AIM: To investigate the effects of Conbercept on various optical coherence tomography(OCT)biomarkers in patients with retinal vein occlusion-related macular edema(RVO-ME), and to analyze the correlation of these biomarker changes with visual prognosis.METHODS: Retrospective study. A total of 57 patients(57 eyes)with RVO-ME, including 25 patients(25 eyes)with central retinal vein occlusion(CRVO)and 32 patients(32 eyes)with branch retinal vein occlusion(BRVO), were enrolled in this study. All the patients received intravitreal injection of conbercept once a month, three times in total. The preoperative and postoperative best-corrected visual acuity(BCVA), and changes in OCT biomarkers, including central macular thickness(CMT), the length of disorganization of the retinal inner layers(DRIL), the number of hyperreflective dots(HRD), the area of intraretinal fluid(IRF), the area of subretinal fluid(SRF), and the length of ellipsoid zone(EZ)disruption were compared. Furthermore, the relationship of these changes with BCVA was analyzed.RESULTS:Compared with the baseline, at 3 mo post-treatment, BCVA(LogMAR)was improved, CMT was decreased, the length of DRIL was shortened, the number of HRD was reduced, the area of IRF was decreased, the area of SRF was reduced, and the length of EZ disruption was shortened(all P<0.05). Spearman correlation analysis showed that there was no correlation between the changes in CMT, the length of DRIL, the number of HRD, the area of IRF, the area of SRF and the change in BCVA before and after treatment(P>0.05). However, the change in the length of EZ disruption was positively correlated with the change in BCVA(rs=0.34, P=0.011), and the R2 value of the fitting curve between the change in the length of EZ disruption and the change in BCVA was 0.113(P=0.011). When comparing the pre- and post-treatment changes in BCVA, the length of DRIL, the number of HRD, the area of IRF, the area of SRF, and the length of EZ disruption between patients in the CRVO group and BRVO group, no significant differences were observed(all P>0.05). In contrast, a significant difference was found in the change in CMT between the two groups(P=0.002).CONCLUSION:Conbercept effectively improves multiple OCT biomarkers in patients with RVO-ME. Repair of EZ disruption is a key driver of visual recovery, and its stability may serve as a novel indicator for personalized decision-making in anti-vascular endothelial growth factor therapy.

This study aims to explore the effects and mechanisms of 4'-O-methylbavachalcone(MeBavaC), an active compound from Psoraleae Fructus, in regulating white matter neuroinflammation to improve vascular cognitive impairment. Male Sprague-Dawley(SD) rats were randomly divided into four groups: sham group, model group, high-dose MeBavaC group(14 mg·kg~(-1)), and low-dose MeBavaC group(7 mg·kg~(-1)). The rat model of chronic cerebral hypoperfusion(CCH) was established using bilateral common carotid artery occlusion. The Morris water maze test was performed to evaluate the learning and memory abilities of the rats. Luxol fast blue staining, Nissl staining, immunofluorescence, immunohistochemistry, and transmission electron microscopy were utilized to observe the morphology and ultrastructure of the white matter myelin sheaths, axon integrity, the morphology and number of hippocampal neurons, and the loss and activation of glial cells in the white matter. Transcriptome analysis was performed to explore the potential mechanisms of white matter injury induced by CCH. Western blot and quantitative real-time polymerase chain reaction(qRT-PCR) assays were conducted to measure the expression levels of NOD-like receptor protein 3(NLRP3), absent in melanoma 2(AIM2), gasdermin D(GSDMD), cysteinyl aspartate-specific proteinase-1(caspase-1), interleukin-18(IL-18), interleukin-1β(IL-1β), erythropoietin(EPO), nuclear factor erythroid 2-related factor 2(Nrf2), and heme oxygenase-1(HO-1) in the white matter of rats. The results showed that compared with the model group, MeBavaC significantly improved the learning and memory abilities of rats with CCH, improved the damage of white matter myelin sheath, maintained axonal integrity, reduced the loss of hippocampal neurons and oligodendrocytes in the white matter, inhibited the activation of microglia and the proliferation of astrocytes in the white matter, and suppressed the NLRP3/AIM2/caspase-1/GSDMD pathway. The expression levels of inflammatory cytokines IL-1β and IL-18 were significantly reduced, while EPO expression and the expression of Nrf2/HO-1 antioxidant pathway were notably elevated. In conclusion, MeBavaC can alleviate cognitive impairment in rats with CCH and suppress neuroinflammation in cerebral white matter. The mechanism of action may involve activation of EPO activity, promotion of endogenous antioxidant pathways, and inhibition of neuroinflammation in the white matter. This study suggests that MeBavaC exhibits antioxidant and anti-neuroinflammatory effects, showing potential application in improving cognitive dysfunction.
Animals ; Male ; Rats, Sprague-Dawley ; NF-E2-Related Factor 2/immunology* ; Rats ; Chalcones/administration & dosage* ; Cognitive Dysfunction/metabolism* ; Signal Transduction/drug effects* ; Neuroinflammatory Diseases/drug therapy* ; Heme Oxygenase-1/metabolism* ; Humans ; Heme Oxygenase (Decyclizing)/genetics*

