ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, S_max) alternated with one minute at low speed (50%-55% S_max), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.

ObjectiveThis paper aims to use the digital muscle function assessment system Myoton PRO to assess the correlation between muscle tension，clinical characteristics， and traditional Chinese medicine（TCM） syndromes in patients with hepatolenticular degeneration ［also known as Wilson disease（WD）］. MethodsA total of 104 patients with WD accompanied by abnormal muscle tension（increased or decreased，hereinafter the same） who were hospitalized in the Brain Disease Centre of the First Affiliated Hospital of Anhui University of Chinese Medicine from April 2021 to November 2023 were selected，all of whom were subjected to TCM syndrome diagnosis and Myoton PRO for the measurement of F value of muscle tension，Goldstein， and UWDRS-N scales. The age of onset of the disease and disease duration were analyzed，and the differences and correlations of the above indexes in different TCM syndromes of WD were analyzed ResultsAmong the 104 patients with WD ，the phlegm and stasis syndrome was the most common（60 patients），followed by the damp-heat syndrome（33 patients），and the least common was the liver-kidney Yin deficiency syndrome（11 patients）. The F value of the phlegm and stasis syndrome group was higher than that of the liver-kidney Yin deficiency syndrome group and the damp-heat syndrome group（P<0.01）. The F value of the damp-heat syndrome group was higher than that of the liver-kidney Yin deficiency syndrome group（P<0.05），and the F value of the lower limbs of each group was higher than that of the upper limbs（P<0.01）. Goldstein and UWDRS-N scores of the patients in the phlegm and stasis syndrome group were higher than those in the damp-heat syndrome group and the liver-kidney Yin deficiency syndrome group（P<0.05）. There was no significant difference between the Goldstein and UWDRS-N scores of patients in the liver-kidney Yin deficiency syndrome group and the damp-heat syndrome group. Correlation analysis revealed that the age of onset and duration of the disease were positively correlated with the F values of the lower limbs（r=0.20，P<0.05，r=0.38，P<0.01）and had no significant correlation with those of the upper limbs. The F value levels of muscle tension of all limbs in the three groups of patients were positively correlated with the Goldstein and UWDRS-N scores（muscle tension of the upper limbs in the phlegm and stasis syndrome group，r=0.36，P<0.01，r=0.42，P<0.01. muscle tension of the lower limbs in the phlegm and stasis syndrome group，r=0.70，P<0.01，r=0.60，P<0.01. muscle tension of the upper limbs in the damp-heat syndrome group，r=0.64，P<0.01，r=0.53，P<0.01. muscle tension of the lower limbs in the damp-heat syndrome group，r=0.59，P<0.01，r=0.70，P<0.01. muscle tension of the upper limbs in the liver-kidney Yin deficiency syndrome group，r=0.70，P<0.01，r=0.74，P<0.01. muscle tension of the lower limbs in the liver-kidney Yin deficiency syndrome group，r=0.85，P<0.01，r=0.62，P<0.01）. Conlusion： The digital muscle function assessment system Myoton PRO can objectively evaluate the muscle tension level of patients with WD accompanied by abnormal muscle tension. This level has significant differences among different TCM syndromes and can evaluate the patient's condition to some extent.

