OBJECTIVE To investigate the effects and potential mechanism of persimmon leaf （PL） extract against ferroptosis induced by H2O2 in IEC-6 cells. METHODS Using IEC-6 cells as object， the effects of ferroptosis inhibitor ferrostatin-1 on IEC-6 cell viability induced by H2O2 were investigated； IEC-6 cells were divided into control group， H2O2 group， H2O2+PL 25 μg/mL group and H2O2+PL 50 μg/mL group. The levels of oxidant stress indexes [content of malondialdehyde （MDA）， activity of superoxide dismutase （SOD）， and levels of reactive oxygen species （ROS）]， mitochondrial membrane potential （MMP） as well as mRNA and protein expressions of nuclear factor-erythroid-2 related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， NADPH/quinone oxidoreductase-1 （NQO-1）， cystine/glutamate anti-porter （xCT）， glutathione peroxidase 4 （GPX4） and ferritin heavy chain （FTH） were detected. RESULTS Ferroptosis inhibitor ferrostatin-1 could significantly increase the survival rate of H2O2-induced cells （P＜ 0.01）. Compared with the control group， MDA content， ROS level， mRNA expressions of Nrf2 and NQO-1 as well as protein expressions of Nrf2 and HO-1 were increased or up-regulated significantly， while SOD activity， MMP， mRNA expressions of xCT， GPX4 and FTH as well as protein expressions of GPX4 and FTH were decreased or down-regulated significantly （P＜0.01 or P＜0.05）. Compared with the H2O2 group， oxidative stress Δ indexes of H2O2+PL 25， 50 μg/mL groups were reversed to different extents， MMP level was increased significantly， as well as mRNA and protein expressions of Nrf2， HO-1， NQO-1，xCT， GPX4 and FTH were up-regulated to different extents；there were statistical significances in some indexes between groups （P＜0.01 or P＜0.05）. CONCLUSIONS PL extract can alleviate mitochondrial membrane damage and abnormal accumulation of ROS caused by H2O2， which may be related to the inhibition of ferroptosis by activating the Nrf2/HO-1 signaling pathway.

Objective To explore the safety of Yttrium-90 resin microsphere selective internal radiation therapy (⁹⁰Y-SIRT) on malignant liver tumors. Methods A retrospective analysis was conducted on 64 patients with malignant liver tumors who underwent ⁹⁰Y-SIRT from February 2023 to November 2024 at Weifang People’s Hospital. The clinical characteristics of the patients and the occurrence of adverse reactions after treatment were analyzed to assess the safety of ⁹⁰Y-SIRT. Results Among the 64 patients, there were 52 males (81.25%) and 12 females (18.75%); the average age was (56.29±11.08) years. Seven patients (10.94%) had tumors with maximum diameter of less than 5 cm, 38 patients (59.38%) had tumors with maximum diameter of 5-10 cm, and 19 patients (29.68%) had tumors with maximum diameter of greater than 10 cm. There were 47 cases (73.44%) of solitary lesions and 17 cases (26.56%) of multiple lesions; 53 cases (82.81%) were primary liver cancers and 11 cases (17.19%) were metastatic liver cancers. Of the 64 patients, 63 successfully completed the Technetium-99m macroaggregated albumin (^99mTc-MAA) perfusion test and received the ⁹⁰Y-SIRT; one patient received ⁹⁰Y-SIRT after the second ^99mTc-MAA perfusion test due to a work error. The most common adverse reactions included grade 1 alanine aminotransferase (ALT) elevation in 26 cases (40.62%) and grade 2 in 2 cases (9.37%), grade 1 aspartate aminotransferase (AST) elevation in 27 cases (42.18%) and grade 2 in 7 cases (10.93%); grade 1 nausea in 17 cases (26.56%) and grade 2 in 6 cases (9.37%); grade 1 abdominal pain in 12 cases (18.75%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%); grade 1 vomiting in 11 cases (17.18%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%). Conclusion The adverse reactions of ⁹⁰Y-SIRT for treating malignant liver tumors are mild, indicating good safety.

