Objective To explore the effects of exosomes loaded with ginsenoside Rh2 on the biological functions of hepatocellular carcinoma cells. Methods Both Huh7 and PLC/PRF/5 cell were equally divided into control group, exosome group (Exos group), drug group (G-Rh2 group), and exosomes-loaded-with-ginsenoside Rh2 group (Exos@G-Rh2 group). The effects of each group on the viability, clonogenic ability, migration ability, invasion ability, and apoptotic level of hepatocellular carcinoma cells were detected through CCK-8 assay, colony formation assay, cell scratch assay, Transwell assay, and flow cytometry. Results Compared with the control group, the Exos@G-Rh2 group and G-Rh2 group showed significantly decreased cell viability, clonogenic ability, and migration and invasion capabilities, along with a markedly increased cell apoptosis rate (P<0.05). These changes were more pronounced in the Exos@G-Rh2 group than in the G-Rh2 group (P<0.05). Conclusion Exos@G-Rh2 can effectively inhibit the viability and clonogenic, migration, and invasion abilities of liver cancer cells and induce cell apoptosis. This effect is stronger than that of free G-Rh2 at the same concentration.

Cancer immunotherapy is currently a very promising therapeutic strategy for treating tumors. However, its effectiveness is restricted by insufficient antigenicity and an immunosuppressive tumor microenvironment (ITME). Pyroptosis, a unique form of programmed cell death (PCD), causes cells to swell and rupture, releasing pro-inflammatory factors that can enhance immunogenicity and remodel the ITME. Nanomaterials, with their distinct advantages and different techniques, are increasingly popular, and nanomaterial-based delivery systems demonstrate significant potential to potentiate, enable, and augment pyroptosis. This review summarizes and discusses the emerging field of nanomaterials-induced pyroptosis, focusing on the mechanisms of nanomaterials-induced pyroptosis pathways and strategies to activate or enhance specific pyroptosis. Additionally, we provide perspectives on the development of this field, aiming to accelerate its further clinical transition.

Objective:To establish high performance liquid chromatography (HPLC) wavelength switching method to simultaneously determine the contents of chlorogenic acid, hydroxysafflor yellow A, ferulic acid, Nicotiflorin, Osthole and columbianadin in Tongluo Zhibi Prescription.Methods:The column was XBridge C18 column (250 mm × 4.6 mm, 5 μm); the mobile phase was acetonitrile (A)-0.1% phosphate water (B); gradient eluted, with flow rate: 1 ml/min, column temperature: 30 °C, detection wavelength 330 nm (0-14 min detection of chlorogenic acid, 15-80 min detection of ferulic acid, Nicotiflorin, Osthole, and columbianadin), 403 nm (14-15 min detection of hydroxysafflower yellow pigment A).Results:Chlorogenic acid, hydroxyrhodopsin A, ferulic acid, kaempferol 3-O-rutinoside, serpentin, and dihydroeurobicarpus angelicus acid ester showed good linearity ( R2 ≥ 0.999 8) within 0.029 7-1.485 0, 0.030 0-1.500 0, 0.009 9-0.495 0, 0.017 5-0.875 0, 0.028 4-1.420 0, 0.013 7-0.685 0 μg, respectively. The precision, stability (24 h), repeatability relative standard deviation ( RSD) were all <2%. The average spiked recoveries were all in the range of 95%-105%, and the RSDs were all in the range of 0.32%-1.67%. In 10 batches of test samples of Tongluo Zhibi Prescription, the content of the above six components, including chlorogenic acid, was determined to be 0.221 60, 0.314 30, 0.085 10, 0.032 95, 0.043 87, 0.026 21 mg/g in the following order. Conclusion:The established HPLC wavelength switching method is fast, simple and accurate, which can be used for simultaneous determination of the content of the above six components in Tongluo Zhibi Prescription, which provides reference for quality monitoring and new dosage form research of Tongluo Zhibi Prescription.

