BACKGROUND:We have successfully established an animal model of small ear pig in southern Yunnan province with internal tension relieving technique combined with autologous Achilles tendon for anterior cruciate ligament reconstruction,and verified the stability and reliability of the model.However,whether internal tension relieving technique can promote the ligamentalization process of autologous Achilles tendon graft has not been studied. OBJECTIVE:To investigate the differences in the process of ligamentalization between conventional reconstruction and internal reduction reconstruction of the anterior cruciate ligament by gross view,histology and electron microscopy. METHODS:Thirty adult female small ear pigs in southern Yunnan province were selected.Anterior cruciate ligament reconstruction was performed on the left knee joint with the ipsilateral knee Achilles tendon(n=30 in the normal group),and anterior cruciate ligament reconstruction was performed on the right knee joint with the ipsilateral knee Achilles tendon combined with the internal relaxation and enhancement system(n=30 in the relaxation group).The autogenous right forelimb was used as the control group;the anterior cruciate ligament was exposed but not severed or surgically treated.At 12,24,and 48 weeks after surgery,10 animals were sacrificed,respectively.The left and right knee joint specimens were taken for gross morphological observation to evaluate the graft morphology.MAS score was used to evaluate the excellent and good rate of the ligament at each time point.Hematoxylin-eosin staining was used to evaluate the degree of ligament graft vascularization.Collagen fibers and nuclear morphology were observed,and nuclear morphology was scored.Ultrastructural remodeling was evaluated by scanning electron microscopy and transmission electron microscopy. RESULTS AND CONCLUSION:(1)The ligament healing shape of the relaxation group was better at various time points after surgery,and the excellent and good rate of MAS score was higher(P<0.05).Moreover,the relaxation group could obtain higher ligament vascularization score(P<0.05).(2)The arrangement of collagen bundles and fiber bundles in the two groups gradually tended to be orderly,and the transverse fiber connections between collagen gradually increased and thickened,suggesting that the strength and shape degree of the grafts were gradually improved,but the ligament remodeling in the relaxation group was always faster than that in the normal group at various time points after surgery.(3)The diameter,distribution density,and arrangement degree of collagen fibers in the relaxation group were better than those in the normal group at all time points,especially in the comparison of collagen fiber diameter between and within the relaxation group(P<0.05).

Obstructive sleep apnea(OSA)is a common sleep disorder characterized by repeated episodes of upper airway collapse and obstruction during sleep.Polysomnography is the gold standard for diagnosing OSA,but it is expensive,time-consuming,and can cause discomfort for patients.In recent years,acoustic-based approaches for detecting OSA have emerged as a research focus.This review summarizes recent advances in OSA automatic detection techniques based on snoring and speech signals,and systematically examines their applications in diagnosis,severity assessment,and localization of obstruction sites.Findings indicate that the acoustic features of snoring and speech signals hold significant value for OSA screening,and when combined with machine learning and deep learning models,it can achieve high diagnostic accuracy.Future research should focus on elucidating the relationship between acoustic features and the pathophysiological mechanisms of OSA,integrating multimodal information,and advancing the clinical application of wearable devices,with the aim of promoting intelligent,non-invasive,and cost-effective screening technologies for OSA.