ObjectiveTo investigate the value of noninvasive imaging detection （FibroScan）， two serological models of gamma-glutamyl transpeptidase-to-platelet ratio （GPR） score and S index， and two inflammatory factors of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in predicting liver fibrosis in patients with HBeAg-positive chronic hepatitis B （CHB）， as well as the consistency of liver biopsy in pathological staging， and to provide early warning for early intervention of CHB. MethodsA retrospective analysis was performed for 131 HBeAg-positive CHB patients who underwent liver biopsy in The Third People’s Hospital of Kunming from January 2019 to December 2023. The results of liver biopsy were collected from all patients， and related examinations were performed before liver biopsy， including total bilirubin， alanine aminotransferase， platelet count， gamma-glutamyl transpeptidase， albumin， IL-6， TNF-α， liver stiffness measurement （LSM）， and abdominal ultrasound. An analysis of variance was used for comparison of normally distributed continuous data between groups， and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical data between groups. A Kappa analysis was used to investigate the consistency between LSM noninvasive histological staging and pathological staging based on liver biopsy， and the Spearman analysis was used to investigate the correlation between each variable and FibroScan in the diagnosis of liver fibrosis stage. The Logistic regression analysis was used to construct joint predictive factors. The receiver operating characteristic （ROC） curve was used to evaluate the value of each indicator alone and the joint predictive model in the diagnosis of liver fibrosis， and the Delong test was used for comparison of the area under the ROC curve （AUC）. ResultsIn the consistency check， inflammation degree based on liver biopsy had a Kappa value of 0.807 （P<0.001）， and liver fibrosis degree based on liver biopsy had a Kappa value of 0.827 （P<0.001）， suggesting that FibroScan noninvasive histological staging and liver biopsy showed good consistency in assessing inflammation degree and liver fibrosis stage. Age was positively correlated with LSM， GPR score， S index， IL-6， and TNF-α （all P<0.05）， and GPR score， S index， IL-6， and TNF-α were positively correlated with LSM （all P<0.05）. GPR score， S index， IL-6， and TNF-α were all independent risk factors for diagnosing significant liver fibrosis （≥S2） and progressive liver fibrosis （≥S3） （all P<0.05）. As for each indicator alone， GPR score had the highest value in the diagnosis of significant liver fibrosis （≥S2）， followed by S index， IL-6， and TNF-α， while S index had the highest value in the diagnosis of progressive liver fibrosis （≥S3）， followed by GPR score， TNF-α， and IL-6. The joint model had a higher predictive value than each indicator alone （all P<0.05）. ConclusionThere is a good consistency between FibroScan noninvasive histological staging and pathological staging based on liver biopsy. GPR score， S index， IL-6， and TNF-α are independent risk factors for evaluating different degree of liver fibrosis in CHB， and the combined prediction model established by them can better diagnose liver fibrosis.

BACKGROUND:Type 2 diabetes mellitus impairs renal function,and studies have shown that exercise interventions can protect the kidneys.Irisin can protect renal function in diabetic nephropathy patients by restoring autophagy through inhibition of the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway. OBJECTIVE:To explore whether exercise can restore autophagy and ameliorate renal injury by inhibiting over-activation of the renal PI3K/Akt/mTOR signaling pathway,as well as to analyze the differences in the effects of different modalities of exercise. METHODS:Six-week-old Sprague-Dawley rats were randomly divided into a blank control group(normal rats)and a diabetic group,and then the diabetic group was randomly divided into a diabetic model group,a moderate-intensity continuous exercise group,and a high-intensity intermittent exercise group after successful modeling using high-fat,high-sugar feeding plus intraperitoneal administration of low-dose 1%streptozotocin(30 mg/kg).The two exercise groups were subjected to 8 weeks of exercise intervention with different exercise intensities.The fasting blood glucose concentration was detected by glucose oxidase method,glycated