Objective: To investigate the effect of auricular therapy on sleep improvement and the GABAergic system pathway in a rat model of insomnia and to explore its possible mechanism. Methods: According to the random number table, 60 male SD rats were randomly divided into blank control, model, auricular point sticking, auricular bloodletting, and auricular bloodletting combined with sticking groups, with 12 rats per group. Insomnia was induced by intraperitoneal injection of p-chlorophenylalanine. After establishing the insomnia model, 36 rats were treated once a day with auricular point sticking or bloodletting for 5 consecutive days. After the intervention, the general condition and body weight of rats were observed; the righting reflex test was used to detect the sleep latency and duration; HE staining was used to observe the morphology of hypothalamic neuron cells; and an enzyme-linked immunosorbent assay was used to detect the GABA and glutamate content in rat serum. Immunohistochemistry(IHC) and real-time fluorescence quantitative PCR were used to detect GABA ARα1 and GABA ARγ2 protein and mRNA expression in the hypothalamus of rats, and Western blotting(WB) was used to detect GABA ARα1, GABA ARγ2, GAD65/67, GAT-1, and GABA-T protein expression in the hypothalamus of rats. Results: Compared with the blank control group, the model group had a lower body weight, a significantly shorter sleep duration (P<0.05), severe damage to the morphological structure of hypothalamic neurons with disordered cell arrangement, larger intercellular gaps, enlarged cell bodies, and a vacuolated appearance. All the intervention groups had significantly higher body weight and longer sleep duration than the model group (P<0.05). Compared with the other intervention groups, the auricular point sticking group had a longer sleep duration (P<0.05), and the hypothalamic neuron cells in all intervention groups improved, with the auricular point sticking group showing more apparent improvement. The model group had a lower GABA and higher glutamate contents, and GABA ARα1, GABA ARγ2, and GAD65/67 protein expression in the hypothalamus were lower than in the blank control group. In contrast, GAT-1 and GABA-T protein expression was higher, and GABA ARα1 and GABA ARγ2 mRNA expression was lower (P<0.05). The serum GABA content in the auricular point sticking and auricular bloodletting groups was higher, and the serum glutamate content in the auricular point sticking and auricular bloodletting combined sticking groups was lower than in the model group. GABA ARα1 mRNA expression in the hypothalamus of each intervention group was significantly increased, and GABA ARγ2 mRNA expression in the hypothalamus of the auricular point sticking and auricular bloodletting combined sticking groups increased. GABA ARα1(IHC, WB), GABA ARγ2(WB), and GAD65/67 protein expression in the hypothalamus of the auricular point sticking group increased, whereas GAT-1 and GABA-T protein expression decreased. GABA ARα1 and GABA ARγ2 protein expression(IHC, WB) in the hypothalamus of the auricular bloodletting group increased, whereas GABA-T protein expression decreased. GABA ARγ1(IHC) and GABA ARγ2(WB) protein expression in the hypothalamus of the auricular bloodletting combined sticking group increased, whereas GAT-1 and GABA-T protein expression decreased (P<0.05). Compared with in the inventation groups, the serum GABA content in the auricular point sticking group increased, the serum glutamate content decreased, GABA ARα1 and GABA ARγ2 mRNA expression in the hypothalamus increased, and GABA ARα1(IHC), GAD65/67 protein expression increased. In contrast, GABA-T protein expression decreased (P<0.05), and GABA ARγ2 protein expression(IHC) in the hypothalamus of the auricular bloodletting group increased (P<0.05). Conclusion Auricular therapy, particularly auricular point sticking, may have modulated the GABAergic system pathway by upregulating hypothalamic GABA ARα1, GABA ARγ2, and GAD65/67 protein expression while downregulating GAT-1 and GABA-T protein expression to alleviate symptoms in an insomnia rat model.

