Renal lymphatic vessel density is clinically relevant in kidney disease but is still assessed by slow, subjective visual estimation. We evaluated a weakly supervised, attention-based multiple-instance learning framework for automated detection and quantification of renal lymphatic vessel density on D2-40-stained whole-slide images (WSIs). Methods: Two independent internal datasets from Tongji Hospital were collected, including 198 cases of chronic kidney disease (CKD) and 50 cases of hypertensive nephropathy (HTN). All biopsies were immunohistochemically stained for D2-40 and digitized as WSIs. Pathologists provided only slide-level labels (D2-40 high vs. D2-40 low). Tissue regions were automatically segmented, tiled into patches, and encoded using a pretrained convolutional neural network. Patch embeddings were then analyzed with a clustering-constrained attention multiple-instance learning (CLAM) model. Unlike conventional multiple-instance learning (MIL) methods that only weight instances, CLAM jointly performs attention-based instance selection and instance-level clustering to distinguish positive from negative evidence within each slide, yielding more discriminative slide-level features and interpretable attention maps. Performance was compared with a classic MIL model trained on the same features. Results: CLAM achieved area under the receiver operating characteristic curves of 0.942 and 0.858 on the CKD and HTN datasets, respectively, outperforming classic MIL (0.866 and 0.801). Attention maps highlighted lymphatic-rich regions consistent with renal pathologists’ assessments. Conclusions: This clustering-constrained, attention-based weakly supervised framework enables fully automated, reproducible quantification of renal lymphatic vessel density from WSIs, providing renal pathologists with rapid visual and numerical support for diagnosis and risk stratification in CKD and HTN.

BackgroundThe prevalence， disability rate and mortality rate of cerebral small vessel disease （CSVD） are relatively high among the elderly population， imposing a heavy burden on families and society. Among the various clinical manifestations of CSVD， cognitive impairment is the most common， and it is also the most closely related neuro-psychiatric syndrome to clinical practice in psychiatry. Previous studies on CSVD-related cognitive impairment （CSVD-CI） have mostly focused on the field of imaging， while studies on non-invasive electrophysiological and cerebral hemodynamic assessments are relatively scarce. ObjectiveTo analyze the characteristics of event-related potential （ERP） and functional near-infrared spectroscopy （fNIRS） in patients with CSVD-CI， and to explore their correlations with the severity of white matter lesions， in order to provide references for the objective assessment and early identification of CSVD-CI. MethodsA total of 40 patients with CSVD who met the diagnostic criteria of the Chinese Guideline for Diagnosis and Treatment of Cerebral Small Vessel Disease （2020） and had cognitive impairment， as well as were admitted to the Affiliated Hospital of North Sichuan Medical College from December 2024 to December 2025， were enrolled as the case group. Meanwhile， 40 healthy volunteers matched for gender， age and education level were recruited as the control group. Both groups underwent assessment using the Mini-Mental State Examination （MMSE）， ERP-P300 detection， and fNIRS examination. The ERP-P300 indicators， functional connectivity strength of the whole brain and cognitive-related regions of interest （ROI） in fNIRS of the two groups were compared. The severity of the patients' white matter lesions was classified as follows： the Fazekas grade I group （mild white matter lesions） and the Fazekas grades II to III group （moderate to severe white matter lesions）. Spearman correlation analysis was employed to investigate the correlation between the Fazekas grading of brain white matter lesions and the latency of ERP-P300， as well as the strength of functional connectivity measured by fNIRS. ResultsThe MMSE score of the CSVD-CI group was lower than that of the control group （Z=-6.250， P<0.01）， and ERP-P300 lantency was significantly longer than that of the control group （t=12.291， P<0.01）. The MMSE score of the sub-group with Fazekas grade I was higher than that of the sub-groups with grades II to III （Z=-2.420， P<0.05）， and showed a shorter P300 latency than that of the sub-groups with grades II to III （Z=-4.210， P<0.01）. All the differences were statistically significant. The resting-state whole-brain functional connectivity strength in the CSVD-CI group was lower than that in the control group， and the difference was statistically significant （t=10.243， P<0.05）. Compared with the control group， the differences in the functional connectivity strength within the left premotor cortex （PMC）， right PMC， left frontopolar cortex （FPC）， right FPC， left dorsolateral prefrontal cortex （DLPFC）， right DLPFC， left orbitofrontal cortex （OFC）， and right OFC regions in the CSVD-CI group were all statistically significant （P_{FDR correction}<0.01）. The differences in the functional connectivity strength between multiple prefrontal-related brain regions between the CSVD-CI group and the control group were all statistically significant （P_{FDR correction}<0.01）. The severity of white matter lesions in CSVD-CI patients was positively correlated with the P300 latency （r_s=0.891， P<0.05）， and negatively correlated with the fNIRS functional connectivity strength （r_s=-0.359， P<0.05）. ConclusionPatients with CSVD-CI exhibit prolonged P300 latency， as well as decreased functional connectivity strength in multiple brain regions including the whole brain and the prefrontal lobe during the resting state. Moreover， these indicators are correlated with the severity of white matter lesions.

