Neurodegenerative diseases are a group of chronic progressive diseases characterized by inflammation,degenera-tion and apoptosis.Chronic neuroinflammation is gradually becoming a potential pathogenic and predisposing factor.As a widely expressed non-histone nucleoprotein,HMGB1 participates in inflammatory process of human body through receptors of advanced glycation end products and Toll-like receptors while maintaining chromosome homeostasis.As a key factor of neuroinflammation,HMGB1 is widely involved in development of neurodegenerative diseases and may become a biomarker and a potential therapeutic target of neurodegenerative diseases.This article reviews the role of HMGB1 in neurodegenerative diseases and tries to provide ground-work for basic research and clinical application for targeting HMGB1 in the treatment of neurodegenerative diseases.

Objective To investigate the relationship between the serum levels of lncRNA mathematically expressed gene 3(lncRNA MEG3),lncRNA SRY-box transcription factor 2 overlapping transcript(lncRNA SOX2OT)and renal function and prognosis in patients with type 2 diabetic nephropathy(T2DN).Methods 205 patients with T2DN admitted to Shaanxi Provincial People's Hospital from January 2019 to January 2021(T2DN group)were selected,as well as 150 simple T2DM patients(T2DM group)and 150 healthy individuals(control group)during the same period.And the patients with T2DN were classified into the poor prognosis group(n=73)and the good prognosis group(n=132)according to the 3-year prognosis.Serum levels of lncRNA MEG3 and lncRNA SOX2OT were detected.Pearson analysis was used for correlation analysis;The influencing factors were analyzed using logistic regression,and the predictive value was evaluated using the subject's work characteristic curve.Results The serum lncRNA MEG3(2.20±0.32)in the T2DN group was higher than that in the T2DM group(1.49±0.20)and control group(1.00±0.06),and the lncRNA SOX2OT(0.50±0.11)was lower than that in the T2DM group(0.73±0.15)and control group(1.05±0.16),the differences were statistically significant(t=23.960,45.322;28.745,16.670,all P<0.01).The serum lncRNA MEG3 levels in T2DN patients were negatively correlated with estimated glomerular filtration rate(eGFR)and positively correlated with urinary albumin/creatinine ratio(UACR)levels(r=-0.532,0.485,all P<0.01)and the serum lncRNA SOX2OT level was positively correlated with eGFR and negatively correlated with UACR(r=0.421,-0.517,all P<0.01).The risk factors for poor prognosis in T2DN patients were chronic kidney disease stage 4,UACR and lncRNA MEG3(Wald χ2=6.360,6.678,16.652,all P＜0.05)while the protective factors were eGFR,lncRNA SOX2OT(Wald χ2=5.463,11.797,all P＜0.05).The AUC predicted by the combination of serum lncRNA MEG3 and lncRNA SOX2OT was larger than that predicted by lncRNA MEG3 and lncRNA SOX2OT predicts separately,and the differences were statistically significant(Z=3.841,3.337,all P<0.05).Conclusion Elevated serum lncRNA MEG3 levels and reduced lncRNA SOX2OT levels are associated with reduced renal function and poor prognosis in patients with T2DN,and the combination of the two tests has a high predictive value for poor prognosis in patients with T2DN.

Eight new diterpenoids, Isodons A-H (1-8), comprising seco-abietane and abietane-type structures, together with 13 known analogues (9-21), were isolated from Isodon lophanthoides (Buch.-Ham. ex D. Don) Hara. The compounds (+)-3/(-)-3, (+)-4/(-)-4, and (+)-5/(-)-5 were identified as three enantiomeric pairs. The planar structures and absolute configurations of 1-8 were determined through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1D & 2D nuclear magnetic resonance (NMR) spectroscopy, electronic circular dichroism (ECD) calculations, and X-ray diffraction crystallography. A cholesterol 7α-hydroxylase (Cyp7a1) luciferase reporter assay revealed significant anti-cholestatic activities for compounds 1, (+)-4, 6, 7, 12-14, and 16. Additionally, compound 6 demonstrated anti-cholestatic effects through the farnesoid X receptor (FXR)-associated signaling pathways in vitro and in vivo. These findings suggest potential applications for I. Lophanthoides in pharmaceutical development.
Abietanes/pharmacology* ; Molecular Structure ; Animals ; Isodon/chemistry* ; Humans ; Diterpenes/pharmacology* ; Plant Extracts/chemistry*