【Objective】 To investigate the correlation between heart rate variability (HRV) and the degree of nervousness before blood donation. 【Methods】 The psychological state of 253 blood donors before blood donation was assessed by the self-rating anxiety scale (SAS) and the degree of nervousness and their HRV were measured. The correlation between the SAS score, the degree of nervousness and the HRV parameters was analyzed, and the differences were compared among different types of donors by multivariate linear regression. 【Results】 A total of 247 blood donors were included in the study. Five HRV parameters in blood donors aged 18-24 were higher than in those aged 25 years and above(all P<0.05), and the anxiety level was higher in female donors(SAS score 41-46) than in males(SAS score 35-43)(P<0.001); the pre-donation SAS score was consistent with the assessment of the tension level (r=0.970, P<0.001); the pre-donation tension level and the SAS score were all significantly negatively correlated with VLF in HRV parameters(r=0.179, P=0.005), and the associations were independent of confounders such as age, body mass index and gender (P<0.05). 【Conclusion】 Compared with SAS and tension assessment, HRV is more objective, and can be used as one of the tests for assessing the tension level of blood donors. The inclusion of HRV in the routine screening of blood donors deserves further study for its application in assessing the anxiety level of blood donors before blood donation, identifying people prone to blood donation-related vasovagal reaction (DRVR), preventing and reducing the risk of DRVR, and improving the safety of blood donation.

Objective:To investigate the feasibility and clinical effects of the application of augmented reality (AR) navigation on assisted design of the chimeric twin-paddled anterolateral thigh perforator flap (ALTPF) in reconstruction of soft tissue defects in extremities.Methods:From June 2017 to June 2023, 8 patients with soft tissue defects in extremities received reconstruction of chimeric twin-paddled ALTPF designed with the assistance of AR navigation in Department of Hand & Foot Microsurgery Orthopaedics, Guigang City People’s Hospital. All of them were traffic accidents or machine injuries, with 3 cases of calf, 2 cases of ankle, 1 case of foot, and 2 cases of hand defects. All the wounds were wide or irregular (defect sized 14 cm×14 cm-25 cm×13 cm). The images of bilateral thighs were acquired by CT angiography preoperatively. The dominant side and dominant perforators were selected. Three dimensional reconstruction was performed by Mimics software. AR technology was applied to guide the design and harvest of the chimeric twin-paddled ALTPF. Flap area was 15 cm × 16 cm to 26 cm × 14 cm. The donor site was sutured directly. Follow-up with outpatient visits or WeChat images and videos at 1, 3, 6 and 12 months postoperatively to record the appearance, colour, texture, recurrence of infection, and knee extension function of the flap donor site.Results:According to the preoperative design, the perforator flaps were harvested and transferred in all the 8 patients. All flaps survived and the recipient and donor sites healed in one stage. All patients entered postoperative follow-up for 3 to 12 (mean, 8.6)months. The colour and texture of the flaps were excellent, and the appearance of donor and recipient sites was satisfactory. Two patients with hand injuries were evaluated using the brief Michigan Hand Outcomes Questionnaire (MHQ), with scores of 43.74 and 81.25, respectively. Six patients with lower limb injuries were evaluated using the Maryland foot score, with scores of 2 excellent, 3 good and 1 fair.Conclusion:The application of AR navigation can effectively assist the design of a chimeric twin-paddled ALTPF. It also provides an effective basis for clinical personalised flap design.

