Objective To investigate the effects and mechanism of Yuyin Qianyang Tongluo Formula on cognitive function in Alzheimer's disease mice.Methods Transgenic negative mice were designated as the normal group,while APP/PS1 double transgenic mice were randomly divided into six groups(ni=6 per group):model group,low-dose Yuyin Qianyang Tongluo Formula group,medium-dose group,high-dose group,and positive drug group.The Yuyin Qianyang Tongluo Formula low-,medium-,high-dose groups correspondingly received intragastric administration of 0.75,1.5,and 3 g·kg-1·d-1,respectively.The positive drug group received 2 mg·kg-1·d-1 donepezil hydrochloride tablets,while the model and normal groups received equal volumes of saline.All groups were treated once daily for 8 weeks.Behavioral tests were conducted using the Morris water maze and Y-maze.Hippocampal β-amyloid(Aβ)1-42 level was measured by enzyme-linked immunosorbent assay(ELISA).Hippocampal CA1 and CA3 neurons were observed hematoxylin-eosin(HE)staining,and Nissl bodies were examined Nissl staining.Protein expression levels of Aβ transporter low-density lipoprotein receptor-related protein 1(LRP-1)and endoplasmic reticulum stress marker glucose-regulated protein 78(GRP78)were detected by Western Blot analysis.Results(1)Compared with the normal group,the model group showed significantly prolonged escape latency(P＜0.000 1),reduced platform crossings,decreased movement distance and time around the platform of Morris water maze test(P＜0.05 or P＜0.01),significantly lower spontaneous alternation percentage in Y-maze test(P＜0.05),and significantly elevated hippocampal Aβ1-42 level(P＜0.000 1).Compared with the model group,all Yuyin Qianyang Tongluo Formula dose groups and the positive drug group exhibited significantly shortened escape latency of Morris water maze test(P＜0.000 1).The high-dose Yuyin Qianyang Tongluo Formula group and positive drug group showed significantly increased platform crossings,movement distance and time around the platform of Morris water maze test(P＜0.05),significantly higher spontaneous alternation percentage in Y-maze test(P＜0.05).All Yuyin Qianyang Tongluo Formula dose groups and the positive drug group showed significantly reduced hippocampal Aβ1-42 level(P＜0.000 1).(2)Compared with the normal group,the model group exhibited disordered and deformed hippocampal neurons and Nissl bodies.Compared with the model group,all Yuyin Qianyang Tongluo Formula groups and positive drug group showed improved neuronal and Nissl body organization,with the improvement degree positively correlated with dosage.(3)Compared with the normal group,the model group showed decreased LRP1 level and increased GRP78 level,but there were no statistically significant differences(P＞0.05).Compared with the model group,the high-dose Yuyin Qianyang Tongluo Formula group and positive drug group showed increased LRP1 level,while all Yuyin Qianyang Tongluo Formula dose groups and positive drug group exhibited decreased GRP78 level,but there were no statistically significant differences(P＞0.05).Conclusion Yuyin Qianyang Tongluo Formula significantly improves cognitive and memory function in model mice in a dose-dependent manner,potentially through reducing Aβ aggregation in the brain via endoplasmic reticulum stress pathway.

The application of mechanics in clinical wound healing has a long history;however,the systematic underlying mechanisms remain unclear.With recent advancements in biomechanics and mechanobiology,the principles regarding how mechanical factors influence the formation,progression,and healing of wounds have gradually been elucidated.Herein,based on progress in theories,technologies,and clinical practices concerning the interplay between mechanics and wound healing,this study introduces the concept of wound-repairing mechanomedicine.Relevant research is systematically reviewed from the perspectives of biomechanics,mechanobiology,and mechanotherapy.Additionally,potential future development directions are prospectively analyzed to provide novel insights into wound care and strategies for preventing scar formation.

