ObjectiveTo investigate whether the effect of Danggui Shaoyaosan （DSS） on cognitive impairment is related to its promotion of ketone body metabolism in the brain and regulation of glutamate/α-amino-3-hydroxy-5-methyl-4-isox-azolepropionic acid receptor （AMPAR） pathway. MethodsMale APP/PS1 mice were randomized into model， low-dose （3.2 g·kg^-1） DSS， medium-dose （6.4 g·kg^-1） DSS， high-dose （12.8 g·kg^-1） DSS， ketogenic diet， and inhibitor （talampanel， 5 mg·kg^-1） groups. C57BL/6J wild-type mice were selected as the normal group. The talampanel group was intragastrically administered for 2 consecutive weeks from the 6th week， and the other groups were continuously treated for 8 weeks before behavioral testing. The ultrastructure of synapses in hippocampal CA1 region was observed by transmission electron microscopy， and calcium/calmodulin-dependent kinase Ⅱ （CaMKⅡ） expression was detected by immunohistochemistry （IHC）. The levels of β-hydroxybutyrate （BHB） and lactic acid （LAC） were measured by biochemical kits， and those of glutamate （Glu）， glutamine （Gln）， γ-aminobutyric acid （GABA）， and synaptophysin （SYP） by enzyme-linked immunosorbent assay （ELISA）. The mRNA levels of glutamine synthetase （GS）， glutaminase （GLS）， glutamate decarboxylase （GAD）， CaMKⅡ， and AMPAR subunits GluA1 and GluA2 were quantified by Real-time quantitative polymerase chain reaction （Real-time PCR）， and the protein levels of GS， GLS， GAD， GluA1， and GluA2 by Western blot. ResultsCompared with the normal group， the model group exhibited decreased recognition index， spontaneous alternation rate， and residence time in the target quadrant （P<0.01）， increased escape latency and ratio of the time in the opposite side of the target quadrant to the time in the target quadrant （P<0.05， P<0.01）， damaged synaptic ultrastructure of hippocampal CA1 region， increased positive expression of CaMKⅡ， no significant difference in BHB level， elevated LAC and Glu levels （P<0.01）， declined SYP， Gln， and GABA levels （P<0.01）， downregulated mRNA and protein levels of GS， GAD， and GluA2 （P<0.05， P<0.01）， and upregulated mRNA and protein levels of GLS and GluA1 （P<0.05， P<0.01） and mRNA level of CaMKⅡ （P<0.01）. Compared with the model group， DSS intervention improved the behavioral indexes of mice （P<0.05， P<0.01）， enhanced the synaptic ultrastructure plasticity in hippocampal CA1 region， decreased the positive expression of CaMKⅡ， raised the BHB level （P<0.01）， reduced the LAC and Glu levels （P<0.01）， elevated the SYP， Gln， and GABA levels （P<0.01）， upregulated the mRNA and protein levels of GS， GAD， and GluA2， and downregulated the mRNA and protein levels of GLS and GluA1 （P<0.05， P<0.01） and the mRNA level of CaMKⅡ （P<0.01）. ConclusionDSS can improve the learning and memory and enhance the synaptic plasticity of APP/PS1 mice. Its neuroprotective effect is coupled with the promotion of ketone body formation and remodeling of brain energy metabolism， and is related to the regulation of glutamate/AMPAR pathway.