ObjectiveTo explore the feasibility and rationality of applying relevant diagnostic and treatment programmes from textbooks as evidence in traditional Chinese medicine （TCM） diagnosis and treatment guidelines， using allergic rhinitis as an example. MethodsTextbooks published from October 1949 to December 2022， as well as TCM diagnosis and treatment guidelines published until December 2022 on allergic rhinitis were searched， and the contents of diagnosis and treatment related to allergic rhinitis were extracted. The similarities and differences between textbooks in different periods， between textbooks in different versions， and between textbooks and guidelines were compared and analyzed. ResultsA total of 12 national planning textbooks on TCM otolaryngology and 4 Chinese medicine diagnosis and treatment guidelines on allergic rhinitis from 1975 to 2021 were included. The evolution of diagnostic and treatment programmes was shown by the textbooks in different periods. Since 2003， syndrome of latent heat in lung channel has been added in the published textbook， and TCM featured therapies， such as nasal packing， intranasal spray were enriched， as well as the contents related to prevention and prognosis. The main syndromes included lung qi deficiency and cold， spleen qi deficiency， kidney yang deficiency， and latent heat in lung meridian. The most common recommended prescriptions were Wenfei Zhiliu Pill （温肺止流丹）， Yupingfeng Powder （玉屏风散） and Cangerzi Powder （苍耳子散）； Buzhong Yiqi Decoction （补中益气汤）， Shenling Baizhu Powder （参苓白术散）； Shenqi Pill （肾气丸） or Zhenwu Decoction （真武汤）； Xinyi Qingfei Decoction （辛夷清肺饮）. A comparison of different versions of textbooks showed that the classification of syndromes was consistent， while the formulas were slightly different. The comparison between different versions of the current textbooks and the guidelines showed that the recommended prescriptions of the textbooks had more Cangerzi Powder， Xiaoqinglong Decoction （小青龙汤）， Zhenwu Decoction， etc.， while TCM featured therapies such as nose blowing， smelling， nasal plugging， nasal washing were enriched， and information on formula modification， prevention and adjustment， prognosis were also added， which can supplement the corresponding evidence for the guidelines. ConclusionTextbooks could serve as a strong supplement for the evidence-based development of TCM clinical guidelines. However， there is still a need for further research on the quality assessment system of textbook evidence to improve the credibility of its applicability of the guidelines evidence.

This study used the Appraisal of Guidelines Research & Evaluation-Health Systems （AGREE-HS） to demonstratively compare 34 global coronavirus disease-2019 （COVID-19） health systems guidance documents （HSGs） and 6 World Health Organization （WHO） standard HSGs. The comparison involved topic， participants， methods， recommendations， and implementability， with the aim of exploring the characteristics of emergency HSGs. The results showed that the emergency HSGs had an overall average score of 49%， with topic having the highest score， recommendations having the second highest score， and participants having the lowest score. The standard HSGs had an overall average score of 79%， with high scores in all items. The emergency HSGs had lower scores in participants， methods， recommendations， and implementability than the standard HSGs （P<0.001）， while the COVID-19 emergency HSGs developed by the WHO had higher score in topic than the standard HSGs （P<0.05）. Compared with those released by countries， the COVID-19 emergency HSG developed by the WHO showed superiority in all items and overall scores （P=0.000 2）. This indicates that emergency HSGs， represented by the COVID-19 emergency HSG， place equal emphasis on topic and recommendations as standard HSGs but have low requirements in terms of expert participation， evidence support， and comprehensive consideration in the time- and resource-limited context. They have the characteristics of prominent topics， clear purposes， orientation to demand， keeping up with the latest evidence， flexible adjustment， and timeliness， emphasizing immediate implementation effects， weakening long-term effects， and focusing on comprehensive benefits. Additionally， developers， types， and report completeness are important influencing factors.

The scientific rigor and efficacy of methodologies employed in drafting emergency health systems guidance documents （HSGs） are paramount in guaranteeing the quality， reliability， and applicability of HSGs. According to the Appraisal of Guidelines for Research and Evaluation- Health Systems （AGREE-HS）， we demonstratively assessed both global coronavirus disease-2019 （COVID-19） emergency HSGs and World Health Organization （WHO） standard HSGs to uncover the core attributes of methods employed in the development of emergency HSGs. Our evaluation findings revealed that across the five assessment items of AGREE-HS， methods in the 34 emergency HSGs evaluated ranked third， trailing behind topic and recommendations. Notably， criterion 2 （the best available and most contextually relevant evidence is considered） received the highest score， whereas criterion 5 （evidence of cost and cost-effectiveness of the potential options is described） scored the lowest. Compared with the WHO standard HSGs， the COVID-19 emergency HSGs exhibited low scores in methods （P<0.05）， which was reflected in nine criteria （P<0.05）， especially in criteria 1 （systematic and transparent methods are used to identify and review the evidence） and 9 （systematic and transparent methods are used to agree upon the final recommendations）. Among the COVID-19 emergency HSGs， that developed by the WHO achieved higher scores in eight out of all nine criteria， excluding criterion 8 （P<0.05）. The clinically relevant emergency HSGs had higher scores in the criteria 3 （the evidence base is current） and 8 （the rationale behind the recommendations is clear） than other types of emergency HSGs. Collectively， the methodology for developing emergency HSGs， represented by the COVID-19 emergency HSG， underscores evidence orientation and integrates expert consensus. It is characterized by adaptable evidence synthesis strategies， streamlined evidence review protocols， and contextual relevance， all of which are influenced by external， internal， and implementation-specific factors.