Objective To explore the risk factors of acute respiratory failure(ARF)in adult patients with community-acquired pneu-monia(CAP),and thereby construct and validate the efficacy of nomogram model.Methods The clinical and laboratory data of 172 adult CAP patients admitted to Taikang Xianlin Drum Tower Hospital affiliated to Nanjing University School of Medicine from January 2018 to December 2021 were retrospectively collected.The patients were divided into two groups based on whether they had concurrent ARF.After the comparison for the differences of single factor between the two groups,collinearity analysis was assessed.The risk fac-tors were then screened by binary logistic regression analysis with forward stepwise regression method.A nomogram model was subse-quently constructed and the discrimination and accuracy of the model were evaluated by ROC and colibration curves.Results Among the 172 CAP patients,53 cases(30.8％)developed ARF.The results of univariate analysis showed that the CAP patients with concur-rent ARF group had higher age,CURB-65 score and inflammatory markers than the non-concurrent ARF group,and the incidence of complex infection(culturing two or more pathogenic bacteria)was high.The values of CRP(C-reactive protein)and BUN/Alb(blood urea nitrogen/albumin)were significantly different between the two groups(53.910[25.900,101.200]vs.23.300[6.800,48.930],0.231[0.160,0.302]vs.0.123[0.089,0.171],P＜0.05).Multivariate analysis indicated:glucose(Glu)≥6.06 mmol/L(odds ra-tio(OR):2.737,95％confidence interval(CI):1.116-7.037),AST(aspartate aminotransferase)≥22.5 U/L(OR:4.291,95％CI:1.779-11.120),fibrinogen(Fib)≤3.83 g/L(OR:3.955,95％CI:1.631-10.237),uric acid(UA)188.07 μmol/L(OR:4.617,95％CI:1.859-12.489),BUN/Alb≥0.15 mmol/g(OR:6.381,95％CI:2.423-18.513),total number of multicomor-bidity≥3(OR:6.191,95％CI:2.088-21.905)were the risk factors(P＜0.05).All the screened indicators were incorporate into the nomogram model and its efficacy was verified.The results showed that the area under the curve of the model was 0.888[95％CI:0.840-0.935](P＜0.05),the sensitivity was 0.868,and the specificity was 0.790.The calibration curve showed that the predicted probability of adult CAP patients-associated with ARF was in good consistency with the observed probability(Briser Score:0.125;H-L test:x2=7.563,P=0.477).Conclusion The established model has a good ability to predict adult CAP associated with ARF,and can provide a reference basis for early clinical prediction and intervention treatment.

OBJECTIVE To observe the expressions of transforming growth factor-β1(TGF-β1)/Smads signaling pathways in the primary nephrotic syndrome(NS)patients complicated with pulmonary infection and analyze the values in diagnosis of pulmonary infection and assessment of illness condition.METHODS A total of 108 NS pa-tients complicated with pulmonary infection who were treated in Huaihe Hospital of Henan University from Jan.2020 to Mar.2024 were assigned as the infection group and were divided into the mild group with 32 cases and the severe group with 76 cases according to the severity of pulmonary infection.The distribution of the pathogens was analyzed.Meanwhile,97 NS patients who were not complicated with pulmonary infection were chosen as the no infection group.The relative expression levels of peripheral blood TGF-β1,Smad2,Smad3 mRNA and proteins were detected for the patients confirmed with infection within 24 hours(for the patients with infection within 24 hours after the admission)by means of real-time fluorescent quantitative polymerase chain reaction.The values of the three indexes in diagnosis of the pulmonary infection and assessment of illness condition of the NS patients were analyzed.RESULTS Totally 122 strains of pathogens were isolated from sputum specimens of the 108 NS pa-tients complicated with pulmonary infection,78.69％of which were gram-negative bacteria.The relative expres-sion levels of TGF-β1,Smad2,Smad3 mRNA and proteins of the infection group were respectively 8.69±1.33,6.07±0.75 and 5.94±0.88,higher than 3.76±0.3,2.38±0.24 and 3.15±0.35 of the no infection group(P＜0.05);the levels of the indexes of the severe group were higher than those of the mild group(P＜0.05).Receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC)of the joint detection of TGF-β1,Smad2 and Smad3 was 0.972 in diagnosis of the pulmonary infection in the NS patients,0.912 in as-sessment of the severe pulmonary infection.CONCLUSIONS The NS patients complicated with pulmonary infection show remarkable rise of expressions of TGF-β1,Smad2 and Smad3.The joint detection of the above indexes has high clinical value in diagnosis of the pulmonary infection and assessment of illness condition.

