Objective To evaluate the value of serum Mac-2 binding protein (M2BP) for assessment of the severity of schisto somiasis-induced liver fibrosis, so as to provide insights into non-invasive diagnosis and disease surveillance of liver fibrosis caused by schistosomiasis. Methods A total of 234 individuals with a history of Schistosoma japonicum infection were sampled from Xinhua Village, Lushan City, Jiangxi Province from 2019 to 2020, and 234 serum samples were collected from all participants. All participants received B-ultrasound examinations of the liver. Serum samples were categorized into four groups (grades 0, Ⅰ, Ⅱ and Ⅲ schistosomiasis-induced liver fibrosis groups) according to B-ultrasound examination results, and then, each group was randomly divided into a receiver operating characteristic (ROC) curve group and an efficacy assessment group at a ratio of 7∶3. Serum M2BP concentration was measured in four groups using the enzyme-linked immunosorbent assay (ELISA), and differences in serum M2BP concentrations were compared with analysis of variance and Spearman correlation analysis. Serum M2BP concentration was subjected to ROC curve analysis among individuals with different grades of schistosomiasis-induced liver fibrosis in the ROC curve group to determine the optimal diagnostic threshold of M2BP concentration at different fibrosis grades, and the area under the ROC curve (AUC) was calculated to evaluate the diagnostic performance. The diagnostic accuracy was verified by comparing the accordance rate and Kappa consistency test in the efficacy assessment group. Results Among 234 serum samples, there were 79 samples with grade 0 schistosomiasis-induced liver fibrosis, 87 samples with Grade Ⅰ, 46 samples with Grade Ⅱ and 22 samples with Grade Ⅲ according to the B-ultrasound examinations. The mean serum M2BP concentrations were (0.40 ± 0.31) [95% confidence interval (CI): (0.33, 0.47)], (0.64 ± 0.48) [95% CI: (0.53, 0.74)], (1.76 ± 0.58) [95% CI: (1.59, 1.93)] μg/mL and (2.56 ± 0.93) [95% CI: (2.14, 2.97)] μg/mL in the four groups, respectively (F = 150.796, P < 0.001), and the severity of schistosomiasis-induced liver fibrosis significantly positively correlated with serum M2BP concentration (rs = 0.715, P < 0. 001). The sample sizes of grades 0, Ⅰ, Ⅱ and Ⅲ schistosomiasis-induced liver fibrosis sera were randomly allocated as follows: 55 versus 24, 61 versus 26, 32 versus 14, and 15 versus 7 in the ROC curve and efficacy assessment groups, respectively, and the serum M2BP concentrations were (0.39 ± 0.29) μg/mL and (0.42 ± 0.36) μg/mL (F = 0.196, P > 0.05), (0.59 ± 0.47) μg/mL and (0.75 ± 0.51) μg/mL (F = 1.967, P > 0.05), (1.73 ± 0.59) μg/mL and (1.85 ± 0.57) μg/mL (F = 0.417, P > 0.05), and (2.46 ± 0.64) μg/mL and (2.76 ± 1.41) μg/mL (F = 0.491, P > 0.05), respectively. ROC curve analysis showed that the optimal diagnostic thresholds of serum M2BP concentration were 0.347 86 μg/mL (AUC = 0.635, P < 0.05), 1.188 83 μg/mL (AUC = 0.938, P < 0.000 1) and 2.021 21 μg/mL (AUC = 0.821, P < 0.000 1) for grade Ⅰ, Ⅱ and Ⅲ schistosomiasis-induced liver fibrosis. In addition, the accordance rates between the optimal diagnostic threshold of serum M2BP and B-ultrasound examinations for predicting grade Ⅰ, Ⅱ and Ⅲ schistosomiasis-induceed liver fibrosis were 69.23%, 85.71% and 71.43% (χ2 = 1.340, P > 0.05), and the overall Kappa consistency test showed moderate consistency [Kappa = 0.608, 95% CI: (0.428, 0.788); Z = 6.609, P < 0.000 1]. Conclusions Serum M2BP may serve as a potential biomarker for assessing moderate to advanced schistosomiasis-induced liver fibrosis; however, its diagnostic value for early-stage schistosomiasis-induced liver fibrosis remains limited.

