Hemodynamic monitoring can reflect cardiac function and blood perfusion and is an indispensable monitoring method in clinical practice. Invasive hemodynamic monitoring methods represented by the thermodilution method are limited in their clinical application scope because they require vascular cannulation. Non-invasive hemodynamic monitoring has attracted extensive attention from medical companies and clinicians at home and abroad in recent years due to its advantages such as safety, non-invasiveness, continuous monitoring, simple operation, and low cost. This paper designs a non-invasive hemodynamic monitoring system based on the impedance cardiography, including hardware, algorithm, software design, and performance parameter evaluation. Among them, the hardware part mainly includes a differential high-frequency constant current source stimulation circuit, impedance cardiogram signal acquisition, and ECG signal acquisition circuit. Signal processing includes wave filtering, impedance cardiogram signal calibration, and ECG signal and impedance cardiogram signal feature point recognition. According to the collected impedance cardiogram and ECG signals, hemodynamic parameters such as heart rate (HR), stroke volume (SV), cardiac output (CO), stroke index (SI), cardiac index (CI), and cardiac contractility index (ICON) are calculated based on the Nyboer thoracic cylinder model. After testing, the key technical indicators of the system hardware are better than that of the relevant medical device standards. The system was used to collect impedance cardiogram and ECG signal data from 40 volunteers. The calculated HR, SV, and CO, three important hemodynamic indicators, were compared with the ICONCore non-invasive cardiac output monitor of OSYPKA Medical in Germany. Their Pearson correlation coefficients were 0.992 ( P<0.001), 0.948 ( P<0.001), and 0.933 ( P<0.001), respectively, verifying that the designed system has high accuracy and reliability.
Cardiography, Impedance/methods* ; Humans ; Hemodynamic Monitoring/methods* ; Equipment Design ; Signal Processing, Computer-Assisted ; Hemodynamics ; Algorithms ; Monitoring, Physiologic/methods* ; Electrocardiography

End-tidal carbon dioxide monitoring is an important means of evaluating human lung function and is widely used in fields such as clinical emergency treatment and cardiopulmonary resuscitation. This paper develops a microstream end-tidal carbon dioxide monitoring system. It adopts an integrated gas circuit design to further reduce the size of the equipment. The system uses the method of calculating the root mean square (RMS) of differential pressure signals to regulate the gas circuit flow, enabling the system to stably operate at a flow state of 30 mL/min. In addition, by simultaneously detecting multiple environmental parameters such as temperature and pressure, the system realizes system state monitoring and gas parameter compensation. The test results show that various indicators of the system meet the requirements of relevant standards, laying a good foundation for subsequent engineering applications.
Carbon Dioxide/analysis* ; Equipment Design ; Monitoring, Physiologic/methods* ; Humans

In order to improve the effect of transcranial electrical stimulation treatment and realize personalized treatment for patients with varying severity levels, this paper designed an integrated four-channel EEG recording multimodal transcranial electrical stimulation system. This system can conduct real-time monitoring on EEG and related characteristic analysis before stimulation, in stimulation, and after stimulation. This enables physicians and researchers to resolve real-time brain states, evaluate transcranial electrical stimulation effect, and then artificially adjust the stimulation parameters. After relevant testing and verification, the system can select four stimulation modes: TACS, TDCS, TPCS and TRNS, which can output the constant stimulation current of 0.03 mA accuracy in the range of ±2 mA and the stimulation frequency of low frequency of 0~4 kHz (precision of 0.01 Hz) and high frequency 50~100 kHz, which can obtain more accurate EEG signals under stimulation interference, demonstrating a good market application prospect.
Electroencephalography/methods* ; Transcranial Direct Current Stimulation/instrumentation* ; Humans ; Equipment Design