This study applied the grading of recommendations assessment, development and evaluation(GRADE) system and the integrated evidence chain-based effectiveness evaluation of traditional Chinese medicine(Eff-iEC) to evaluate the evidence for 12 commonly used Chinese patent medicines for the treatment of osteoporosis, which are frequently recommended in guidelines or expert consensuses. The results showed that Xianling Gubao Capsules/Tablets were rated as C(low-level evidence) according to the GRADE system, and as BA~+B~+(intermediate evidence) according to the Eff-iEC system. Jintiange Capsules were rated as C(low-level evidence) by the GRADE system, and as AA~+B(high-level evidence) by the Eff-iEC system. Gushukang Granules/Capsules were rated as C(low-level evidence) by GRADE system, and as BA~+B~+(intermediate evidence) by Eff-iEC system. Zuogui Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Qianggu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B~+(high-level evidence) by Eff-iEC system. Zhuanggu Zhitong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BA~+B(intermediate evidence) by Eff-iEC system. Jingui Shenqi Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B(high-level evidence) by Eff-iEC system. Quanduzhong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AD~+B~+(low-level evidence) by Eff-iEC system. Epimedium Total Flavones Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AAB~+(high-level evidence) by Eff-iEC system. Yougui Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~(++)B~(+ )(high-level evidence) by Eff-iEC system. Qigu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BB~+B(intermediate evidence) by Eff-iEC system. Liuwei Dihuang Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Overall, the Eff-iEC system provides a more comprehensive assessment of the effectiveness evidence for traditional Chinese medicine(TCM) than the GRADE system. However, it still has certain limitations that hinder its wider promotion and application. In terms of clinical evidence evaluation, both the Eff-iEC and GRADE systems reflect that the current clinical research quality on Chinese patent medicines for the treatment of osteoporosis is generally low. High-quality clinical trials are still needed in the future to further validate clinical efficacy.
Drugs, Chinese Herbal/therapeutic use* ; Osteoporosis/drug therapy* ; Humans ; Nonprescription Drugs/therapeutic use* ; Evidence-Based Medicine ; Medicine, Chinese Traditional

Cervical spine health issues not only seriously affect patients' quality of life but also impose a heavy burden on the social healthcare system. Existing guidelines lack sufficient clinical guidance on lifestyle and work habits, such as exercise, posture, daily routine, and diet, making it difficult to meet practical needs. To address this, relying on the China Association of Chinese Medicine, Wangjing Hospital of China Academy of Chinese Medical Sciences took the lead and joined hands with more than ten institutions to form a multidisciplinary guideline development group. For the first time, the group developed the Guidelines for Cervical Spine Health Intervention based on evidence-based medicine methods, strictly following the standardized procedures outlined in the World Health Organization Handbook for Guideline Development and the Guiding Principles for the Formulation/Revision of Clinical Practice Guidelines in China (2022 Edition). This proposal systematically explains the methods and steps for developing the guideline, aiming to make the guideline development process scientific, standardized, and transparent.
Humans ; Practice Guidelines as Topic/standards* ; Cervical Vertebrae ; China

