OBJECTIVE To investigate the mechanism by which Naozhenning granules （NZN） improve learning and memory impairment in a rat model of multiple cerebral concussion （MCC）. METHODS The MCC rat model was established using the closed controlled cortical impact method. The experiment was set up with a blank group （normal saline）， a model group （normal saline）， a piracetam group （positive control group， 0.324 g/kg）， and high-， medium-， and low-dose NZN groups （5.4， 2.7， 1.35 g/kg）， with 11 rats in each group. Drugs or normal saline were administered by gavage once daily for 28 consecutive days. General condition and body weight were monitored throughout the experiment. The sucrose preference rate and novel object recognition index were measured； Evans blue （EB） extravasation in the cerebral cortex was detected； pathological changes of cortical neurons were observed； the levels of B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， interleukin-6 （IL-6）， IL-10， and tumor necrosis factor-α （TNF-α） in the cerebral cortex were determined； and the phosphorylation levels of AMP-activated protein kinase （AMPK）， glycogen synthase kinase 3β （GSK3β）， and Tau protein were detected. RESULTS Compared with the blank group， the model group showed poor mental state， sluggish response to external stimuli， reduced food and water intake， decreased limb flexibility， and disheveled fur. Body weight， sucrose preference rate， and novel object recognition index were significantly decreased （ P ＜0.05）； EB extravasation in the cerebral cortex was significantly increased （ P ＜0.05）， with severe neuronal damage. The positive area ratio of Bax protein， IL-6 and TNF-α levels， and Tau protein phosphorylation level were all significantly increased （ P ＜0.05）， whereas the positive area ratio of Bcl-2 protein， IL-10 level， and AMPK and GSK3β protein phosphorylation levels were significantly decreased （ P ＜0.05）. Compared with the model group， all NZN dose groups showed improvements in general condition and pathological damage， with quantitative indices partially restored， and the differences in quantitative indices in high-dose NZN group were statistically significant （ P ＜0.05）. CONCLUSIONS NZN can effectively improve learning and memory impairment in MCC model rats. The mechanism may be related to activating the AMPK/GSK3β pathway， inhibiting inflammatory response， reducing Tau protein phosphorylation level， and then repairing the neuronal injury.

ObjectiveTo evaluate the clinical efficacy and safety of Baoshen prescription in the treatment of stage Ⅳ diabetic nephropathy （DN） in the patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction， and to explore the mechanism of this prescription delaying the disease progression. MethodsA randomized， controlled， double-blind， multicenter clinical trial was conducted， in which 94 stage Ⅳ DN patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction were randomly assigned into Baoshen prescription and control groups （47 cases）. The treatment lasted for 12 weeks. The primary efficacy indicators were mainly renal function indexes， including urine albumin-to-creatinine ratio （UACR）， 24-hour urine total protein （24 h-UTP）， serum creatinine （SCr）， and estimated glomerular filtration rate （eGFR）. The secondary efficacy indicators were metabolic memory of hyperglycemia， podocyte epithelial-to-mesenchymal transdifferentiation-related indexes， and TCM syndrome score. ResultsAfter 12 weeks of treatment， the Baoshen prescription group showed lowered levels of advanced glycation end products （lgAGEs）， connective tissue growth factor （CTGF）， type Ⅳ collagen （Col-Ⅳ）， receptor of AGEs （RAGE）， urinary fibroblast-specific protein-1 （FSP-1）， UACR， 24 h-UTP， and glycated hemoglobin （HbAlc） （P<0.05）， and an upward trend of miR-21 mRNA. The control group showed elevated levels of SCr and UREA and lowered levels of urinary FSP-1， eGFR， and HbAlc （P<0.05）. After treatment， the Baoshen prescription group had lower levels of lgAGEs， CTGF， urinary FSP-1， SCr， UACR， and 24 h-UTP and higher levels of Col-Ⅳ and eGFR than the control group （P<0.05）. In addition， the Baoshen prescription group showed statistically significant differences in SCr， eGFR， UACR， and 24 h-UTP before and after treatment （P<0.05）. ConclusionBaoshen prescription can effectively improve the renal function， reduce the urinary protein level， and alleviate clinical symptoms in stage Ⅳ DN patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction. The mechanism may be related to the metabolic memory of hyperglycemia and epithelial-to-mesenchymal transdifferentiation of podocytes.