This paper introduces a 16-channel multimodal high-precision transcranial electrical stimulation system specifically for non-invasive brain stimulation. This system added TMCS mixed four traditional stimulation modes with TACS, TDCS, TPCS and TRNS. By designing a compensated high-precision constant current source, the constant stimulation current with an accuracy of 0.03 mA in the range of ±2 mA and the stimulation frequency of 50~200 kHz with low frequency of 0~4 kHz (high frequency of 0.1 Hz) are realized. In TACS stimulation mode, there are five adjustable wave forms: triangular wave, sine wave, sawtooth wave, square wave and mixed wave. The system has dual closed-loop control overcurrent detection and simultaneous real-time electrode contact impedance detection. After relevant tests and verification, the system has good stimulation accuracy, high safety and reliability. Compared with the existing products at home and abroad, it features lower cost, richer stimulation mode and waveforms, demonstrating a certain market application value.
Transcranial Direct Current Stimulation/instrumentation* ; Equipment Design ; Humans

OBJECTIVE: To investigate the effect and mechanism of Shuangshi Tonglin Capsules (SSTL) in the treatment of prostate fibrosis (PF). METHODS: Human prostate stromal cells (WPMY-1) were used for in vitro experiments to establish PF cell models induced with estradiol (E₂). The cell proliferation, migration and clonogenic capacity were determined by cell counting kit-8, scratch assay, and crystal violet staining, respectively. Sprague-Dawley rats were used for in vivo experiments. The changes in histomorphology and organ index of rat prostate by SSTL were determined. Pathologic changes and collagen deposition changes in rat prostate were observed by haematoxylin and eosin (HE) and Masson staining. Enzyme-linked immunosorbent assay kits were used to determine changes in rat PF markers fibroblast growth factor-23 (FGF-23), E₂ and prostate specific antigen (PSA). Mechanistically, changes in oxidative stress indicators by SSTL were determined in WPMY-1 cells and PF rats. Then the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) and transforming growth factor-β1 (TGF-β1)/Smad pathway-related proteins as well as Nrf2 and TGF-β1 mRNA were further detected by Western blot or quantitative real-time polymerase chain reaction both in vivo and in vitro. RESULTS: In the efficacy study, SSTL significantly reduced the proliferation, migration, and clonogenic ability of cells, improved the morphology of the glandular tissue, significantly reduced the prostate index, reduced glandular fibrous tissue and collagen deposition, and resulted in a significant decrease in the levels of FGF-23, E₂ and PSA (P<0.01 or P<0.05). In the mechanistic study, SSTL ameliorated oxidative stress by significantly increasing superoxide dismutase and glutathione peroxidase levels and decreasing malondialdehyde level in WPMY-1 cells and rats (P<0.01 or P<0.05). SSTL significantly elevated the expressions of Nrf2, HO-1, NAD(P)H quinone oxidoreductase 1 (NQO-1), and Smad7 proteins in both cells and rats, and significantly decreased the expressions of TGF-β1, collagen I, α-smooth muscle actin and Smad4 proteins (P<0.01 or P<0.05). SSTL also elevated the content of Nrf2 mRNA and decreased the content of TGF-β1 mRNA in cells and rats (P<0.01 or P<0.05). The Nrf2 inhibitor ML385 was added in in vitro experiments to further validate the pathway relevance. CONCLUSION SSTL was effective in improving PF in vivo and in vitro, and its mechanism of action may function through the Nrf2/TGF-β1 signaling pathway.
Male ; NF-E2-Related Factor 2/metabolism* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Signal Transduction/drug effects* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Humans ; Fibrosis ; Prostate/drug effects* ; Cell Proliferation/drug effects* ; Capsules ; Cell Movement/drug effects* ; Oxidative Stress/drug effects* ; Rats

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

Alzheimer's disease (AD) is regarded as a neurodegenerative disease, and it has been proposed that AD may be a systemic disease. Studies have reported associations between non-neurological diseases and AD. The correlations between AD pathology and systemic (non-neurological) pathological changes are intricate, and the mechanisms underlying these correlations and their causality are unclear. In this article, we review the association between AD and disorders of other systems. In addition, we summarize the possible mechanisms associated with AD and disorders of other systems, mainly from the perspective of AD pathology. Regarding the relationship between AD and systemic pathological changes, we aim to provide a new outlook on the early warning signs and treatment of AD, such as establishing a diagnostic and screening system based on more accessible peripheral samples.
Alzheimer Disease/therapy* ; Humans ; Brain/pathology*