hemoglobin levels was measured using a kit,serum insulin concentration was detected by Elisa method,and insulin resistance index was calculated.Gene expression of PI3K,AKT,mTOR,Beclin-1,podocin,and nephrin was detected by RT-PCR.Protein expression of mTOR and autophagy marker proteins LC3-1,LC3-2,and Beclin-1 was detected by western blot RESULTS AND CONCLUSION:Fasting blood glucose and glycosylated hemoglobin levels were highly significantly increased,insulin resistance levels were significantly increased,and insulin levels were significantly decreased in type 2 diabetic rats.Both exercises resulted in highly significant decreases in fasting blood glucose and glycosylated hemoglobin levels,significant decreases in insulin resistance levels and significant increases in insulin levels in type 2 diabetic rats.Insulin levels were significantly higher in the high-intensity intermittent exercise group compared with the moderate-intensity continuous exercise group.The expression of podocin and nephrind genes was significantly reduced in type 2 diabetic rats and two different forms of exercise significantly the gene expression.There was a further trend toward an increase in gene expression of podocyte-associated proteins in the moderate-intensity continuous exercise group compared with the high-intensity intermittent exercise group,but there was no significant difference.The mRNA and protein expression of PI3K,AKT and mTORC1 in kidney tissues of type 2 diabetic rats were significantly increased,and the expression of autophagy marker proteins Beclin-1 and LC3-2 and LC3-2/LC3-1 were significantly decreased.Both different forms of exercise significantly decreased the mRNA and protein expression of PI3K,AKT,and mTORC1,and significantly increased the autophagy marker proteins Beclin-1,LC3-2,and LC3-2/LC3-1 in renal tissues.Compared with the moderate-intensity continuous exercise group,there was a trend toward further decreases in mRNA expression of PI3K,AKT,and mTORC1 and protein expression of mTOR,and a trend toward further elevation of Beclin-1,LC3-2,and LC3-2/LC3-1 in the high-intensity intermittent exercise group,but only Beclin-1 showed a significant difference between groups.In summary,renal podocyte injury in type 2 diabetes mellitus with suppressed autophagy is closely related to aberrant activation of the PI3K/AKT/mTORC1 signaling pathway.Both moderate-intensity continuous exercise and high-intensity intermittent exercise can protect the diabetic kidney,reduce podocyte damage,and restore renal podocyte autophagy,which may be achieved by inhibiting the excessive activation of the PI3K/AKT/mTOR signaling pathway.High-intensity intermittent exercise shows a trend toward more favorable restoration of autophagy compared with moderate-intensity continuous exercise,but with a slight decrease in podocyte protein expression.

ObjectiveBased on transcriptomics， to explore the mechanism of Hei Xiaoyaosan regulating the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway to improve the learning and memory ability of insomnia rats with liver depression syndrome. MethodsSixty 8-week-old male SD rats were randomly divided into the blank group， model group， eszopiclone group （0.09 mg·kg^-1）， and low， medium， and high dose groups of Hei Xiaoyaosan （3.82， 7.65， 15.30 g·kg^-1）， with ten rats in each group. Except for the blank group， the other groups were induced insomnia rat model with liver depression by chronic restraint， tail clamping stimulation and intraperitoneal injection of p-chlorophenylalanine （PCPA）. Each treatment group received intragastric administration according to the specified dosage， once a day for 14 consecutive days. The pentobarbital sodium cooperative sleep test， open field test， and Morris water maze test were used to test the sleep quality， depressive-like behavior， and learning and memory abilities of rats. Additionally， enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of 5-hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， brain-derived neurotrophic factor （BDNF）， glial cell line-derived neurotrophic factor （GDNF） and nitric oxide （NO） in hippocampus. Hematoxylin-eosin （HE） staining was performed to observe pathological changes of the hippocampal tissue， while terminal deoxynucleotidyl transferase deoxyuridine triphosphate （dUTP） nick end labeling （TUNEL） was used to evaluate apoptosis of hippocampal neurons. Transcriptomic sequencing technology was employed to identify differentially expressed genes in hippocampus between the model group and the blank group， as well as between the medium-dose group of Hei Xiaoyaosan and the model group. