OBJECTIVE To investigate the effect and potential mechanism of toosendanin in enhancing the antileukemic activity of cytosine arabinoside against acute myeloid leukemia （AML） based on the mammalian target of rapamycin complex 1 （mTORC1） signaling pathway.METHODS Female NSG immunodeficient mice were used to establish an AML model via a single γ-ray irradiation followed by a single tail-vein injection of a U937 cell suspension. The effects of cytosine arabinoside （2.5 mg/kg）， toosendanin （1.0 mg/kg）， and cytosine arabinoside+toosendanin （2.5 mg/kg+1.0 mg/kg） on body weight， survival time， peripheral blood routine indicators， histopathological morphology， and the expressions of autophagy-related proteins were explored. Using U937 cells as the subject， the effects of cytosine arabinoside （1 μmol/L）， toosendanin （160 nmol/L）， and cytosine arabinoside+toosendanin （1 μmol/L+160 nmol/L） on the expressions of autophagy-related proteins， mTORC1 signaling pathway-related proteins and mRNAs were investigated. The targeting relationship between toosendanin and the selective autophagy ligand 1 （also known as p62） was validated， and the Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses， as well as molecular docking， were performed. A p62 -knockdown U937 stable cell line was constructed， and the underlying mechanism of toosendanin-induced sensitization was verified.RESULTS Animal experiments confirmed that the combination of toosendanin and cytosine arabinoside significantly improved body weight， survival time and peripheral blood routine indicators in AML mice （ P ＜0.05）， alleviated pathological changes such as leukemic cell infiltration and focal necrosis in bone marrow， liver， and spleen tissues， and modulated the expressions of autophagy-related proteins. Cell experiments confirmed that toosendanin could reverse cytosine arabinoside-induced activation of the autophagy cascade （manifested by downregulation of the protein expressions of microtubule-associated protein 1 light chain 3B and Beclin-1， upregulation the protein expression of p62）， and might inhibit the expression of the downstream Unc-51-like autophagy activating kinase 1 （ULK1） complex （including ULK1， ULK2， autophagy-related protein 13， and FAK family interacting protein of 200 kDa） by activating the mTORC1 signaling pathway （ P ＜0.05）. The sensitizing effect of toosendanin was associated with the inhibition of autophagy and the regulation of the mTORC1 signaling pathway； it could stably bind to p62 via hydrophobic interactions. Mechanism verification experiments indicated that upon p62 knockdown， toosendanin was no longer able to activate the mTORC1 signaling pathway or inhibit autophagy.CONCLUSIONS Toosendanin may enhance chemo-sensitivity of AML cells to cytosine arabinoside by directly targeting the p62 protein， which subsequently activates the mTORC1 signaling pathway， and thereby suppresses cytosine arabinoside-induced protective autophagy.

An ideal guided bone regeneration(GBR)membrane usually needs to possess good biocompatibility,appropriate me-chanical properties,reasonable degradability and clinical manageability.However,traditional biological barrier membranes cannot meet clinical requirements such as high mechanical strength and controllable degradation simultaneously,so it is necessary to de-velop a new type of guided bone regeneration membrane material.Degradable magnesium-based alloy guided bone regeneration membranes have the characteristics and potential to become new guided bone regeneration membrane materials.This review intro-duces the research history and field applications of magnesium-based alloys,as well as the advantages and limitations of degradable magnesium-based alloy GBR membranes.Finally,it presents the applications and prospects of degradable magnesium-based alloy GBR membranes in various oral medicine fields,providing a scientific basis for their clinical transformation.

An ideal guided bone regeneration(GBR)membrane usually needs to possess good biocompatibility,appropriate me-chanical properties,reasonable degradability and clinical manageability.However,traditional biological barrier membranes cannot meet clinical requirements such as high mechanical strength and controllable degradation simultaneously,so it is necessary to de-velop a new type of guided bone regeneration membrane material.Degradable magnesium-based alloy guided bone regeneration membranes have the characteristics and potential to become new guided bone regeneration membrane materials.This review intro-duces the research history and field applications of magnesium-based alloys,as well as the advantages and limitations of degradable magnesium-based alloy GBR membranes.Finally,it presents the applications and prospects of degradable magnesium-based alloy GBR membranes in various oral medicine fields,providing a scientific basis for their clinical transformation.

