ObjectiveTo investigate the mechanism of liver injury induced by tripterygium glycosides tablets （TG） and the molecular mechanism of compound glycyrrhizin tablets （CG） in alleviating the abnormalities of cholesterol metabolism caused by TG via cholesterol metabolism. MethodsAccording to the body weights， male Sprague-Dawley （SD） rats were randomly grouped as follows： control （pure water）， low-dose TG （TG-L， 189.0 mg·kg^-1·d^-1）， high-dose TG （TG-H， 472.5 mg·kg^-1·d^-1）， TG-L+CG （189.0 mg·kg^-1·d^-1 TG + 20.25 mg·kg^-1·d^-1 CG）， and TG-H+CG （472.5 mg·kg^-1·d^-1 TG + 20.25 mg·kg^-1·d^-1 CG）， with 6 rats in each group. Rats were administrated with corresponding drugs once daily for 3 weeks. At the end of the last administration， the mRNA and protein levels of liver X receptor-alpha （LXR-α）， low-density lipoprotein receptor （LDLR）， adenosine triphosphate-binding cassette transporter A1 （ABCA1）， adenosine triphosphate-binding cassette transporter G1 （ABCG1）， 3-hydroxy-3-methylglutaryl coenzyme A reductase （HMGCR）， cholesterol 7α-hydroxylase （CYP7A1）， cholesterol 12α-hydroxylase （CYP8B1）， and sterol 27-hydroxylase （CYP27A1） in the liver tissue were determined by Real-time PCR and Western blotting， respectively. The level of 3-hydroxy-3-methylglutaryl coenzyme A reductase （HMG-CoAR）， a regulatory enzyme of cholesterol synthesis， was measured by enzyme-linked immunosorbent assay （ELISA）. HepG2 cells were used to observe the effect of TG on the cell proliferation in vitro. Specifically， HepG2 cells were grouped as follows： Low-dose TG （TG-l， 15 mg·L^-1）， medium-dose TG （TG-m， 45 mg·L^-1）， high-dose TG （TG-h， 135 mg·L^-1）， fenofibrate （FB， 10 μmol·L^-1）， CG extract， TG-h+FB （135 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-m+FB （45 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-l+FB （15 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-h+CG （135 mg·L^-1 TG + 60 μmol·L^-1 CG）， TG-m+CG （45 mg·L^-1 TG + 60 μmol·L^-1 CG）， and TG-l+CG （15 mg·L^-1 TG + 60 μmol·L^-1 CG）. The mRNA and protein levels of LXR-α， ABCG1， LDLR， CYP7A1， CYP8B1， and CYP27A1 in HepG2 cells were determined by Real-time PCR and Western blotting， respectively. ResultsThe rat experiment showed that compared with the control group， the TG-H group showed down-regulated mRNA levels of CYP7A1， CYP8B1， and CYP27A1 in the liver tissue （P<0.05， P<0.01）， which were up-regulated by the application of CG （P<0.05， P<0.01）， and the TG-H+CG group showed up-regulated mRNA level of LDLR （P<0.01）. Compared with the control group， the TG-L and TG-H groups showed down-regulated protein levels of LDLR， CYP7A1， and CYP8B1 in the liver tissue （P<0.05， P<0.01）. In addition， the protein levels of ABCG1 and LXR-α were down-regulated in the TG-H and TG-L groups， respectively （P<0.05）. Compared with TG alone， TG+CG up-regulated the protein levels of ABCG1 and LDLR （P<0.05， P<0.01）， and the protein levels of CYP7A1 and CYP8B1 in the TG-H+CG group were up-regulated （P<0.05， P<0.01）. The cell experiment showed that compared with the control group， the TG-h group presented up-regulated mRNA level of LXR-α （P<0.01）， and the TG-m and TG-h groups showcased down-regulated mRNA levels of LDLR and CYP7A1 （P<0.01） and up-regulated mRNA level of CYP27A1 （P<0.01） in HepG2 cells. The combination of CG with TG restored the above changes （P<0.01）. Western blotting results showed that compared with the control group， the TG-m and TG-h groups showed down-regulated protein levels of LXR-α， ABCG1， LDLR， CYP7A1， CYP8B1， and CYP27A1 in HepG2 cells （P<0.01）. Compared with the TG-h group， the TG-h+CG group showed up-regulated protein level of LDLR （P<0.05）. Compared with the TG-m group， the TG-m+CG group showcased up-regulated protein levels of LDLR， ABCG1， CYP7A1， and CYP27A1 （P<0.05， P<0.01）. ConclusionThe administration of TG at 189.0， 472.5 mg·kg^-1 for 3 weeks could modulate the signaling pathways associated with cholesterol efflux， endocytosis， and cholesterol biotransformation in hepatocytes， leading to the accumulation of cholesterol and subsequent liver injury in rats. CG could ameliorate the liver injury induced by lipid metabolism disorders caused by TG by up-regulating the expression of LXR-α， LDLR， ABCG1， CYP7A1， CYP8B1， and CYP27A1 to promote cholesterol biotransformation.