OBJECTIVE To explore the effects and potential mechanism of Huangqi jianzhong decoction on intestinal inflammation in the rats of irritable bowel syndrome with diarrhea （IBS-D） based on the mitogen-activated protein kinase （MAPK）/ nuclear factor-κB （NF-κB） signaling pathway. METHODS Male SD rats were selected. Ten rats were randomly chosen as the control group， and the remaining rats （50 rats） were used to prepare the IBS-D model by acetic acid enema+restraint stress. The rats with successful modeling were randomly divided into the IBS-D group， the traditional Chinese medicine （TCM） group （Huangqi jianzhong decoction 15 g/kg）， the positive control drug group （Rifaximin tablets 150 mg/kg）， the activator group （anisomycin 125 μg/kg， the activator of p38 MAPK）， and the TCM+activator group （Huangqi jianzhong decoction 15 g/kg+ anisomycin 125 μg/kg）， with 10 rats in each group. Rats in each group were given a gavage or tail vein injection of the corresponding medicine liquid or the same volume of normal saline， once a day for two consecutive weeks. After the last administration， feces within 24 hours were collected for the calculation of fecal water content and fecal trait score， and the minimum volume threshold was detected. The levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and IL-6 in serum were detected； the pathological changes of colonic tissue were observed； the expressions of tight junction protein ZO-1， occludin mRNAs and proteins related to the MAPK/NF- κB signaling pathway in colonic tissue were determined. RESULTS Compared with the control group， obvious edema and inflammatory cell infiltration could be observed in the colonic tissue of rats in the IBS-D group. The fecal water content and trait score， serum levels of inflammatory factors， as well as the protein phosphorylation levels of p38 MAPK and NF-κB p65 in the colonic tissue were significantly increased， while the minimum volume threshold and the mRNA expressions of ZO-1 and occludin were significantly decreased or down-regulated （P＜0.05）. Compared with the IBS-D group， the pathological changes of colonic tissue in the TCM group and positive control drug group were alleviated， and the above indicators improved significantly （P＜0.05）， while the above indicators in the activator group deteriorated further （P＜0.05）. Compared with the TCM group， the above indicators in the TCM+activator group were significantly reversed （P＜0.05）. CONCLUSIONS Huangqi jianzhong decoction can alleviate colonic inflammation in IBS-D rats， relieve visceral hypersensitivity， and has a certain protective effect on their intestinal barrier function. The above-mentioned effects may be related to the inhibition of the MAPK/NF- κB signaling pathway.

Objective Melatonin has been shown to have neuroprotective effects.This study is aimed at observing the effects of copper deposition on cognitive function in a toxic milk(TX)mouse model of Wilson disease(WD),and investigating the effects and mechanisms of action of Gandou Bushen Decoction(GDBSD)on melatonin synthesis and pineal function in the WD model mice.Methods A total of 30 homozygous TX mice were randomly assigned to 3 groups(n=10 in each group),including a WD group,a GDBSD group,and a dimercaptosuccinic acid(DMSA)group.A total of 10 DL mice were included in the normal control(NC)group.The structure and copper content of pineal gland tissues,oxidative stress and apoptosis-related markers,and serum melatonin levels were evaluated using hematoxylin-eosin(HE)staining,enzyme-linked immunosorbent assay(ELISA),flow cytometry,and Western blot.Results Compared with the NC group,the WD group exhibited decreased learning and cognitive abilities(P＜0.05),damaged pineal gland structure,increased copper content,reactive oxygen species(ROS)levels,and mitochondrial damage rate in the pineal gland(P＜0.01),altered levels of melatonin and oxidative stress-related markers(P＜0.05),upregulated expression levels of pro-apoptotic proteins Bax and Caspase-3,and decreased expression of the anti-apoptotic protein Bcl-2(P＜0.01).After treatment with GDBSD and DMSA,the SIRT3/FOXO3α signaling pathway was activated,the copper content in the pineal gland was reduced,and oxidative stress and apoptosis-related damages were improved,leading to an improvement in learning and memory abilities(P＜0.05).Conclusion GDBSD can alleviate cognitive impairments in WD mice caused by pineal gland copper deposition by inhibiting oxidative stress and apoptosis in the pineal gland.The underlying molecular mechanism is associated with the regulation of the SIRT3/FOXO3α signaling pathway.

