best other standard of care therapy including transarterial therapies. The primary objective is to determine whether SABR results in superior freedom from local progression (FFLP) at 2 years compared to thermal ablation in cohort 1 and compared to best standard of care therapy in cohort 2. Secondary endpoints include progression free survival, overall survival, adverse events, patient reported outcomes and health economic analyses., Discussion: The SOCRATES-HCC study will provide the first randomized, multicentre evaluation of the efficacy, safety and cost effectiveness of SABR versus other standard of care therapies in the first line treatment of unresectable, early-stage HCC. It is a broad, multicentre collaboration between hepatology, interventional radiology and radiation oncology groups around Australia, coordinated by TROG Cancer Research., Trial Registration: anzctr.org.au, ACTRN12621001444875, registered 21 October 2021., (© 2024. The Author(s).)

Objective: To investigate the association between liver enzymes and ovarian cancer (OC), and to validate their potential as biomarkers and their mechanisms in OC. Methods Genome-wide association studies for OC and levels of enzymes such as Alkaline phosphatase (ALP), Aspartate aminotransferase (AST), Alanine aminotransferase, and gamma-glutamyltransferase were analyzed. Univariate and multivariate Mendelian randomization (MR), complemented by the Steiger test, identified enzymes with a potential causal relationship to OC. Single-cell transcriptomics from the GSE130000 dataset pinpointed pivotal cellular clusters, enabling further examination of enzyme-encoding gene expression. Transcription factors (TFs) governing these genes were predicted to construct TF-mRNA networks. Additionally, liver enzyme levels were retrospectively analyzed in healthy individuals and OC patients, alongside the evaluation of correlations with cancer antigen 125 (CA125) and Human Epididymis Protein 4 (HE4)., Results: A total of 283 single nucleotide polymorphisms (SNPs) and 209 SNPs related to ALP and AST, respectively. Using the inverse-variance weighted method, univariate MR (UVMR) analysis revealed that ALP (P = 0.050, OR = 0.938) and AST (P = 0.017, OR = 0.906) were inversely associated with OC risk, suggesting their roles as protective factors. Multivariate MR (MVMR) confirmed the causal effect of ALP (P = 0.005, OR = 0.938) on OC without reverse causality. Key cellular clusters including T cells, ovarian cells, endothelial cells, macrophages, cancer-associated fibroblasts (CAFs), and epithelial cells were identified, with epithelial cells showing high expression of genes encoding AST and ALP. Notably, TFs such as TCE4 were implicated in the regulation of GOT2 and ALPL genes. OC patient samples exhibited decreased ALP levels in both blood and tumor tissues, with a negative correlation between ALP and CA125 levels observed., Conclusion: This study has established a causal link between AST and ALP with OC, identifying them as protective factors. The increased expression of the genes encoding these enzymes in epithelial cells provides a theoretical basis for developing novel disease markers and targeted therapies for OC., (© 2024. The Author(s).)

A significant decrease in estrogen levels puts menopausal women at high risk for major depression, which remains difficult to cure despite its relatively clear etiology. With the discovery of abnormally elevated inflammation in menopausal depressed women, immune imbalance has become a novel focus in the study of menopausal depression. In this paper, we examined the characteristics and possible mechanisms of immune imbalance caused by decreased estrogen levels during menopause and found that estrogen deficiency disrupted immune homeostasis, especially the levels of inflammatory cytokines through the ERα/ERβ/GPER-associated NLRP3/NF-κB signaling pathways. We also analyzed the destruction of the blood-brain barrier, dysfunction of neurotransmitters, blockade of BDNF synthesis, and attenuation of neuroplasticity caused by inflammatory cytokine activity, and investigated estrogen-immuno-neuromodulation disorders in menopausal depression. Current research suggests that drugs targeting inflammatory cytokines and NLRP3/NF-κB signaling molecules are promising for restoring homeostasis of the estrogen-immuno-neuromodulation system and may play a positive role in the intervention and treatment of menopausal depression., (© 2024. The Author(s).)

Background: Cognitive impairment is a recognized fundamental deficit in individuals diagnosed with schizophrenia (SZ), bipolar II disorder (BD II), and major depressive disorder (MDD), among other psychiatric disorders. However, limited research has compared cognitive function among first-episode drug-naïve individuals with SZ, BD II, or MDD., Methods: This study aimed to address this gap by assessing the cognitive performance of 235 participants (40 healthy controls, 58 SZ patients, 72 BD II patients, and 65 MDD patients) using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) before and after 12 weeks of treatment in SZ, BD II, and MDD patients. To clarify, the healthy controls only underwent RBANS testing at baseline, whereas the patient groups were assessed before and after treatment. The severity of symptoms in SZ patients was measured using the Positive and Negative Syndrome Scale (PANSS), and depression in BD II and MDD patients was assessed using the Hamilton Depression Scale-24 items (HAMD-24 items)., Results: Two hundred participants completed the 12-week treatment period, with 35 participants dropping out due to various reasons. This group included 49 SZ patients, 58 BD II patients, and 53 MDD patients. Among SZ patients, significant improvements in immediate and delayed memory were observed after 12 weeks of treatment compared to their initial scores. Similarly, BD II patients showed significant improvement in immediate and delayed memory following treatment. However, there were no significant differences in RBANS scores for MDD patients after 12 weeks of treatment., Conclusions: In conclusion, the findings of this study suggest that individuals with BD II and SZ may share similar deficits in cognitive domains. It is important to note that standardized clinical treatment may have varying degrees of effectiveness in improving cognitive function in patients with BD II and SZ, which could potentially alleviate cognitive dysfunction., (© 2024. The Author(s).)