Objective To analyze the preferences of elderly cancer patients for internet hospital diagnosis and treatment services,providing a reference for the sustainable development of internet hospitals.Methods This study was based on the method of discrete choice experiments.By combining literature review and expert consultation,10 relevant attributes affecting the choice of internet hospitals by elderly cancer patients were determined.Through KANO questionnaires,6 key attributes were se-lected to form the final DCE questionnaire,consisting of 11 choice sets and 1"quality control"set.Using the convenience sam-pling method,elderly cancer patients visiting a certain tertiary hospital in Tianjin were selected to collect 318 valid question-naires.The obtained data were analyzed using mixed Logit regression.Results Patients visiting a certain specialized cancer hos-pital in Tianjin tend to prefer hospitals with a grade of Grade Ⅲ-A(β=0.661 6,P＜0.05)and those offering out-of-hospital rehabilitation guidance for cancer patients(β=0.559 9,P＜0.05).The page operation process(β=0.352 2,P＜0.05)and the accessibility mode for the elderly(β=0.357 5,P＜0.05)are the attributes with lower attention.In the subgroup analysis,for patients of different genders and different family incomes,hospital grade and out-of-hospital rehabilitation guidance for cancer patients remain the most influential factors,but male patients pay more attention to the page operation process(β=0.378 3,P＜0.05)and the accessibility mode for the elderly(β=0.373 7,P＜0.05),while female patients pay more attention to the cover-age of medical insurance reimbursement(β=0.435 9,P＜0.05),which has a greater impact than that of male patients(β=0.394 7,P＜0.05);patients with a monthly per capita income of less than 5 000 yuan pay more attention to the coverage of medical insurance reimbursement(β=0.423 0,P＜0.05)and the self-appointment check function(β=0.467 0,P＜0.05);while patients with a monthly per capita income of more than 5 000 yuan pay more attention to the page operation process(β=0.364 7,P＜0.05)and the accessibility mode for the elderly(β=0.359 1,P＜0.05).Conclusion Hospitals should en-hance elderly patients' awareness and trust in internet hospitals by providing comprehensive health education and support,simpli-fying operational processes,strengthening age-friendly design,and highlighting medical insurance coverage to address the diverse needs across genders and income levels.

Myelodysplastic syndrome (MDS), a myeloid tumor derived from the malignant clones of hematopoietic stem cells, has an annually increasing incidence. The contemporary research direction has shifted to analyzing the synergistic effect of immune surveillance collapse and abnormal bone marrow microenvironment in the pathological process of MDS. Against this backdrop, the immune checkpoint molecule TIM3 has emerged as a key target because of its persistently high expression on the surface of important immune cells such as T and NK cells. The abnormal activation of the TIM3 pathway is the mechanism by which solid tumors and hematological malignancies achieve immune escape and is a key hub in the formation of immune exhaustion phenotypes. This work integrates the original discoveries of our team with the latest international progress, systematically demonstrating the bidirectional regulatory network of TIM3 between the malignant clone proliferation of MDS and the immunosuppressive microenvironment. Integrating the evidence from emerging clinical trials allows us to consider the clinical significance of TIM3-targeted blocking for MDS, providing a transformative path to overcome the resistance of traditional treatments and marking a new chapter in the active immune reconstitution of MDS treatment.

