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.

OBJECTIVES: To evaluate the therapeutic effect of gastrodin against hypoxic-ischemic brain damage (HIBD) in neonatal mice and explore the role of GPX4/SLC7A11/FTH1 signaling in mediating its effect. METHODS: Twenty-four 9- to 11-day-old C57BL/6J mice were randomized equally into 4 groups for sham operation, HIBD modeling by right common carotid artery ligation and subsequent exposure to hypoxia for 1 h, or gastrodin treatment at 100 or 200 mg/kg before and at 1 and 2 days after modeling. The mice then underwent neurological assessment (Zea-Longa scores), and the cerebral cortical penumbra tissue were collected for HE and Nissl staining, detection of ferroptosis biomarkers and protein expressions of GPX4, SLC7A11, and FTH1 with Western blotting and immunofluorescence co-localization, and observation of mitochondrial ultrastructure with electron microscopy. In cultured HT22 neuronal cells with oxygen-glucose deprivation (OGD) for 2 h, the effects of pretreatments with 0.5 mmol/L gastrodin, 10 μmol/L RSL3 (a GPX4 inhibitor), alone or in combination, were analyzed on expressions of ferroptosis-related proteins, cellular Fe²⁺, ROS, lipid peroxidation, MDA, and GSH levels, mitochondrial membrane potential (JC-1), and cell viability. RESULTS: Gastrodin treatment at the two doses both significantly ameliorated HIBD and neurological deficits of the mice, reduced mitochondrial damage and Fe²⁺, MDA and ROS levels, increased GSH level, and upregulated GPX4, SLC7A11, and FTH1 protein expressions. In HT22 cells, gastrodin pretreatment obviously attenuated OGD-induced ferroptosis and improved cell viability and mitochondrial function. Co-treatment with RSL3 potently abrogated the inhibitory effects of gastrodin on Fe²⁺, ROS, BODIPY-C11, and MDA levels and attenuated its protective effects on GSH level, cell viability, and mitochondrial membrane potential. CONCLUSIONS Gastrodin provides neuroprotective effects in neonatal mice with HIBD by suppressing neuronal ferroptosis via upregulating the GPX4/SLC7A11/FTH1 signaling pathway.
Animals ; Ferroptosis/drug effects* ; Hypoxia-Ischemia, Brain/drug therapy* ; Mice ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Glucosides/pharmacology* ; Animals, Newborn ; Benzyl Alcohols/pharmacology* ; Amino Acid Transport System y+/metabolism*

Objective To investigate the clinical efficacy of Yinhuo Guiyuan moxibustion as an adjunc-tive therapy to Yaotongning Capsules in treating kidney deficiency-related lumbago in patients with stage 3-4 chronic kidney disease.Methods Sixty patients with stage 3-4 chronic kidney disease admitted from Janu-ary 2021 to June 2023 were randomly divided into a control group and an observation group,with 30 cases in each group.Both groups received basic treatment interventions during the study period.The control group re-ceived Yaotongning Capsules orally,while the observation group received additional Yinhuo Guiyuan moxibus-tion therapy.Clinical efficacy,pain scores,renal function indicators,satisfaction scores,and adverse reaction rates were compared between the two groups.Results The total effective rate was significantly higher in the observation group(93.33％)than in the control group(73.33％,P＜0.05).At the 4th,8th,and 12th weeks of treatment,the VAS scores of both groups were lower than baseline values,with the observation group dem-onstrating significantly lower scores compared to the control group at the same time points(P＜0.05).After treatment,both groups showed reductions in BUN,Scr,and 24hUP levels,with the observation group showing lower levels than the control group(P＜0.05).The observation group demonstrated higher satisfaction scores than the control group(P＜0.05).No significant difference was found in adverse reaction rates between groups(x2=0.218,P=0.640).Conclusion Yinhuo Guiyuan moxibustion combined with Yaotongning Cap-sules is effective in treating stage 3-4 chronic kidney disease patients,effectively alleviating low back pain,improving renal function indicators,enhancing treatment satisfaction,with lower incidence of adverse reac-tions.