BACKGROUND:The patient underwent multiple hypoproteinemia after total hip arthroplasty,which affected postoperative healing and rehabilitation.OBJECTIVE:To investigate and screen the risk factors for hypoproteinemia after total hip arthroplasty,and to establish a nomogram prediction model so as to provide guidance for judging whether hypoproteinemia occurs after total hip arthroplasty.METHODS:A total of 355 patients who underwent total hip arthroplasty were included,and according to whether hypoproteinemia occurred on the first day after surgery,they were divided into 238 cases in the hypoproteinemia group and 117 cases in the normal group,with a hypoproteinemia rate of 67％.Data were collected,including age,gender,diabetes mellitus,hypertension,hyperuricemia,hyperlipidemia,anesthesia method,preoperative leukocytes,preoperative erythrocytes,preoperative hemoglobin,preoperative platelets,preoperative plasma prothrombin time,preoperative activated partial prothrombin time,preoperative international normalized ratio,preoperative thrombin time,preoperative fibrinogen,preoperative erythrocyte sedimentation rate,preoperative C-reactive protein,preoperative D-dimer,preoperative mean corpuscular hemoglobin content,preoperative mean corpuscular volume,operation time,body mass index,preoperative procalcitonin,and preoperative hematocrit.SPSS 27.0 software was used for univariate analysis,followed by R language(4.3.1)to perform least absolute shrinkage and selection operator regression and 10-fold cross-validation of the observation indicators to obtain the intersection of the two risk factors.SPSS 27.0 software was used to perform multivariate binary logistic regression to obtain the final risk factors.The prediction model of hypoproteinemia after total hip arthroplasty was constructed by R language.The receiver operating characteristic curve,calibration curve,and clinical decision curve were constructed to assess the predictive model predictive ability.RESULTS AND CONCLUSION:(1)Univariate analysis,least absolute shrinkage and selection operator regression,and multivariate logistic regression were used to screen out significant differences in age(OR=1.024,P=0.023),preoperative platelets(OR=0.995,P=0.028),and preoperative erythrocyte sedimentation rate(OR=1.031,P=0.045)in judging whether hypoproteinemia would occur after surgery(P＜0.05).(2)The nomogram prediction model was constructed based on the final risk factors screened by multivariate Logistic regression,and the prediction ability of the model was evaluated by constructing the receiver operating characteristic curve,and the area under the calculated receiver operating characteristic curve reached 0.835(95％CI=0.779-0.891),C-index=0.835.A threshold of 0-0.83 could bring better clinical efficacy calculated by the decision curve analysis.The model has good sensitivity and accuracy,which can better identify the risk of postoperative hypoproteinemia for medical staff and patients before total hip arthroplasty.

BACKGROUND:The patient underwent multiple hypoproteinemia after total hip arthroplasty,which affected postoperative healing and rehabilitation.OBJECTIVE:To investigate and screen the risk factors for hypoproteinemia after total hip arthroplasty,and to establish a nomogram prediction model so as to provide guidance for judging whether hypoproteinemia occurs after total hip arthroplasty.METHODS:A total of 355 patients who underwent total hip arthroplasty were included,and according to whether hypoproteinemia occurred on the first day after surgery,they were divided into 238 cases in the hypoproteinemia group and 117 cases in the normal group,with a hypoproteinemia rate of 67％.Data were collected,including age,gender,diabetes mellitus,hypertension,hyperuricemia,hyperlipidemia,anesthesia method,preoperative leukocytes,preoperative erythrocytes,preoperative hemoglobin,preoperative platelets,preoperative plasma prothrombin time,preoperative activated partial prothrombin time,preoperative international normalized ratio,preoperative thrombin time,preoperative fibrinogen,preoperative erythrocyte sedimentation rate,preoperative C-reactive protein,preoperative D-dimer,preoperative mean corpuscular hemoglobin content,preoperative mean corpuscular volume,operation time,body mass index,preoperative procalcitonin,and preoperative hematocrit.SPSS 27.0 software was used for univariate analysis,followed by R language(4.3.1)to perform least absolute shrinkage and selection operator regression and 10-fold cross-validation of the observation indicators to obtain the intersection of the two risk factors.SPSS 27.0 software was used to perform multivariate binary logistic regression to obtain the final risk factors.The prediction model of hypoproteinemia after total hip arthroplasty was constructed by R language.The receiver operating characteristic curve,calibration curve,and clinical decision curve were constructed to assess the predictive model predictive ability.RESULTS AND CONCLUSION:(1)Univariate analysis,least absolute shrinkage and selection operator regression,and multivariate logistic regression were used to screen out significant differences in age(OR=1.024,P=0.023),preoperative platelets(OR=0.995,P=0.028),and preoperative erythrocyte sedimentation rate(OR=1.031,P=0.045)in judging whether hypoproteinemia would occur after surgery(P＜0.05).(2)The nomogram prediction model was constructed based on the final risk factors screened by multivariate Logistic regression,and the prediction ability of the model was evaluated by constructing the receiver operating characteristic curve,and the area under the calculated receiver operating characteristic curve reached 0.835(95％CI=0.779-0.891),C-index=0.835.A threshold of 0-0.83 could bring better clinical efficacy calculated by the decision curve analysis.The model has good sensitivity and accuracy,which can better identify the risk of postoperative hypoproteinemia for medical staff and patients before total hip arthroplasty.