OBJECTIVES: To explore the mechanism by which histone deacetylase 1 (HDAC1) regulates steroid-induced apoptosis of mouse osteocyte-like MLO-Y4 cells. METHODS: MLY-O4 cells were treated with 400 nmol/L trichostatin A (TSA) or 1 mmol/L dexamethasone for 24 h or transfected with a HDAC1-overexpressing vector prior to TSA or dexamethasone treatment. The changes in the expressions of HDAC1, SP1, cleaved caspase-3 and Bax, SP1 acetylation level, cell proliferation, and cell apoptosis were examined. The interaction between HDAC1 and SP1 was determined with immunoprecipitation assay and Western blotting. RESULTS: Treatment with dexamethasone significantly increased cell apoptosis, enhanced the expressions of cleaved caspase-3 and Bax, reduced HDAC1 expression, and suppressed proliferation of MLO-Y4 cells. Both TSA and dexamethasone obviously increased SP1 acetylation level and the expression of SP1 in MLO-Y4 cells. HDAC1 overexpression in the cells significantly attenuated the effect of TSA and dexamethasone, promoted cell proliferation, lowered the expressions of SP1, cleaved caspase-3 and Bax, and inhibited dexamethasone-induced cell apoptosis. Immunoprecipitation assay and Western blotting demonstrated the interaction between HDAC1 and SP1 in the cells. CONCLUSIONS HDAC1 inhibits dexamethasone-induced apoptosis and promotes proliferation of cultured mouse osteocytes by suppressing SP1 expression via promoting its deacetylation.
Animals ; Apoptosis/drug effects* ; Mice ; Histone Deacetylase 1/genetics* ; Osteocytes/drug effects* ; Sp1 Transcription Factor/metabolism* ; Acetylation ; Dexamethasone/pharmacology* ; Cell Proliferation/drug effects* ; Caspase 3/metabolism* ; Cell Line ; Hydroxamic Acids/pharmacology* ; bcl-2-Associated X Protein/metabolism*

Objective To analyze the preferences of elderly cancer patients for internet hospital diagnosis and treatment services,providing a reference for the sustainable development of internet hospitals.Methods This study was based on the method of discrete choice experiments.By combining literature review and expert consultation,10 relevant attributes affecting the choice of internet hospitals by elderly cancer patients were determined.Through KANO questionnaires,6 key attributes were se-lected to form the final DCE questionnaire,consisting of 11 choice sets and 1"quality control"set.Using the convenience sam-pling method,elderly cancer patients visiting a certain tertiary hospital in Tianjin were selected to collect 318 valid question-naires.The obtained data were analyzed using mixed Logit regression.Results Patients visiting a certain specialized cancer hos-pital in Tianjin tend to prefer hospitals with a grade of Grade Ⅲ-A(β=0.661 6,P＜0.05)and those offering out-of-hospital rehabilitation guidance for cancer patients(β=0.559 9,P＜0.05).The page operation process(β=0.352 2,P＜0.05)and the accessibility mode for the elderly(β=0.357 5,P＜0.05)are the attributes with lower attention.In the subgroup analysis,for patients of different genders and different family incomes,hospital grade and out-of-hospital rehabilitation guidance for cancer patients remain the most influential factors,but male patients pay more attention to the page operation process(β=0.378 3,P＜0.05)and the accessibility mode for the elderly(β=0.373 7,P＜0.05),while female patients pay more attention to the cover-age of medical insurance reimbursement(β=0.435 9,P＜0.05),which has a greater impact than that of male patients(β=0.394 7,P＜0.05);patients with a monthly per capita income of less than 5 000 yuan pay more attention to the coverage of medical insurance reimbursement(β=0.423 0,P＜0.05)and the self-appointment check function(β=0.467 0,P＜0.05);while patients with a monthly per capita income of more than 5 000 yuan pay more attention to the page operation process(β=0.364 7,P＜0.05)and the accessibility mode for the elderly(β=0.359 1,P＜0.05).Conclusion Hospitals should en-hance elderly patients' awareness and trust in internet hospitals by providing comprehensive health education and support,simpli-fying operational processes,strengthening age-friendly design,and highlighting medical insurance coverage to address the diverse needs across genders and income levels.

