Objective: To analyze the causes of abnormal blood agglutination caused by high-titer cold antibodies in blood donors from a serological perspective. Methods: The donor's blood type was identified using the tube method. Direct antiglobulin test (DAT), indirect antiglobulin test (IAT), and antibody titer detection were performed on the samples. Results: The blood type of the donor was type B, and the DAT was negative. No complement components were detected on the surface of the donor's red blood cells. The supernatant of the suspended red blood cells was clear without abnormal coloration, and the agglutinated clumps were intact and difficult to dissociate. The antibody was identified as an IgM-type anti-IH cold agglutinin. At 4℃, this antibody reacted with autologous red blood cells, adult group B red blood cells, adult group O red blood cells, cord blood group B red blood cells and cord blood group O red blood cells, with a stronger reaction intensity observed with group O cells than with B cells. The titers were 512, 128, 256, 32 and 128, respectively. Conclusion: High-titer anti-IH can cause abnormal agglutination of blood at low temperatures. During blood distribution and clinical use, the appearance of blood products shall be strictly inspected to prevent the release of non-conforming blood products.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Pharmacological inhibitors targeting CDK4/6 have demonstrated promising efficacy across various cancer types. However, their clinical benefits in ovarian cancer patients fall short of expectations, with only a subset of patients experiencing these advantageous effects. This study aims to provide further clinical and biological evidence for antineoplastic effects of a CDK4/6 inhibitor (TQB4616) in ovarian cancer and explore underlying mechanisms involved. Patient-derived ovarian cancer organoid models were established to evaluate the effectiveness of TQB3616. Potential key genes related to TQB3616 sensitivity were identified through RNA-seq analysis, and TRIM4 was selected as a candidate gene for further investigation. Subsequently, co-immunoprecipitation and GST pull-down assays confirmed that TRIM4 binds to hnRNPDL and promotes its ubiquitination through RING and B-box domains. RIP assay demonstrated that hnRNPDL binded to CDKN2C isoform 2 and suppressed its expression by alternative splicing. Finally, in vivo studies confirmed that the addition of siTRIM4 significantly improved the effectiveness of TQB3616. Overall, our findings suggest that TRIM4 modulates ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitors in ovarian cancer treatment. TRIM4 may serve as a valuable biomarker for predicting sensitivity to CDK4/6 inhibitors in ovarian cancer.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Animals ; Tripartite Motif Proteins/genetics* ; Mice ; Cyclin-Dependent Kinase 4/antagonists & inhibitors* ; Cell Line, Tumor ; Cyclin-Dependent Kinase 6/antagonists & inhibitors* ; Protein Kinase Inhibitors/pharmacology* ; Ubiquitin/metabolism* ; Xenograft Model Antitumor Assays ; Ubiquitination ; Antineoplastic Agents/pharmacology*

Objective To analyze changes in sleep,mood state,and brain function in healthy populations living in near-sea-level environments before and after exposure to high-altitude environment,and to explore the correlations between regional brain functional changes and variations in sleep and mood states.Methods A total of 45 healthy volunteers were enrolled.The participants came from regions of near-sea-level altitudes and were exposed to the high-altitude environment for a short period of time.The Pittsburgh Sleep Quality Index(PSQI),Zung Self-Rating Depression Scale(SDS),Patient Health Questionnaire-9(PHQ-9),Zung Self-Rating Anxiety Scale(SAS),and Generalized Anxiety Disorder-7(GAD-7)were administered to assess sleep quality as well as depressive and anxiety symptoms at 4 time points—prior to high-altitude exposure,immediately after exposure,one month after returning to low-altitude regions,and three months after returning to low-altitude regions.Resting-state functional magnetic resonance imaging(rs-fMRI)data were collected before and after high-altitude exposure,and regional brain functional parameters,including the amplitude of low-frequency fluctuations(ALFF)and functional connectivity strength,were analyzed.Statistical analyses were performed,including a linear mixed-effects model to evaluate longitudinal changes in scale scores,paired-sample t-tests to compare brain function differences before and after exposure,and Pearson correlation analyses to examine the relationship between brain functional changes and alterations in sleep and mood states.Results Compared with the pre-exposure findings,the participants exhibited significantly increased PSQI scores(8.89±4.41 vs.5.08±2.69,P<0.05)and PHQ-9 scores(3.60±4.19 vs.1.54±2.30,P<0.05)immediately after high-altitude exposure.One month after returning to the low-altitude environment,both sleep and depression scores decreased relative to the findings immediately after exposure(PSQI:3.88±2.13 vs.8.89±4.41,P<0.05;PHQ-9:1.50±2.25 vs.3.60±4.19,P<0.05)and showed no statistically significant difference compared with the pre-exposure findings(P>0.05).Three months after returning to near-sea-level environment,sleep,depression,and anxiety scores were all reduced compared with the findings immediately after exposure(PSQI:3.76±2.31 vs.8.89±4.41,P<0.05;PHQ-9:1.24±2.13 vs.3.60±4.19,P<0.05;SAS:23.84±5.93 vs.27.93±7.05,P<0.05),also showing no significant difference compared with the pre-exposure levels(P>0.05).Brain function analysis revealed that,relative to the pre-exposure levels,ALFF in the bilateral superior temporal gyrus,insula,and dorsolateral prefrontal cortex(DLPFC)increased after high-altitude exposure(P<0.05),and that functional connectivity strength in the DLPFC was also elevated(P<0.05).Furthermore,changes in DLPFC functional connectivity strength were positively correlated with changes in sleep and mood scores(P<0.05).Conclusion High-altitude exposure has a significant impact on the sleep,mood states,and brain function of populations from near-sea-level regions,and DLPFC,in particular,is closely associated with changes in sleep and mood states.The findings of this study provide a theoretical basis for health management and intervention strategies in high-altitude environments.

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

Recurrent spontaneous abortion （RSA） is a common gynecological disease during pregnancy， clinically characterized by repeated spontaneous abortions， yet its pathological mechanism remains incompletely understood. Traditional Chinese medicine attributes the pathogenesis of RSA to the deficiency of Chong Ren and the lack of fetal solidity. It has amassed experience in treating RSA， with Shoutaiwan being widely utilized for addressing miscarriage symptoms such as habitual abortion due to kidney deficiency， bleeding during pregnancy， and fetal movement. In recent years， there has been a gradual increase in experimental studies on the application of Shoutaiwan in treating RSA and on related experiments. These studies have demonstrated that Shoutaiwan preserves the fetus mainly by modulating hormone balance， alleviating immune inflammation， and enhancing blood coagulation equilibrium during pregnancy. Besides， through the modulation of key signaling pathways such as nuclear factor， erythroid 2 like 2 （Nrf2）/heme oxygenase-1 （HO-1） and Janus kinase 1 （JAK1）/signal transducer and activator of transcription （STAT）， as well as mitogen-activated protein kinase （MAPK）， Shoutaiwan has improved cellular antioxidant capacity， adjusted the phenotype of trophoblast and metaphase cells， and inhibited immune rejection， thus improving the pregnancy success rate. These findings not only elucidate the diverse biological foundations underlying Shoutaiwan's efficacy in treating RSA but also offer a scientific rationale for its clinical application and further mechanism research. Nonetheless， there remains a dearth of systematic reviews on RSA treatment with Shoutaiwan. Therefore， this review summarizes and synthesizes existing research findings to systematically analyze existing literature and studies， delving deeply into the principal pharmacological effects and associated signaling pathways of Shoutaiwan in regulating RSA. It aims to establish crucial reference points for its clinical application in RSA treatment and future experiments and research.

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.