Objective: To investigate the mechanism of shed syndecan-4 (sSDC4) in temporomandibular joint osteoarthritis (TMJOA) in rats, aiming to provide experimental evidence for its prevention and treatment. Methods: This study was approved by the Institutional Animal Ethics Committee. Twelve 6-week-old female Sprague Dawley (SD) rats were randomly divided into two groups. They received a single intra-articular injection into the bilateral superior cavity of temporomandibular joint, which consisted of either 50 μL of 4 mg/mL monosodium iodoacetate (TMJOA model group) or 50 μL of phosphate-buffered saline (PBS, control group). After 4 weeks, the mandibular condylar cartilage was harvested for hematoxylin & eosin (H&E) staining, Safranin O-fast green (SO) staining, and type II collagen (Col-Ⅱ) immunohistochemical staining to assess the degree of cartilage degeneration. The synovium of the temporomandibular joint was collected for immunohistochemical staining to detect the expression levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) to evaluate the degree of synovial inflammation. Synovial fluid from the temporomandibular joint cavity was collected to measure sSDC4 levels by enzyme-linked immunosorbent assay (ELISA). In addition, 12 6-week-old female SD rats were randomly divided into a His-SDC4 group and a control group, receiving injections into the bilateral superior cavity of temporomandibular joint of either 100 ng/mL (50 μL) of His-SDC4 protein or 50 μL of PBS once every 3 days for a total of 28 days. The same experimental procedures were performed for H&E staining, SO staining, and immunohistochemical staining (Col-Ⅱ IL-6, TNF-α) to observe condylar cartilage degeneration and detect synovial inflammation. Rat synovial fibroblasts and condylar chondrocytes were cultured in vitro and randomly divided into a His-SDC4-stimulated (10 ng/mL) group and control group. Perform CCK-8 cytotoxicity assays and observe cellular morphology under optical microscopy, the mRNA expression levels of IL-6 and TNF-α were detected by real-time quantitative polymerase chain reaction (RT-qPCR), and the levels of IL-6 and TNF-α in cell culture supernatants were measured by ELISA. Results: Compared with the control group, the TMJOA group showed decreased condylar cartilage thickness, percentage of SO-positive area, and percentage of Col-Ⅱ-positive area (all P<0.001); an increased synovitis score (P<0.001) and increased percentages of IL-6- and TNF-α-positive cells in the synovium (all P<0.001); and a significant increase in sSDC4 levels in the synovial fluid (P=0.011). Following intra-articular injection of His-SDC4, condylar cartilage thickness, percentage of SO-positive area, and percentage of Col-Ⅱ-positive area all decreased (all P<0.001); the synovitis score increased (P=0.006), and the percentages of IL-6- and TNF-α-positive cells in the synovium increased (all P<0.001). In vitro experiments showed that His-SDC4 stimulation significantly upregulated the expression levels of IL-6 and TNF-α in both synovial fibroblasts and condylar chondrocytes (all P<0.01), and the levels of these two cytokines in the culture supernatants also significantly increased (all P<0.01). Conclusion During TMJOA progression, the level of sSDC4 in the synovial fluid is significantly elevated, which can directly stimulate synovial fibroblasts and condylar chondrocytes to secrete more pro-inflammatory cytokines, forming a vicious cycle that accelerates TMJOA progression.

One of the most common adverse reactions associated with cancer and its treatment is sarcopenia,a syndrome primarily caused by the disruption of muscle homeostasis,leading to excessive muscle atrophy and decreased muscle strength.For cancer patients,sarcopenia reflects not only a state of muscle mass loss but also serves as an important factor affecting treatment efficacy and survival rates.However,cancer-related sarcopenia often has a more insidious onset,is not visible to the naked eye,and is easily overlooked.Therefore,it is necessary to recognize the dangers of sarcopenia throughout the cancer treatment process and to identify low muscle mass early.In recent years,as healthcare professionals have increasingly focused on sarcopenia,research on cancer-related sarcopenia has gradually deepened,with new advancements in its assessment,diagnosis,intervention,and impact on anti-cancer treatment.This article provides a review of these key areas to offer a theoretical basis for the clinical practice of cancer-related sarcopenia.