Background: Liver cancer is one of the most common cancers in China. To understand the basic death situation and disease burden change trend, we analyze the death information of liver cancer among Chinese residents from 2008 to 2021., Methods: Data was collected from the Cause-of-Death Surveillance dataset of the National Cause-of-Death Surveillance System from 2008 to 2021. Excel 2016 was used for data entry and to calculate the Crude Mortality Rate (CMR), Age-Standardized Mortality Rate (ASMR), Potential Years of Life Lost (PYLL), and Potential Years of Life Lost Rate (PYLLR). SPSS 25.0 was used to statistically analyze CMR, ASMR, PYLL, and other indicators. Annual percent change (APC) and average APC(AAPC) was used for trend analysis and tested by t tests. Joinpoint 4.9.1.0 was used to calculate APC and AAPC. Age-Period-Cohort model was used to assess the effects of age, period, and birth cohort on liver cancer mortality., Results: From 2008 to 2021, 491,701 liver cancer deaths were reported in the National Disease Surveillance Points System. The ASMR of liver cancer in Chinese residents decreased from 27.58/100,000 in 2008 to 17.95/100,000 in 2021 at an average annual rate of 3.40% (t = -5.10, P < 0.001). The mortality rate was higher in males than in females (all P < 0.001) and higher in rural areas than in urban areas (all P < 0.001). The mortality rate of liver cancer varied significantly among eastern, central, and western China (all P < 0.001). The PYLLR of liver cancer in Chinese residents decreased from 2.89‰ in 2008 to 2.06‰ in 2021 at an average annual rate of 2.40% (t = -5.10, P < 0.001). Males had a lower PYLLR than females, decreasing at average annual rates of 2.20% (t = -5.40, P < 0.001) and 2.90% (t = -8.40, P < 0.001), respectively. Urban areas had a lower PYLLR than rural areas, decreasing at average annual rate of 3.30% (t = -4.00, P < 0.001) and 2.50% (t = -11.60, P < 0.001), respectively. Eastern, central, and western China decreased at average annual rates of 3.40%, 2.30%, and 2.10%, respectively (t = -7.80, -3.60, -7.10, P < 0.001 for all). The risk of China liver cancer mortality increased with age, decreased with birth cohort., Conclusions: The mortality and disease burdens of liver cancer in China decreased yearly and were higher in males and in people living in rural areas, with significant differences among those living in eastern, central, and western China., (© 2024. The Author(s).)

Background: Exploring the pathogenesis of osteoarthritis (OA) is important for its prevention, diagnosis, and treatment. Therefore, we aimed to construct novel signature genes (c-FRGs) combining cuproptosis-related genes (CRGs) with ferroptosis-related genes (FRGs) to explore the pathogenesis of OA and aid in its treatment., Materials and Methods: Differentially expressed c-FRGs (c-FDEGs) were obtained using R software. Enrichment analysis was performed and a protein-protein interaction (PPI) network was constructed based on these c-FDEGs. Then, seven hub genes were screened. Three machine learning methods and verification experiments were used to identify four signature biomarkers from c-FDEGs, after which gene set enrichment analysis, gene set variation analysis, single-sample gene set enrichment analysis, immune function analysis, drug prediction, and ceRNA network analysis were performed based on these signature biomarkers. Subsequently, a disease model of OA was constructed using these biomarkers and validated on the GSE82107 dataset. Finally, we analyzed the distribution of the expression of these c-FDEGs in various cell populations., Results: A total of 63 FRGs were found to be closely associated with 11 CRGs, and 40 c-FDEGs were identified. Bioenrichment analysis showed that they were mainly associated with inflammation, external cellular stimulation, and autophagy. CDKN1A, FZD7, GABARAPL2, and SLC39A14 were identified as OA signature biomarkers, and their corresponding miRNAs and lncRNAs were predicted. Finally, scRNA-seq data analysis showed that the differentially expressed c-FRGs had significantly different expression distributions across the cell populations., Conclusion: Four genes, namely CDKN1A, FZD7, GABARAPL2, and SLC39A14, are excellent biomarkers and prospective therapeutic targets for OA., (© 2024. The Author(s).)

Background: Microsatellite instability-high (MSI-H) has emerged as a significant biological characteristic of colorectal cancer (CRC). Studies reported that MSI-H CRC generally had a better prognosis than microsatellite stable (MSS)/microsatellite instability-low (MSI-L) CRC, but some MSI-H CRC patients exhibited distinctive molecular characteristics and experienced a less favorable prognosis. In this study, our objective was to explore the metabolic transcript-related subtypes of MSI-H CRC and identify a biomarker for predicting survival outcomes., Methods: Single-cell RNA sequencing (scRNA-seq) data of MSI-H CRC patients were obtained from the Gene Expression Omnibus (GEO) database. By utilizing the copy number variation (CNV) score, a malignant cell subpopulation was identified at the single-cell level. The metabolic landscape of various cell types was examined using metabolic pathway gene sets. Subsequently, functional experiments were conducted to investigate the biological significance of the hub gene in MSI-H CRC. Finally, the predictive potential of the hub gene was assessed using a nomogram., Results: This study revealed a malignant tumor cell subpopulation from the single-cell RNA sequencing (scRNA-seq) data. MSI-H CRC was clustered into two subtypes based on the expression profiles of metabolism-related genes, and ENO2 was identified as a hub gene. Functional experiments with ENO2 knockdown and overexpression demonstrated its role in promoting CRC cell migration, invasion, glycolysis, and epithelial-mesenchymal transition (EMT) in vitro. High expression of ENO2 in MSI-H CRC patients was associated with worse clinical outcomes, including increased tumor invasion depth (p = 0.007) and greater likelihood of perineural invasion (p = 0.015). Furthermore, the nomogram and calibration curves based on ENO2 showed potential prognosis predictive performance., Conclusion: Our findings suggest that ENO2 serves as a novel prognostic biomarker and is associated with the progression of MSI-H CRC., (© 2024. The Author(s).)