Objective: To explore the relationship between parenting styles and depressive symptoms in adolescents with nightmare disorder, so as to provide a scientific basis for formulating effective family intervention measures and psychological counseling. Methods: From January 2023 to August 2024, 90 adolescents diagnosed with nightmare disorder and admitted to Hangzhou Seventh Peoples Hospital, along with 176 healthy controls from the urban areas of Hangzhou, were recruited as participants in the study. All participants were assessed using the Nightmare Experience Questionnaire (NEQ), Family Relationship Questionnaire (FRQ), and Plutchik-van Praag Selfreport Depression Scale (PVP). The ttest and Chisquare test were conducted to compare two groups. Pearson correlation and stepwise multiple linear regression were employed to explore the correlations between PVP and NEQ or FRQ. The Process model was used to testing the mediating effects among NEQ/FRQ/PVP. Results: The nightmare disorder group had higher scores in nightmare frequency, the four factors of NEQ (physical effect, negative emotion, meaning interpretation, horrible stimulation), and PVP than the healthy control group (24.86±18.89, 10.12±3.67, 19.01±3.51, 17.02±3.31, 15.14±3.26, 14.02±4.38; 2.34±1.04, 6.49±2.18, 17.63±4.76, 13.91±4.24, 12.40±4.49, 9.39±3.28)(t=15.79, 10.11, 2.43, 6.09, 5.14, 27.46, P<0.05). The nightmare disorder group reported significantly lower scores in FRQ general attachment and maternal encouragement than the healthy control group (7.22±2.81, 16.39±3.28) (t=-5.53, -4.95). In contrast, they exhibited significantly higher scores in maternal abuse, maternal dominance, paternal freedom release, and paternal dominance than the healthy control group (8.23±1.80, 13.11±3.73, 18.36±3.37, 12.04±3.29; 6.07±1.85, 8.48±3.80, 15.15±2.51, 9.47±3.03) (t=6.70, 8.96, 5.90, 7.04, P<0.01). The results of Pearson correlation analysis showed that, in the nightmare disorder group, the PVP score was positively correlated with negative emotion, nightmare frequency, maternal abuse, and maternal dominance score (r=0.14, 0.63, 0.26, 0.51, P<0.05). The results of multiple linear regression analysis showed that when using FRQ score to predict NEQ score, the adjusted R2 in the nightmare disorder group was 0.01-0.59. Mother abuse could prediced physical effect (β=0.33); maternal dominance significantly predicted negative emotion, horrible stimulation, and nightmare frequency (β=0.29, 0.30, 0.79); paternal freedom release could predict negative emotion (β=0.26), paternal dominance predicted both negative emotion and nightmare frequency (β=0.22, 0.45) (P<0.05). Mediation analysis further revealed that, in the nightmare disorder group, PVP scores served as a mediating variable between FRQ and NEQ. Conclusion Abusive, controlling, and neglectful family upbringing styles as well as depression maybe are key factors that may contribute to the development of nightmare disorder among adolescents.

Rice (Oryza sativa L.), as a thermophilic crop, is highly susceptible to cold stress during its growth process. Chilling injury at the plumule stage and seedling stage often affects the morphological development and leads to yield reduction of rice. The exploration and utilization of cold tolerance genes are among the most direct and effective approaches to address cold stress in rice. To identify quantitative trait loci (QTLs) associated with cold tolerance at plumule and seedling stages, in this study, we measured the seedling rates and survived seedling rates of the indica rice cultivar 'HZ', the japonica cultivar 'Nekken2', and their 120 recombinant inbred lines (RILs) under cold stress. A previously constructed high-density genetic linkage map was used for the mapping of the QTLs conferring cold tolerance at the plumule and seedling stages. A total of 4 QTLs for plumule-stage cold tolerance and 9 QTLs for seedling-stage cold tolerance were detected, with the maximum limit of detection reaching 5.20. Notably, a genetically overlapping QTL for both plumule and seedling stages was identified on chromosome 8, spanning a physical interval of 24 432 953-25 295 129 bp. Candidate genes within the detected QTL intervals were screened, and quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to analyze the gene expression during the plumule and seedling stages. The results revealed that LOC_Os03g06570, LOC_Os03g07100, LOC_Os06g08280, LOC_Os08g38440, LOC_Os08g39100, and LOC_Os08g39540 exhibited significantly differential expression between the parental lines. These genes were either significantly downregulated or upregulated under cold stress. Among them, the first three gene (LOC_Os03g06570, LOC_Os03g07100, and LOC_Os06g08280) were hypothesized to be key candidates regulating the cold tolerance of rice seedlings, while the latter three genes (LOC_Os08g38440, LOC_Os08g39100, and LOC_Os08g39540) were identified as comprehensive regulators of cold tolerance during both plumule and seedling stages. These findings lay a foundation for the fine mapping and cloning of cold tolerance genes at the plumule and seedling stages, providing valuable insights for breeding cold-tolerant rice varieties.