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis were performed on the intersecting genes. Subsequently， the enriched key genes and signaling pathways were analyzed and verified. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was utilized to assess the mRNA expression levels of phosphatase and tensin homolog （PTEN）， B-cell lymphoma-2 （Bcl-2）-like protein 11 （BCL2L11）， and mitogen-activated protein kinase 1 （MAPK1） in hippocampus， and Western blot was employed to evaluate the protein expressions of PI3K， phosphorylation （p）-PI3K， Akt， p-Akt， Bcl-2， Bcl-2-associated X protein （Bax）， and cleaved Caspase-3 in the same tissue. ResultsCompared with the blank group， the model group exhibited a reduction in body weight， an increase in sleep latency， and a decrease in sleep duration （P<0.01）. Additionally， rats showed obvious depression-like behavior， and their learning and memory abilities decreased. Furthermore， the contents of 5-HT， GABA， NO， BDNF and GDNF in hippocampus decreased （P<0.01）. Histological examination revealed a disorganized cell arrangement in the CA1 region of the hippocampus， characterized by irregular cell shapes， a reduced cell count， deeply stained and pyknotic nuclei， increased vacuolar degeneration， and an elevated apoptosis rate （P<0.01）. Compared with the model group， the body weight of the high and medium dose groups of Hei Xiaoyaosan increased， the sleep latency shortened and the sleep time prolonged （P<0.05， P<0.01）. Additionally， depression-like behavior and learning and memory abilities of rats were significantly improved， the levels of 5-HT， GABA， NO， BDNF and GDNF in the hippocampus increased （P<0.05， P<0.01）. These interventions also ameliorated pathological damage in the hippocampal CA1 area and reduced the apoptosis of hippocampal neurons （P<0.01）. Transcriptomic sequencing results indicated that Hei Xiaoyaosan might exert a therapeutic effect by regulating PI3K/Akt pathway through key mRNAs such as PTEN， BCL2L11， and MAPK1. The roles of these key mRNAs and proteins within PI3K/Akt pathway were further validated. In comparison to the blank group， the expression levels of PTEN， BCL2L11 and MAPK1 mRNA in the hippocampus of rats in the model group were increased （P<0.01）， while the protein expression levels of p-PI3K， p-Akt and Bcl-2 were decreased （P<0.01）， and the protein expression levels of PTEN， Bax and cleaved Caspase-3 were increased （P<0.01）. Compared with the model group， the high-dose and medium-dose groups of Hei Xiaoyaosan could down-regulate the expressions of PTEN， BCL2L11 and MAPK1 mRNAs （P<0.01）， up-regulate the expressions of p-PI3K， p-Akt and Bcl-2 proteins （P<0.01）， and down-regulate the protein expressions of PTEN， Bax and cleaved Caspase-3 （P<0.05， P<0.01）. ConclusionHei Xiaoyaosan may regulate PI3K/Akt signaling pathway by down-regulating expressions of key genes such as PTEN， BCL2L11 and MAPK1， and thus improve the learning and memory abilities of insomnia rats with liver depression syndrome.

Objective: To analyze the HLA typing and STR loci chimerism in a patient with recurrent acute lymphoblastic leukemia after HLA-haploidentical hematopoietic stem cell transplantation. Methods: HLA typing was performed on peripheral blood, buccal swabs and saliva samples after transplantation using PCR-sequence-specific oligonucleotide probes (PCR-SSOP) and next-generation sequencing (NGS). Additionally, STR analysis was conducted on these samples using a 21-locus STR assay kit to detect STR loci. Results: The HLA typing and STR locus outcomes of the patient's peripheral blood and the second saliva sample post-transplantation were in full concordance with the test results of the donor (father), whereas the HLA typing and STR locus results derived from the buccal swabs and the first saliva sample indicated chimerism between the donor and the recipient. Conclusion: In the follow-up and monitoring after transplantation, apart from focusing on peripheral blood samples, it is recommended to regularly monitor HLA typing and STR loci chimerism in patients' buccal swabs and saliva samples to comprehensively evaluate the transplantation effect and recurrence risk.

