In recent years, hybrid brain-computer interfaces (BCIs) have gained significant attention due to their demonstrated advantages in increasing the number of targets and enhancing robustness of the systems. However, Existing studies usually construct BCI systems using intense auditory stimulation and strong central visual stimulation, which lead to poor user experience and indicate a need for improving system comfort. Studies have proved that the use of peripheral visual stimulation and lower intensity of auditory stimulation can effectively boost the user's comfort. Therefore, this study used high-frequency peripheral visual stimulation and 40-dB weak auditory stimulation to elicit steady-state visual evoked potential (SSVEP) and auditory steady-state response (ASSR) signals, building a high-comfort hybrid BCI based on weak audio-visual evoked responses. This system coded 40 targets via 20 high-frequency visual stimulation frequencies and two auditory stimulation frequencies, improving the coding efficiency of BCI systems. Results showed that the hybrid system's averaged classification accuracy was (78.00 ± 12.18) %, and the information transfer rate (ITR) could reached 27.47 bits/min. This study offers new ideas for the design of hybrid BCI paradigm based on imperceptible stimulation.
Brain-Computer Interfaces ; Humans ; Evoked Potentials, Visual/physiology* ; Acoustic Stimulation ; Photic Stimulation ; Electroencephalography ; Evoked Potentials, Auditory/physiology* ; Adult

ObjectiveTo investigate the effects of Jiaohong pills （JHP） and its prescription， Pericarpium Zanthoxyli （PZ） and Rehmanniae Radix （RR） cognitive dysfunction in scopolamine-induced Alzheimer's disease （AD） mice and its mechanism through pharmacodynamic and metabolomics study. MethodThe animal model of AD induced by scopolamine was established and treated with PZ， RG and JHP， respectively. The effects of JHP and its formulations were investigated by open field test， water maze test， object recognition test， avoidance test， cholinergic system and oxidative stress related biochemical test. Untargeted metabolomics analysis of cerebral cortex was performed by ultra-performance liquid chromatography-Quadrupole/Orbitrap high resolution mass spectrometry （UPLC Q-Exactive Orbitrap MS）. ResultThe behavioral data showed that， compared with the model group， the discrimination indexes of the high dose of JHP， PZ and RR groups was significantly increased （P<0.05）. The staging rate of Morris water maze test in the PZ， RR， high and low dose groups of JHP was significantly increased （P<0.05， P<0.01）， the crossing numbers in the PZ， JHP high and low dose groups were significantly increased （P<0.05， P<0.01）； the number of errors in the avoidance test were significantly reduced in the PZ and high-dose JHP groups （P<0.01）， and the error latencies were significantly increased in the JHP and its prescription drug groups （P<0.01）. Compared with the model group， the activities of acetylcholinesterase in the cerebral cortex of the two doses of JHP group and the PZ group were significantly increased （P<0.05， P<0.01）， and the activity of acetylcholinesterase in the high-dose JHP group was significantly decreased （P<0.05）， and the level of acetylcholine was significantly increased （P<0.01）. At the same time， the contents of malondialdehyde in the serum of the two dose groups of JHP decreased significantly （P<0.05， P<0.01）. The results of metabolomics study of cerebral cortex showed that 149 differential metabolites were identified between the JHP group and the model group， which were involved in neurotransmitter metabolism， energy metabolism， oxidative stress and amino acid metabolism. ConclusionJHP and its prescription can antagonize scopolamine-induced cognitive dysfunction， regulate cholinergic system， and reduce oxidative stress damage. The mechanism of its therapeutic effect on AD is related to the regulation of neurotransmitter， energy， amino acid metabolism， and improvement of oxidative stress.