Objective:To investigate the expression levels and clinical significance of miR-627 and miR-448 in colorectal cancer tissues.Methods:Ninety-eight patients with colorectal cancer admitted to Xi’an Jiaotong University Affiliated Red Cross Hospital from Apr. 2019 to Apr. 2021 were gathered. Colorectal cancer tissue and adjacent tissues were collected during surgery, and the expression levels of miR-627 and miR-448 were detected by qRT-PCR. According to postoperative follow-up, patients were separated into a good prognosis group and a poor prognosis group. Kaplan-Meier survival curve was applied to analyze the relationship between miR-627, miR-448 and the prognosis of colorectal cancer patients. ROC curve was plotted to analyze the predictive value of miR-627 and miR-448 for poor prognosis in colorectal cancer. The prognostic factors of colorectal cancer patients were analyzed using COX regression.Results:There was a difference in the expression levels of miR-627 and miR-448 between colorectal cancer tissue and adjacent tissues ( P<0.05). The expression of miR-627 and miR-448 in colorectal cancer tissue was related to clinical features (TNM stage, differentiation degree, lymph node metastasis, and depth of infiltration) ( P<0.05). The survival rate of patients with high expression of miR-627 was higher than that of patients with low expression ( χ2=10.050, P<0.05); the survival rate of patients with high expression of miR-448 was higher than that of patients with low expression ( χ2=9.033, P<0.05). The expression levels of miR-627 and miR-448 in the poor prognosis group were greatly lower than those in the good prognosis group ( P<0.05). According to the ROC curve, the AUC of miR-627 in predicting poor prognosis of colorectal cancer was 0.811, the AUC of miR-448 in predicting poor prognosis of colorectal cancer was 0.772, and the AUC of combination of the two in predicting poor prognosis of colorectal cancer was 0.859. The combination of the two was better than their individual predictions (Z combination vs. miR-627=2.538, Z combination vs. miR-448=2.572, P<0.05). Multivariate COX regression found that miR-627, miR-448, and clinical features (TNM stage, degree of differentiation, lymph node metastasis, and depth of infiltration) were risk factors affecting the prognosis of colorectal cancer patients ( P<0.05) . Conclusion:The expression levels of miR-627 and miR-448 in colorectal cancer tissues were greatly reduced. The combination of the two is related to the clinical characteristics and prognosis of patients, and can greatly improve the predictive value for prognosis of colorectal cancer patients.