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese. METHODS: Consecutive participants aged ≥ 65 years attending outpatient clinics were enrolled for AF screening using handheld single-lead electrocardiogram (ECG) from April 2017 to December 2022. Each ECG rhythm strip was reviewed from the research team. AF or uninterpretable single-lead ECGs were referred for 12-lead ECG. Primary study outcome comparison was between rural and urban areas for the prevalence of AF. The Student's t-test was used to compare mean values of clinical characteristics between rural and urban participants, while the Pearson's chi-square test was used to compare between-group proportions. Multivariate stepwise logistic regression analysis was performed to estimate the association between AF and various patient characteristics. RESULTS: The 29,166 study participants included 13,253 men (45.4%) and had a mean age of 72.2 years. The 7073 rural participants differed significantly (P ≤ 0.02) from the 22,093 urban participants in several major characteristics, such as older age, greater body mass index, and so on. The overall prevalence of AF was 4.6% (n = 1347). AF was more prevalent in 7073 rural participants than 22,093 urban participants (5.6% vs. 4.3%, P < 0.01), before and after adjustment for age, body mass index, blood pressure, pulse rate, cigarette smoking, alcohol consumption and prior medical history. Multivariate logistic regression analysis identified overweight/obesity (OR = 1.35, 95% CI: 1.17-1.54) in urban areas and cigarette smoking (OR = 1.62, 95% CI: 1.20-2.17) and alcohol consumption (OR = 1.42, 95% CI: 1.04-1.93) in rural areas as specific risk factors for prevalent AF. In patients with known AF in urban areas (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received AF treatment (P < 0.01), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.05). CONCLUSIONS In China, there are urban-rural disparities in AF in the elderly, with a higher prevalence and worse management in rural areas than urban areas. Our study findings provide insight for health policymakers to consider urban-rural disparity in the prevention and treatment of AF.

BACKGROUND: The beneficial effects of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on adverse cardiac outcomes in diabetic patients are well-established. However, the effects of SGLT2i against cancer therapy-related cardiotoxicity remain understudied. We investigated the association between SGLT2i and cardiac outcomes in cancer patients. METHODS: PubMed, Embase, and the Cochrane Library were searched from their inception until September 30, 2024 for studies evaluating the effects of SGLT2i in patients with cancer. The primary outcomes included incident heart failure (HF), HF exacerbation, HF hospitalization, atrial fibrillation/atrial flutter (AF/AFL), myocardial infarction, and all-cause mortality. The secondary outcomes included acute kidney injury and sepsis. Odds ratio (OR) with 95% CI was pooled. RESULTS: Thirteen studies with 85,596 patients were included. Compared to non-SGLT2i use, SGLT2i treatment was associated with lower risks of incident HF (OR = 0.51, 95% CI: 0.32-0.79, P = 0.003), HF exacerbation (OR = 0.74, 95% CI: 0.63-0.87, P < 0.001), AF/AFL (OR = 0.67, 95% CI: 0.55-0.82, P < 0.001), myocardial infarction (OR = 0.61, 95% CI: 0.41-0.90, P = 0.01), and all-cause mortality (OR = 0.44, 95% CI: 0.28-0.69, P < 0.001), but not for HF hospitalization (OR = 0.58, 95% CI: 0.22-1.55, P = 0.28). As for safety outcomes, SGLT2i use was associated with lower risks of acute kidney injury (OR = 0.68, 95% CI: 0.57-0.81, P < 0.001) and sepsis (OR = 0.32, 95% CI: 0.23-0.44, P < 0.001). CONCLUSIONS SGLT2i were associated with lower risks of incident HF, HF exacerbation, AF/AFL, myocardial infarction, all-cause mortality, acute kidney injury, and sepsis in cancer patients.