Objective: This study synthesizes evidence from the Loughborough Passing Test to evaluate the short-passing ability of soccer players and summarizes the reported variables that affect this ability to provide support for the development and improvement of short-passing abilities in soccer players., Methods: In this systematic review using the PRISMA guidelines, a comprehensive search was conducted in Web of Science, PubMed, and EBSCOhost from inception to July 2023 to identify relevant articles from the accessible literature. Only studies that used the Loughborough test to assess athletes' short-passing ability were included. The quality of the included studies was independently assessed by two reviewers using the PEDro scale, and two authors independently completed the data extraction., Results: Based on the type of intervention or influencing factor, ten studies investigated training, nine studies investigated fatigue, nine studies investigated supplement intake, and five studies investigated other factors., Conclusion: Evidence indicates that fitness training, small-sided games training, and warm-up training have positive effects on athletes' short-passing ability, high-intensity special-position training and water intake have no discernible impact, mental and muscular exhaustion have a significantly negative effect, and the effect of nutritional ergogenic aid intake is not yet clear. Future research should examine more elements that can affect soccer players' short-passing ability., Trial Registration: https://inplasy.com/ ., identifier: INPLASY20237., (© 2024. The Author(s).)

Background: Jasmonate (JA) is the important phytohormone to regulate plant growth and adaption to stress signals. MYC2, an bHLH transcription factor, is the master regulator of JA signaling. Although MYC2 in maize has been identified, its function remains to be clarified., Results: To understand the function and regulatory mechanism of MYC2 in maize, the joint analysis of DAP-seq and RNA-seq is conducted to identify the binding sites and target genes of ZmMYC2. A total of 3183 genes are detected both in DAP-seq and RNA-seq data, potentially as the directly regulating genes of ZmMYC2. These genes are involved in various biological processes including plant growth and stress response. Besides the classic cis-elements like the G-box and E-box that are bound by MYC2, some new motifs are also revealed to be recognized by ZmMYC2, such as nGCATGCAnn, AAAAAAAA, CACGTGCGTGCG. The binding sites of many ZmMYC2 regulating genes are identified by IGV-sRNA., Conclusions: All together, abundant target genes of ZmMYC2 are characterized with their binding sites, providing the basis to construct the regulatory network of ZmMYC2 and better understanding for JA signaling in maize., (© 2024. The Author(s).)

Background: Brainstem cavernous malformations (BCMs) are benign lesions that typically have an acute onset and are associated with a high rate of morbidity. The selection of the optimal surgical approach is crucial for obtaining favorable outcomes, considering the different anatomical locations of various brainstem lesions. Endoscopic surgery is increasingly utilized in treating of BCMs, owing to its depth illumination and panoramic view capabilities. For intra-axial ventral BCMs, the best surgical options are endoscopic endonasal approaches, following the "two-point method. For cavernous hemangiomas on the dorsal side of the brainstem, endoscopy proves valuable by providing enhanced visualization of the operative field and minimizing the need for brain retraction., Methods: In this review, we gathered data on the fully endoscopic approach for the resection of BCMs, and outlined technical notes and tips. Total of 15 articles were included in this review. The endoscopic endonasal approach was utilized in 19 patients, and the endoscopic transcranial approach was performed in 3 patients., Results: The overall resection rate was 81.8% (18/22). Among the 19 cases of endoscopic endonasal surgery, postoperative cerebrospinal fluid (CSF) leakage occurred in 5 cases, with lesions exceeding 2 cm in diameter in 3 patients with postoperative CSF rhinorrhea. Among the 20 patients with follow-up data, 2 showed no significant improvement after surgery, whereas the remaining 18 patients showed significant improvement compared to their admission symptoms., Conclusions: This systematic literature review demonstrates that a fully endoscopic approach is a safe and effective option for the resection of BCMs. Further, it can be considered an alternative to conventional craniotomy, particularly when managed by a neurosurgical team with extensive experience in endoscopic surgery, addressing these challenging lesions., (© 2024. The Author(s).)

Background: Temporary ileostomy (TI) has proven effective in reducing the severity of anastomotic leakage after rectal cancer surgery; however, some ileostomies fail to reverse over time, leading to conversion into a permanent stoma (PS). In this study, we aimed to investigate the preoperative risk factors and cumulative incidence of TI non-closure after sphincter-preserving surgery for rectal cancer., Materials and Methods: We conducted a meta-analysis after searching the Embase, Web of Science, PubMed, and MEDLINE databases from their inception until November 2023. We collected all published studies on the risk factors related to TI non-closure after sphincter-preserving surgery for rectal cancer., Results: A total of 1610 studies were retrieved, and 13 studies were included for meta-analysis, comprising 3026 patients. The results of the meta-analysis showed that the identified risk factors included older age (p = 0.03), especially > 65 years of age (p = 0.03), male sex (p = 0.009), American Society of Anesthesiologists score ≥ 3 (p = 0.004), comorbidity (p = 0.001), and distant metastasis (p < 0.001). Body mass index, preoperative hemoglobin, preoperative albumin, preoperative carcinoma embryonic antigen, tumor location, neoadjuvant chemoradiotherapy, smoking, history of abdominal surgery, and open surgery did not significantly change the risk of TI non-closure., Conclusion: We identified five preoperative risk factors for TI non-closure after sphincter-preserving surgery for rectal cancer. This information enables surgeons to identify high-risk groups before surgery, inform patients about the possibility of PS in advance, and consider performing protective colostomy or Hartmann surgery., (© 2024. The Author(s).)