Quantitative Trait Loci/genetics* ; Oryza/growth & development* ; Seedlings/growth & development* ; Cold Temperature ; Chromosome Mapping ; Gene Expression Regulation, Plant

Objective To evaluate the recognition capability of AI-enabled Cellsee CS-BM1 automatic cell morphology analyzer for pe-ripheral blood smears and its roles in assisting manual classification,and explore the application value of AI system in the diagnosis network of tiered primary medical units.Methods The blood samples which triggered the re-examination rules were collected from six primary medical units,including the Laboratory Department of Shanghai Jiahui International Hospital,and so on,from March to No-vember 2023.The smears of peripheral blood were prepared and AI analyzer was used for pre-classification to evaluate its recognition performance in identifying the samples with abnormal WBC and RBC.The sensitivity,specificity,and accuracy of WBC classification by six junior and intermediate technicians,both with and without AI assistance,were analyzed.Additionally,the roles of the AI system in tiered diagnosis of primary medical units were also evaluated.Results The sensitivity,specificity,and accuracy of AI system in recognizing malignant primitive cells were 92.86％,95.16％,and 95.10％,respectively.The sensitivities of AI system in recognizing immature granulocytes,reactive lymphocytes,and nucleated RBCs were all greater than 90％.The sensitivity of AI system in identif-ying abnormal morphology of RBCs reached 99.59％,along with rapid quantitative analysis for various anomalous types of RBCs.In AI-assisted mode,the sensitivity of recognition for all cell types was improved to varying degrees by junior and intermediate technicians,and the sensitivity for recognizing malignant primitive cells,reactive lymphocytes,and immature granulocytes increased to 58.24％,53.39％,and 62.37％for junior technicians,and to 92.06％,83.24％,and 83.12％for intermediate technicians,respectively.The improvements for junior technicians were particularly significant,with increases of 12.46％,10.61％,and 3.71％for each cell type,respectively.Both groups achieved higher specificity and accuracy.Through AI pre-classification and manual review,a variety of pe-ripheral blood cell-related diseases were accurately diagnosed in the tiered healthcare practice of primary medical units,including 339 cases(11.13％)of red blood cell diseases,5 cases(0.16％)of platelet diseases,2 343 cases(76.90％)of infection-related disea-ses,and 28 cases(0.92％)of malignant hematological diseases.In addition,332 cases(10.90％)which lacked an obvious related cause or required further examinations were identified as well.Conclusion AI pre-classification has demonstrated strong cell recogni-tion capabilities and may assist technicians in improving the sensitivity,specificity,and accuracy of blood cell classification.AI could en-hance the disease-screening capabilities in the tiered diagnosis network of primary medical units,presenting a broad application prospect.

Objective To investigate the effects of asperuloside(ASP)on airway inflammation and the interleukin-6/Janus kinase 2/signal transducer and activator of transcription 3(IL-6/JAK2/STAT3)signaling pathway in juvenile rats with bronchial asthma.Methods A juvenile rat model of bronchial asthma was constructed and randomly separated into a Model group,low,medium,and high dose asperuloside groups(ASP-L,ASP-M,ASP-H groups),and high-dose asperuloside+pathway activator group(ASP-H+CA1 group),with 12 rats in each group.An additional 12 healthy rats were included as Control group.All rats were evaluated for lung function.The number of inflammatory cells in bronchoalveolar lavage fluid(BALF),and the levels of inflammatory factors in BALF and serum were detected.HE staining was applied to observe the pathological morphology of lung tissue.Western blot was applied to detect the expression of proteins related to the IL-6/JAK2/STAT3 signaling pathway.Results Compared with Control group,the lung tissue of rats in the Model group showed severe damage and higher levels of inflammatory cell infiltration,the PEF,Cdyn,and FEV/FVC indexes were greatly decreased,the numbers of inflammatory cells(WBC,EOS,NEU,LYM),levels of inflammatory factors(IL-1β,TNF-α,and IL-6)in BALF and serum,and the expression levels of signaling pathway proteins(IL-6,p-JAK2/JAK2,p-STAT3/STAT3)were obviously increased(P＜0.05).Compared with the Model group,with the increase of ASP dosage,the degree of lung tissue damage and inflammatory cell infiltration of rats in the ASP-L,ASP-M,and ASP-H groups were significantly reduced,the PEF,Cdyn,and FEV/FVC indexes were gradually increased,the numbers of inflammatory cells(WBC,EOS,NEU,LYM),levels of inflammatory factors(IL-1β,TNF-α,and IL-6)in BALF and serum,and the expression levels of signaling pathway proteins(IL-6,p-JAK2/JAK2,p-STAT3/STAT3)were gradually decreased(P＜0.05).Compared with the ASP-H group,the lung tissue of rats in the ASP-H+CA1 group showed severe damage,the infiltration of inflammatory cells increased,the PEF,Cdyn,and FEV/FVC indexes were decreased,the numbers of inflammatory cells(WBC,EOS,NEU,LYM),levels of inflammatory factors(IL-1β,TNF-α,and IL-6)in BALF and serum,and the expression levels of signaling pathway proteins(IL-6,p-JAK2/JAK2,p-STAT3/STAT3)were greatly increased(P＜0.05).Conclusion Asperuloside can improve lung tissue damage,reduce inflammation levels,and improve lung ventilation function in rats with bronchial asthma.Its effect may be related to the regulation of the IL-6/JAK2/STAT3 signaling pathway.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