Chronic obstructive pulmonary disease (COPD) currently lacks effective treatments to halt disease progression, making the search for preventive and therapeutic drugs a pressing issue. Natural products, with their accessibility, affordability, and low toxicity, offer promising avenues. Investigating the pharmacological effects and related signaling mechanisms of active components from natural products on COPD animal models induced by various triggers has become an important focus. In animal models induced by cigarette smoke, cigarette smoke combined with lipopolysaccharide (LPS), air pollution, elastase, bacterial or viral infections, the active compounds of natural products, such as flavonoids, terpenoids, and phenolics, can exert anti-inflammatory, antioxidant, mucus-regulating, and airway remodeling-inhibiting effects through key signaling pathways including nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), nuclear factor-kappa B (NF-κB), and mitogen-activated protein kinase (MAPK). These findings not only provide a theoretical basis for the clinical diagnosis and treatment of COPD but also point to new directions for future scientific research.
Pulmonary Disease, Chronic Obstructive/etiology* ; Animals ; Disease Models, Animal ; Biological Products/pharmacology* ; Humans ; NF-kappa B/metabolism* ; Flavonoids/pharmacology* ; Signal Transduction/drug effects* ; Anti-Inflammatory Agents/pharmacology* ; Heme Oxygenase-1/metabolism* ; Terpenes/pharmacology* ; Antioxidants/pharmacology* ; NF-E2-Related Factor 2/metabolism* ; Smoke/adverse effects* ; Phenols/therapeutic use*

Objective:To explore the application value of radiomics models based on MRI of vertebrae and paravertebral muscles in identifying potential vertebral fragility fracture risk in osteoporosis and osteopenia.Methods:This cross-sectional study collected data from patients who underwent both dual-energy X-ray absorptiometry (DXA) and lumbar MRI at the Third Affiliated Hospital of Southern Medical University between January 2014 and December 2023,retrospectively. Based on DXA results, patients were categorized into osteoporosis group ( n=302) and osteopenia group ( n=264), with fracture and non-fracture patients matched at 1∶1 ratio by propensity score matching based on age, gender, and body mass index. The fourth lumbar vertebra was selected as the region of interest (ROI) for the vertebral body, and the bilateral psoas major, erector spinae, and multifidus muscles were selected as the ROIs for the paraspinal muscles. A total of 7 259 radiomics features were extracted from these ROIs. The dataset was divided into a training set and a test set in an 8∶2 ratio by simple random sampling (osteoporosis group 241 and 61 cases, osteopenia group 211 and 53 cases). The T-score was used to establish the clinical model. After feature normalization and dimensionality reduction, logistic regression was applied to build three radiomics models: vertebral model, paraspinal muscle model, and vertebral-paraspinal muscle model. The T-score was then combined with the radiomics model that achieved the highest area under the receiver operating characteristic curve (AUC) in the test set to construct a clinical-radiomics combined model. Model performance was evaluated using the AUC. The DeLong test was used to compare the diagnostic efficacy between models. Results:In the test set, the vertebral-paravertebral muscle model achieved the highest AUC among radiomics models and was selected for combination with the T-score. In identifying potential vertebral fragility fractures of osteoporosis group, the AUC (95% CI) of the clinical model, vertebral model, paraspinal muscle model, vertebral-paraspinal muscle model, and clinical-radiomics model were 0.523 (0.373-0.672), 0.869 (0.779-0.959), 0.608 (0.464-0.752), 0.876 (0.791-0.961), and 0.860 (0.769-0.952), respectively. For osteopenia group, the corresponding AUC(95% CI) were 0.625 (0.467-0.783), 0.696 (0.547-0.845), 0.706 (0.563-0.848), 0.816 (0.702-0.930), and 0.820 (0.710-0.930). The DeLong test showed that the vertebral model for identifying the potential vertebral fracture risk in osteoporosis group had better performance than the paraspinal muscle model ( Z=3.28, P=0.001). While for osteopenia group, there was no significant difference in diagnostic performance between the vertebral model and the paraspinal muscle model ( Z=0.09, P=0.932). The recognition efficacy of the clinical model and the vertebral-paraspinal muscle model was significantly different ( Z=3.69, 1.98; P<0.001, P=0.047), while there was no significant difference between the clinical-radiomics combined model and the vertebral-paraspinal muscle model ( Z=1.51, 0.12; P=0.131, 0.904). Conclusion:The MRI-based vertebral-paraspinal muscle radiomics model can effectively identify osteoporosis or osteopenia patients with potential fragility fracture risk. In osteopenia group, the efficacy of the MRI radiomics models based on the vertebra and paraspinal muscles in identifying potential vertebral fragility fracture risk is comparable.