Objective:To investigate the clinical, radiological, and pathological features of anaplastic gangliogliomas (AGGs) and to determine whether these tumors represent a distinct entity.Methods:Consecutive 667 cases of ganglioglioma (GG) diagnosed at the Xuanwu Hospital, Capital Medical University, Beijing, China between January 2015 and July 2023 were screened. Among these cases, 9 pathologically confirmed AGG cases were identified. Their clinical, radiological, treatment, and outcome data were analyzed retrospectively. Most of the tumor samples were subject to next-generation sequencing, while a subset of them were subject to DNA methylation profiling.Results:Among the 9 patients, there were five males and four females, with a median age of 8 years. Epileptic seizures (5/9) were the most frequently presented symptom. Radiological examinations showed three types of radiological manifestations: four cases showed abnormal MRI signals with no significant mass effects and mild enhancement; two cases demonstrated a mixed solid-cystic density lesion with peritumoral edema, which showed significant heterogeneous enhancement and obvious mass effects, and one case displayed cystic cavity formation with nodules on MRI, which showed evident enhancements. All cases exhibited mutations that were predicted to activate the MAP kinase signaling pathway, including seven with BRAF p.V600E mutation and two with NF1 mutation. Five AGGs with mutations involving the MAP kinase signaling pathway also had concurrent mutations, including three with CDKN2A homozygous deletion, one with a TERT promoter mutation, one with a H3F3A mutation, and one with a PTEN mutation.Conclusions:AGG exhibits a distinct spectrum of pathology, genetic mutations and clinical behaviors, differing from GG. Given these characteristics suggest that AGG may be a distinct tumor type, further expansion of the case series is needed. Therefore, a comprehensive integration of clinical, histological, and molecular analyses is required to correctly diagnose AGG. It will also help guide treatments and prognostication.

Objective:To explore the effect of continuous nursing based on Siebens domain management model in patients with Parkinson's disease after deep brain stimulation.Methods:From January 2021 to June 2022, convenience sampling was used to select 169 Parkinson's disease patients who underwent deep brain electrical stimulation in the Functional Neurosurgery of Beijing Tiantan Hospital as the study subject. The patients were divided into a control group of 84 cases and an observation group of 85 cases using the random number table method. The control group received routine continuous nursing, while the observation group received the continuous nursing based on Siebens domain management model on the basis of the control group. This study compared the Activity of Daily Living (ADL) Scale, Morisky Medication Adherence Scale (MMAS), 39-item Parkinson Disease Questionnaire (PDQ-39), Parkinson's Disease Sleep Scale (PDSS) scores, and unexpected program control rate between two groups of patients after six months of discharge.Results:After six months of discharge, the ability of daily living score, quality of life score, and sleep quality score of both groups of patients improved compared to before intervention ( P<0.05), and the medication adherence of the observation group patients improved compared to before intervention ( P<0.05), and the differences were statistically significant. The ability of daily living score, medication adherence, quality of life score, and sleep quality score of the observation group patients after six months were higher than those of the control group, and the differences were statistically significant ( P<0.05). Within six months after discharge, the unexpected program control rate of the observation group was statistically lower than that of the control group ( P<0.05) . Conclusions:In the treatment and discharge rehabilitation process of Parkinson's patients treated with deep brain electrical stimulation, adopting continuous nursing based on the Siebens domain management model can help ensure patient medication compliance, improve postoperative sleep quality and quality of life, reduce unexpected program control frequency, and have certain clinical practice value.