OBJECTIVE: To observe the effects of Huayu Tongluo (transforming stasis and unblocking collaterals) moxibustion on learning-memory ability and hippocampal mammalian sterile 20-like kinase 1 (Mst1)/nuclear factor κB (NF-κB) p65 pathway related to inflammatory response in rats with vascular dementia (VD). METHODS: A total of 60 male Wistar rats of SPF grade were randomly divided into a sham operation group (12 rats) and a modeling group (48 rats). VD model was established by the method of modified bilateral common carotid artery permanent ligation in the modeling group. Thirty-six rats with successful modeling were randomly divided into a model group, a moxibustion group and a western medication group, with 12 rats in each group. Huayu Tongluo moxibustion was applied at "Dazhui" (GV14), "Baihui" (GV20) and "Shenting" (GV24) in the moxibustion group, 20 min each time, once a day, 7 day-intervention was as one course, and 1 day-interval was taken between two courses, for a total of 3 courses. In the western medication group, piracetam was given 0.72 mg/kg by intragastric administration, twice a day, the course of intervention was same as that of the moxibustion group. The learning-memory ability was detected by Morris water maze test; the morphology of hippocampal CA1 region was observed by HE staining; the mRNA expression of Mst1, M1 microglia markers CD86, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) was detected by real-time PCR; the levels of IL-6 and TNF-α in hippocampus were detected by ELISA; and the protein expression of Mst1 and NF-κB p65 in hippocampus was detected by Western blot in rats of each group. RESULTS: Compared with the sham operation group, the escape latency was prolonged in the model group (P<0.05); compared with the model group, the escape latency was shortened in the moxibustion group and the western medication group (P<0.05). The cells in the CA1 region of hippocampus were disordered, cell collapse and irregular nuclei could be observed in the model group; compared with the model group, the cell arrangement in the CA1 region of hippocampus was more regular, and the damage was improved in the moxibustion group and the western medication group. Compared with the sham operation group, the mRNA expression of Mst1, CD86, IL-6 and TNF-α, as well as the protein expression of Mst1, NF-κB p65 in hippocampus were increased in the model group (P<0.05). Compared with the model group, the mRNA expression of Mst1, CD86, IL-6 and TNF-α, as well as the protein expression of Mst1, NF-κB p65 in hippocampus were decreased in the moxibustion group and the western medication group (P<0.05). Compared with the sham operation group, the levels of IL-6 and TNF-α in hippocampus were increased in the model group (P<0.05). Compared with the model group, the levels of IL-6 and TNF-α in hippocampus were decreased in the moxibustion group and the western medication group (P<0.05). CONCLUSION Huayu Tongluo moxibustion can improve the learning-memory ability of VD rats, the mechanism may be related to regulating the activation of microglia through Mst1/NF-κB p65 pathway, reducing the release of pro-inflammatory factors i.e. IL-6 and TNF-α, so as to alleviating the damage of inflammatory factors in the hippocampus of VD rats.
Animals ; Male ; Rats ; Moxibustion ; Hippocampus/metabolism* ; Rats, Wistar ; Dementia, Vascular/genetics* ; Memory/drug effects* ; Humans ; Transcription Factor RelA/genetics* ; Learning ; Protein Serine-Threonine Kinases/genetics* ; Acupuncture Points ; Interleukin-6/genetics* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal

In order to characterize the characteristics of pathological tremor of human upper limb, a simulation system of pathological tremor of human arm was provided and its dynamic response was analyzed. Firstly, in this study, a two-degree-of-freedom human arm dynamic model was established and linearized according to the arbitrary initial angle of joints. After solving the analytical solutions of steady-state responses of the joints, the numerical solution was used to verify it. The results of theoretical analysis show that the two natural frequencies of the developed dynamic model are 2.9 Hz and 5.4 Hz, respectively, which meet the characteristic frequency range of pathological tremors. Then, combined with the measured parameters of human arm, a tremor simulation system was built, and the measured results of joint responses are in good agreement with the theoretical and simulation analysis results, which verifies the effectiveness of the theoretical model. The results show that the human arm pathological tremor simulation system designed in this paper can characterize the frequency and response amplitude of the human upper limb pathological tremor. Moreover, the relevant research lays a theoretical foundation and experimental conditions for the subsequent development of wearable tremor suppression devices.
Humans ; Tremor/physiopathology* ; Computer Simulation ; Arm/physiopathology* ; Joints/physiopathology* ; Biomechanical Phenomena ; Upper Extremity/physiopathology* ; Models, Biological