Objective:To explore the clinical and biochemical characteristics of patients with hyperuricemia according to different pathophysiological subtypes. This may facilitate rapid identification of each subtype in clinical settings and provide evidence for personalized urate-lowering treatment.Methods:Patients diagnosed with hyperuricemia at the Department of Endocrinology and Metabolism, Tenth People′s Hospital of Tongji University between October 2015 and January 2024 were included. Based on 24-h urinary uric acid excretion(UUE) and the fractional excretion of uric acid(FEUA), patients were classified into four subtypes: renal uric acid underexcretion type(RUE), renal uric acid overload type(ROL), combined type and renal normal type. Clinical and biochemical variables-including sex, age, BMI, smoking history, comorbidities, blood glucose, and serum uric acid-were analyzed. Binary logistic regression was used to identify factors associated with each subtype.Results:Among 2 073 patients with hyperuricemia, 55.8% were RUE type, 6.9% were ROL type, 31.3% were combined type and 6.0% were renal normal type. RUE type had lower blood glucose levels and fewer cases of diabetes [ OR=0.685(95% CI 0.478-0.980), P<0.05]. ROL type showed a higher incidence of tophi, positively correlated with smoking history [ OR=1.672(95% CI 1.009-2.771), P<0.05], and negatively correlated with serum uric acid levels [ OR=0.994(95% CI 0.990-0.998), P=0.001]. Combined type had the youngest onset age, shortest disease duration, and the fewest comorbidities, and was associated with higher BMI [ OR=1.035(95% CI 1.001-1.070), P<0.05]. Renal normal type had the oldest age of onset, the highest proportion of female patients and comorbidities, and was associated with lower serum uric acid levels[ OR=0.994(95% CI 0.989-0.998), P=0.007], higher BMI[ OR=1.064(95% CI 1.003-1.129), P<0.05], and increased tophi incidence[ OR=2.261(95% CI 1.206-4.237), P=0.011]. Conclusion:Each pathophysiological subtype of hyperuricemia exhibits distinct clinical and biochemical characteristics, which may serve as useful references for subtype identification and personalized management in clinical practice.

Nonalcoholic steatohepatitis(NASH)is a chronic metabolic disease characterized by hepatocyte fatty degeneration and ballooning degeneration,and it plays an important role in the progression of hepatic steatosis.Recent studies have shown that immune homeostasis imbalance between T helper 17(Th17)and regulatory T(Treg)cells are closely associated with the pathological process of NASH.Transforming growth factor-β1(TGF-β1)is a key cytokine for regulating the differentiation and proliferation of Th17/Treg cells,and TGF-β1 binds to its receptor and activates the Smad signaling pathway,thereby regulating the immune balance of Th17/Treg cells and the expression of inflammatory factors and participating in the repair of liver inflammation.This article systematically reviews the molecular mechanism of the TGF-β1/Smad signaling pathway in affecting NASH by regulating the immune balance of Th17/Treg cells,in order to provide a theoretical basis for the research on the pathogenesis of NASH and related treatment strategies.

Nonalcoholic steatohepatitis （NASH） is a chronic metabolic disease characterized by hepatocyte fatty degeneration and ballooning degeneration， and it plays an important role in the progression of hepatic steatosis. Recent studies have shown that immune homeostasis imbalance between T helper 17 （Th17） and regulatory T （Treg） cells are closely associated with the pathological process of NASH. Transforming growth factor-β1 （TGF-β1） is a key cytokine for regulating the differentiation and proliferation of Th17/Treg cells， and TGF-β1 binds to its receptor and activates the Smad signaling pathway， thereby regulating the immune balance of Th17/Treg cells and the expression of inflammatory factors and participating in the repair of liver inflammation. This article systematically reviews the molecular mechanism of the TGF-β1/Smad signaling pathway in affecting NASH by regulating the immune balance of Th17/Treg cells， in order to provide a theoretical basis for the research on the pathogenesis of NASH and related treatment strategies.