Aneurysmal subarachnoid hemorrhage(aSAH)is one of the most damaging diseases in the brain.It is caused by multiple mechanisms and increased intracranial pressure is one of the most important.In clinical practice,it has been found that aSAH patients have a series of pathophysiological changes after increased intracranial pressure,which not only aggravates the secondary damage of brain tissue,but also becomes an unfavorable factor for the repair of damaged brain tissue.In many past studies on intracranial pressure,the application of intracranial pressure monitoring to guide the treatment of traumatic brain injury(TBI)patients has improved the prognosis of TBI patients,and intracranial pressure monitoring has become a routine clinical monitoring method.However,there are few clinical studies on intracranial pressure in aSAH patients,and it is not clear whether the research results and experience from TBI patients are applicable to the clinical practice of aSAH patients.The authors reviewed the reported clinical studies,and reviewed the change rule,application range and intervention threshold of intracranial presssure in aSAH patients.

Objective:To explore the safety and efficacy of Obinutuzumab in the treatment of immune thrombotic thrombocytopenic purpura.Methods:Data from a case of immune thrombotic thrombocytopenic purpura (iTTP) admitted to the Department of haematology of the First Affiliated Hospital of Harbin Medical University were evaluated retrospectively and a literature review was performed.Results:A 66-year-old female patient was admitted to our hospital for thrombocytopenia. On admission, physical examination showed that yellow skin and sclera. The patient was fully conscious but had a decreasing ability to calculate. Laboratory examination revealed a platelet count of 7×10 9/L; liver function: alanine aminotransferase 55.2 U/L, azelaic aminotransferase 117.5 U/L; total bilirubin 142.7 μmol/L, direct bilirubin 64.6 μmol/L, indirect bilirubin 78.1 μmol/L; lactate dehydrogenase: 2362 U/L; creatinine: 260.7 μmol/L; peripheral blood smear showed 4% fragmented erythrocytes; ADAMTS13 activity 2.7% and positive inhibitor (1.12 BU). The patient is treated with plasma exchange and glucocorticoids, but the patient’s symptoms worsened. Rituximab was permanently discontinued for severe infusion reactions. Treatment with Obinutuzumab (1000 mg, qw×2 w) and she achieved a complete remission for 18 months. The treatment was well tolerated with no adverse events related to Obinutuzumab. Conclusion:For iTTP patients with rituximab intolerance, obinutuzumab is a safe and effective alternative treatment option.

Objective:To explore the safety and efficacy of Obinutuzumab in the treatment of immune thrombotic thrombocytopenic purpura.Methods:Data from a case of immune thrombotic thrombocytopenic purpura (iTTP) admitted to the Department of haematology of the First Affiliated Hospital of Harbin Medical University were evaluated retrospectively and a literature review was performed.Results:A 66-year-old female patient was admitted to our hospital for thrombocytopenia. On admission, physical examination showed that yellow skin and sclera. The patient was fully conscious but had a decreasing ability to calculate. Laboratory examination revealed a platelet count of 7×10 9/L; liver function: alanine aminotransferase 55.2 U/L, azelaic aminotransferase 117.5 U/L; total bilirubin 142.7 μmol/L, direct bilirubin 64.6 μmol/L, indirect bilirubin 78.1 μmol/L; lactate dehydrogenase: 2362 U/L; creatinine: 260.7 μmol/L; peripheral blood smear showed 4% fragmented erythrocytes; ADAMTS13 activity 2.7% and positive inhibitor (1.12 BU). The patient is treated with plasma exchange and glucocorticoids, but the patient’s symptoms worsened. Rituximab was permanently discontinued for severe infusion reactions. Treatment with Obinutuzumab (1000 mg, qw×2 w) and she achieved a complete remission for 18 months. The treatment was well tolerated with no adverse events related to Obinutuzumab. Conclusion:For iTTP patients with rituximab intolerance, obinutuzumab is a safe and effective alternative treatment option.