BACKGROUND:Non-traumatic necrosis of the femoral head is a difficult joint disease,and preserving one's own femoral head is of great significance for young patients.Currently,there is a lack of regular and unified functional exercise plans.OBJECTIVE:To investigate the effect of hip abductor muscle exercise on the three-dimensional gait and collapse rate of patients with non-traumatic femoral head necrosis,and to provide theoretical basis for effective rehabilitation of patients with non-traumatic femoral head necrosis.METHODS:Totally 81 non-traumatic and non-surgical patients with femoral head necrosis(81 hips)admitted to the Third Affiliated Hospital of Guangzhou University of Chinese Medicine from June 2020 to June 2022 were included.Patients were randomly divided into a control group(n=40)and a hip abductor muscle exercise group(n=41).The control group received routine physical therapy and medication treatment.The hip abductor muscle exercise group underwent hip abductor muscle exercise on the basis of the control group.The gait status(hip joint range of motion,step length difference,and ground contact time difference)of two groups of patients was evaluated using the Tecnobody balance assessment system before and 12 weeks after treatment.The BIODEX-S4 isokinetic muscle strength testing system was used to test the peak force distance of hip abduction isokinetic muscle strength.Gluteus medius width ratio was compared between two groups.The collapse rate was compared between two groups of patients 1 year after treatment.RESULTS AND CONCLUSION:(1)There was no statistically significant difference between the hip abductor muscle exercise group and the control group in terms of age,gender,side profile,body mass index,and etiology(P＞0.05).(2)Before treatment,there was no significant statistical difference in the range of motion of the affected hip joint between the two groups(P＞0.05).After treatment,the range of motion of the affected hip joint in both groups improved compared to before treatment(P＜0.05),and the range of motion of the affected hip joint in the hip abductor muscle exercise group was significantly higher than that in the control group(P＜0.05).(3)Before treatment,there was no significant statistical difference in the step length and touchdown time between the two groups(P＞0.05).12 weeks after treatment,the difference in step length and touchdown time between the two groups decreased compared to before treatment(P＜0.05),and the difference in step length and touchdown time between the hip abductor muscle exercise group after treatment was significantly greater than that of the control group(P＜0.05).(4)Before treatment,there was no significant statistical difference in gluteus medius width ratio between the two groups(P＞0.05).12 weeks after treatment,the gluteus medius width ratio of both groups increased compared to that before treatment(P＜0.05),and the gluteus medius width ratio of the hip abductor muscle exercise group was significantly higher than that of the control group(P＜0.05).(5)At 1 year after treatment,the comparison of femoral head collapse rates between the two groups showed significant statistical significance(P＜0.05),and that in the hip abductor muscle exercise group(22％)was significantly lower than that in the control group(45％).(6)It is concluded that exercise of the hip abductor muscle effectively enhances hip joint function,improves gait,and reduces the rate of femoral head collapse in patients with non-traumatic femoral head necrosis.It is recommended to use hip abductor muscle exercise as one of the basic methods for hip preservation in non-traumatic femoral head necrosis.