Objective To look for cognitive assessment paradigms and electrocardiographic(ECG)characteristics sensitive to mental fatigue through an experimental study.Methods Data were collected from 10 healthy students of the University of Shanghai for Science and Technology who participated in the 4-day National Undergraduate Electronics Design Contest,including their Stanford sleepiness scale(SSS)scores,sleep duration,cognitive task performance,and ECG signal data.Ten ECG features,including time-domain,frequency-domain,and information-domain characteristics,were extracted during cognitive tasks.The cognitive task performance and ECG features sensitive to changes in mental fatigue were analyzed.Results Significant differences were observed in SSS scores(x2=23.116,P＜0.001)and sleep duration(x2=19.608,P＜0.001)across the 4 d.For cognitive task performance,word-color congruent accuracy and word-color incongruent accuracy in the Stroop task and Single-visual target stimulus accuracy and Visual target-auditory non-target stimulus accuracy in the audiovisual competition task all showed significant negative correlations with SSS scores(all P＜0.05).Regarding ECG features,Poincaré plot SD2 during the Stroop task was positively correlated with sleep duration(P＜0.05),while Poincaré plot SD2 during the 2-back task was positively correlated with mental fatigue assessment scores and was negatively correlated with sleep duration(both P＜0.05).Conclusion The accuracy of the Stroop task and audiovisual competition task is a cognitive ability indicator sensitive to mental fatigue,while the Poincaré plot SD2 during Stroop and 2-back tasks is an ECG indicator sensitive to mental fatigue.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Epilepsy is a chronic neurological disease caused by abnormal synchronous discharge of the brain, which is characterized by recurrent and transient neurological abnormalities, mainly manifested as loss of consciousness and limb convulsions, and can occur in people of all ages. At present, anti-epileptic drugs (AEDs) are still the main means of treatment, but their efficacy is limited by the problem of drug resistance, and long-term use can cause serious side effects, such as cognitive dysfunction and vital organ damage. Although surgical resection of epileptic lesions has achieved certain results in some patients, the high cost and potential risk of neurological damage limit its scope of application. Therefore, the development of safe, accurate and personalized non-invasive treatment strategies has become one of the key directions of epilepsy research. In recent years, photobiomodulation (PBM) has gained significant attention as a promising non-invasive therapeutic approach. PBM uses light of specific wavelengths to penetrate tissues and interact with photosensitive molecules within cells, thereby modulating cellular metabolic processes. Research has shown that PBM can enhance mitochondrial function, promote ATP production, improve meningeal lymphatic drainage, reduce neuroinflammation, and stimulate the growth of neurons and synapses. These biological effects suggest that PBM not only holds the potential to reduce the frequency of seizures but also to improve the metabolic state and network function of neurons, providing a novel therapeutic avenue for epilepsy treatment. Compared to traditional treatment methods, PBM is non-invasive and avoids the risks associated with surgical interventions. Its low risk of significant side effects makes it particularly suitable for patients with drug-resistant epilepsy, offering new therapeutic options for those who have not responded to conventional treatments. Furthermore, PBM’s multi-target mechanism enables it to address a variety of complex etiologies of epilepsy, demonstrating its potential in precision medicine. In contrast to therapies targeting a single pathological mechanism, PBM’s multifaceted approach makes it highly adaptable to different types of epilepsy, positioning it as a promising supplementary or alternative treatment. Although animal studies and preliminary clinical trials have shown positive outcomes with PBM, its clinical application remains in the exploratory phase. Future research should aim to elucidate the precise mechanisms of PBM, optimize light parameters, such as wavelength, dose, and frequency, and investigate potential synergistic effects with other therapeutic modalities. These efforts will be crucial for enhancing the therapeutic efficacy of PBM and ensuring its safety and consistency in clinical settings. This review summarizes the types of epilepsy, diagnostic biomarkers, the advantages of PBM, and its mechanisms and potential applications in epilepsy treatment. The unique value of PBM lies not only in its multi-target therapeutic effects but also in its adaptability to the diverse etiologies of epilepsy. The combination of PBM with traditional treatments, such as pharmacotherapy and neuroregulatory techniques, holds promise for developing a more comprehensive and multidimensional treatment strategy, ultimately alleviating the treatment burden on patients. PBM has also shown beneficial effects on neural network plasticity in various neurodegenerative diseases. The dynamic remodeling of neural networks plays a critical role in the pathogenesis and treatment of epilepsy, and PBM’s multi-target mechanism may promote brain function recovery by facilitating neural network remodeling. In this context, optimizing optical parameters remains a key area of research. By adjusting parameters such as wavelength, dose, and frequency, researchers aim to further enhance the therapeutic effects of PBM while maintaining its safety and stability. Looking forward, interdisciplinary collaboration, particularly in the fields of neuroscience, optical engineering, and clinical medicine, will drive the development of PBM technology and facilitate its transition from laboratory research to clinical application. With the advancement of portable devices, PBM is expected to provide safer and more effective treatments for epilepsy patients and make a significant contribution to personalized medicine, positioning it as a critical component of precision therapeutic strategies.

Objective To explore the therapeutic effect of precise disconnection of pargastric varices guided by endoscopic ultrasound in the treatment of esophagogastric variceal bleeding.Method A retrospective analysis was conducted on 20 patients with cirrhosis esophagogastric variceal bleeding treated with endoscopic ultrasound-guided precise disconnection of pargastric varices from January 1,2024 to December 31,2024.The efficacy was analyzed.Result All 20 patients successfully completed the precise disconnection of pargastric varices under the guidance of endoscopic ultrasound.The injection of tissue gel combined with the placement of spring coils(14 cases)and the injection of tissue gel alone(4 cases)successfully blocked the pargastric varices.All patients did not experience perforation,esophageal and cardia stenosis,massive bleeding,septicemia,or ectopic embolization.One patient who received tissue gel alone had slight bleeding from the pargastric varices after surgery and improved after 3 days of treatment to reduce portal vein pressure.Another one patient who received tissue gel alone had a low-grade fever and normal body temperature after 3 days of anti-infection treatment.Conclusion Precise disconnection of pargastric varices under the guidance of endoscopic ultrasound has a good therapeutic effect on esophagogastric variceal bleeding,with fewer complications such as ectopic embolization,massive bleeding,infection,and perforation.However,close follow-up observation is still needed to address the issue of pargastric varices.