Objective To investigate the relationship between the serum levels of lncRNA mathematically expressed gene 3(lncRNA MEG3),lncRNA SRY-box transcription factor 2 overlapping transcript(lncRNA SOX2OT)and renal function and prognosis in patients with type 2 diabetic nephropathy(T2DN).Methods 205 patients with T2DN admitted to Shaanxi Provincial People's Hospital from January 2019 to January 2021(T2DN group)were selected,as well as 150 simple T2DM patients(T2DM group)and 150 healthy individuals(control group)during the same period.And the patients with T2DN were classified into the poor prognosis group(n=73)and the good prognosis group(n=132)according to the 3-year prognosis.Serum levels of lncRNA MEG3 and lncRNA SOX2OT were detected.Pearson analysis was used for correlation analysis;The influencing factors were analyzed using logistic regression,and the predictive value was evaluated using the subject's work characteristic curve.Results The serum lncRNA MEG3(2.20±0.32)in the T2DN group was higher than that in the T2DM group(1.49±0.20)and control group(1.00±0.06),and the lncRNA SOX2OT(0.50±0.11)was lower than that in the T2DM group(0.73±0.15)and control group(1.05±0.16),the differences were statistically significant(t=23.960,45.322;28.745,16.670,all P<0.01).The serum lncRNA MEG3 levels in T2DN patients were negatively correlated with estimated glomerular filtration rate(eGFR)and positively correlated with urinary albumin/creatinine ratio(UACR)levels(r=-0.532,0.485,all P<0.01)and the serum lncRNA SOX2OT level was positively correlated with eGFR and negatively correlated with UACR(r=0.421,-0.517,all P<0.01).The risk factors for poor prognosis in T2DN patients were chronic kidney disease stage 4,UACR and lncRNA MEG3(Wald χ2=6.360,6.678,16.652,all P＜0.05)while the protective factors were eGFR,lncRNA SOX2OT(Wald χ2=5.463,11.797,all P＜0.05).The AUC predicted by the combination of serum lncRNA MEG3 and lncRNA SOX2OT was larger than that predicted by lncRNA MEG3 and lncRNA SOX2OT predicts separately,and the differences were statistically significant(Z=3.841,3.337,all P<0.05).Conclusion Elevated serum lncRNA MEG3 levels and reduced lncRNA SOX2OT levels are associated with reduced renal function and poor prognosis in patients with T2DN,and the combination of the two tests has a high predictive value for poor prognosis in patients with T2DN.

Objective:To investigate the role of vitamin E succinate (VES) in inducing autophagy of human gastric cancer cells by activating calcium redistribution through inositol 1, 4, 5-trisphosphate receptors (IP 3R) pathway. Methods:Human gastric cancer lines MKN28 (moderately differentiated) and MKN45 (poorly differentiated) cells were cultured in vitro in March 2022. Gastric cancer cells were treated with VES at different doses for 24 h, and cell viability was measured by CCK-8 method to determine VES dose for subsequent study. The experiment was set up with solvent control group (0.1% ethanol), VES dose groups, 100 nmol/L rapamycin (RAPA) as autophagy positive control group (RAPA group), 15 μg/ml tunicamycin (TM) was used as the endoplasmic reticulum stress (ERS) positive control group (TM group), 10 μmol/ml 2-aminoethyl diphenylborinate (2-APB group) was used to inhibit IP 3R (2-APB group) and VES+2-APB group. The occurrence of autophagosomes in gastric cancer cells was observed by transmission electron microscopy, and microtubule associated protein 1 light chain 3 (LC3), Beclin1, IP 3R, glucose-regulated protein 75 (Grp75), voltage-dependent anion channel 1 (VDAC1) protein expression was detected by western blotting. Fluo-4 AM was used to label intracellular calcium ions, Rhod-2 AM was used to label mitochondrial calcium ions, and the fluorescence intensity of calcium ions was observed by fluorescence microscope. One-way analysis of variance was used to compare the means among multiple groups, and LSD- t method was used for pairwise comparison. Results:CCK-8 results showed that compared with solvent control group, the proliferation rates of MKN28 cells in 10-100 μg/ml VES group and MKN45 cells in 20-100 μg/ml VES group were significantly decreased ( P<0.05). Subsequent VES dosages were determined according to the growth curve, MKN28 was 5, 10, 20, 40 μg/ml, and MKN45 was 10, 20, 40, 80 μg/ml. The results of transmission electron microscopy and fluorescence showed that autophagosomes were formed in MKN28 cells in 5 and 20 μg/ml VES groups and MKN45 cells in 10 and 40 μg/ml VES groups, and the fluorescence intensity of calcium ions in cytoplasm and mitochondria was significantly higher than that in solvent control group ( P<0.05). Compared with solvent control group, LC3, Beclin1, IP 3R, Grp75 and VDAC1 protein expressions of MKN28 cells in 20 and 40 μg/ml VES groups and MKN45 cells in 40 and 80 μg/ml VES groups were significantly increased ( P<0.05). After inhibiting IP 3R with 2-APB, the expression levels of IP 3R, Grp75 and VDAC1 in two kinds of gastric cancer cells in VES+2-APB group were significantly decreased compared with VES group ( P<0.05). The fluorescence results showed that the fluorescence intensity of cytoplasmic and mitochondrial calcium ions in VES+2-APB groups was significantly lower than that in VES group ( P<0.05). Compared with VES group, LC3 and Beclin1 protein expressions in two kinds of gastric cancer cells in VES+2-APB groups were significantly decreased ( P<0.05) . Conclusion:VES may activate intracellular calcium redistribution through IP 3R-Grp75-VDAC1 calcium channel and induce autophagy in gastric cancer cells.