Objective:To analyze the association between waist circumference (WC) and ischemic stroke (IS).Methods:The data for the present study were from the prospective cohort study of China Kadoorie Biobank in Qingdao. Using baseline information and IS events of the participants, the Cox proportional hazard regression model and restricted cubic spline (RCS) were used to analyze the association between WC and IS.Results:A total of 33 355 participants were included in the study, with 302 008.88 person-years of follow-up. A total of 1 093 new cases of IS were observed. Multivariate Cox proportional hazard regression model analysis showed that compared to the respondents with normal WC (male <85.0 cm, female <80.0 cm), respondents with excessive WC (male ≥85.0 cm, female ≥80.0 cm) had a 78% higher risk of IS incidence [hazard ratio( HR)=1.78, 95% CI: 1.51-2.10], and the risk increased by 72% ( HR=1.72, 95% CI: 1.40-2.12) and 83% ( HR=1.83, 95% CI: 1.40-2.39) in men and women. According to the RCS, the increase in WC and the risk of IS showed an "S" trend of nonlinear dose-response relationship. Conclusions:The risk of IS would increase with the WC. Keeping a normal WC is important for preventing IS.

Objective:To investigate the association between solid fuel use for heating, smoking, and respiratory diseases.Methods:This study is based on the Qingdao project of the China Kadoorie Biobank. After screening, 26 165 individuals were included in the study. We employed Cox proportional hazards regression models, stratified by risk age (in 5-year intervals) and sex while adjusting for confounding variables such as occupation and physical activity level to analyze the association between solid fuel use for heating, smoking, and increased risk of respiratory diseases.Results:Among the 26 165 participants, the average age of those using solid fuel for heating was (52.57±10.31) years, with females constituting 58.04% and former/current smokers accounting for 65.38%. The results indicated that both the solid fuel group and the former/current smoking group had a higher risk of respiratory diseases, with hazard ratios ( HR) (95% CI) of 1.21 (1.04-1.41) and 1.41 (1.16-1.71), respectively. For the duration of solid fuel use, the HR (95% CI) for 20 years or more, it was 1.27 (1.07-1.51). The multiplicative interaction term between solid fuel use and smoking was statistically significant. Conclusions:The use of solid fuel for heating and smoking significantly increases the risk of respiratory diseases, and there may be a multiplicative interaction between solid fuel use and smoking.

Objective:To study the alveolar bone remodeling of maxillary anterior teeth after extraction treatment and 2-year recovery period in adolescent patients with maxillary anterior arch protrusion.Methods:15 adolescent patients with maxillary anterior arch protru-sion were included,2 maxillary first premolars were extracted and implant anchorage combined with sliding method were used to close the extraction gap.CBCT images were taken before treatment(T0),after treatment(T1)and 2 years of recorvery period(T2),respectively.After multi-plane reconstruction with Dophin Imaging,the alveolar bone area(ABA)changes of maxillary central incisor,lateral incisor and canine at cementoenamel junction(CEJ-3 mm),root neck,central part,and root tip were measured and recorded as TAC,TA1,TA2 and TA3 respectively.The labial palatal alveolar crest to CEJ bone height(BH)of each tooth was recorded as BCL,BCP respectively.The data were analyzed by IBM SPSS statistics 25.0.Results:In T0-T2 phase,TA1 of each tooth was reduced.In T0-T1 phase,the horizontal adsorption of teeth was significantly correlated with ΔBCP,followed by ΔTA3.In T0-T2 phase,ΔBCP,ΔTA2,ΔTA3 and the horizontal adsorption of teeth showed low negative correlation.In T0-T1 phase,the vertical reduction of teeth was significantly positively correlated with ΔTAC,followed by low correlation with ΔTA3 and ΔTA1.Conclusion:In the treatment of anterior arch protrusion after extraction correction in adolescent patients the more the vertical reduction and horizontal adsorption of teeth in the treatment phase,the more the alveolar bone thickness and height around the tooth root in the maintenance phase,which were significantly positively correlated.Reasonable control of the vertical move-ment of teeth in the alveolar bone can improve the periodontal condition around the teeth to a certain extent.