Background: Gestational diabetes mellitus (GDM) is a common complication of pregnancy, with significant short-term and long-term implications for both mothers and their offspring. Previous studies have indicated the potential benefits of vitamin D in reducing the risk of GDM, yet little is known about this association in twin pregnancies. This study aimed to investigate maternal vitamin D status in the second trimester and examine its association with the risk of GDM in twin pregnancies., Methods: We conducted a prospective cohort study based on data from the Chongqing Longitudinal Twin Study (LoTiS). Peripheral blood serum was collected from the mothers in the second trimester to measure 25(OH)D concentrations. GDM was diagnosed at 23-26 weeks of gestation using a 75-g 2-h oral glucose tolerance test. We used multivariable logistic regression analyses to examine the correlations between vitamin D status and the risk of GDM., Results: Of the total participants, 93 (29.9%) women were diagnosed with GDM. The mean serum 25(OH)D concentration in the second trimester was 31.1 ± 11.2 ng/mL, and the rate of vitamin D insufficiency and deficiency were 23.5% and 18.7%, respectively. Compared to women with a 25(OH)D concentration < 30 ng/mL, those with a 25(OH)D concentration ≥ 30 ng/mL had a significantly lower risk of GDM (RR 0.61; 95% CI: 0.43, 0.86), especially those who were overweight before pregnancy (RR 0.32; 95% CI: 0.16, 0.64). The restricted cubic splines model showed an inverted J-shaped relationship between vitamin D concentrations and GDM risk., Conclusions: The risk of GDM was significantly reduced in twin pregnant women with vitamin D concentrations ≥ 30 ng/mL in the second trimester., Trial Registration: ChiCTR-OOC-16,008,203. Retrospectively registered on 1 April 2016., (© 2024. The Author(s).)

Thrombotic diseases impose a significant global health burden, and conventional drug-based thrombolytic therapies are encumbered by the risk of bleeding complications. In this study, we introduce a novel drug-free nanomedicine founded on tea polyphenols nanoparticles (TPNs), which exhibits multifaceted capabilities for localized photothermal thrombolysis. TPNs were synthesized through a one-pot process under mild conditions, deriving from the monomeric epigallocatechin-3-gallate (EGCG). Within this process, indocyanine green (ICG) was effectively encapsulated, exploiting multiple intermolecular interactions between EGCG and ICG. While both TPNs and ICG inherently possessed photothermal potential, their synergy significantly enhanced photothermal conversion and stability. Furthermore, the nanomedicine was functionalized with cRGD for targeted delivery to activated platelets within thrombus sites, eliciting robust thrombolysis upon laser irradiation across diverse thrombus types. Importantly, the nanomedicine's potent free radical scavenging abilities concurrently mitigated vascular inflammation, thus diminishing the risk of disease recurrence. In summary, this highly biocompatible multifunctional nanomaterial holds promise as a comprehensive approach that combines thrombolysis with anti-inflammatory actions, offering precision in thrombosis treatment., (© 2024. The Author(s).)

Background: The cardiometabolic index (CMI) is a new metric derived from the triglyceride-glucose index and body mass index and is considered a potential marker for cardiovascular risk assessment. This study aimed to examine the correlation between the CMI and the presence and severity of arteriosclerosis in patients with type 2 diabetes mellitus (T2DM)., Methods: This study involved 2243 patients with T2DM. The CMI was derived by dividing the triglyceride level (mmol/L) by the high-density lipoprotein level (mmol/L) and then multiplying the quotient by the waist-to-height ratio. Multivariate logistic regression was used to analyze the correlations between the CMI and BMI blood biomarkers, blood pressure, and brachial-ankle pulse wave velocity (baPWV)., Results: Patients were categorized into three groups based on their CMI: Group C1 (CMI < 0.775; n = 750), Group C2 (CMI: 0.775-1.355; n = 743), and Group C3 (CMI > 1.355; n = 750). Increased BMI, fasting glucose, insulin (at 120 min), total cholesterol (TC), and baPWV values were observed in Groups C2 and C3, with statistically significant trends (all trends P < 0.05). The CMI was positively correlated with systolic blood pressure (r = 0.74, P < 0.001). Multivariate analysis revealed that an increased CMI contributed to a greater risk for arteriosclerosis (OR = 1.87, 95%CI: 1.66-2.10, P < 0.001). Compared to the C1 group, the C2 group and C3 group had a greater risk of developing arteriosclerosis, with ORs of 4.55 (95%CI: 3.57-5.81, P<0.001) and 5.56 (95%CI: 4.32-7.17, P<0.001), respectively. The association was notably stronger in patients with a BMI below 21.62 kg/m² than in those with a BMI of 21.62 kg/m² or higher (OR = 4.53 vs. OR = 1.59)., Conclusions: These findings suggest that the CMI is a relevant and independent marker of arteriosclerosis in patients with T2DM and may be useful in the risk stratification and management of these patients., (© 2024. The Author(s).)

Background: Bladder urothelial carcinoma (BLCA) is the most common malignancy of the urinary tract, presenting with a wide range of clinical symptoms and prognosis. Disulfidptosis is a newly identified cell death method and closely associated with BLCA progression, prognosis, and treatment outcome. Currently, we need to construct a new prognostic model for disulfidptosis-related long noncoding RNAs (drlncRNAs) to improve the treatment strategy of BLCA., Methods: The data for BLCA samples were obtained from The Cancer Genome Atlas (TCGA), and then 10 unique genes related to disulfidoptosis (DRGs) were identified from research papers. The differences between the two groups showed in this study were used to create the "disulfidptosis-related long noncoding RNAs score" (disulfidptosis-score) prognostic model., Results: We identified two groups of drlncRNAs with high and low disulfidptosis scores in this study. Patients with low disulfidptosis scores had a better overall survival rate compared to those with high scores in bladder cancer, and the high disulfidptosis score subtype exhibited more active malignant pathways related to cancer than the low score subtype. We found that the low disulfidptosis-score subgroup had better prognosis than the high disulfidptosis-score subgroup. The expression of mutation burden was much higher in the low disulfidptosis-score group than in the high disulfidptosis-score group. The low disulfidptosis-score subgroup of patients exhibited significantly higher proportions of plasma cells, T cells CD8, and Tregs, while the high-risk subgroup had a greater abundance of Macrophages M0 and Macrophages M2. The disulfidptosis-score showed a strong correlation with the sensitivity of chemotherapeutic drugs, and patients in the low disulfidptosis-score group were more likely to exhibit an immune response and respond positively to immunotherapy. Additionally, we developed a nomogram to enhance the accuracy of the disulfidptosis-clinical score., Conclusion: Based on our investigation of disulfidptosis-score in BLCA, disulfidptosis-score may have an important role in TME, prognosis, and drug sensitivity. We also investigated the significance of the disulfidoptosis-score in relation to immunotherapy and immune response, providing a basis for improving prognosis and responding to immunotherapy among patients with BLCA., (© 2024. The Author(s).)