Objective To investigate the relationship between the expression of absent in melanoma 2(AIM2)gene in peripheral blood peripheral blood mononuclear cell(PBMC)of patients with advanced gastric cancer(GC)and the intestinal flora and the efficacy of targeted therapy.Methods 83 patients with advanced GC who were treated from January to December 2023 were all given Trastuzumab/Nebuliumab combined with conventional chemotherapy for 4 weeks/course and 3 continuous courses of treatment to evaluate the efficacy of targeted therapy.The abundance of intestinal flora was analyzed using 16S rDNA sequencing technologies.Quantitative real-time PCR(qRT-PCR)was used to detect AIM2 mRNA expression levels in PBMC,which were divided into a high expression group and a low expression group according to the median digit.Pearson correlation analysis was used to investigate the relationship between AIM2 expression and the relative abundance of intestinal flora,the efficacy of targeted therapy and clinical features.Results At the phylum level,the relative abundance of Bacteroidetes(0.70±0.15)and Proteobacteria(0.71±0.21)in the high expression group of AIM2 was significantly lower than that in the low expression group(0.81±0.17,0.80±0.16),and the relative abundance of Firmicutes(0.73±0.12)was significantly higher than that in the low expression group(0.64±0.08),and the differences were statistically significant(t=3.108,2.210,4.061,all P＜0.05).At the genus level,the relative abundance of Bacteroides(0.13±0.02)in the high expression group of AIM2 was significantly lower than that in the low expression group(0.19±0.04),and the relative abundance of Enterococcus(0.31±0.08 vs 0.12±0.05)and Escherichia coli(0.18±0.04 vs 0.10±0.02)was significantly higher than that in the low expression group(0.12±0.05,0.10±0.02),and the differences were statistically significant(t=8.472,153.462,11.722,all P<0.05).Pearson correlation showed that at phylum level,AIM2 expression was positively correlated with the relative abundance of Firmicutes(r=0.598,P<0.05),and negatively correlated with the relative abundance of Bacteroides and Proteobacteria(r=-0.641,-0.520,all P<0.05).At the genus level,AIM2 expression was positively correlated with the relative abundance of Enterococcus and Escherichia coli(r=0.529,0.577,all P<0.05),and negatively correlated with the relative abundance of Bacteroides(r=-0.574,P<0.05).Among the 83 patients with advanced GC,17 cases were effective and 66 cases were ineffective,and the Overall response rate(ORR)was 20.48%.The lesion diameter(5.73±0.74cm)and the proportion of cTNM stage IV(53.85%)in AIM2 high expression group were significantly lower than those in low expression group(6.08±0.51cm,75.00%),and the targeted therapy ORR(30.77%)was higher than that in low expression group(11.36%),with statistical significance(t/χ2/Z=2.477,6.558,4.780,all P<0.05).Conclusion The expression of AIM2 in PBMC of advanced GC patients is closely related to the imbalance of intestinal flora and the effect of targeted therapy.Detection of AIM2 expression is conducive to guiding clinical screening of patients who benefit from targeted therapy.

Objective To investigate the relationship between the expression of absent in melanoma 2(AIM2)gene in peripheral blood peripheral blood mononuclear cell(PBMC)of patients with advanced gastric cancer(GC)and the intestinal flora and the efficacy of targeted therapy.Methods 83 patients with advanced GC who were treated from January to December 2023 were all given Trastuzumab/Nebuliumab combined with conventional chemotherapy for 4 weeks/course and 3 continuous courses of treatment to evaluate the efficacy of targeted therapy.The abundance of intestinal flora was analyzed using 16S rDNA sequencing technologies.Quantitative real-time PCR(qRT-PCR)was used to detect AIM2 mRNA expression levels in PBMC,which were divided into a high expression group and a low expression group according to the median digit.Pearson correlation analysis was used to investigate the relationship between AIM2 expression and the relative abundance of intestinal flora,the efficacy of targeted therapy and clinical features.Results At the phylum level,the relative abundance of Bacteroidetes(0.70±0.15)and Proteobacteria(0.71±0.21)in the high expression group of AIM2 was significantly lower than that in the low expression group(0.81±0.17,0.80±0.16),and the relative abundance of Firmicutes(0.73±0.12)was significantly higher than that in the low expression group(0.64±0.08),and the differences were statistically significant(t=3.108,2.210,4.061,all P＜0.05).At the genus level,the relative abundance of Bacteroides(0.13±0.02)in the high expression group of AIM2 was significantly lower than that in the low expression group(0.19±0.04),and the relative abundance of Enterococcus(0.31±0.08 vs 0.12±0.05)and Escherichia coli(0.18±0.04 vs 0.10±0.02)was significantly higher than that in the low expression group(0.12±0.05,0.10±0.02),and the differences were statistically significant(t=8.472,153.462,11.722,all P<0.05).Pearson correlation showed that at phylum level,AIM2 expression was positively correlated with