Neurodegenerative diseases are a group of chronic progressive diseases characterized by inflammation,degenera-tion and apoptosis.Chronic neuroinflammation is gradually becoming a potential pathogenic and predisposing factor.As a widely expressed non-histone nucleoprotein,HMGB1 participates in inflammatory process of human body through receptors of advanced glycation end products and Toll-like receptors while maintaining chromosome homeostasis.As a key factor of neuroinflammation,HMGB1 is widely involved in development of neurodegenerative diseases and may become a biomarker and a potential therapeutic target of neurodegenerative diseases.This article reviews the role of HMGB1 in neurodegenerative diseases and tries to provide ground-work for basic research and clinical application for targeting HMGB1 in the treatment of neurodegenerative diseases.

Objective:To investigate the role of vitamin E succinate (VES) in inducing autophagy of human gastric cancer cells by activating calcium redistribution through inositol 1, 4, 5-trisphosphate receptors (IP 3R) pathway. Methods:Human gastric cancer lines MKN28 (moderately differentiated) and MKN45 (poorly differentiated) cells were cultured in vitro in March 2022. Gastric cancer cells were treated with VES at different doses for 24 h, and cell viability was measured by CCK-8 method to determine VES dose for subsequent study. The experiment was set up with solvent control group (0.1% ethanol), VES dose groups, 100 nmol/L rapamycin (RAPA) as autophagy positive control group (RAPA group), 15 μg/ml tunicamycin (TM) was used as the endoplasmic reticulum stress (ERS) positive control group (TM group), 10 μmol/ml 2-aminoethyl diphenylborinate (2-APB group) was used to inhibit IP 3R (2-APB group) and VES+2-APB group. The occurrence of autophagosomes in gastric cancer cells was observed by transmission electron microscopy, and microtubule associated protein 1 light chain 3 (LC3), Beclin1, IP 3R, glucose-regulated protein 75 (Grp75), voltage-dependent anion channel 1 (VDAC1) protein expression was detected by western blotting. Fluo-4 AM was used to label intracellular calcium ions, Rhod-2 AM was used to label mitochondrial calcium ions, and the fluorescence intensity of calcium ions was observed by fluorescence microscope. One-way analysis of variance was used to compare the means among multiple groups, and LSD- t method was used for pairwise comparison. Results:CCK-8 results showed that compared with solvent control group, the proliferation rates of MKN28 cells in 10-100 μg/ml VES group and MKN45 cells in 20-100 μg/ml VES group were significantly decreased ( P<0.05). Subsequent VES dosages were determined according to the growth curve, MKN28 was 5, 10, 20, 40 μg/ml, and MKN45 was 10, 20, 40, 80 μg/ml. The results of transmission electron microscopy and fluorescence showed that autophagosomes were formed in MKN28 cells in 5 and 20 μg/ml VES groups and MKN45 cells in 10 and 40 μg/ml VES groups, and the fluorescence intensity of calcium ions in cytoplasm and mitochondria was significantly higher than that in solvent control group ( P<0.05). Compared with solvent control group, LC3, Beclin1, IP 3R, Grp75 and VDAC1 protein expressions of MKN28 cells in 20 and 40 μg/ml VES groups and MKN45 cells in 40 and 80 μg/ml VES groups were significantly increased ( P<0.05). After inhibiting IP 3R with 2-APB, the expression levels of IP 3R, Grp75 and VDAC1 in two kinds of gastric cancer cells in VES+2-APB group were significantly decreased compared with VES group ( P<0.05). The fluorescence results showed that the fluorescence intensity of cytoplasmic and mitochondrial calcium ions in VES+2-APB groups was significantly lower than that in VES group ( P<0.05). Compared with VES group, LC3 and Beclin1 protein expressions in two kinds of gastric cancer cells in VES+2-APB groups were significantly decreased ( P<0.05) . Conclusion:VES may activate intracellular calcium redistribution through IP 3R-Grp75-VDAC1 calcium channel and induce autophagy in gastric cancer cells.