Objective To analyze the risk factors of cancer fatigue in patients with postoperative chemotherapy for lung cancer and establish a Nomogram prediction model.Methods Collect clinical data of 172 postoperative chemotherapy patients with lung cancer at the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine from October 2021 to September 2023.A survey was conducted using the revised Piper fatigue scale(RPFS)to evaluate the degree of cancerous fatigue in patients.A logistic multiple regression model was used to analyze the risk factors affecting the degree of cancerous fatigue in postoperative chemotherapy patients with lung cancer,and a Nomogram prediction model was constructed to evaluate the predictive performance of the model.Results There were statistically significant differences in RPFS scores in terms of education level,tumornede metastasis classification,(TNM)staging,depression,adverse reactions,and white blood cells(P＜0.05).The proportion of high school education or above,TNM stageⅢ/Ⅳ,depression,moderate/severe adverse reactions,and the proportion of white blood cells count below the lower limit of normal in postoperative chemotherapy patients with lung cancer were significantly higher than those without/with mild cancer fatigue,and the differences were statistically significant(P＜0.05).Logistic analysis showed that education level(above high school level),TNM staging(Ⅲ/Ⅳ),depression(present),degree of adverse reactions(moderate/severe),and white blood cells(below the lower limit of normal values)were independent risk factors affecting the degree of cancer-related fatigue in postoperative chemotherapy patients with lung cancer(P＜0.05).The internal validation results show that the C-index is 0.899(0.842-0.955),with good consistency.The threshold of the Nomogram model is greater than 0.21,and the clinical net benefit provided by the Nomogram model is higher than that of educational level,TNM stage,depression,degree of adverse reactions,and a single predictor of white blood cells.Conclusion This study constructs a Nomogram model based on risk factors for cancerous fatigue in postoperative chemotherapy patients with lung cancer,which can provide a good prediction for cancerous fatigue in clinical lung cancer patients undergoing postoperative chemotherapy.

【Objective】 To explore the relationship between the storage time of leukodepleted red blood cells and transfusion adverse reactions by analyzing the occurrence of transfusion adverse reactions of patients after leukodepleted red blood cells transfusion from four hospitals. 【Methods】 By using the electronic medical record management system, the collection and transfusion dates of leukodepleted red blood cells from four hospitals in Enshi Prefecture from 2018 to 2022, as well as the information on transfusion adverse reactions, were retrieved. 【Results】 From 2018 to 2022, a total of 697 61 bags of leukodepleted red blood cells were transfused in four hospitals, resulting in 166 cases of transfusion adverse reactions, among which 93 were allergic reactions, 63 were non hemolytic febrile reactions, and 10 were others, with a total incidence rate of transfusion adverse reactions at 0.24%. The average storage time of leukodepleted red blood cells with and without transfusion adverse reactions was (20.25±6.31) and (19.88±5.50) days, respectively. With a storage time of 7 days as the threshold, the incidence of transfusion adverse reactions was the lowest for a storage time of 15~21 days. The incidence of transfusion adverse reactions of leukodepleted red blood cells in two groups (with storage days ≤21 days and >21 days) was not statistically significant(P>0.05). 【Conclusion】 Allergic reactions were the main type of transfusion adverse reaction caused by leukodepleted red blood cells, and the incidence of transfusion adverse reactions decreased and then increased with the prolongation of the storage time of leukodepleted red blood cells. There was no significant difference in the incidence of transfusion adverse reactions with leukodepleted red blood cells stored for ≤ 21 days and >21 days.

ObjectiveTo evaluate the efficacy and safety of a perioperative rehabilitation clinical pathway of acetabular fracture in light of orthopedics rehabilitation team approach. MethodsA prospective randomized control trial was conducted in 82 patients with acetabular fractures who had been admitted from the Emergency Department of Orthopaedic Trauma, Beijing Jishuitan Hospital from June, 2019 to January, 2021. The patients were randomly divided into control group (n = 41) and intervention group (n = 41). The control group was managed routinely, while the intervention group received the rehabilitation clinical pathway, for 24 weeks. The Visual Analogue Score (VAS) of pain, the Barthel Index (BI) and Majeed Pelvic Score were compared. ResultsFinally, 76 patients completed the trial. There was no statistical difference in VAS score between two groups in all periods (|Z| < 1.926, P > 0.05). The BI score was higher in the intervention group than in the control group at discharge, two weeks, six weeks and twelve weeks after operation (|Z| > 2.121, P < 0.05); and no significant difference was found before operation and 24 weeks after operation (|Z| < 1.862, P > 0.05). Majeed Pelvic Score was higher in the intervention group than in the control group two weeks, six weeks, twelve weeks and 24 weeks after operation (|Z| > 2.428, P < 0.05). Six, twelve and 24 weeks after operation, the excellent rate of Majeed Pelvic Score was higher in the intervention group than in the control group (χ² > 6.136, P < 0.05). ConclusionIn comparison with traditional protocol in acetabular fracture, the perioperative rehabilitation clinical pathway was proved effective and of great safety in the light of the integration of orthopedics and rehabilitation mode for improving the function and activities of daily living of patients.