ObjectiveTo investigate the protective effect of the extract of Liuwei Dihuangwan （LW） on mitochondrial damage in the Alzheimer's disease （AD） model of Caenorhabditis elegans （C. elegans）. MethodC. elegans transfected with human β-amyloid protein （Aβ） _1-42 gene was used as an AD model. The rats were divided into blank group， model group， metformin group （50 mmol·L^-1）， and low， medium， and high dose （1.04， 2.08， 4.16 g·kg^-1） LW groups. Behavioral methods were used to observe the sensitivity of 5-hydroxytryptamine （5-HT） in nematodes. Western blot was used to detect the expression of Aβ in nematodes. Total ATP content in nematodes was detected by the adenine nucleoside triphosphate （ATP） kit， and mitochondrial membrane potential was detected by the JC-1 method. In addition， the mRNA expression of Aβ expression gene （Amy-1）， superoxide dismutase-1 （SOD-1）， mitochondrial transcription factor A homologous gene-5 （HMG-5）， mitochondrial power-associated protein 1 （DRP1）， and mitochondrial mitoprotein 1 （FIS1） was detected by real-time fluorescence quantitative polymerase chain reaction （RT-PCR）. ResultThe extract of LW could reduce the hypersensitivity of the AD model of nematodes to exogenous 5-HT （P<0.05） and delay the AD-like pathological characteristics of hypersensitivity to exogenous 5-HT caused by toxicity from overexpression of Aβ in neurons of the AD model of nematodes. Compared with the blank group， in the model group， the mRNA expression of Aβ protein and Amy-1 increased （P<0.01）， and the mRNA expression of SOD-1 and HMG-5 decreased （P<0.01）. The mRNA expression of DRP1 and FIS1 increased （P<0.01）， and the level of mitochondrial membrane potential decreased （P<0.05）. The content of ATP decreased （P<0.01）. Compared with the model group， in the positive medicine group and medium and high dose LW groups， the mRNA expression of Aβ protein and Amy-1 decreased （P<0.05，P<0.01）， and the mRNA expression of SOD-1 and HMG-5 increased （P<0.01）. The mRNA expression of DRP1 decreased （P<0.05，P<0.01）， and that of FIS1 decreased （P<0.01）. The level of mitochondrial membrane potential increased （P<0.01）， and the content of ATP increased （P<0.05，P<0.01）. ConclusionThe extract of LW may enhance the antioxidant ability of mitochondria， protect mitochondrial DNA， reduce the fragmentation of mitochondrial division， repair the damaged mitochondria， adjust the mitochondrial membrane potential， restore the level of neuronal ATP， and reduce the neuronal damage caused by Aβ deposition.

Bronchial asthma （asthma for short） is a common clinical respiratory disease mainly characterized by chronic airway inflammation， with complicated pathogenesis and a long treatment cycle. It is lingering and difficult to be cured， and lack specific drugs. Oxidative stress is a new focus in the research on the pathogenesis of asthma and a potential key target for the treatment. Under physiological conditions， the oxidative and antioxidative systems in the body are in a dynamic balance， and the two antagonize each other to maintain normal life activities. In the case of asthma attack， oxidation products such as reactive oxygen species （ROS）， malondialdehyde （MDA）， and nitric oxide （NO） are produced excessively， while the content of antioxidants such as superoxide dismutase （SOD）， catalase （CAT）， and glutathione （GSH） is reduced. As a result， the oxidation exceeds the removal of oxidation products， which aggravates oxidative stress. In addition， the overproduction of ROS activates oxidative stress-related signaling pathways to produce pro-inflammatory factors， exacerbating inflammation， which leads to lung and airway tissue damage. In recent years， traditional Chinese medicine has garnering increasing attention because of the unique advantages in the treatment of asthma， especially in regulating redox balance， alleviating oxidative stress in asthma patients， and reducing inflammation. On the one hand， by inhibiting the mitogen-activated protein kinase （MAPK） and transcription factor （NF）-κB signaling pathways， traditional Chinese medicine can reduce the content of oxidation products and pro-inflammatory factors from the source. On the other hand， by activating the nuclear factor-erythroid 2-related factor 2 （NrF2） signaling pathway， traditional Chinese medicine can elevate the levels of antioxidant enzymes and enhance the antioxidant system to neutralize the excessive accumulation of oxidation products. Therefore， the adjustment of redox balance state by traditional Chinese medicine may be a new means and a new direction for the prevention and treatment of asthma in the future. This paper summarizes the oxidative stress-related pathways in the pathogenesis of asthma and reviews the latest research progress in the regulation of oxidative stress-related pathways by Chinese medicine extracts and prescriptions in the treatment of asthma， with a view to providing a fuller， more solid， and more scientific theoretical basis for the clinical and basic research on the prevention and treatment of asthma by traditional Chinese medicine.

Objective To analyze risk factors of acute respiratory failure(ARF)in patients with hypertriglyceridemia acute pancreatitis(HTG-AP)and construct a risk prediction model.Methods A total of 222 HTG-AP patients were included in this study and divided into the non-ARF group(176 cases)and the ARF group(46 cases)according to diagnostic guidelines for ARF.Clinical data of the two groups were compared and the predictive factors were screened.These selected factors were then utilized in a multivariate Logistic regression analysis to construct a Logistic regression model.Subsequent evaluation of the model′s predictive ability,accuracy and clinical utility was conducted through ROC,curve analysis,calibration plot examination and decision curve analysis(DCA),respectively.Results Compared with the non-ARF group,the levels of high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL)-C and albumin(ALB)were decreased in the ARF group(P＜0.05),while the levels of creatinine(Cr),urea nitrogen(BUN),aspartate aminotransferase(AST)and C-reactive protein(CRP)were increased,and the incidence of pleural fluid and ascites was also increased(P＜0.05).Multivariate Logistic regression analysis showed that higher levels of Cr and AST,lower levels of ALB,HDL-C and ascites were independent risk factors for HTG-AP complicated ARF(P＜0.05).Based on these results,a column-line prediction model for HTG-AP complicated ARF was established.After internal verification,the area under curve(AUC)of receiver operating characteristic(ROC)curve of the nomogram model was 0.952(95%CI:0.923-0.981),the Youden index was 0.808 and the sensitivity and specificity were 93.33%and 87.43%,respectively.The calibration curve showed that the probability of HTG-AP concurrent ARF predicted by the model was in good agreement with the actual probability.The DCA curve showed that the model had certain clinical value.Conclusion The nomogram prediction model combined could provide a scheme for the clinical prevention of HTG-AP complicated with ARF.