BACKGROUND:Cerebral ischemic stroke is one of the main fatal and disabling diseases in the clinic,but only a few patients benefit from vascular recanalization in time,so it is urgent to explore new and effective therapy.As one of the critical pathological changes of ischemic stroke,the glial scar formed mainly by astrocytes is one major cause that hinders axonal regeneration and neurological recovery at the late stage of stroke. OBJECTIVE:To elucidate the pathological process and crucial signal regulatory mechanism of astrocytes in the formation of glial scar after ischemic stroke,as well as the potential therapeutic targets,to provide a theoretical reference for intervening astrocytic scar formation against ischemic stroke effectively,and novel strategies for promoting post-stroke rehabilitation. METHODS:The relevant articles published in CNKI,PubMed and Web of Science databases from 2010 to 2022 were retrieved.The search terms were"Ischemic stroke,Brain ischemi*,Cerebral ischemi*,Astrocyt*,Astroglia*,Glial scar,Gliosis,Astrogliosis"in Chinese and English.Finally,78 articles were included after screening and summarized. RESULTS AND CONCLUSION:(1)Astrocytes play an important role in the maintenance of central nervous system homeostasis.After ischemic stroke,astrocytes change from a resting state to an active state.According to the different severities of cerebral ischemic injury,astrocyte activation changes dynamically from swelling and proliferation to glial scar formation.(2)Mature astrocytes are stimulated to restart the cell cycle,then proliferate and migrate to lesions,which is the main source of the glial scar.Neural stem cells in the subventricular zone,neuron-glial antigen 2 precursor cells and ependymal precursor cells in the brain parenchyma can also differentiate into astrocytes.Endothelin-1,aquaporin 4,ciliary neurotrophic factor and connexins are involved in this process.In addition,chondroitin sulfate proteoglycan,as the main component of the extracellular matrix,forms the dense glial scar barrier with proliferated astrocytes,which hinders the polarization and extension of axons.(3)Activation or inhibition of crucial signal molecules involved in astrocyte activation,proliferation,migration and pro-inflammation functions regulate the glial scar formation.Transforming growth factor beta 1/Smad and Janus kinase/signal transducer and activator of transcription 3 are classical pathways related to astrogliosis,while receptor-interacting protein 1 kinase and glycogen synthase kinase 3β are significant molecules regulating the inflammatory response.However,there are relatively few studies on Smad ubiquitination regulatory factor 2 and Interleukin-17 and their downstream signaling pathways in glial scar formation,which are worthy of further exploration.(4)Drugs targeting astrogliosis-related signaling pathways,cell proliferation regulatory proteins and inflammatory factors effectively inhibit the formation of glial scar after cerebral ischemic stroke.Among them,the role of commonly used clinical drugs such as melatonin and valproic acid in regulating glial scar formation has been verified,which makes it possible to use drugs that inhibit glial scar formation to promote the recovery of neurological function in patients with stroke.(5)Considering the protective effects of glial scar in the acute phase,how to choose the appropriate intervention chance of drugs to maintain the protective effect of the glial scar while promoting nerve regeneration and repair in the local microenvironment is the direction of future efforts.