Objective:To investigate the impact of altering brain gray matter volume (GMV) on cognition and gait disorder in patients with amnestic mild cognitive impairment (aMCI).Methods:Thirty-six patients with aMCI, who admitted to the First Affiliated Hospital of Anhui Medical University from July 2018 to August 2020, were collected, and 33 normal controls (NC) matched with age, sex and education level were included in the same period. The neuropsychological assessment was done in all the subjects using Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment scale (MoCA), Cambridge Cognitive Examination-Chinese version (CAMCOG-C), Geriatric Depression Scale (GDS) and Activities of Daily Living scale (ADL). The timed up and go test (TUG), dual task of timed up and go test (D-TUG) and Berg Balance Scale (BBS) were used in the subjects for assessment. The parameters such as stride length, gait speed, gait frequency were collected by intelligent device for energy expenditure and activity. All the subjects received 3.0 T magnetic resonance imaging scan to obtain high-resolution T 1 structural images. Voxel-based morphometry (VBM) was used to compare the difference of GMV between aMCI patients and NC. Partial correlation analysis was performed among altering GMV in the regions of interest (ROI), cognitive score and gait parameters, respectively. Linear regression analysis was used between whole brain GMV and gait parameters. Results:The scores of MMSE, MoCA, CAMCOG-C and the subitems of CAMCOG-C in aMCI group were significantly lower than those in NC group ( P<0.05). In aMCI patients, both the test time of TUG and D-TUG increased, gait speed slowed down, stride length shortened, and stride frequency and BBS score decreased ( P<0.05).VBM analysis showed that the whole brain GMV in aMCI patients was obviously lower than that of NC. In the aMCI group, GMV in ROI1 (right hippocampus, right parahippocampal gyrus, right amygdala and right fusiform gyrus), ROI2 (right middle temporal gyrus), ROI3 (right angular gyrus), ROI4 (right occipital lobe), ROI5 (bilateral orbital frontal lobe), ROI6 (left middle frontal gyrus and rectus gyrus), ROI7 (left fusiform gyrus and left parahippocampal gyrus) was significantly decreased compared with the NC group [Gaussian random field (GRF) correction, two-tailed test, voxel level P<0.001, cluster level P<0.05). In the aMCI group, GMV in ROI1 was positively correlated with orientation ( r=0.437, P=0.012), memory ( r=0.360, P=0.043), execution ( r=0.414, P=0.019), and negatively correlated with ADL score ( r=-0.529, P=0.002). GMV in ROI2 was negatively correlated with ADL score ( r=-0.400, P=0.023). GMV in ROI4 and in ROI5 was positively correlated with the calculation ( r=0.370, P=0.037) and execution ( r=0.360, P=0.043), respectively. GMV in ROI6 was positively correlated with MMSE score ( r=0.357, P=0.045), CAMCOG-C total score ( r=0.503, P=0.003) and calculation ( r=0.395, P=0.025), and negatively correlated with ADL score ( r=-0.387, P=0.028). GMV in ROI5 was positively correlated with gait speed ( r=0.391, P=0.027). In the aMCI group, CAMCOG-C total score was negatively correlated with D-TUG results ( r=-0.387, P=0.035), executive function was negatively correlated with TUG results ( r=-0.450, P=0.013) and D-TUG results ( r=-0.553, P=0.002), and positively correlated with gait speed ( r=0.379, P=0.039). Attention was positively correlated with gait speed ( r=0.590, P=0.001), and computing was positively correlated with gait speed ( r=0.371, P=0.044). The linear regression of whole brain GMV and gait parameters showed negative correlation between the GMV of left occipital lobe and TUG results in the aMCI group. The GMV of bilateral prefrontal cortex, right occipital lobe and surrounding cortex was positively correlated with gait speed (GRF correction, two-tailed test, voxel level P<0.001, cluster level P<0.05). Conclusions:Patients with aMCI presented with gray matter atrophy, cognition impairment, and gait disorders. The cognition impairment was closely related to the atrophy of medial temporal lobe. Gait disorders were not only associated with cognition impairment but also with gray matter volume in the prefrontal lobe, occipital lobe and its surrounding cortex, and anterior central gyrus.