ObjectiveTo study the plasma pharmacokinetics and tissue distribution of five representative components in Wujiwan， and to illustrate the difference of metabolism and tissue distribution before and after compatibility. MethodHealthy male SD rats were divided into four groups， including Wujiwan group（A group， 62.96 g·L^-1）， Coptidis Rhizoma group（B group， 38.4 g·L^-1）， processed Euodiae Fructus group（C group， 5.88 g·L^-1） and fried Paeoniae Radix Alba group（D group， 18.68 g·L^-1）， with 65 rats in each group， and were administered the drugs according to the clinical dose of decoction pieces converted into the dose of the extracts. Then plasma， liver， small intestine and brain were taken at pharmacokinetic set time in each group after administration. Ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry was developed for the quantitative analysis of five representative components［berberine（Ber）， palmatine（Pal）， evodiamine（Evo）， rutecarpine（Rut） and paeoniflorin（Pae）］ in Wujiwan， their concentrations in plasma， liver， small intestine and brain were detected at different time， plasma samples were processed by protein precipitation， and tissue samples were pretreated by protein precipitation plus liquid-liquid extraction. Non-atrioventricular model was used to calculate the pharmacokinetic parameters of each component， and the parameters of each group were compared. ResultPharmacokinetic results of A group showed that area under the curve（AUC_0-t） of the five representative components were ranked as follows：Ber and Pal were small intestine>liver>blood， Evo and Rut were liver>small intestine>plasma， Pae was small intestine>plasma， which was not detected in the liver， no other components were detected in brain except for Ber. In comparison with plasma and other tissues， peak concentration（C_max） of Ber， Pal， Evo， and Rut were the highest and time to peak（t_max） were the lowest in the liver of A group. In plasma， the AUC_0-t and C_max of Evo and Rut were increased in A group compared with C group， t_max of Pea was elevated and its C_max was decreased in A group compared with D group. In the liver， compared with B-D groups， C_max values of 5 representative components except Pae were elevated， AUC_0-t of Pae was decreased and AUC_0-t of Evo and Rut were increased in the A group. In the small intestine， half-life（t_1/2） of each representative components in A group was elevated and t_max was decreased， and C_max of each representative ingredient except Pal was decreased， AUC_0-t values of Ber and Pal were increased， whereas the AUC_0-t values of Evo and Rut were decreased. ConclusionThe small intestine， as the effector organ， is the most distributed， followed by the liver. The pharmacokinetic parameters of the representative components in Wujiwan are changed before and after compatibility， which is more favorable to the exertion of its pharmacodynamic effects.

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 resource allocation status of blood testing laboratories in 14 blood stations in Gansu Province, explore the impact of differences in basic conditions on the comprehensive testing ability of laboratories, so as to promote the homogenization and standardization of blood screening capacity in blood stations in Gansu and improve blood safety and effectivenes. 【Methods】 An evaluation index system of laboratory resource allocation was constructed and a question-naire was designed. The data of human resources, infrastructure and key equipment of 14 blood stations were collected. The entropy weight -TOPSIS method was used to evaluate and rank the resource allocation of 14 blood stations. 【Results】 In the comprehensive evaluation of blood testing laboratory resource allocation in 14 blood stations in Gansu, the top three were laboratories A, B and I, and the last three were laboratories G, M and J. On the whole, the main issue was unreasonable structure of human resources: most laboratories had unreasonable age structure; except for Laboratory A, there was no personnel with bachelor's degree or above in laboratories; most laboratories had not established a team with intermediate professional titles. In terms of infrastructure, the size of seven laboratories could not meet the needs of modern laboratory testing, and all eight blood stations had no spare nucleic acid laboratories nor a mutual spare laboratory with other blood stations As for the key equipment, 5 laboratories had no automatic blood grouping diagnostic instrument, 5 laboratories only had one set of enzyme immunoassay detection system, 3 laboratories had no spare equipment for the key equipment, which means if the equipment failure could not be repaired in time, the release of results would be affected. 【Conclusion】 There were significant differences in human resources, infrastructure and key equipment of blood testing laboratories in 14 blood stations in Gansu, which had a great impact on laboratory testing capacity and subsequent development. It is suggested that governments at all levels and health administrative departments optimize the input of laboratory resource allocation according to the blood collection volume of blood stations to gradually narrow the differences in resource distribution between different regions, improve the degree of laboratory automation and optimize the personnel structure, so as to build high-quality and efficient blood testing laboratories and ensure the safety of clinical blood use.