Objective:To evaluate the validity and reliability of the Chinese version of the Lubeck Alcohol Withdrawal Risk Scale(C-LARS).Methods:Referring to previous literature and clinical expert opinions using the Delphi method,a C-LARS was established through translation and back-translation.Principal component analysis was used to evaluate the structural validity of C-LARS,and the maximum variance method was used to calculate factors and factor loadings to evaluate the structural validity of C-LARS.The severity of alcohol withdrawal syn-drome in patients was evaluated using the the Alcohol Withdrawal Scale(AWS),and the criterion validity of C-LARS was evaluated by calculating the correlation coefficient between AWS and C-LARS.Results:The internal correlation coefficient(ICC)of the evaluation factors was 0.972,and the total Cronbach α coefficient was 0.938.Factor analysis and ROC analysis showed that a C-LARS score of ≥ 3 could predict the occurrence of mild alcohol withdrawal syndrome,with sensitivity and specificity of 0.945 and 0.899,respectively.The C-LARS scores of ≥ 5 could predict the occurrence of moderate alcohol withdrawal syndrome,with sensitivity and specificity of 0.910 and 0.905,respectively.The C-LARS scores of≥7 could predict the occurrence of severe alcohol with-drawal syndrome within 12 hours,the sensitivity and specificity were 0.990 and 0.877,respectively.Conclusion:The C-LARS has good validity and reliability,which could be used as a tool to assess the incidence and severity of alcohol withdrawal syndrome within 12 hours after visit.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To investigate the determinants of linezolid-associated neurological adverse reactions in patients with multidrug-resistant tuberculosis and develop a risk prediction model for such adverse events.Methods A prospective cohort study design was employed to select 120 patients with drug-resistant pulmonary tuberculosis who received a chemotherapy regimen containing linezolid at Guangzhou Chest Hospital from April 2023 to January 2024 as the study population.Clinical data,adverse reactions,and plasma concentration of linezolid were collected during fasting and at 2 hours post-medication.Univariate analysis and multivariate logistic regression were conducted to identify factors influencing linezolid-related neurological adverse reactions.Furthermore,a prediction model for such adverse reactions was developed,and its predictive efficacy and calibration ability were evaluated using ROC analysis.Results Re-treatment(OR=2.540,P=0.028),coexistence of cavities(OR=4.092,P=0.021),anemia(OR=10.921,P=0.005),and Cmin≥0.7665 mg/L(OR=6.813,P<0.001)are independent risk factors for the occurrence of linezolid-related neurological adverse reactions.The prediction model,based on these four factors,exhibits an AUC of 0.851(95%CI:0.774～0.929),accompanied by a Youden index of 0.590,a sensi-tivity of 66.7%,and a specificity of 92.3%.Moreover,the prediction model demonstrates excellent calibration ability.(Hosmer-lemeshow χ2=8.719,P=0.273).Conclusion In MDR/RR-TB patients,the presence of cavita-tion,retreatment,and anemia may confer a heightened risk of linezolid-related neurological adverse reactions.A risk prediction model incorporating these four indicators demonstrates significant predictive value for the occurrence of such adverse events.

To report a case with hereditary spastic paraplegia type 11(SPG11)in association with typical thin corpus callosum(TCC)and"Ears-of-the-lynx sign"on MRI imaging.The patient was a 13-year-old boy.The main symptoms are walking instability and falling easily.Over the period of one year,the symptoms gradually progressed when accompanied by poor handwriting and a decrease in learning ability.The parents are not related.Brain MRI shows a thin corpus callosum,and high symmetric signals in the anterior horn of the lateral ventricles on T2 and Flair sequence.WES detected two heterozygous mutations in the SPG11 gene,NM_025137:c.2073delT and c.257+5G>A,respectively from the parents.The proband was finally diagnosed with SPG11.Brain MRI found that TCC and"lynx ear sign"are highly sensitive and specific for the diagnosis of SPG11.The patients with spastic paraplegia should be considered the possibility of SPG11.