Objective:To evaluate the efficacy and safety of CD30 antibody-drug conjugates (ADC) brentuximab vedotin (BV) combined with chemotherapy in children with refractory or relapsed classic Hodgkin′s lymphoma (R/R cHL).Methods:Clinical data (including age, gender, B symptoms, clinical stage, previous treatment, etc.) of the 10 R/R cHL children diagnosed and treated at Beijing Children′s Hospital Affiliated to Capital Medical University from October 2021 to August 2023 were analyzed retrospectively. According to the different intensity of chemotherapy drugs, the dose of BV applied in the same course of treatment was 1.8 mg/kg for BV applied once every 3 weeks, and 1.2 mg/kg for BV applied once every 2 weeks. All 10 patients received at least 2 cycles of BV combined with chemotherapy and were evaluated every 2 cycles. The patients were followed up until May 31, 2024. The infusion reactions and adverse reactions after treatment were recorded.Results:In all 10 patients, there were 7 males and 3 females, the age ranged from 5.3-16.9 years, and there were 6 cases of refractory and 4 cases of relapsed. There were 6 cases of nodular sclerosis type, 2 cases of mixed cell type, 1 case of lymphocyte-rich type, and 1 case of lymphodepletion type. There were 5 cases of stage Ⅳ and 5 cases of stage Ⅲ. Previous treatment was mainly chemotherapy, 4 cases received radiotherapy and 1 case received programmed cell death protein 1 (PD-1) antibody therapy. The follow-up time ranged from 9 to 27 months. A total of 43 courses with 49 doses of BV alone or combined with chemotherapy were recorded, and the number of courses was 2 to 10 times. All 10 children responded to the treatment, and 9 achieved complete remission. BV infusion was successfully completed in all cases. A total of 28 cases of grade 3 or above adverse events were recorded, mainly myelosuppression, all of which were related to chemotherapy and did not affect sequential treatment.Conclusion:Brentuximab vedotin has demonstrated efficacy and a tolerable safety profile in the treatment of refractory and relapsed CD30-positive Hodgkin′s lymphoma in children.

Objective:To explore the application effect of integrated Chinese and Western medicine nursing based on the individual and family self-management theory (IFSMT) in patients with urinary incontinence after stroke, and provide reference for clinical nurses to effectively rehabilitate these patients.Methods:This was a quasi-experimental study. A total of 136 patients with urinary incontinence after stroke who were hospitalized in the Department of Encephalopathy of Shanxi Acupuncture and Moxibology Hospital from February 2022 to May 2023 were selected as the study objects by convenience sampling method. The subjects were divided into the control group and the experimental group with 68 cases in each group by random number table method. The control group received routine rehabilitation nursing, and the experimental group received integrated Chinese and western medicine nursing based on IFSMT on the basis of routine rehabilitation nursing. Urinary status, activities of daily living and quality of life of 2 groups were compared.Results:Ultimately, there were 68 cases were admitted in each group. In the control group, male 45 cases, female 23 cases, aged (62.35 ± 4.94) years old. In the experimental group, male 49 cases, female 19 cases, aged (61.94 ± 5.02) years old. There was no statistical significance in urinary status, activities of daily living and quality of life scores between the 2 groups before the intervention (all P>0.05). After the intervention, the average daily urination frequency of experimental group was (7.94 ± 1.08) times, which was lower than that of control group (9.88 ± 1.09) times; the average daily frequency of incontinence in the experimental group was (3.63 ± 1.65) times, lower than (5.03 ± 3.35)times in the control group; the average daily urine volume of experimental group was (107.34 ± 4.15) ml, higher than (89.62 ± 19.71) ml of control group, and the differences were statistically significant ( t=10.46,3.09, -7.23, all P<0.05). The scores of activities of daily living in the experimental group was (60.44 ± 3.65) points, which were higher than (46.24 ± 3.29) points in the control group; the Incontinence Quality of Life Questionnaire score of experimental group was (80.38 ± 4.65) points, which was higher than (64.62 ± 5.62) points of control group; Insomnia Severity Index-Short Form score of the experimental group was (10.94 ± 5.17) points, which was lower than (12.85 ± 4.30) points of the control group, and the differences were statistically significant ( t=23.85, -17.86, 2.34, all P<0.05). Conclusions:Integrated Chinese and western medicine nursing intervention based on IFSMT has a positive effect on patients with urinary incontinence after stroke, and can significantly improve patients' urination and daily living activities, thus improving patients' quality of life.