the relative abundance of Firmicutes(r=0.598,P<0.05),and negatively correlated with the relative abundance of Bacteroides and Proteobacteria(r=-0.641,-0.520,all P<0.05).At the genus level,AIM2 expression was positively correlated with the relative abundance of Enterococcus and Escherichia coli(r=0.529,0.577,all P<0.05),and negatively correlated with the relative abundance of Bacteroides(r=-0.574,P<0.05).Among the 83 patients with advanced GC,17 cases were effective and 66 cases were ineffective,and the Overall response rate(ORR)was 20.48%.The lesion diameter(5.73±0.74cm)and the proportion of cTNM stage IV(53.85%)in AIM2 high expression group were significantly lower than those in low expression group(6.08±0.51cm,75.00%),and the targeted therapy ORR(30.77%)was higher than that in low expression group(11.36%),with statistical significance(t/χ2/Z=2.477,6.558,4.780,all P<0.05).Conclusion The expression of AIM2 in PBMC of advanced GC patients is closely related to the imbalance of intestinal flora and the effect of targeted therapy.Detection of AIM2 expression is conducive to guiding clinical screening of patients who benefit from targeted therapy.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To investigate the role of theophylline drugs in acute exacerbation stage of chron-ic obstructive pulmonary disease (AECOPD).Methods The clinical data of 401 patients with AECOPD ad-mitted and treated in this hospital from January 2016 to September 2022 were retrospectively analyzed.The patients were divided into the drug group (n=308) and control group (n=93) according to whether or not u-sing theophylline drugs.The control group was given the conventional treatment,and the drug group was giv-en theophylline drugs on the basis of conventional treatment.The hospitalization duration,C-reactive protein (CRP),procalcitonin (PCT),blood routine[WBC,neutrophil,hemoglobin,hematocrit (HCT),platelet-lym-phocyte ratio (PLR),neutrophil to lymphocyte ratio (NLR),eosinophils,basophil]changes were compared between the two groups,and the parameters with differences conducted the subgroup analysis to observe the effect of different types of theophylline.Results Before treatment,there was no statistically significant differ-ence in the baseline data between the drug group and the control group,and the number of basophils between the aminophylline group and doxophylline group (P>0.05).After treatment,there was no statistically signif-icant difference in PCT,CRP,WBC,neutrophil,hemoglobin,HCT,PLR,NLR and eosinophil between the drug group and control group (P>0.05).The length of hospital stay in the drug group was shorter than that of the control group,and the basophils count was less than that of the control group,and the difference was statisti-cally significant (P<0.05).After treatment,there was no statistically significant difference in the hospitaliza-tion duration in the aminophylline group and doxophylline group in the drug group subgroups (P>0.05),but the basophils count was higher than that of the doxofylline group (P<0.05).Conclusion Theophylline drugs could significantly shorten the hospitalization duration and reduce the basophils in the patients with AECO-PD.There is no significant difference in shortening the hospitalization duration between aminophylline and doxophylline,but aminophylline's effect on basophils is significantly stronger than that of doxophylline.

Objective:To investigate the relationship between brain derived neurotrophic factor (BDNF) gene polymorphism and the change of grey matter volume (GMV) and fractional amplitude of low-frequency fluctuation (fALFF) in cerebral small vessel disease (CSVD) patients with subcortical ischemic depression (SID).Methods:Eighty-seven CSVD patients in the First Affiliated Hospital of Anhui Medical University were enrolled from July 2017 to November 2020 and divided into CSVD-SID group [Geriatric Depression Scale (GDS) score>10] and CSVD-non - depression group (CSVD-ND group, GDS score≤10) according to GDS. Both GMV and fALFF were calculated based on structural and functional magnetic resonance imaging data, and the interactions between SID diagnosis and BDNF gene on brain function and structure alteration were explored.Results:GMV was significantly increased in the posterior default network (pDMN; such as posterior cingulate gyrus/precuneus and middle temporal gyrus) in the CSVD-SID group compared with the CSVD-ND group. On GMV property, significant interactions between BDNF gene and SID were found in the cuneus ( F=25.50, P<0.001), precuneus lobe ( F=13.61, P<0.001) and cerebellum ( F=17.23, P<0.001). In the aspect of fALFF, the brain functional activity in the superior frontal gyrus was significantly increased in the CSVD-SID group compared with that in the CSVD-ND group (0.363±0.648 vs -0.427±0.514,cluster size=48 voxels, t=5.63, P<0.001). But there was no significant interaction between diagnosis and BDNF genotype on brain function. Conclusions:Both the GMV and fALFF were increased in CSVD-SID, mainly located in the pDMN and frontal lobe. Significant interaction was found between CSVD-SID and BDNF genotype on GMV.