Objective To explore the risk factors of acute respiratory failure(ARF)in adult patients with community-acquired pneu-monia(CAP),and thereby construct and validate the efficacy of nomogram model.Methods The clinical and laboratory data of 172 adult CAP patients admitted to Taikang Xianlin Drum Tower Hospital affiliated to Nanjing University School of Medicine from January 2018 to December 2021 were retrospectively collected.The patients were divided into two groups based on whether they had concurrent ARF.After the comparison for the differences of single factor between the two groups,collinearity analysis was assessed.The risk fac-tors were then screened by binary logistic regression analysis with forward stepwise regression method.A nomogram model was subse-quently constructed and the discrimination and accuracy of the model were evaluated by ROC and colibration curves.Results Among the 172 CAP patients,53 cases(30.8％)developed ARF.The results of univariate analysis showed that the CAP patients with concur-rent ARF group had higher age,CURB-65 score and inflammatory markers than the non-concurrent ARF group,and the incidence of complex infection(culturing two or more pathogenic bacteria)was high.The values of CRP(C-reactive protein)and BUN/Alb(blood urea nitrogen/albumin)were significantly different between the two groups(53.910[25.900,101.200]vs.23.300[6.800,48.930],0.231[0.160,0.302]vs.0.123[0.089,0.171],P＜0.05).Multivariate analysis indicated:glucose(Glu)≥6.06 mmol/L(odds ra-tio(OR):2.737,95％confidence interval(CI):1.116-7.037),AST(aspartate aminotransferase)≥22.5 U/L(OR:4.291,95％CI:1.779-11.120),fibrinogen(Fib)≤3.83 g/L(OR:3.955,95％CI:1.631-10.237),uric acid(UA)188.07 μmol/L(OR:4.617,95％CI:1.859-12.489),BUN/Alb≥0.15 mmol/g(OR:6.381,95％CI:2.423-18.513),total number of multicomor-bidity≥3(OR:6.191,95％CI:2.088-21.905)were the risk factors(P＜0.05).All the screened indicators were incorporate into the nomogram model and its efficacy was verified.The results showed that the area under the curve of the model was 0.888[95％CI:0.840-0.935](P＜0.05),the sensitivity was 0.868,and the specificity was 0.790.The calibration curve showed that the predicted probability of adult CAP patients-associated with ARF was in good consistency with the observed probability(Briser Score:0.125;H-L test:x2=7.563,P=0.477).Conclusion The established model has a good ability to predict adult CAP associated with ARF,and can provide a reference basis for early clinical prediction and intervention treatment.

OBJECTIVE To observe the expressions of transforming growth factor-β1(TGF-β1)/Smads signaling pathways in the primary nephrotic syndrome(NS)patients complicated with pulmonary infection and analyze the values in diagnosis of pulmonary infection and assessment of illness condition.METHODS A total of 108 NS pa-tients complicated with pulmonary infection who were treated in Huaihe Hospital of Henan University from Jan.2020 to Mar.2024 were assigned as the infection group and were divided into the mild group with 32 cases and the severe group with 76 cases according to the severity of pulmonary infection.The distribution of the pathogens was analyzed.Meanwhile,97 NS patients who were not complicated with pulmonary infection were chosen as the no infection group.The relative expression levels of peripheral blood TGF-β1,Smad2,Smad3 mRNA and proteins were detected for the patients confirmed with infection within 24 hours(for the patients with infection within 24 hours after the admission)by means of real-time fluorescent quantitative polymerase chain reaction.The values of the three indexes in diagnosis of the pulmonary infection and assessment of illness condition of the NS patients were analyzed.RESULTS Totally 122 strains of pathogens were isolated from sputum specimens of the 108 NS pa-tients complicated with pulmonary infection,78.69％of which were gram-negative bacteria.The relative expres-sion levels of TGF-β1,Smad2,Smad3 mRNA and proteins of the infection group were respectively 8.69±1.33,6.07±0.75 and 5.94±0.88,higher than 3.76±0.3,2.38±0.24 and 3.15±0.35 of the no infection group(P＜0.05);the levels of the indexes of the severe group were higher than those of the mild group(P＜0.05).Receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC)of the joint detection of TGF-β1,Smad2 and Smad3 was 0.972 in diagnosis of the pulmonary infection in the NS patients,0.912 in as-sessment of the severe pulmonary infection.CONCLUSIONS The NS patients complicated with pulmonary infection show remarkable rise of expressions of TGF-β1,Smad2 and Smad3.The joint detection of the above indexes has high clinical value in diagnosis of the pulmonary infection and assessment of illness condition.