BACKGROUND:With the continuous improvement of artificial biological materials and surgical techniques,total knee arthroplasty has become the preferred way to improve the quality of life of patients with knee osteoarthritis. However,patients with knee osteoarthritis have severe pain after knee arthroplasty,and there is no good treatment at present. Electroacupuncture therapy is a low-cost option for pain relief and has wide application prospects in combination with preemptive analgesia.OBJECTIVE:To investigate the effect of opposing needling acupuncture with preemptive analgesia on postoperative analgesia after initial unilateral total knee arthroplasty in patients with knee osteoarthritis.METHODS:Using a randomized controlled design,120 participants were selected from Shanghai Guanghua Hospital of Integrative Medicine. All of them received the initial unilateral total knee arthroplasty. The patients were divided into three groups by using the statistical software SPSS 25:pre-electroacupuncture group,post-electroacupuncture group,and sham group,with 40 patients in each group. In pre-electroacupuncture group,opposing needling acupuncture was performed 1 day before operation,30 minutes before anesthesia induction,and 1-3 days after operation. In post-electroacupuncture group,opposing needling acupuncture was performed with the same acupoints and parameters 1-3 days after operation,thus the sham electroacupuncture was performed 1 day before operation and 30 minutes before anesthesia induction. The sham group was treated with the same acupuncture point parameters with five times of sham electroacupuncture. The improvement of numerical rating scale after operation,the consumption of remifentanil and propofol used during operation,the time when patient first used the patient-controlled analgesia,the number of postoperative nausea and vomiting,the increase rate of thigh circumference,and the success rate of blind method were compared among the three groups.RESULTS AND CONCLUSION:(1) Compared with the pre-electroacupuncture group,the improvement of numerical rating scale at rest between post-electroacupuncture group and sham group on day 4 after operation was significantly reduced;the improvement of numerical rating scale at rest in sham group on day 7 after operation was significantly reduced (P<0.05). (2) Compared with the pre-electroacupuncture group,the improvement of numerical rating scale score between post-electroacupuncture group and sham group on day 4 after operation was significantly reduced (P<0.05),and the improvement of numerical rating scale with movement on day 7 after operation was not significant among the three groups (P>0.05). (3) Compared with the pre-electroacupuncture group,the remifentanil consumption was significantly increased in post-electroacupuncture group and sham group (P<0.05). (4) Compared with the pre-electroacupuncture group,the first time used the patient-controlled analgesia pump was significantly shortened in post-electroacupuncture group and sham group (P<0.05). (5) Compared with the pre-electroacupuncture group,the number of postoperative nausea was increased in post-electroacupuncture group and sham group (P<0.05). (6) Compared with the pre-electroacupuncture group,the increase rate of thigh circumference in post-electroacupuncture group and sham group was significantly increased on day 3 and day 7 after operation (P<0.05). Compared with the post-electroacupuncture group,the increase rate of thigh circumference in sham group was significantly increased on day 3 and day 7 after operation (P<0.05). (7) There was no significant difference in the success rate of blind method among the three groups (P>0.05). (8) The artificial knee prosthesis has good biocompatibility. To conclude,opposing needling acupuncture with preemptive analgesia can relieve acute pain after total knee arthroplasty,reduce the consumption of intraoperative anesthesia,prolong the time of postoperative analgesia,alleviate postoperative adverse reactions,and reduce the increase rate of thigh circumference.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.

Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) can enhance the anti-tumor activity of the anti-programmed cell death-1 (anti-PD-1) antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not performed, and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared with VEGFRi alone, the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and a similar adverse event incidence. Through single-cell and spatial transcriptomic analysis, we determined ten MSS CRC-enriched immune cell types and their spatial distribution, including naive CD4⁺ T, regulatory CD4⁺ T, CD4⁺ Th17, exhausted CD8⁺ T, cytotoxic CD8⁺ T, proliferated CD8⁺ T, natural killer (NK) cells, plasma, and classical and intermediate monocytes. Based on a systemic meta-analysis and ten machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
Humans ; Colorectal Neoplasms/drug therapy* ; Male ; Female ; Immunotherapy ; Middle Aged ; Aged ; Tumor Microenvironment/immunology* ; Retrospective Studies ; Microsatellite Instability ; Transcriptome ; Single-Cell Analysis ; Programmed Cell Death 1 Receptor/immunology* ; Gene Expression Profiling ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.