Objective: To analyze the HLA typing and STR loci chimerism in a patient with recurrent acute lymphoblastic leukemia after HLA-haploidentical hematopoietic stem cell transplantation. Methods: HLA typing was performed on peripheral blood, buccal swabs and saliva samples after transplantation using PCR-sequence-specific oligonucleotide probes (PCR-SSOP) and next-generation sequencing (NGS). Additionally, STR analysis was conducted on these samples using a 21-locus STR assay kit to detect STR loci. Results: The HLA typing and STR locus outcomes of the patient's peripheral blood and the second saliva sample post-transplantation were in full concordance with the test results of the donor (father), whereas the HLA typing and STR locus results derived from the buccal swabs and the first saliva sample indicated chimerism between the donor and the recipient. Conclusion: In the follow-up and monitoring after transplantation, apart from focusing on peripheral blood samples, it is recommended to regularly monitor HLA typing and STR loci chimerism in patients' buccal swabs and saliva samples to comprehensively evaluate the transplantation effect and recurrence risk.

Objective: To develop a simple digital chylous plasma device and validate its ability to accurately, standardly, and non-destructively determine chylous plasma in blood banks and clinical transfusions in hospitals. Methods: A digital chylous plasma assessment device was designed and manufactured. This device was used to measure the chylous degrees of chylous plasma samples before freezing, after freeze-thawing, before viral inactivation, and after viral inactivation. The measured chylosity index values were categorized according to the requirements specified in Appendix A of the Chinese national standard GB 18469-2001 "Quality Requirements for Whole Blood and Blood Components". This process established a digital standard for chylous plasma, enabling the identification of severe, moderate and mild chylous plasma, and non-chylous plasma. Results: The initial simple product of the digital chylous assessment device was successfully designed and manufactured. There was no significant difference in the degree of chylous plasma between pre-freezing 468.11±217.73 lux and post-thawing 538.91±273.39 lux of chylous plasma (P>0.05), or between pre-viral inactivation 858.33±387.79 lux and post-viral inactivation 928.33±166.51 lux of chylous plasma (P>0.05). The median of chylous degree values for plasma chylous index grades 0 to 6 were 45 lux, 250 lux, 620 lux, 835 lux, 1 130 lux, 1 390 lux, and 1 700 lux, respectively. The defined cutoff values/ranges for the chylous degree values corresponding to plasma chylous index grade 0 to 6 were ≤125 lux, 126-465 lux, 466-740 lux, 741-1 000 lux, 1 001-1 233 lux, 1 234-1 560 lux, and ≥1 561 lux. Conclusion: This study successfully developed the initial product of the digital chylous device and established digital standards for classifying chylous plasma. The device demonstrates the potential to meet the needs for assessment of chylous plasma in both blood banks and clinical transfusions in hospitals, thereby promoting the development and application of standardized, non-destructive chylous plasma assessment technology.

OBJECTIVE To explore comprehensive management and potential issues associated with long-term prescriptions medications of psychiatry， in order to provide a reference for the comprehensive management of long-term prescriptions of psychiatry in psychiatric hospitals and other medical institutions’ pharmacies. METHODS Starting from the applicable principles for long-term prescriptions of psychiatry， this study introduced the standardized assessment and precautions before issuing long-term prescriptions， the formulation and adjustment of the drug list， as well as the rational management of the long-term prescriptions. It also analyzed potential issues that may arise in the comprehensive management of long-term prescription medications and proposed corresponding countermeasures and suggestions. RESULTS & CONCLUSIONS Prior to initiating long-term prescriptions， a standardized assessment should be conducted on patients from the aspects of their psychiatric condition and long-term potential risk factors， pharmacological treatment plans and other non-pharmacological therapies， physical illnesses. Additionally， healthcare providers should fulfill their obligation to inform patients or their family members. The comprehensive management of long-term prescription medications should be jointly established and improved by multiple departments， and the formulation of drug catalogs should avoid including drugs with potential social harm or medication risks while complying with policy requirements. Furthermore， measures such as adding special identifiers to long-term prescriptions， providing patients with reminders about （No.YGLX202537） prescription expiration， or offering online consultations can also effectively enhance the rationality of medication use under long-term prescriptions. Currently， the implementation of long-term prescriptions in psychiatry remains challenged by inconsistencies in prescription duration， incomplete coverage of diagnostic categories， poor patient adherence， and the risk of deviation in clinical assessments. In this regard， measures such as collaborating with multiple departments to strengthen long-term prescription information management， providing matching pharmaceutical services， ensuring the quality and rationality of long-term prescription implementation， and using modern methods to screen high-risk patients can be taken to improve patient medication compliance and safety.