ObjectiveTo investigate the anti-inflammatory, antioxidant, and goblet cell-stimulating effects of a suspension of Ophiopogon japonicus (L. f.) Ker Gawl. (O. japonicus, Mai Dong) extract combined with hyaluronic acid (HA) in the mouse model with dry eye disease (DED).MethodsA DED mouse model was induced using benzalkonium chloride (BAK), followed by treatment with O. japonicus extract-containing eye drops at varying concentrations. Experimental groups included a normal control, a DED model control, a positive control, and an O. japonicus extract-treated group. Corneal fluorescein staining and tear break-up time (TBUT) were used to assess tear film stability and ocular surface integrity. Enzyme-linked immunosorbent assay (ELISA) measured inflammatory factor levels in corneal and conjunctival tissues, whereas Western blot (WB) analyzed key antioxidant and inflammatory markers, including nuclear factor erythroid 2-related factor (2Nrf2) and heme oxygenase 1 (HO-1). Periodic acid-schiff (PAS) staining and immunofluorescence were used to evaluate goblet cell density and mucin secretion.ResultsO. japonicus extract significantly improved corneal damage, reduced fluorescein staining scores, prolonged TBUT, and increased tear secretion. It downregulated inflammatory markers, including interleukin-8 (IL-8), interleukin-1β (IL-1β), and interferon-γ (IFN-γ) while upregulating Nrf2, HO-1, and the interleukin-13 (IL-13)/IFN-γ ratio, alleviating oxidative stress and inflammation. PAS staining showed increased conjunctival goblet cell density and restored mucin secretion, enhancing tear film stability.ConclusionO. japonicus extract demonstrated significant anti-inflammatory, antioxidant, and goblet cell-stimulating effects in a DED model, with good biocompatibility and promising therapeutic potential. Future research should optimize extraction processes and validate their efficacy and safety in clinical settings.

Objective To explore the changes in β-hydroxybutyrate levels in rat brains after endurance and resistance exercises,as well as its role and mechanism in regulating the levels of Brain-Derived Neurotrophic Factor(BDNF)in the rat brain.Methods Thirty Sprague-Dawley(SD)rats were randomly divided into a control group(n=10),a treadmill exercise group(n=10),and a ladder-climbing exercise group(n=10).The control group did not do any exercise,while the treadmill group and ladder-climbing group exercised for 8 weeks according to the reported endurance and resistance exercise model.After the exercise intervention,the tail vein blood,brain tissue,and triceps brachii muscle tissue of the rats were collected,and the tissues were frozen in liquid nitrogen and fixed in paraformaldehyde.Record the weight and training load of rats.Cross-sectional area(CSA)was quantified.The levels of BDNF,β-hydroxybutyrate,silence infor-mation regulator 1(SIRT 1),and PGC-1α were measured by ELISA or/and Western blot,and the expression of histone deacetylase 3(HDAC3)was detected by RT-PCR.Results After 8 weeks,the body weight of rats in each group increased significantly,but the body weight of rats in the treadmill group was significantly lower than that of the control group(P<0.01).Both treadmill exercise and ladder-climbing exercise for 8 weeks caused an increase in the CSA of skeletal muscle,but the increase in CSA was more pronounced in the ladder-climbing exercise group(P<0.001).After 8 weeks of treadmill exercise,the BDNF level in the rat brain was significantly higher than that in the control group(P<0.05).At the same time,the level of fatty acid metabolite β-hydroxybutyrate in the brain increased significantly(P<0.05),and the expression of HDAC3 decreased significantly(P<0.001);In contrast,8 weeks of ladder-climbing training did not cause a significant increase in BDNF levels,a significant decrease in β-hydroxybutyrate(P<0.001),in the expression of SIRT 1 and PGC-1α in the brain were observed(P<0.01),and no significant change in the expression of HDAC3 was found.Conclusion The level of fatty acid metabolite β-hydroxybutyrate plays a key role in the regulation of BDNF levels caused by different exercise modes through different epigenetic mechanisms.

Current experimental and computational methods have limitations in accurately and efficiently classi-fying ion channels within vast protein spaces.Here we have developed a deep learning algorithm,GPT2 Ion Channel Classifier(GPT2-ICC),which effectively distinguishing ion channels from a test set con-taining approximately 239 times more non-ion-channel proteins.GPT2-ICC integrates representation learning with a large language model(LLM)-based classifier,enabling highly accurate identification of potential ion channels.Several potential ion channels were predicated from the unannotated human proteome,further demonstrating GPT2-ICC's generalization ability.This study marks a significant advancement in artificial-intelligence-driven ion channel research,highlighting the adaptability and effectiveness of combining representation learning with LLMs to address the challenges of imbalanced protein sequence data.Moreover,it provides a valuable computational tool for uncovering previously uncharacterized ion channels.