【Objective】 To evaluate the efficacy and safety of different doses and frequencies of oral Sildenafil in the treatment of erectile dysfunction (ED). 【Methods】 The randomized,open clinical trial included 120 ED patients who met the inclusion and exclusion criteria. The patients were randomly divided into the following groups:on-schedule (25 mg/day),on-demand (50 mg,taken irregularly half an hour before each sexual life),new regular group (25 mg/day,50 mg more before each sexual life),regular group (100 mg/time,twice/week). All treatments lasted for 8 weeks. The follow-up indexes included the five-item International Index of Erectile Function (IIEF-5),Erection Hardness Scale (EHS) and Sexual Encounter Profile (SEP2/3). The adverse reactions were recorded. 【Results】 The IIEF-5 scores of the four groups were significantly higher than those after baseline treatment (P<0.001),but there was no significant difference among the four groups (P>0.05). In terms of effective rate,at the 16th week,there were significant differences between the on-demand group (10.7%) and new regular group (62.1%),and between the on-demand group (10.7%) and regular group (50.0%) (P<0.001). In terms of EHS, the percentage of grade 4 patients in regular group was significant higher than that in the on-demand group at the 8th week and 16th week (all P<0.05). In terms of positive rate of SEP-3,there was a significant difference between the on-demand group and regular group (P=0.042) at the 16th week. In the course of treatment,there were transient adverse reactions such as headache,blurred vision,stuffy nose and back pain,which did not affect the treatment. 【Conclusion】 All of the four treatment methods of oral sildenafil showed good efficacy. Both regular group and new regular group maintained good clinical efficacy during the follow-up,which is better than that of the on-demand group. The new regular scheme can be used as a new,safe and effective treatment option.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

OBJECTIVES: In this study, we explored how adiponectin mediated urotensin II (UII)‍-induced tumor necrosis factor-‍α (TNF-‍α) and α‍-smooth muscle actin (α‍-SMA) expression and ensuing intracellular signaling pathways in adventitial fibroblasts (AFs). METHODS: Growth-arrested AFs and rat tunica adventitia of vessels were incubated with UII and inhibitors of signal transduction pathways for 1‍‒‍24 h. The cells were then harvested for TNF-α receptor (TNF-‍α-R) messenger RNA (mRNA) and TNF-‍α protein expression determination by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Adiponectin and adiponectin receptor (adipoR) expression was measured by RT-PCR, quantitative real-time PCR (qPCR), immunohistochemical analysis, and cell counting kit-8 (CCK-8) cell proliferation experiments. We then quantified TNF-α and α-SMA mRNA and protein expression levels by qPCR and immunofluorescence (IF) staining. RNA interference (RNAi) was used to explore the function of the adipoR genes. To investigate the signaling pathway, we applied western blotting (WB) to examine phosphorylation of adenosine 5'-monophosphate (AMP)‍-activated protein kinase (AMPK). In vivo, an adiponectin (APN)‍-knockout (APN-KO) mouse model mimicking adventitial inflammation was generated to measure TNF-α and α‍-SMA expression by application of qPCR and IF, with the goal of gaining a comprehensive atlas of adiponectin in vascular remodeling. RESULTS: In both cells and tissues, UII promoted TNF-α protein and TNF-α-R secretion in a dose- and time-dependent manner via Rho/protein kinase C (PKC) pathway. We detected marked expression of adipoR1, T-cadherin, and calreticulin as well as a moderate presence of adipoR2 in AFs, while no adiponectin was observed. Globular adiponectin (gAd) fostered the growth of AFs, and acted in concert with UII to induce α-SMA and TNF-α through the adipoR1/T-cadherin/calreticulin/AMPK pathway. In AFs, gAd and UII synergistically induced AMPK phosphorylation. In the adventitial inflammation model, APN deficiency up-regulated the expression of α-SMA, UII receptor (UT), and UII while inhibiting TNF-‍α expression. CONCLUSIONS From the results of our study, we can speculate that UII induces TNF‍-‍α protein and TNF-‍α‍-R secretion in AFs and rat tunica adventitia of vessels via the Rho and PKC signal transduction pathways. Thus, it is plausible that adiponectin is a major player in adventitial progression and could serve as a novel therapeutic target for cardiovascular disease administration.
Mice ; Rats ; Animals ; Adventitia/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Calreticulin/metabolism* ; Vascular Remodeling ; AMP-Activated Protein Kinases/metabolism* ; Cells, Cultured ; RNA, Messenger/genetics* ; Inflammation