BACKGROUND:Non-traumatic necrosis of the femoral head is a difficult joint disease,and preserving one's own femoral head is of great significance for young patients.Currently,there is a lack of regular and unified functional exercise plans.OBJECTIVE:To investigate the effect of hip abductor muscle exercise on the three-dimensional gait and collapse rate of patients with non-traumatic femoral head necrosis,and to provide theoretical basis for effective rehabilitation of patients with non-traumatic femoral head necrosis.METHODS:Totally 81 non-traumatic and non-surgical patients with femoral head necrosis(81 hips)admitted to the Third Affiliated Hospital of Guangzhou University of Chinese Medicine from June 2020 to June 2022 were included.Patients were randomly divided into a control group(n=40)and a hip abductor muscle exercise group(n=41).The control group received routine physical therapy and medication treatment.The hip abductor muscle exercise group underwent hip abductor muscle exercise on the basis of the control group.The gait status(hip joint range of motion,step length difference,and ground contact time difference)of two groups of patients was evaluated using the Tecnobody balance assessment system before and 12 weeks after treatment.The BIODEX-S4 isokinetic muscle strength testing system was used to test the peak force distance of hip abduction isokinetic muscle strength.Gluteus medius width ratio was compared between two groups.The collapse rate was compared between two groups of patients 1 year after treatment.RESULTS AND CONCLUSION:(1)There was no statistically significant difference between the hip abductor muscle exercise group and the control group in terms of age,gender,side profile,body mass index,and etiology(P＞0.05).(2)Before treatment,there was no significant statistical difference in the range of motion of the affected hip joint between the two groups(P＞0.05).After treatment,the range of motion of the affected hip joint in both groups improved compared to before treatment(P＜0.05),and the range of motion of the affected hip joint in the hip abductor muscle exercise group was significantly higher than that in the control group(P＜0.05).(3)Before treatment,there was no significant statistical difference in the step length and touchdown time between the two groups(P＞0.05).12 weeks after treatment,the difference in step length and touchdown time between the two groups decreased compared to before treatment(P＜0.05),and the difference in step length and touchdown time between the hip abductor muscle exercise group after treatment was significantly greater than that of the control group(P＜0.05).(4)Before treatment,there was no significant statistical difference in gluteus medius width ratio between the two groups(P＞0.05).12 weeks after treatment,the gluteus medius width ratio of both groups increased compared to that before treatment(P＜0.05),and the gluteus medius width ratio of the hip abductor muscle exercise group was significantly higher than that of the control group(P＜0.05).(5)At 1 year after treatment,the comparison of femoral head collapse rates between the two groups showed significant statistical significance(P＜0.05),and that in the hip abductor muscle exercise group(22％)was significantly lower than that in the control group(45％).(6)It is concluded that exercise of the hip abductor muscle effectively enhances hip joint function,improves gait,and reduces the rate of femoral head collapse in patients with non-traumatic femoral head necrosis.It is recommended to use hip abductor muscle exercise as one of the basic methods for hip preservation in non-traumatic femoral head necrosis.

Objective:The current study aimed to evaluate the possible protective effects of N-acetylcysteine (NAC) against Indum-tin oxide (ITO) nanoparticle (Nano-ITO) -induced pulmonary alveolar proteinosis (PAP) in rats, especially via modulation of nuclear factor kappa B (NF-κB) signaling.Methods:In October 2019, 50 adult male Sprague-Dawley rats were randomly allocated into five groups (10 rats each) as follows: blank control group, saline control group, NAC control group (200 mg/kg), Nano-ITO group (receiving a repeated intratracheal dose of 6 mg/kg Nano-ITO) and NAC intervention group (pre-treated intraperitoneally with 200 mg/kg NAC 1.5 h before the administration of an intratracheal dose of 6 mg/kg Nano-ITO). The rats were exposed twice a week for 12 weeks. Rats were then euthanized under anesthesia, and their lungs were removed for histopathological and immunohistochemical analysis. The comparison of indicators reflecting oxidative stress and pulmonary inflammation among groups was conducted using one-way analysis of variance (ANOVA) and Bonferroni's test. The effect of NAC on Nano-ITO induced NF-κB signaling pathway in rats was analyzed.Results:Histopathological examination of Nano-ITO exposed rats revealed diffuse alveolar damage, including PAP, cholesterol crystals, alveolar fibrosis, pulmonary fibrosis, and alveolar emphysema. Immunohistochemical results of Nano-ITO exposed rats showed strong positive for nuclear factor κB p65 (NF-κB p65) and nuclear factor Kappa B inhibitory factor kinase (IKK-β) and weak positive for nuclear factor κB inhibitory protein α (IκB-α) in the nuclei of bronchiolar and alveolar epithelial cells. Compared with blank control group, saline control group and NAC control group, the level of total protein (TP) in bronchoalveolar lavage fluid of rats in Nano-ITO group was significantly increased ( P<0.05), and the activities of lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA) content and total antioxidant capacity (T-AOC) were significantly increased ( P<0.05), the levels of proinflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were significantly increased ( P<0.05), and the levels of NF-κB p65, IKK-β, inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) in lung tissue were significantly increased ( P<0.05). Compared with Nano-ITO group, the levels of TP, T-AOC, MDA and TNF-α in bronchoalveolar lavage fluid of rats in NAC intervention group were significantly decreased ( P<0.05), and the levels of NF-κB p65 and ROS in lung tissue were significantly decreased (P<0.05). Western blot results showed that compared with the control groups, the protein expressions of NF-κB p65 and IKK-β in the lung tissue of Nano-ITO group were increased, while the protein expression of IκB-α was decreased ( P<0.05). Compared with Nano-ITO group, the protein expressions of NF-κB p65 and IKK-β in lung tissue of rats in NAC intervention group were decreased, while the protein expression of IκB-α was increased ( P<0.05) . Conclusion:The study demonstrated that Nano-ITO might induce pulmonary toxicity through the activation of NF-κB signaling pathway, and NAC could antagonize the pulmonary toxicity of Nano-ITO by inhibiting the NF-κB signaling pathway.