Objective: Exploring the effect and mechanism of Xinyang Tablet on reduction of ferroptosis in myocardial cells from mice with chronic heart failure. Methods: Sixty C57BL/6J mice were randomly assigned to the sham, model, Xinyang Tablet low-dose (0.34 g/kg), Xinyang Tablet medium-dose (0.68 g/kg), Xinyang Tablet high-dose (1.36 g/kg), and perindopril (0.607 mg/kg) groups using a random number table method (10 mice in each group). Except for the sham group, all other groups underwent aortic arch constriction surgery to construct a chronic heart failure model. On the third day after completion of the modeling, each treatment group was administered the corresponding medication by gavage, while the sham and model groups were administered equal volumes of water by gavage once a day for eight consecutive weeks. After treatment, cardiac ultrasound was used to detect the structure and function of the mouse heart. Hematoxylin and eosin staining was used to detect pathological changes in mouse heart tissue. Masson staining was used to detect the proportion of fibrotic area of mouse heart tissue. Realtime fluorescence PCR was used to detect the mRNA expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), collagen 3α (Col3α), and myosin heavy chain 7 (MYH7) in mouse myocardial tissue. Transmission electron microscope was used to detect the ultrastructure of myocardial cell mitochondria. Reactive oxygen species (ROS) staining was used to detect the mean fluorescence intensity of ROS in myocardial tissue. Micro-determination was used to detect superoxide dismutase (SOD) activity in myocardial tissue. An immunofluorescence assay was used to detect the mean fluorescence intensity of phosphorylated histone deacetylase 2 (p-HDAC2) in myocardial cell. Western blotting was used to detect the protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), p-HDAC2, nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), glutathione peroxidase 4 (GPX4), and cystine glutamate reverse transporter (xCT) in mouse myocardial tissue. Results: Compared to the sham group, the model group showed a decrease in left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), an increase in left ventricular end-systolic diameter(LVESD) and left ventricular end-diastolic diameter (LVEDD), an increase in the proportion of cardiac fibrosis area, an increase in relative expression levels of ANP, BNP, Col3α, and MYH7 mRNA, an increase in ROS mean fluorescence intensity, a decrease in SOD activity, an increase in mean fluorescence intensity of p-HDAC2, an increase in relative expression levels of p-HDAC2 and NOX1 proteins, and a decrease in relative expression levels of Nrf2, GPX4, and xCT proteins (P<0.05). Myocardial fibrosis lesions are obvious, with disordered mitochondrial arrangement, decreased volume and shrinkage, increased membrane density, and reduced mitochondrial cristae. Compared to the model group, the LVEF and LVFS of mice in each dose group of Xinyang Tablet and the perindopril group increased, LVESD and LVEDD decreased, the proportion of fibrotic area of heart tissue decreased, the relative expression levels of ANP, BNP, Col3α, MYH7 mRNA decreased, ROS mean fluorescence intensity decreased, SOD activity increased, mean fluorescence intensity of p-HDAC2 decreased, relative expression levels of p-HDAC2 and NOX1 proteins decreased, and relative expression levels of Nrf2 and xCT proteins increased (P<0.05). Myocardial fibrosis was reduced, the mitochondrial arrangement was more regular, the mitochondria enlarged, the membrane density was reduced, and mitochondrial cristae increased. Compared to the model group, the relative expression level of the GPX4 protein in myocardial tissue increased in the Xinyang Tablet medium-, high-dose, and the perindopril groups (P<0.05). Conclusion Xinyang Tablet can improve ferroptosis and ventricular remodeling in mice with chronic heart failure by regulating the HDAC2-mediated Nrf2 antioxidant pathway.