Objective: To investigate the physical and intellectual development and mutation characteristics of the phenylalanine hydroxylase (PAH) gene among 53 newborns with phenylketonuria (PKU), so as to provide insights into the management and genetic counseling of PKU Methods: The medical records of 54 children with definitive diagnosis of PKU and standardized therapy until 2 years at the Center for Neonatal Disease Screening of Shanxi Children' s Hospital from 2018 to 2021 were collected. Newborns' body weight and height developments were evaluated using the World Health Organization growth chart (2006 version), and the intellectual development was assessed using the national criteria of Development Behavior Assessment Scale among Children at Ages of 0 to 6 Years (WS/T 580-2017). The gene mutations were detected among neonates and their children, and the physical, intellectual developments and genetic characteristics of neonates with PKU were descriptively analyzed. Results: The 53 PKU cases included 29 male children and 24 female children, 36 cases with classic PKU and 17 cases with mild PKU, and 30 cases from rural areas and 23 cases from urban areas. The study subjects had a median age of 30 (10) d at initial therapy, and a mean blood phenylalanine concentration of (1 507±685) μmol/L at definitive diagnosis. There were 52 cases with normal height developments (98.11%), and all cases had normal weight and intellectual developments. The mean developmental functional quotient (DFQ) was significantly greater among urban children with PKU than among rural children [(94.92±8.57) vs. (87.65±6.57); t=-3.498, P=0.001], and the mean DFQ was significantly higher among children with mild PKU than among those with classic PKU [(95.55±8.76) vs. (88.57±7.11); t=-3.095, P=0.003]. There were 37 mutations detected in the PAH gene, which were mainly distributed in exons 3, 6, 7, 11, 12 and intron 4. Three high-frequency mutation sites were detected, including c.728G>A, c.611A>G and c.1197A>T, including three novel mutations (c.674C>G, c.1316-2A>C and c.1069T>C). Conclusions Following standardized treatment, the children with PKU have comparable physical and intellectual developments as compared to normal children. c.728G>A, c.611A>G and c.1197A>T were predominant mutations in the PAH gene among these 53 children with PKU, and three novel mutations were identified, including c.674C>G, c.1316-2A>C and c.1069T>C.

Objective:The aims of this study were to investigate the effect of gas explosion on rats and to explore the pulmonary function alterations associated with gas explosion-induced acute blast lung injury (ABLI) in real roadway environment.Methods:In April 2018, the large coal mine gas explosion test roadway and explosion test system were used to simulate the real gas explosion roadway environment, fixed the cage and set the explosion parameters. 72 SD rats, male, SPF grade, were randomly divided into nine groups by completely random grouping method according to their body weight: control group, close range group (160 m) , and long range group (240 m) . In each group, there were wound groups (24 h group and 48h group, 8/group, total 48 in six groups) and no wound groups (8/group, total 24 in three groups) . Except for the control group, the other groups were placed in cages at different distances under anesthesia, the experiment of gas explosion was carried out by placing the rats in a position that could force the lungs. The changes of respiratory function of the rats in the non-invasive group were monitored with pulmonary function instrument at 2 h, 24 h, 48 h, 72 h and 168h after the explosion, and were killed under anesthesia 7 days later; the rats in invasive groups were anesthetized and killed at 24 h, 48 h and 168 h, respectively. Gross observation, lung wet-dry ratio and lung histopathology were performed.Results:Compared with the control group, f (respiratory frequency, f) , MV (minute ventilation, MV) , PEF (peak expiratory flow rate, PEF) , PIF (peak inspiratory flow rate, PIF) and EF50 (1/2 tidal volume expiratory flow, EF50) of rats in the close and long range groups decreased significantly after gas explosion 2 h. PAU (respiration pause, PAU) , Te (expiratory time, Te) , Ti (inspiratory time, Ti) and Tr (relaxation time, Tr) were significantly increased ( P<0.05) . After 48 h, TV (tidal volume, TV) , Penh (enhanced respiration pause, Penh) , PAU, and PIF of rats in the long range group were significantly increased ( P<0.05) . After 72 h, MV in the long range group was significantly decreased ( P<0.05) . Compared with the control group, Penh, PAU, Ti and Te were significantly decreased after 168 h in the close and long range groups, with statistical significance ( P<0.05) . At the same time, the body weight of rats in different range groups was significantly decreased ( P<0.05) . In addition, both HE staining and routine observation of lung tissues of rats in different range groups showed that gas explosion caused pulmonary edema, obviously congested pulmonary capillaries, a large number of inflammatory cells and infiltrated red blood cells. Conclusion:Gas explosion in real roadway environment can cause the change of respiratory function phase and lung tissue damage in rats, suggesting that the model of gas explosion-induced ABLI has been initially established successfully, which would provide a basis for further study on the pathogenesis of ABLI.