Background: Type 2 diabetes mellitus (T2DM) causes severe bone loss after tooth extraction as a hyperglycemic environment causes aberrant bone homeostasis. Artesunate (ART) is known to possess anti-inflammation and osteogenic properties. However, its osteogenesis property in alveolar bone remains unclear. This study aimed to explore the osteogenic and immunoregulatory effects of artesunate-loaded thermosensitive chitosan hydrogel (ART-loaded TCH) on maxilla tooth extraction in T2DM rats., Methods: T2DM rats were induced by a high-fat diet and streptozotocin. Different concentrations of ART-loaded TCH were applied in tooth extraction sockets. Bone loss and the expression of osteogenic regulatory factors (OPG, ALP, RANK) were evaluated. The immunoregulatory effects of ART-loaded TCH were observed through detecting the infiltration of T lymphocytes and their cytokines. The underlying mechanisms were explored., Results: Results showed that the 150 mg/ml ART-loaded TCH group significantly ameliorated maxilla bone height and bone mineral density when compared with the T2DM group (p < 0.05). It also improved the expression of OPG, ALP, and RANK. Although the alteration of CD4 + T, CD8 + T, and CD4 + :CD8 + T ratio has no significant difference among groups, the release of Th1 and Th2 in the 150 mg/ml ART-loaded TCH group has been significantly regulated than in the T2DM group (p < 0.05). Besides, ART-loaded TCH treatment inhibited the expression of p38 MAPK and ERK1 in T2DM maxilla., Conclusions: Therefore, the results indicated that 150 mg/ml ART-loaded TCH could be an effective method to prevent bone loss in T2DM tooth extraction rats by modulating the immunoregulation of Th1 and Th2 and the MAPK signaling pathway., (© 2024. The Author(s).)

Background: Ischemic stroke and transient ischemic attack (TIA) are the most prevalent cerebrovascular diseases. The conventional antiplatelet drugs are associated with an inherent bleeding risk, while indobufen is a new antiplatelet drug and has the similar mechanism of antiplatelet aggregation as aspirin with more safety profile. However, there have been no studies evaluating the combination therapy of indobufen and clopidogrel for antiplatelet therapy in cerebrovascular diseases., Objective: The CARMIA study aims to investigate the effectiveness and safety of a new dual antiplatelet therapy consisting of indobufen and clopidogrel comparing with the conventional dual antiplatelet therapy consisting of aspirin and clopidogrel in patients with minor ischemic stroke or high-risk TIA., Methods: An open-label randomized controlled clinical trial was conducted at a clinical center. We randomly assigned patients who had experienced a minor stroke or transient ischemic attack (TIA) within 72 h of onset, or within 1 month if they had intracranial stenosis (IS), to receive either indobufen 100 mg twice daily or aspirin 100 mg once daily for 21 days. For patients with IS, the treatment duration was extended to 3 months. All patients received a loading dose of 300 mg clopidogrel orally on the first day, followed by 75 mg once daily from the second day to 1 year. We collected prospective data using paper-based case report forms, and followed up on enrolled patients was conducted to assess the incidence of recurrent ischemic stroke or TIA, mRS score, NIHSS (National Institutes of Health Stroke Scale) score, and any bleeding events occurring within 3 month after onset., Results: We enrolled 202 patients diagnosed with ischemic stroke or transient ischemic attack. After applying the criteria, 182 patients were eligible for data analysis. Endpoint events (recurrence of ischemic stroke/TIA, myocardial infarction, or death) were observed in 6 patients (6.5%) receiving aspirin and clopidogrel, including 4 (4.3%) with stroke recurrence, 1 (1.1%) with TIA recurrence, and 1 (1%) with death. In contrast, no endpoint events were reported in the indobufen and clopidogrel group (P = 0.029). The group of patients receiving indobufen and clopidogrel exhibited significantly lower modified Rankin Scale (mRS) score. (scores range from 0 to 6, with higher scores indicating more severe disability) compared to the aspirin and clopidogrel group (common odds ratio 3.629, 95% CI 1.874-7.036, P < 0.0001). Although the improvement rate of NIHSS score in the indobufen and clopidogrel group was higher than that in the aspirin and clopidogrel group, the difference was not statistically significant (P > 0.05). Bleeding events were observed in 8 patients (8.6%) receiving aspirin and clopidogrel, including 4 (4.3%) with skin bleeding, 2 (2.2%) with gingival bleeding, 1 (1.1%) with gastrointestinal bleeding, and 1 (1.1%) with urinary system bleeding. On the other hand, only 1 patient (1.1%) in the indobufen and clopidogrel group experienced skin bleeding (P = 0.035)., Conclusion: The combination of indobufen and clopidogrel has shown non-inferior and potentially superior effectiveness and safety compared to aspirin combined with clopidogrel in patients with minor ischemic stroke and high-risk TIA in the CARMIA study (registered under chictr.org.cn with registration number ChiCTR2100043087 in 01/02/2021)., (© 2024. The Author(s).)