Objective:To investigate the protective mechanism of TRPV4 channel inhibitor on blood-brain barrier(BBB)damage after traumatic brain injury(TBI).Methods:The TBI rat model was established.TRPV4 channel inhibitor HC067047 or PKC-δ inhibitor Rottlerin was used to detect changes in BBB permeability,neurological function score,and the expression of microvascular endothelial tight junction proteins ZO-1 and ZO-2 in brain injury areas after TBI.Results:Compared with the Sham group,BBB permeability significantly increased,brain neurological function score significantly decreased,and the expression of ZO-1 and ZO-2 significantly decreased in TBI group(P＜0.05).Compared with the TBI group,after administration of HC067047 or Rottlerin,changes in BBB permeability,brain neurological function score,the expression of ZO-1 and ZO-2 were partially reversed(P＜0.05).Conclusions:TBI-induced BBB injury may be mediated by TRPV4 channel regulating PKC-δ signaling pathway to affect the expression of tight junction proteins ZO-1 and ZO-2.Inhibition of TRPV4 channel function or PKC-δ signal molecule can partially alleviate BBB damage induced by TBI.This study may provide new ideas for the treatment of clinical TBI.

BACKGROUND:Intervertebral disc degeneration is an important cause of low back pain.At present,there are many modeling methods for disc degeneration in China and abroad,but there is not a model for low back pain due to disc degeneration. OBJECTIVE:To compare the effect of mechanical puncture combined with tumor necrosis factor α and complete Freund's adjuvant with a conventional disc mechanical puncture alone. METHODS:A total of 18 male adult Sprague-Dawley rats were randomly divided into 3 groups,with 6 animals in each group.No treatment was given in the blank group.Animal models of intervertebral disc degeneration were made in the L4-5 segments of rats in the control using conventional mechanical puncture.In the experimental group,on the basis of mechanical puncture,tumor necrosis factor α+complete Freund's adjuvant was injected into the L4-5 intervertebral discs using a microinjector to establish a model of disc degeneration induced by mechanical puncture combined with inflammatory factors.Four weeks after surgery,the pain threshold of rats was measured by the hot plate method for assessing the perception of heat injury in rats with intervertebral disc degeneration.MRI examination was performed to observe the disc degeneration in each group.ELISA was used to detect the levels of serum tumor necrosis factor α,interleukin 1β,interleukin 6 and prostaglandin E2.Hematoxylin-eosin and Safranin O-fast green staining were used to observe the morphological changes of the disc. RESULTS AND CONCLUSION:In terms of pain,the behavioral pain threshold of the experimental group was continuously decreased,and the levels of serum inflammatory factors were significantly higher compared with the control group.In terms of morphology,the MRI results showed that the L4-5 nucleus pulposus signal completely disappeared in the experimental group.Histopathological results showed that in the control group,the nucleus pulposus was intact,more notochord cells were visible,and some fiber rings were ruptured,while in the experimental group,there are fewer notochord cells and the structure of the nucleus pulposus and fibrous ring is disturbed,with the boundary disappearing.To conclude,mechanical puncture combined with tumor necrosis factor alpha and complete Freund's adjuvant can successfully establish a discogenic low back pain model in rats.This operation is simple and economical to achieve obvious disc degeneration and low back pain,with greatly shortened molding cycle.This model can be used as a reference for studying discogenic low back pain models.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.