Hemorrhagic shock is a common clinical emergency that can aggravate cell injury after resuscitation. Astrocytes are crucial for the survival of neurons because they regulate the surrounding ionic microenvironment of neurons. Although hemorrhagic shock and resuscitation (HSR) injury can impair cognition, it remains unclear how this insult directly affects astrocytes. In this study, we established an HSR model by bleeding and re-transfusion in mice. The social interaction test and new object recognition test were applied to evaluate post-operative cognitive changes, and the results suggest that mice experience cognitive impairment following exposure to HSR. In the HSR group, the power spectral density of β and γ oscillations decreased, and the coupling of the θ oscillation phase and γ oscillation amplitude was abnormal, which indicated abnormal neuronal oscillation and cognitive impairment after HSR exposure. In brief, cognitive impairment in mice is strongly correlated with Ca²⁺ signal strength in lateral septum astrocytes following HSR.
Animals ; Astrocytes/metabolism* ; Shock, Hemorrhagic/metabolism* ; Resuscitation/adverse effects* ; Male ; Mice ; Calcium Signaling/physiology* ; Mice, Inbred C57BL ; Septal Nuclei/metabolism* ; Cognitive Dysfunction/etiology* ; Disease Models, Animal ; Cognition Disorders/etiology*

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

OBJECTIVE: To identify prognostic genes associated with lysosome-dependent cell death (LDCD) in patients with gastric cancer (GC). METHODS: Differentially expressed genes (DEGs) were identified using The Cancer Genome Atlas - Stomach Adenocarcinoma. Weighted gene co-expression network analysis was performed to identify the key module genes associated with LDCD score. Candidate genes were identified by DEGs and key module genes. Univariate Cox regression analysis, and least absolute shrinkage and selection operator regression and multivariate Cox regression analyses were performed for the selection of prognostic genes, and risk module was established. Subsequently, key cells were identified in the single-cell dataset (GSE183904), and prognostic gene expression was analyzed. Cell proliferation and migration were assessed using the Cell Counting Kit-8 assay and the wound healing assay. RESULTS: A total of 4,465 DEGs, 95 candidate genes, and 4 prognostic genes, including C19orf59, BATF2, TNFAIP2, and TNFSF18, were identified in the analysis. Receiver operating characteristic curves indicated the excellent predictive power of the risk model. Three key cell types (B cells, chief cells, and endothelial/pericyte cells) were identified in the GSE183904 dataset. C19orf59 and TNFAIP2 exhibited predominant expression in macrophage species, whereas TNFAIP2 evolved over time in endothelial/pericyte cells and chief cells. Functional experiments confirmed that interfering with C19orf59 inhibited proliferation and migration in GC cells. CONCLUSION C19orf59, BATF2, TNFAIP2, and TNFSF18 are prognostic genes associated with LDCD in GC. Furthermore, the risk model established in this study showed robust predictive power.
Stomach Neoplasms/pathology* ; Humans ; Prognosis ; Lysosomes/physiology* ; RNA-Seq ; Cell Death ; Single-Cell Analysis ; Gene Expression Regulation, Neoplastic ; Cell Proliferation ; Single-Cell Gene Expression Analysis

Human physiological indicators have become an important standard for assessing health in modern society.Traditional detection methods often require a separate laboratory,complex operation process and long detection time,so it is urgent to develop portable,fast and accurate on-site detection technologies for bioanalysis.Point-of-care testing(POCT),which differs from traditional laboratory testing,can realize the rapid in situ detection of biomarkers without the complicated analytical process of the laboratory.Smartphones,which are an essential tool in our daily life,not only have independent operating systems and built-in storage functions,but also have high-definition cameras,which have great application potential in POCT visualization.The combination of various biosensing technologies and smartphones has developed into a new direction in the field of POCT.This review mainly introduced the research progress of smartphone-based visual biosensors in POCT in recent years,including colorimetric sensors,fluorescence sensors,chemiluminescence sensors and electrochemiluminescence sensors.Finally,the problems faced by smart-phone-based visual biosensors in the application of POCT were summarized,and their future development was prospected.