Background: Forkhead-box protein P1 (FOXP1) has been proposed to have both oncogenic and tumor-suppressive properties, depending on tumor heterogeneity. However, the role of FOXP1 in intrahepatic cholangiocarcinoma (ICC) has not been previously reported., Methods: Immunohistochemistry was performed to detect FOXP1 expression in ICC and normal liver tissues. The relationship between FOXP1 levels and the clinicopathological characteristics of patients with ICC was evaluated. Finally, in vitro and in vivo experiments were conducted to examine the regulatory role of FOXP1 in ICC cells., Results: FOXP1 was significantly downregulated in the ICC compared to their peritumoral tissues (p < 0.01). The positive rates of FOXP1 were significantly lower in patients with poor differentiation, lymph node metastasis, invasion into surrounding organs, and advanced stages (p < 0.05). Notably, patients with FOXP1 positivity had better outcomes (overall survival) than those with FOXP1 negativity (p < 0.05), as revealed by Kaplan-Meier survival analysis. Moreover, Cox multivariate analysis showed that negative FOXP1 expression, advanced TNM stages, invasion, and lymph node metastasis were independent prognostic risk factors in patients with ICC. Lastly, overexpression of FOXP1 inhibited the proliferation, migration, and invasion of ICC cells and promoted apoptosis, whereas knockdown of FOXP1 had the opposite role., Conclusion: Our findings suggest that FOXP1 may serve as a novel outcome predictor for ICC as well as a tumor suppressor that may contribute to cancer treatment., (© 2024. The Author(s).)

Antimicrobial resistance is a global public health threat, and the World Health Organization (WHO) has announced a priority list of the most threatening pathogens against which novel antibiotics need to be developed. The discovery and introduction of novel antibiotics are time-consuming and expensive. According to WHO's report of antibacterial agents in clinical development, only 18 novel antibiotics have been approved since 2014. Therefore, novel antibiotics are critically needed. Artificial intelligence (AI) has been rapidly applied to drug development since its recent technical breakthrough and has dramatically improved the efficiency of the discovery of novel antibiotics. Here, we first summarized recently marketed novel antibiotics, and antibiotic candidates in clinical development. In addition, we systematically reviewed the involvement of AI in antibacterial drug development and utilization, including small molecules, antimicrobial peptides, phage therapy, essential oils, as well as resistance mechanism prediction, and antibiotic stewardship., (© 2024. The Author(s).)

Background: Neonatal sepsis, a perilous medical situation, is typified by the malfunction of organs and serves as the primary reason for neonatal mortality. Nevertheless, the mechanisms underlying newborn sepsis remain ambiguous. Programmed cell death (PCD) has a connection with numerous infectious illnesses and holds a significant function in newborn sepsis, potentially serving as a marker for diagnosing the condition., Methods: From the GEO public repository, we selected two groups, which we referred to as the training and validation sets, for our analysis of neonatal sepsis. We obtained PCD-related genes from 12 different patterns, including databases and published literature. We first obtained differential expressed genes (DEGs) for neonatal sepsis and controls. Three advanced machine learning techniques, namely LASSO, SVM-RFE, and RF, were employed to identify potential genes connected to PCD. To further validate the results, PPI networks were constructed, artificial neural networks and consensus clustering were used. Subsequently, a neonatal sepsis diagnostic prediction model was developed and evaluated. We conducted an analysis of immune cell infiltration to examine immune cell dysregulation in neonatal sepsis, and we established a ceRNA network based on the identified marker genes., Results: Within the context of neonatal sepsis, a total of 49 genes exhibited an intersection between the differentially expressed genes (DEGs) and those associated with programmed cell death (PCD). Utilizing three distinct machine learning techniques, six genes were identified as common to both DEGs and PCD-associated genes. A diagnostic model was subsequently constructed by integrating differential expression profiles, and subsequently validated by conducting artificial neural networks and consensus clustering. Receiver operating characteristic (ROC) curves were employed to assess the diagnostic merit of the model, which yielded promising results. The immune infiltration analysis revealed notable disparities in patients diagnosed with neonatal sepsis. Furthermore, based on the identified marker genes, the ceRNA network revealed an intricate regulatory interplay., Conclusion: In our investigation, we methodically identified six marker genes (AP3B2, STAT3, TSPO, S100A9, GNS, and CX3CR1). An effective diagnostic prediction model emerged from an exhaustive analysis within the training group (AUC 0.930, 95%CI 0.887-0.965) and the validation group (AUC 0.977, 95%CI 0.935-1.000)., (© 2024. The Author(s).)

Background: Abnormal lipid metabolism poses a risk for prediabetes. However, research on lipid parameters used to predict the risk of prediabetes is scarce, and the significance of traditional and untraditional lipid parameters remains unexplored in prediabetes. This study aimed to comprehensively evaluate the association between 12 lipid parameters and prediabetes and their diagnostic value., Methods: This cross-sectional study included data from 100,309 Chinese adults with normal baseline blood glucose levels. New onset of prediabetes was the outcome of concern. Untraditional lipid parameters were derived from traditional lipid parameters. Multivariate logistic regression and smooth curve fitting were used to examine the nonlinear relationship between lipid parameters and prediabetes. A two-piecewise linear regression model was used to identify the critical points of lipid parameters influencing the risk of prediabetes. The areas under the receiver operating characteristic curve estimated the predictive value of the lipid parameters., Results: A total of 12,352 participants (12.31%) were newly diagnosed with prediabetes. Following adjustments for confounding covariables, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol were negatively correlated with prediabetes risk. Conversely, total cholesterol, triglyceride (TG), lipoprotein combine index (LCI), atherogenic index of plasma (AIP), non-HDL-C, atherogenic coefficient, Castelli's index-I, remnant cholesterol (RC), and RC/HDL-C ratio displayed positive correlations. In younger adults, females, individuals with a family history of diabetes, and non-obese individuals, LCI, TG, and AIP exhibited higher predictive values for the onset of prediabetes compared to other lipid profiles., Conclusion: Nonlinear associations were observed between untraditional lipid parameters and the risk of prediabetes. The predictive value of untraditional lipid parameters for prediabetes surpassed that of traditional lipid parameters, with LCI emerging as the most effective predictor for prediabetes., (© 2024. The Author(s).)