Current experimental and computational methods have limitations in accurately and efficiently classifying ion channels within vast protein spaces. Here we have developed a deep learning algorithm, GPT2 Ion Channel Classifier (GPT2-ICC), which effectively distinguishing ion channels from a test set containing approximately 239 times more non-ion-channel proteins. GPT2-ICC integrates representation learning with a large language model (LLM)-based classifier, enabling highly accurate identification of potential ion channels. Several potential ion channels were predicated from the unannotated human proteome, further demonstrating GPT2-ICC's generalization ability. This study marks a significant advancement in artificial-intelligence-driven ion channel research, highlighting the adaptability and effectiveness of combining representation learning with LLMs to address the challenges of imbalanced protein sequence data. Moreover, it provides a valuable computational tool for uncovering previously uncharacterized ion channels.

Obstructive sleep apnea(OSA)is a common sleep disorder characterized by repeated episodes of upper airway collapse and obstruction during sleep.Polysomnography is the gold standard for diagnosing OSA,but it is expensive,time-consuming,and can cause discomfort for patients.In recent years,acoustic-based approaches for detecting OSA have emerged as a research focus.This review summarizes recent advances in OSA automatic detection techniques based on snoring and speech signals,and systematically examines their applications in diagnosis,severity assessment,and localization of obstruction sites.Findings indicate that the acoustic features of snoring and speech signals hold significant value for OSA screening,and when combined with machine learning and deep learning models,it can achieve high diagnostic accuracy.Future research should focus on elucidating the relationship between acoustic features and the pathophysiological mechanisms of OSA,integrating multimodal information,and advancing the clinical application of wearable devices,with the aim of promoting intelligent,non-invasive,and cost-effective screening technologies for OSA.

OBJECTIVE To investigate the effects of borneol on pharmacodynamic and pharmacokinetic effects of Corydalis saxicola total alkaloids in depression model rats.METHODS Thirty male SD rats were divided into blank control group,negative control group,positive control group (fluoxetine 10 mg/kg,i.g.),single drug group (C.saxicola total alkaloids 210 mg/kg,i.g.) and combined drug group (C.saxicola total alkaloids 210 mg/kg+borneol 50 mg/kg,i.g.) according to the random number table method,with 6 rats in each group.By lipopolysaccharide (LPS) induction modeling,except blank control group (no model and no administration) received intraperitoneal injection of the same amount of normal saline,the rats in the other groups were intraperitoneally injected with LPS once a day to establish a rat model of depression.After 1 week of modeling,each administration group was given relevant drug intragastrically according to the corresponding dose,and blank control group and negative control group (without drug treatment) were administered intragastrically with an equal volume of solvent to dissolve the drug;continued modeling while administering the drug.After two weeks of continuous administration,the effects of C.saxicola total alkaloids versus the combination of C.saxicola total alkaloids and borneol on the behavior of depressed rats were tested by behavioral experiments;the levels of tumor necrosis factor-α,interleukin-1β and interleukin-6 in rats were determined;the histopathological changes of the hippocampus of rats were observed.Blood sample was collected from the orbit at different time points after administration on the 15th day,and the upper plasma was obtained.Ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry was established for the simultaneous determination of dehydrocarvedine,tetrahydropalmatine,coptisine,palmatine,jatrorrhizine,berberine,berberrubine and epiberberine in rat plasma.The average plasma concentration-time curve was depicted,the area under the curve (AUC) was calculated,and the pharmacokinetic parameters were analyzed by DAS 3.2.2 software.RESULTS Compared with blank control group,the negative control group had a decrease in body mass and sugar water preference rate,a decrease in the total distance of open field,a prolonged swimming immobility time,and a increased in the expression of inflammatory factors in serum (P<0.05);compared with negative control group,the single drug group and the combined drug group increased the preference rate of sugar water,increased the total distance of open field,shortened the time of swimming immobility,and decreased the expression of inflammatory factors in serum (P<0.05).There was no significant difference in the above indicators between the single drug group and the combined drug group in rats (P>0.05).Pharmacokinetic results showed that compared with single drug group,AUC0-t of coptisine,AUC0-t,AUC0-∞,tmax and cmax of jatrorrhizine,AUC0-t,AUC0-∞,t1/2 and cmax of berberrubine,and AUC0-t of epiberberine,cmax of dehydrocarvedine,cmax of palmatine were significantly increased in combined drug group,but there was no significant difference,indicating that borneol didn't have a significant effect on the efficacy of Corydalis saxicola nigra at this dose.CONCLUSIONS Both C.saxicola total alkaloids alone and in combination with borneol can improve depression-like behavior in depression model rats,reduce serum inflammatory cytokine levels,and protect hippocampal neurons.Compared with the use of Corydalis saxicola base alone,the combination with borneol do not show significant pharmacodynamic differences,bu can improve the absorption of coptisine,jatrorrhizine in model rats.