Objective: To investigate the effects of Tiaozhi mixture on lipid metabolism disorder in patients with chronic hepatitis C virus infection and fatty liver. Methods: The clinical data of 122 cases of patients with chronic hepatitis C virus infection and fatty liver admitted to our hospital from January 2016 to January 2017 were retrospectively analyzed. Control group was only given antiviral treatment, and observation group was given antiviral treatment and Tiaozhi mixture. The blood lipids parameters, decrease of HCV RNA load, negative conversion rate of serum anti-HCV. Results: After treatment, the levels of blood lipids, i. e., triglycerides (TG), total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C) were decreased significantly in the two groups, and the decreases of blood lipid levels of TG, TC and LDL-C in observation group were greater than those in control group. The level of high density lipoprotein-colesterol (HDL-C) was increased significantly in observation group, and the level of HDL-C in control group was basically unchanged. The liver function tests for alanine aminotransferase (ALT) and total bile acid (TBA) levels were all decreased effectively, and the decrease in observation group was greater than that in control group, and the aspartate aminotransferase (AST) level in the two groups was reduced, but there was no significant difference between the two groups. The decrease of HCV RNA load and negative conversion rate of serum anti-HCV in observation group were higher than those in control group. There was no significant difference in the incidence rate of adverse reactions between the two groups after treatment(χ²=0.000, P=1.000). Conclusions In the clinical treatment of chronic hepatitis C virus infection with fatty liver, combined Tiaozhi mixture can effectively increase the antiviral efficacy, reduce the possibility of adverse reactions, and help patients with liver function recovery, and it has high safety. Thus it is worthy of clinical promotion.

Objective To study the effect of comprehensive Chinese medicine therapy,including Chinese herbal medicine fumigation,massage,and quadriceps exercise,on adipokines of visfatin and chemerin content in joint fluid of patients with knee osteoarthritis (KOA),and to explore its possible therapeutic mechanism for KOA.Methods A total of 60 cases of KOA patients were randomly divided into treatment group and control group,30 cases in each group.The treatment group was treated with comprehensive Chinese medicine therapy,and the control group was treated with Chinese medicine fumigation alone.After treatment for 2 weeks,the clinical efficacy of both groups was evaluated,and the changes in the scores of the Western Ontario and McMaster Universities Arthritis Index (WOMAC)were observed.Moreover,the contents of visfatin and chemerin in jointfluid were examined.Results (1) The total effective rate of the treatment group was 96.7％ and that of the control group was 83.3％,the difference being significant (P ＜ 0.01).(2) After treatment,WOMAC scores of both groups were obviously decreased(P ＜ 0.01 compared with those before treatment),and the decrease in the treatment group was superior to that in the control group (P ＜ 0.01).(3) The contents of visfatin and chemerint in joint synovial fluid of both groups were decreased (P ＜ 0.01 compared with those before treatment),and the decrease in the treatment group was superior to that in the control group(P ＜ 0.05).Conclusion The comprehensive Chinese medicine therapy of Chinese herbal medicine fumigation,massage and quadriceps exercise is effective for the treatment of KOA,and can decrease the contents of visfatin and chemerin in joint fluid of KOA patients,which may be one of its therapeutic mechanisms.

Lesch-Nyhan syndrome(LNS) is a congenital X-linked recessive inherited disorder caused by mutations in the hypoxanthine guanine phosphoribosyl transferase (HPRT) gene.A deficiency of the HPRT enzyme is responsible for the disease.The main clinical manifestation includes hyperuricemia, juvenile-onset gouty arthritis and neurological developmental disorders.Studies have reported there are more than 400 HPRT gene mutation sites, but the incidence of LNS in the Chinese population is extremely low.Here we report a 16-year-old male patient who suffered neurological dysfunction at an early age and gouty arthritis in his youth.DNA of patient and his family members were extracted from peripheral blood lymphocytes.The coding region and the intron-exon boundaries of HPRT gene were sequenced by standard methods.We found a mutation in exon 3 of the HPRT gene of the patient and his mother (Exon3:c.143G>A), which resulted in an arginine to histidine (p.R48H) substitution in the encoded protein.No activity of the enzyme HPRT was detected in the erythrocytes.The same mutation was reported in several European families, but was found in Chinese family for the first time.Clinicians in China have poor experience in diagnosing LNS case, due to the low incidence in China.Therefore LNS screening for infants or adolescents with hyperuricemia, gouty arthritis and neurological dysfunction should be performed.