As the fifth most common cancer in the world, gastric cancer (GC) ranks as the third major cause of cancer-related death globally. Although surgical resection and chemotherapy still remains the mainstay of potentially curative treatment for GC, chemotherapy resistance and adverse side effects limit their clinical applications. Thus, further investigation of the mechanisms of carcinogenesis in GC and discovery of novel biomarkers is of great concern. We herein report that the elevated expression of GPR137 is correlated with GC. Overexpression of GPR137 potentiates human gastric cancer AGS cell malignancy, including proliferation, migration, invasion, colony formation and xenograft growth in nude mice in vivo, whereas knockout of GPR137 by CRISPR/Cas9 gene editing exerts the opposite effects. Mechanistically, GPR137 could bind to MST, the upstream kinases in Hippo pathway, which disrupts the association of MST with LATS, subsequently activating the transcriptional co-activators, YAP and TAZ, and thereby triggering the target transcription and the alterations in GC cell biological actions consequently. Therefore, our findings may provide with the evidence of developing a potentially novel treatment method with specific target for GC., (© 2023. The Author(s).)

Hyaluronic acid (HA) is widely distributed in human connective tissue, and its unique biological and physicochemical properties and ability to facilitate biological structure repair make it a promising candidate for three-dimensional (3D) bioprinting in the field of tissue regeneration and biomedical engineering. Moreover, HA is an ideal raw material for bioinks in tissue engineering because of its histocompatibility, non-immunogenicity, biodegradability, anti-inflammatory properties, anti-angiogenic properties, and modifiability. Tissue engineering is a multidisciplinary field focusing on in vitro reconstructions of mammalian tissues, such as cartilage tissue engineering, neural tissue engineering, skin tissue engineering, and other areas that require further clinical applications. In this review, we first describe the modification methods, cross-linking methods, and bioprinting strategies for HA and its derivatives as bioinks and then critically discuss the strengths, shortcomings, and feasibility of each method. Subsequently, we reviewed the practical clinical applications and outcomes of HA bioink in 3D bioprinting. Finally, we describe the challenges and opportunities in the development of HA bioink to provide further research references and insights., (© 2023. The Author(s).)

Background: This study was conducted to develop and validate an individualized prediction model for spontaneous preterm birth (sPTB) in twin pregnancies., Methods: This a retrospective cohort study included 3845 patients who gave birth at the Chongqing Maternal and Child Health Hospital from January 2017 to December 2022. Both univariable and multivariable logistic regression analyses were performed to find factors associated with sPTB. The associations were estimated using the odds ratio (OR) and the 95% confidence interval (CI). Model performance was estimated using sensitivity, specificity, accuracy, area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA)., Results: A total of 1313 and 564 cases were included in the training and testing sets, respectively. In the training set, univariate and multivariate logistic regression analysis indicated that age ≥ 35 years (OR, 2.28; 95% CI 1.67-3.13), pre-pregnancy underweight (OR, 2.36; 95% CI 1.60-3.47), pre-pregnancy overweight (OR, 1.67; 95% CI 1.09-2.56), and obesity (OR, 10.45; 95% CI, 3.91-27.87), nulliparity (OR, 0.58; 95% CI 0.41-0.82), pre-pregnancy diabetes (OR, 5.81; 95% CI 3.24-10.39), pre-pregnancy hypertension (OR, 2.79; 95% CI 1.44-5.41), and cervical incompetence (OR, 5.12; 95% CI 3.08-8.48) are independent risk factors for sPTB in twin pregnancies. The AUC of the training and validation set was 0.71 (95% CI 0.68-0.74) and 0.68 (95% CI 0.64-0.73), respectively. And then we integrated those risk factors to construct the nomogram., Conclusions: The nomogram developed for predicting the risk of sPTB in pregnant women with twins demonstrated good performance. The prediction nomogram serves as a practical tool by including all necessary predictors that are readily accessible to practitioners., (© 2023. The Author(s).)

Background: Intrahepatic cholangiocarcinoma (ICC) is poorly treated due to the presence of an inhibitory immune microenvironment. Tumor-associated macrophages (TAM) are an important component of TME. ALOX5 is an important lipid metabolism enzyme in cancer progression, but the mechanism by which it regulates TAM to promote ICC progression is unknown. The aim of this study was to investigate the potential mechanism of TAM regulation by ALOX5 and the translational effect of targeting ALOX5., Methods: In this study, we investigated the association between the spatial localization of epithelial cells and TAMs by combining scRNA-seq analysis with multiplex immunofluorescence analysis. Through bulk sequencing analysis and spatial analysis, lipid metabolism genes closely related to TAM infiltration were screened. In vitro co-culture model was constructed to verify that ALOX5 and its downstream metabolite LTB4 promote M2 macrophage migration. Bulk sequencing after co-culture combined with single-cell analysis was performed to identify key pathways for up-regulation of M2 macrophage migration. Finally, the effect of CSF1R inhibitor (PLX3397) combined with ALOX5 inhibitor (Zileuton) in vivo was investigated by by xenograft tumor formation experiment in nude mice., Results: ALOX5 in ICC cells was a key lipid metabolism gene affecting the infiltration of M2 macrophages in TME. Mechanically, LTB4, a metabolite downstream of ALOX5, recruited M2 macrophages to migrate around tumor cells by binding to BLT1/BLT2 and activating the PI3K pathway, which ultimately lead to the promotion of ICC progression. Targeting CSF1R in combination with ALOX5 inhibitor effectively reduced tumor volume and M2 macrophage infiltration abundance., Conclusion: In ICC, LTB4, a metabolite secreted by ALOX5 of epithelial cells, binded to BLT1/BLT2 on TAM surface to activate PI3K pathway and promote TAM migration, thus promoting ICC progression. Targeting CSF1R in combination with ALOX5 inhibitor for ICC is a promising combination therapy modality., (© 2023. The Author(s).)