Objective To explore strategies for further subdivision of DRG in gastrointestinal surgery cases,providing references to enhance the differentiation of DRG subgroups.Methods A total of 5 108 gastrointestinal surgery cases were selected from a tertiary grade A hospital and a tertiary hospital in Hubei Province,spanning from January 2019 to June 30,2023,and another secondary hospital's data from 2020 and 2021.It employs single factor analysis and multiple linear regression analysis to identify factors influencing case costs.Additionally,the opinions of nine clinicans were gathered regarding factors affecting resource consumption in gastrointestinal surgery cases.The four selected case groups were further subdivided considers the peak characteristics of disease costs.It compares subdivided groups with the DRG Payment Subgroups Scheme(Version 2.0).Results Groups GB1,GB2,GC1,and GC2 were subdivided into 7,4,7,and 6 DRG groups,respectively.The coefficient of variation of each subdivided DRG were reduced,homogeneity was increased,and inter-group differentiation was increased.The results were consistent with the DRG Payment Subgroups Scheme(Version 2.0).Conclusion Based on DRG grouping,the DRG groups can be further subdivided according to the peak characteristics presented by case costs.This subdivision strategy is helpful to provide new ideas for case grouping of Medicare payment.

Objective:To explore the application value of radiomics models based on MRI of vertebrae and paravertebral muscles in identifying potential vertebral fragility fracture risk in osteoporosis and osteopenia.Methods:This cross-sectional study collected data from patients who underwent both dual-energy X-ray absorptiometry (DXA) and lumbar MRI at the Third Affiliated Hospital of Southern Medical University between January 2014 and December 2023,retrospectively. Based on DXA results, patients were categorized into osteoporosis group ( n=302) and osteopenia group ( n=264), with fracture and non-fracture patients matched at 1∶1 ratio by propensity score matching based on age, gender, and body mass index. The fourth lumbar vertebra was selected as the region of interest (ROI) for the vertebral body, and the bilateral psoas major, erector spinae, and multifidus muscles were selected as the ROIs for the paraspinal muscles. A total of 7 259 radiomics features were extracted from these ROIs. The dataset was divided into a training set and a test set in an 8∶2 ratio by simple random sampling (osteoporosis group 241 and 61 cases, osteopenia group 211 and 53 cases). The T-score was used to establish the clinical model. After feature normalization and dimensionality reduction, logistic regression was applied to build three radiomics models: vertebral model, paraspinal muscle model, and vertebral-paraspinal muscle model. The T-score was then combined with the radiomics model that achieved the highest area under the receiver operating characteristic curve (AUC) in the test set to construct a clinical-radiomics combined model. Model performance was evaluated using the AUC. The DeLong test was used to compare the diagnostic efficacy between models. Results:In the test set, the vertebral-paravertebral muscle model achieved the highest AUC among radiomics models and was selected for combination with the T-score. In identifying potential vertebral fragility fractures of osteoporosis group, the AUC (95% CI) of the clinical model, vertebral model, paraspinal muscle model, vertebral-paraspinal muscle model, and clinical-radiomics model were 0.523 (0.373-0.672), 0.869 (0.779-0.959), 0.608 (0.464-0.752), 0.876 (0.791-0.961), and 0.860 (0.769-0.952), respectively. For osteopenia group, the corresponding AUC(95% CI) were 0.625 (0.467-0.783), 0.696 (0.547-0.845), 0.706 (0.563-0.848), 0.816 (0.702-0.930), and 0.820 (0.710-0.930). The DeLong test showed that the vertebral model for identifying the potential vertebral fracture risk in osteoporosis group had better performance than the paraspinal muscle model ( Z=3.28, P=0.001). While for osteopenia group, there was no significant difference in diagnostic performance between the vertebral model and the paraspinal muscle model ( Z=0.09, P=0.932). The recognition efficacy of the clinical model and the vertebral-paraspinal muscle model was significantly different ( Z=3.69, 1.98; P<0.001, P=0.047), while there was no significant difference between the clinical-radiomics combined model and the vertebral-paraspinal muscle model ( Z=1.51, 0.12; P=0.131, 0.904). Conclusion:The MRI-based vertebral-paraspinal muscle radiomics model can effectively identify osteoporosis or osteopenia patients with potential fragility fracture risk. In osteopenia group, the efficacy of the MRI radiomics models based on the vertebra and paraspinal muscles in identifying potential vertebral fragility fracture risk is comparable.