ObjectiveBased on the experience of traditional quality evaluation， the quality of Atractylodis Macrocephalae Rhizoma（AMR） with different production methods such as direct seeding， transplanting after seedling raising， topping and non-topping， and difference in growth years was compared. MethodVernier caliper was used to measure the trait data of AMR in different production methods. Paraffin sections of AMR with different production methods were made by saffron solid green staining， and the microstructure was observed. The contents of water-soluble and alcohol-soluble extracts in AMR with different production methods were determined according to the 2020 edition of Chinese Pharmacopoeia. The content of water-soluble total polysaccharides in AMR with different production methods was detected by sulfuric acid-anthrone method. Fiber analyzer was used to detect the content of fiber components in AMR with different production methods. The contents of monosaccharides， oligosaccharides and some secondary metabolites in AMR with different production methods were detected by ultra performance liquid chromatography（UPLC）， and the differences of chemical components were compared by multivariate statistical analysis methods such as principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA）. ResultIn terms of traits， the 3-year-old AMR with direct seeding and without topping was close to the high-quality AMR with "phoenix-head and crane-neck， strong sweetness and clear aroma" recorded in ancient materia medica， followed by the 3-year-old AMR with topping after transplanting， while the 2-year-old AMR with topping after transplanting with high market circulation rate was generally fat and strong with mild odor. In the microscopic aspect， the arrangement of xylem vessels and fiber bundles in the 3-year-old samples formed two obvious rings. Compared with the 2-year-old samples cultivated in Bozhou and Zhejiang， the 3-year-old samples without topping after transplanting had more wood fibers. In terms of chemical composition， the contents of 70% ethanol extract， fructose， glucose， sucrose， 1-kestose， atractylenolide Ⅰ， chlorogenic acid， neochlorogenic acid， cryptochlorogenic acid and other components in 3-year-old AMR with direct seeding and without topping were significantly higher than those in the other three samples（P<0.05）. The contents of cellulose， 70% ethanol extract， sucrose， atractylenolide Ⅰ， atractylone and other components in 3-year-old AMR with topping after transplanting were significantly higher than those in the 2-year-old AMR with high market circulation rate（P<0.05）， while the contents of water-soluble extract and water-soluble total polysaccharides in 2-year-old samples with topping after transplanting were significantly higher than those in the 3-year-old AMR with topping after transplanting， direct seeding and without topping（P<0.05）. ConclusionUnder the current mainstream production mode， too much manual intervention makes AMR heavily enriched in polysaccharides and increased the yield， but the accumulation of sweet substances， fragrant substances and fiber substances is insufficient， which affects its quality. The current quality standard of AMR has some shortcomings in guiding the high quality production of it， it is suggested to revise the quality standard of AMR， supplement the quantitative analysis of secondary metabolites， and strengthen the production of imitation wild AMR.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.