This study was a single-center retrospective study, to investigate the correlation between the relative level of miR-200a in exfoliated cells of peritoneal dialysis (PD) effluent and clinical indicators of peritoneal function in PD patients. Clinical data of PD patients who underwent treatment in the Department of Nephrology, the First Affiliated Hospital of Nanchang University, from January 2024 to December 2024 were collected, and the relative level of miR-200a in exfoliated cells of PD effluent was assessed. Patients were divided into three groups according to dialysis duration (Group A:≤1 year; Group B:>1 to <5 years; Group C:≥5 years), and differences in clinical data among the groups were compared. The correlation between the relative level of miR-200a and serum albumin, serum calcium, serum phosphorus, serum creatinine, hemoglobin, the neutrophil/high-density lipoprotein cholesterol ratio, the monocyte/high-density lipoprotein cholesterol ratio, the lymphocyte/high-density lipoprotein cholesterol ratio, and 24-hour urine volume in PD patients was analyzed. The results showed that there were no statistically significant differences among the three groups in gender, age, creatinine clearance rate, or Kt/V (all P>0.05). However, statistically significant differences were found among the three groups in peritoneal transport type ( χ2=13.518, P=0.001) and ultrafiltration volume ( H=6.905, P=0.032). Based on the 4-hour PD effluent creatinine/blood creatinine in the peritoneal equilibration test, patients were divided into the low transporter/low average transporter group (L group) and the high transporter/high average transporter group (H group). A statistically significant difference in the relative level of miR-200a was observed between the two groups [11.70 (1.09, 20.49) vs. 0.73 (0.46, 1.98), t=4.545, P<0.001]. The relative level of miR-200a was positively correlated with ultrafiltration volume and 24-hour urine output ( r=0.328, P=0.030; r=0.516, P<0.001), and negatively correlated with dialysis vintage ( r=-0.496, P<0.001). These results indicate that miR-200a level in PD effluent may, to some extent, reflect patients' peritoneal membrane function.

Adrenocortical carcinoma（ACC）is a rare and highly aggressive malignant tumor. Currently，mitotane is the first-line treatment. However，reports on neoadjuvant therapy for ACC using mitotane combined with immune checkpoint inhibitors remain scarce. This article reports a case of ACC. The patient was asymptomatic，and a right adrenal mass was detected during examination. Diagnostic imaging and endocrine evaluation confirmed the diagnosis of ACC. Due to the large tumor size，radical resection was initially considered unfeasible. After 7 months of mitotane therapy and two courses of tislelizumab，significant tumor shrinkage was achieved，allowing for successful open resection of the large right adrenal tumor combined with right nephrectomy. Postoperative histopathological examination confirmed the diagnosis of ACC. During the 3-month postoperative follow-up，no evidence of recurrence or metastasis was observed.

Objective:To explore the differences in clinicopathological features and prognosis between conventional adrenocortical carcinoma（ACC）and oncocytic ACC.Methods:The clinical and pathological data of patients with conventional ACC and oncocytic ACC who were admitted to Peking Union Medical College Hospital from March 2012 to Fabruary 2025 were retrospectively analyzed. Differences in clinical and pathological characteristics between the two groups were compared. Survival curves were plotted using the Kaplan-Meier method，and differences in survival rates were compared using the log-rank test.Results:The conventional ACC group comprised 137 cases，with a mean age of（47.5 ± 12.6）years and 37.2%（51/137）being male. The oncocytic ACC group included 22 cases，with a mean age of（49.1 ± 15.3）years and 59.1%（13/22）being male. No statistically significant differences were observed in age or gender distribution between the two groups（ P > 0.05）. The conventional ACC group exhibited a significantly higher prevalence of classic Cushing’s syndrome symptoms compared to the oncocytic ACC group［35.2%（45/128）vs. 5.3%（1/19）； χ2 = 6.876， P < 0.01］. Additionally，the proportion of hypertension was higher in the conventional ACC group［49.2%（65/132）vs. 22.2%（4/18）； χ2 = 5.319， P < 0.05］，whereas the prevalence of adrenal sex characteristics was lower［22.0%（28/127）vs. 63.2%（12/19）； χ2 = 14.043， P < 0.01］. The Ki-67 proliferation index was significantly higher in conventional ACC patients［20%（10%，40%）vs. 12%（9%，20%）； Z = -2.113， P < 0.05］. Furthermore，the conventional ACC group demonstrated a lower 5-year overall survival rate than the oncocytic ACC group（44.5% vs. 67.3%， P < 0.05）. Conclusions:Conventional ACC patients have a higher proportion of Cushing’s symptoms and hypertension，and oncocytic ACC patients have a higher proportion of adrenal sexual characteristics abnormalities. The prognosis of oncocytic ACC is better than that of conventional ACC.