Objective To explore strategies for further subdivision of DRG in gastrointestinal surgery cases,providing references to enhance the differentiation of DRG subgroups.Methods A total of 5 108 gastrointestinal surgery cases were selected from a tertiary grade A hospital and a tertiary hospital in Hubei Province,spanning from January 2019 to June 30,2023,and another secondary hospital's data from 2020 and 2021.It employs single factor analysis and multiple linear regression analysis to identify factors influencing case costs.Additionally,the opinions of nine clinicans were gathered regarding factors affecting resource consumption in gastrointestinal surgery cases.The four selected case groups were further subdivided considers the peak characteristics of disease costs.It compares subdivided groups with the DRG Payment Subgroups Scheme(Version 2.0).Results Groups GB1,GB2,GC1,and GC2 were subdivided into 7,4,7,and 6 DRG groups,respectively.The coefficient of variation of each subdivided DRG were reduced,homogeneity was increased,and inter-group differentiation was increased.The results were consistent with the DRG Payment Subgroups Scheme(Version 2.0).Conclusion Based on DRG grouping,the DRG groups can be further subdivided according to the peak characteristics presented by case costs.This subdivision strategy is helpful to provide new ideas for case grouping of Medicare payment.

Objective To investigate whether activation of mitochondrial acetal dehydrogenase 2(ALDH2)alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.Methods Thirty 8-week-old C57 BL/6 mice were randomized into control,hypoxia,and hypoxia+Alda-1(an ALDH2 activator)group(n=10),and the mice in the latter two groups,along with 10 ALDH2 knockout(ALDH2-/-)mice,were exposed to hypoxia(10%O2,90%N2)with or without daily intraperitoneal injection of Alda-1 for 4 weeks.The changes in right ventricular function and pressure(RVSP)of the mice were evaluated by echocardiography and right ventricular catheter test,and pulmonary artery pressure was estimated based on RVSP.Pulmonary vascular remodeling,right ventricular injury,myocardial α-SMA expression,distal pulmonary arteriole muscle normalization,right ventricular cross-sectional area,myocardial cell hypertrophy,and right cardiac hypertrophy index were assessed with HE staining,immunofluorescence staining and WGA staining,and the expressions of ALDH2,SIRT1,PGC-1α,P16INK4A and P21CIP1 were detected.In pulmonary artery smooth muscle cells with hypoxic exposure,the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.Results The wild-type mice with hypoxic exposure showed significantly increased RVSP,right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1,which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/-mice.In cultured pulmonary artery smooth muscle cells,hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1,which were all lowered by treatment with Alda-1,but its effect was obviously attenuated by EX527 treatment.Conclusion ALDH2 alleviates hypoxia-induced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.