Objective:To investigate the hemodynamic changes of the main arteries and veins of the extremities and the heart in patients with hypertrophic scar secondary to extensive burns after pressure treatment, and to analyze the relevant mechanisms.Methods:A retrospective before-after self-control study was conducted. From January 2017 to February 2022, 37 patients with hypertrophic scar secondary to extensive burns who met the inclusion criteria were hospitalized in the Burn Rehabilitation Department of Guangdong Industrial Injury Rehabilitation Hospital, including 25 males and 12 females, aged 23-52 years. The patients were admitted to the hospital within 12 weeks after wound healing, and within one week after admission, rehabilitation therapists, occupational therapists, and tailors custom-made pressure products such as full-body pressure garment, pressure pants, vests, split finger gloves, split finger socks, hoods, and plastic collars, with the pressure at each part maintained at 2.67-4.00 kPa when wearing. Before the first treatment with pressure products (hereinafter referred to as before pressure treatment) and at 1 h of the first treatment with pressure products (hereinafter referred to as 1 h of pressure treatment), color Doppler ultrasonography was performed to check the pulse rate of the axillary artery, the lumen diameter, peak systolic velocity (PSV), and resistance index of the axillary artery and femoral artery on the left side, the lumen diameter, cross-sectional area, and average blood flow velocity of the axillary vein and femoral vein, and the mitral valve E peak, mitral valve A peak, tricuspid valve E peak, aortic valve PSV, and pulmonary valve PSV of the heart; an optical chromatographic skin detector was used to detect the red color, red pigment, and surface brightness of the scar on the back of the hand to reflect the filling and distribution of the scar microvessels. Data were statistically analyzed with paired sample t test. Results:Compared with those before pressure treatment, the PSV of the axillary artery of patients was significantly slowed down at 1 h of pressure treatment ( t=55.42, P<0.01); the average blood flow velocity of the axillary vein was significantly accelerated ( t=-60.50, P<0.01); the pulse rate, lumen diameter, and resistance index of the axillary artery, as well as the lumen diameter and cross-sectional area of the axillary vein did not change obviously ( P>0.05); the average blood flow velocity of the femoral vein was significantly accelerated ( t=-80.52, P<0.01); the lumen diameter, PSV, and resistance index of the femoral artery, as well as the lumen diameter and cross-sectional area of the femoral vein had no significant change ( P>0.05); the mitral valve E peak and mitral valve A peak of the heart decreased significantly (with t values of 10.71 and 21.96, respectively, P<0.01); the tricuspid valve E peak of the heart increased significantly ( t=7.57, P<0.01); the PSV of the aortic valve and pulmonary valve of the heart did not change obviously ( P>0.05). At 1 h of pressure treatment, the red color and red pigment values of the scar on the back of the hand of patients were 15.3±1.1 and 16.8±1.2, respectively, which were significantly lower than 24.5±1.3 and 23.8±1.2 before pressure treatment (with t values of 8.32 and 8.04, respectively, P<0.01). The brightness value of the scar surface on the back of the hand of patients at 1 h of pressure treatment was similar to that before pressure treatment ( P>0.05). Conclusions:After pressure treatment for the hypertrophic scar in patients secondary to extensive burn, the average blood flow velocity of the axillary vein and femoral vein in patients are obviously accelerated, the PSV of the axillary artery is significantly slowed down, the peak values of mitral valve E and mitral valve A of the heart are significantly decreased, and the tricuspid valve E peak is significantly increased. These hemodynamic changes may be related to the reduction of microvascular blood flow in the local area of scar after systemic pressure treatment.