Objective:The current study aimed to evaluate the possible protective effects of N-acetylcysteine (NAC) against Indum-tin oxide (ITO) nanoparticle (Nano-ITO) -induced pulmonary alveolar proteinosis (PAP) in rats, especially via modulation of nuclear factor kappa B (NF-κB) signaling.Methods:In October 2019, 50 adult male Sprague-Dawley rats were randomly allocated into five groups (10 rats each) as follows: blank control group, saline control group, NAC control group (200 mg/kg), Nano-ITO group (receiving a repeated intratracheal dose of 6 mg/kg Nano-ITO) and NAC intervention group (pre-treated intraperitoneally with 200 mg/kg NAC 1.5 h before the administration of an intratracheal dose of 6 mg/kg Nano-ITO). The rats were exposed twice a week for 12 weeks. Rats were then euthanized under anesthesia, and their lungs were removed for histopathological and immunohistochemical analysis. The comparison of indicators reflecting oxidative stress and pulmonary inflammation among groups was conducted using one-way analysis of variance (ANOVA) and Bonferroni's test. The effect of NAC on Nano-ITO induced NF-κB signaling pathway in rats was analyzed.Results:Histopathological examination of Nano-ITO exposed rats revealed diffuse alveolar damage, including PAP, cholesterol crystals, alveolar fibrosis, pulmonary fibrosis, and alveolar emphysema. Immunohistochemical results of Nano-ITO exposed rats showed strong positive for nuclear factor κB p65 (NF-κB p65) and nuclear factor Kappa B inhibitory factor kinase (IKK-β) and weak positive for nuclear factor κB inhibitory protein α (IκB-α) in the nuclei of bronchiolar and alveolar epithelial cells. Compared with blank control group, saline control group and NAC control group, the level of total protein (TP) in bronchoalveolar lavage fluid of rats in Nano-ITO group was significantly increased ( P<0.05), and the activities of lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA) content and total antioxidant capacity (T-AOC) were significantly increased ( P<0.05), the levels of proinflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were significantly increased ( P<0.05), and the levels of NF-κB p65, IKK-β, inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) in lung tissue were significantly increased ( P<0.05). Compared with Nano-ITO group, the levels of TP, T-AOC, MDA and TNF-α in bronchoalveolar lavage fluid of rats in NAC intervention group were significantly decreased ( P<0.05), and the levels of NF-κB p65 and ROS in lung tissue were significantly decreased (P<0.05). Western blot results showed that compared with the control groups, the protein expressions of NF-κB p65 and IKK-β in the lung tissue of Nano-ITO group were increased, while the protein expression of IκB-α was decreased ( P<0.05). Compared with Nano-ITO group, the protein expressions of NF-κB p65 and IKK-β in lung tissue of rats in NAC intervention group were decreased, while the protein expression of IκB-α was increased ( P<0.05) . Conclusion:The study demonstrated that Nano-ITO might induce pulmonary toxicity through the activation of NF-κB signaling pathway, and NAC could antagonize the pulmonary toxicity of Nano-ITO by inhibiting the NF-κB signaling pathway.