Background: Upper limb dysfunction after stroke seriously affects quality of life. Bilateral training has proven helpful in recovery of upper limb motor function in these patients. However, studies evaluating the effectiveness of bilateral upper limb robot-assisted training on improving motor function and quality of life in stroke patients are lacking. Quantitative electroencephalography (EEG) is non-invasive, simple, and monitors cerebral cortical activity, which can be used to evaluate the effectiveness of interventions. In this study, EEG was used to evaluate the effect of end-drive bilateral upper extremity robot-assisted training on upper extremity functional recovery in stroke patients., Methods: 24 stroke patients with hemiplegia were randomly divided into a conventional training (CT, n = 12) group or a bilateral upper limb robot-assisted training (BRT, n = 12) group. All patients received 60 min of routine rehabilitation treatment including rolling, transferring, sitting, standing, walking, etc., per day, 6 days a week, for three consecutive weeks. The BRT group added 30 min of bilateral upper limb robot-assisted training per day, while the CT group added 30 min of upper limb training (routine occupational therapy) per day, 6 days a week, for 3  weeks. The primary outcome index to evaluate upper limb motor function was the Fugl-Meyer functional score upper limb component (FMA-UE), with the secondary outcome of activities of daily living (ADL), assessed by the modified Barthel index (MBI) score. Quantitative EEG was used to evaluate functional brain connectivity as well as alpha and beta power current source densities of the brain., Results: Significant (p < 0.05) within-group differences were found in FMA-UE and MBI scores for both groups after treatment. A between-group comparison indicated the MBI score of the BRT group was significantly different from that of the CT group, whereas the FMA-UE score was not significantly different from that of the CT group after treatment. The differences of FMA-UE and MBI scores before and after treatment in the BRT group were significantly different as compared to the CT group. In addition, beta rhythm power spectrum energy was higher in the BRT group than in the CT group after treatment. Functional connectivity in the BRT group, under alpha and beta rhythms, was significantly increased in both the bilateral frontal and limbic lobes as compared to the CT group., Conclusions: BRT outperformed CT in improving ADL in stroke patients within three months, and BRT facilitates the recovery of upper limb function by enhancing functional connectivity of the bilateral cerebral hemispheres., (© 2023. The Author(s).)

Background: Pulmonary arterial hypertension (PAH) is a devastating chronic cardiopulmonary disease without an effective therapeutic approach. The underlying molecular mechanism of PAH remains largely unexplored at single-cell resolution., Methods: Single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database (GSE210248) was included and analyzed comprehensively. Additionally, microarray transcriptome data including 15 lung tissue from PAH patients and 11 normal samples (GSE113439) was also obtained. Seurat R package was applied to process scRNA-seq data. Uniform manifold approximation and projection (UMAP) was utilized for dimensionality reduction and cluster identification, and the SingleR package was performed for cell annotation. FindAllMarkers analysis and ClusterProfiler package were applied to identify differentially expressed genes (DEGs) for each cluster in GSE210248 and GSE113439, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) were used for functional enrichment analysis of DEGs. Microenvironment Cell Populations counter (MCP counter) was applied to evaluate the immune cell infiltration. STRING was used to construct a protein-protein interaction (PPI) network of DEGs, followed by hub genes selection through Cytoscape software and Veen Diagram., Results: Nineteen thousand five hundred seventy-six cells from 3 donors and 21,896 cells from 3 PAH patients remained for subsequent analysis after filtration. A total of 42 cell clusters were identified through UMAP and annotated by the SingleR package. 10 cell clusters with the top 10 cell amounts were selected for consequent analysis. Compared with the control group, the proportion of adipocytes and fibroblasts was significantly reduced, while CD8+ T cells and macrophages were notably increased in the PAH group. MCP counter revealed decreased distribution of CD8+ T cells, cytotoxic lymphocytes, and NK cells, as well as increased infiltration of monocytic lineage in PAH lung samples. Among 997 DEGs in GSE113439, module 1 with 68 critical genes was screened out through the MCODE plug-in in Cytoscape software. The top 20 DEGs in each cluster of GSE210248 were filtered out by the Cytohubba plug-in using the MCC method. Eventually, WDR43 and GNL2 were found significantly increased in PAH and identified as the hub genes after overlapping these DEGs from GSE210248 and GSE113439., Conclusion: WDR43 and GNL2 might provide novel insight into revealing the new molecular mechanisms and potential therapeutic targets for PAH., (© 2023. The Author(s).)

Background: The prevalence of bladder urothelial carcinoma (BLCA) is significant on a global scale. Anoikis is a type of procedural cell death that has an important role in tumor invasion and metastasis. The advent of single-cell RNA sequencing (scRNA-seq) approaches has revolutionized the genomics field by providing unprecedented opportunities for elucidating cellular heterogeneity. Understanding the mechanisms associated with anoikis in BLCA is essential to improve its survival rate., Methods: Data on BLCA and clinical information were acquired from the databases of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). ARGs were obtained from Genecards and Harmonizome databases. According to univariate Cox regression analysis, the least absolute shrinkage and selection operator (LASSO) algorithm was utilized to select the ARGs associated with the overall rate (OS). A multivariate Cox regression analysis was carried out to identify eight prognostic ARGs, leading to the establishment of a risk model. The OS rate of BLCA patients was evaluated using Kaplan-Meier survival analysis. To explore the molecular mechanism in low- and high-risk groups, we employed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSVA). Immune infiltration landscape estimation was performed using ESTIMATE, CIBERSOT, and single sample gene set enrichment analysis (ssGSEA) algorithms. Patients were categorized into different subgroups through consensus clustering analysis. We employed biological functional enrichment analysis and conducted immune infiltration analysis to examine the disparities in potential biological functions, infiltration of immune cells, immune activities, and responses to immunotherapy., Results: We identified 647 ARGs and 37 survival-related genes. We further developed a risk scoring model to quantitatively assess the predictive capacity of ARGs. The high-risk score group exhibited an unfavorable prognosis, whereas the low-risk score group demonstrated a converse effect. We also found that the two groups of patients might respond differently to immune targets and anti-tumor drugs., Conclusion: The nomogram with 8 ARGs may help guide treatment of BLCA. The systematic assessment of risk scores can help to design more individualized and precise treatment strategies for BLCA patients., (© 2023. The Author(s).)