Pruritus is one of the serious side effects in patients receiving opioid analgesia in clinic.A lot of studies have eluci-dated the analgesic mechanisms of opioids,but the mechanism of opioid-induced pruritus is still unclear,and the relationship between pruritus and analgesia is ambiguous.In the recent stud-ies,after activation of μ,κ and δ opioid receptors,opioids transmit itch information by interacting with the gastrin-releasing peptide receptor(GRPR)directly or indirectly.Neuropeptides such as neuromedin B(NMB),neuropeptide Y(NPY),B-type natriuretic peptide(BNP)and other receptors transient receptor potential vanilloids 1 receptor(TRPV1R),N-methyl-D-aspar-tate receptor(NMDAR)and 5-hydroxytryptamine(5-HT)re-ceptor also play important roles in morphine-induced itching.In addition,the prevention and treatment of opioid-induced pruritus are still one of the difficulties and hot spots of perioperative mor-phine analgesia.Therefore,it is important to clarify the specific occurrence mechanism of pruritus to find new research ideas for the prevention and treatment of opioid-induced pruritus.

Objective:To investigate the expression levels and clinical significance of miR-627 and miR-448 in colorectal cancer tissues.Methods:Ninety-eight patients with colorectal cancer admitted to Xi’an Jiaotong University Affiliated Red Cross Hospital from Apr. 2019 to Apr. 2021 were gathered. Colorectal cancer tissue and adjacent tissues were collected during surgery, and the expression levels of miR-627 and miR-448 were detected by qRT-PCR. According to postoperative follow-up, patients were separated into a good prognosis group and a poor prognosis group. Kaplan-Meier survival curve was applied to analyze the relationship between miR-627, miR-448 and the prognosis of colorectal cancer patients. ROC curve was plotted to analyze the predictive value of miR-627 and miR-448 for poor prognosis in colorectal cancer. The prognostic factors of colorectal cancer patients were analyzed using COX regression.Results:There was a difference in the expression levels of miR-627 and miR-448 between colorectal cancer tissue and adjacent tissues ( P<0.05). The expression of miR-627 and miR-448 in colorectal cancer tissue was related to clinical features (TNM stage, differentiation degree, lymph node metastasis, and depth of infiltration) ( P<0.05). The survival rate of patients with high expression of miR-627 was higher than that of patients with low expression ( χ2=10.050, P<0.05); the survival rate of patients with high expression of miR-448 was higher than that of patients with low expression ( χ2=9.033, P<0.05). The expression levels of miR-627 and miR-448 in the poor prognosis group were greatly lower than those in the good prognosis group ( P<0.05). According to the ROC curve, the AUC of miR-627 in predicting poor prognosis of colorectal cancer was 0.811, the AUC of miR-448 in predicting poor prognosis of colorectal cancer was 0.772, and the AUC of combination of the two in predicting poor prognosis of colorectal cancer was 0.859. The combination of the two was better than their individual predictions (Z combination vs. miR-627=2.538, Z combination vs. miR-448=2.572, P<0.05). Multivariate COX regression found that miR-627, miR-448, and clinical features (TNM stage, degree of differentiation, lymph node metastasis, and depth of infiltration) were risk factors affecting the prognosis of colorectal cancer patients ( P<0.05) . Conclusion:The expression levels of miR-627 and miR-448 in colorectal cancer tissues were greatly reduced. The combination of the two is related to the clinical characteristics and prognosis of patients, and can greatly improve the predictive value for prognosis of colorectal cancer patients.

INTRODUCTION: Obstructive sleep apnoea (OSA) is common in Singapore, with moderate to severe OSA affecting around 30% of residents. These consensus statements aim to provide scientifically grounded recommendations for the management of OSA, standar-dise the management of OSA in Singapore and promote multidisciplinary collaboration. METHOD: An expert panel, which was convened in 2024, identified several areas of OSA management that require guidance. The expert panel reviewed the current literature and developed consensus statements, which were later independently voted on using a 3-point Likert scale (agree, neutral or disagree). Consensus (total ratings of agree and neutral) was set a priori at ≥80% agreement. Any statement not reaching consensus was excluded. RESULTS: The final consensus included 49 statements that provide guidance on the screening, diagnosis and management of adults with OSA. Additionally, 23 statements on the screening, diagnosis and management of paediatric OSA achieved consensus. These 72 consensus statements considered not only the latest clinical evidence but also the benefits and harms, resource implications, feasibility, acceptability and equity impact of the recommendations. CONCLUSION The statements presented in this paper aim to guide clinicians based on the most updated evidence and collective expert opinion from sleep specialists in Singapore. These recommendations should augment clinical judgement rather than replace it. Management decisions should be individualised, taking into account the patient's clinical characteristics, as well as patient and caregiver concerns and preferences.
Humans ; Sleep Apnea, Obstructive/diagnosis* ; Singapore ; Consensus ; Adult