This article focuses on a case study of sitosterolemia in a child who initially presented with hemolytic anemia and thrombocytopenia. Sitosterolemia is a rare autosomal recessive lipid metabolism disorder, difficult to diagnose due to its non-typical clinical manifestations. The 8-year-old patient was initially misdiagnosed with pyruvate kinase deficiency. Comprehensive biochemical and molecular biology analyses, including gene sequencing, eventually led to the correct diagnosis of sitosterolemia. This case highlights the complexity and diagnostic challenges of sitosterolemia, emphasizing the need for increased awareness and accurate diagnosis in patients presenting with similar symptoms.

Objective To observe the effect of Buyang Huanwu Decoction on hippocampal tissue structure and blood perfusion in rats with focal cerebral ischemia using multi-modal MRI;To analyze the mechanism of Buyang Huanwu Decoction on hippocampal neuroplasticity combined with the expression changes of neuroplasticity proteins and glucose metabolism related transporters.Methods Focal cerebral ischemia rat model induced by right middle cerebral artery occlusion were established.The rats were divided into sham-operation group,sham-operation+Buyang Huanwu Decoction group,model group and model+Buyang Huanwu Decoction group.The rats in the sham-operation group and model group were given normal saline for 30 days,and those in the sham-operation+Buyang Huanwu Decoction group and model+Buyang Huanwu Decoction group were given Buyang Huanwu Decoction for 30 days.T2 mapping imaging was used to detect the changes in hippocampal tissue structure,the changes of cerebral blood perfusion in hippocampus were detected by arterial spin labeling imaging,Western blot was used to detect the protein expressions of SYN,GAP-43,glucose transporters and MCT.Results Compared with the sham-operation group,the T2 relaxation time of the right and left hippocampus in the model group rats significantly increased(P<0.01,P<0.001),the blood flow in the right hippocampus was significantly reduced(P<0.05),the protein expressions of SYN,GAP-43,MCT4 and MCT2 in the right hippocampus were significantly decreased(P<0.01,P<0.001),the protein expressions of GLUT1 and GLUT3 in bilateral hippocappal tissue significantly decreased(P<0.05,P<0.01,P<0.001).Compared with the model group,the T2 relaxation time in the right hippocampus of rats in model+Buyang Huanwu Decoction group was significantly reduced(P<0.05),the blood flow in the right hippocampus significantly increased(P<0.05),the protein expressions of SYN,GAP-43,GLUT1 and GLUT3 in bilateral hippocampal tissues significantly increased(P<0.01,P<0.001),and the protein expressions of MCT4 and MCT2 in right hippocampal tissue significantly increased(P<0.01,P<0.001).Conclusion Buyang Huanwu Decoction can alleviate hippocampal injury in rats with focal cerebral ischemia,which may be related to improving blood perfusion,up-regulating neuroplasticity-related proteins,promoting hippocampal axon regeneration and synaptic remodeling,regulating energy metabolism of nerve cells.

Central nervous system （CNS） is a sophisticated system subject to complex regulation， which dominates the high-level neural activities of the human body. Due to its complex physiological structure and refined regulatory mechanism covering a variety of diseases， CNS is the place where many chronic， refractory and rare diseases occur. Nerve cell is the basic unit of CNS， and its dysfunction and death is the root cause of CNS diseases. Ferroptosis is a new form of programmed cell death proposed in recent years， and has been proved to be closely related to the production and development of multiple CNS diseases. Traditional Chinese medicine （TCM）， including Chinese herbs， acupuncture and moxibustion， and massage， has shown unique advantages in the treatment of CNS diseases for a long time. A large number of studies have demonstrated that TCM participates in the regulation of CNS diseases via regulating ferroptosis and shows a good research prospect. This paper summarized the characteristics of ferroptosis and discussed the association between ferroptosis and CNS diseases in pathological mechanism. We also reviewed the regulation of various CNS diseases by different TCM interventions through ferroptosis， providing references for TCM to participate in the treatment of CNS diseases properly in the future.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.