Objective:To investigate the protective effect of achyranthes bidentata(AB)on sperm quality in mice with sper-matogenic disorder through the glycolytic metabolic pathway and its action mechanism.Methods:We equally randomized 40 Kun-ming mice into a normal control,a model control,a low-dose AB(3.5 g/kg)and a high-dose AB group(7.0 g/kg),and established the model of spermatogenic disorder in the latter three groups of mice by intraperitoneal injection of doxorubicin(30 mg/kg).Two days after modeling,we collected the testis and kidney tissues and blood samples from the mice for observation of the pathological changes in the testis tissue by HE staining,detection of perm motility with the sperm quality analyzer,examination of the apoptosis of testis cells by flow cytometry,measurement of the levels of testosterone(T),malondialdehyde(MDA),superoxide dismutase(SOD)and cata-lase(CAT)in the serum and testis tissue by ELISA,and determination of expressions of the key enzymes of glycolysis hexokinase Ⅱ(HK2),pyruvate kinase M2(PKM2),platelet phosphofructokinase(PFKP),lactate dehydrogenase A(LDHA)and the meiosis pro-teins REC8 and SCP3 by Western blot,and the mRNA expressions of glycolytic phosphofructokinase 1(PFK1),phosphoglycerate ki-nase 1(PGK1),tumor necrosis factor-α(TNF-α)and interleukin-1 β(IL-1β)by fluorescence quantitative PCR(FQ-PCR).Results:Compared with the model controls,the mice in the AB groups showed significant increases in the testis coefficient,kidney in-dex,sperm concentration,sperm motility,spermatogonia,primary spermatocytes,spermatids,sperm count and the serum T level(P＜0.05 orP＜0.01),but dramatic decreases in the apoptosis of testis cells and percentage of morphologically abnormal sperm(P＜0.01).Achyranthes bidentata also significantly elevated the levels of SOD and CAT,and down-regulated the mRNA expressions of MDA,TNF-α and IL-1β(P＜0.05 or P＜0.01),and up-regulated the protein expressions of HK2,PKM2,PFKP,LDHA,REC8 and SCP3,and expressions of the glycolysis key genes Pfk1 and Pgk1(P＜0.05 orP＜0.01).Conclusion:Achyranthes bidentata ameliorates doxorubicin-induced spermatogenic disorder in mice by regulating the glycolytic pathway and reducing oxidative stress and the expressions of inflammatory factors.

Medication adherence is an important indicator for assessing whether patients follow medical advice during treatment， and its level directly affects disease control and the quality of life of patients. Therefore， accurate and effective assessment is essential for chronic disease management and intervention. This paper takes chronic obstructive pulmonary disease （COPD） and asthma， two types of chronic respiratory diseases， as representative to review the existing measurement methods and current application status of medication adherence. It is found that the existing assessment methods for medication adherence can be categorized into objective measurement methods and subjective measurement methods. Objective measures include drug concentration monitoring， pill counting， and electronic medication devices， which generally offer high accuracy. Subjective measures include physician assessments， inhalation technique evaluations， and questionnaires. While these methods are straightforward and easy to implement， their accuracy is often influenced by the subjective factors of assessors of patients， which may lead to biased results. Currently， there is still a lack of a universally accepted “gold standard” for evaluating medication adherence. Selecting the appropriate measurement method requires a comprehensive consideration of factors such as research objectives， disease type， patient characteristics， and data availability to ensure the validity and reliability of the assessment results.