The application of mechanics in clinical wound healing has a long history;however,the systematic underlying mechanisms remain unclear.With recent advancements in biomechanics and mechanobiology,the principles regarding how mechanical factors influence the formation,progression,and healing of wounds have gradually been elucidated.Herein,based on progress in theories,technologies,and clinical practices concerning the interplay between mechanics and wound healing,this study introduces the concept of wound-repairing mechanomedicine.Relevant research is systematically reviewed from the perspectives of biomechanics,mechanobiology,and mechanotherapy.Additionally,potential future development directions are prospectively analyzed to provide novel insights into wound care and strategies for preventing scar formation.

Nanocrystal technology changes the solubility and dissolution rate of insoluble drugs by reducing the particle size to the nanometer level.This technology is not limited by carrier materials and encapsulation rate.It is suitable for a variety of drug delivery routes and easy for industrial production.It has gradually become a cutting-edge hot technology in the international pharmaceutical field to improve the absorption of insoluble drugs and improve their bioavailability.This article introduces the influencing factors and challenges of nanocrystal drugs(NC)in parenteral,ocular,transdermal and pulmonary administration,and focuses on nanocrystal drugs that have been marketed or are still in the preclinical or clinical trial stages of these delivery systems,in order to provide some insight for the further development of poorly soluble drug nanocrystal preparations.

Objective:To summarize the clinical and EEG characteristics of children with self-limited epilepsy with centrotemporal spikes (SeLECTS), and explore the risk factors for comorbid attention-deficit hyperactivity disorder (ADHD).Methods:Demographic and medical history data, seizure characteristics, EEG data, and treatment information of 122 children with SeLECTS admitted to Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from July 2020 to March 2024 were collected. Based on Swanson, Nolan and Pelham-IV Rating Scale (SNAP-IV) results, these patients were divided into comorbid ADHD group ( n=64) and non-ADHD group ( n=58); the clinical data and EEG characteristics (location and lateralization of discharges, synchronicity of bilateral discharges, period of discharges, spike wave frequency and special waveforms) of the patients between the 2 groups were compared to analyze the risk factors for comorbid ADHD. Results:(1) In 122 SeLECTS children, 70 (57.38%) were males and 52 (42.62%) were females; onset age was (7.50±1.98) years (3-12 years); 72.95% (89/122) patients had seizures only within 1 h after falling asleep, 9.84% (12/122) had seizures only 1-2 h before awakening in the morning, 9.84% (12/122) had seizures both after falling asleep and before awakening in the morning; duration of a single episode was (116.60±89.68) seconds (10-600 seconds). (2) Background activity in EEG showed no obvious abnormalities; the discharges were located in the central temporal region in 93.20% (96/103) patients and in the central temporal region and other brain regions (including frontal region, anterior head, bilateral occipital midline and bilateral cerebral hemispheres) in 6.80% (7/103) patients; among 69 patients whose overnight EEG recording was obtained, the spike frequency was 35.00 (20.67, 55.00) times/min (0.33-86.33 times/min). (3) Among 120 patients who accepted drug treatment, 87 (72.50%) received monotherapy, including valproic acid ( n=30, 34.48%), oxcarbazepine ( n=21, 24.14%), lacosamide ( n=17, 19.54%), levetiracetam ( n=17, 19.54%), perampanel ( n=1, 1.15%), and lamotrigine ( n=1, 1.15%); 33 (27.50%) received combination therapy with two or more drugs. (4) The comorbid ADHD group had statistically younger age of onset, longer duration of a single episode, higher proportion of seizures both after falling asleep and before awakening, and higher spike wave frequency in EEG than the non-ADHD group ( P<0.05). Conclusions:SeLECTS patients generally have onset age of 3-12 years, seizures within 1 h after falling asleep or 1-2 h before awakening, normal EEG background activity, and epileptiform discharges mostly located in the centrotemporal area, which are different from other types of epilepsy. SeLECTS patients with young age of onset, long duration of a single episode, seizures both after falling asleep and before awakening and high spike wave frequency in EEG trend to develop ADHD comorbidity.

This study aimed to explore the mechanism of how African swine fever virus (ASFV) I226R protein inhibits the cGAS-STING signaling pathway. We observed that I226R protein (pI226R) significantly inhibited the cGAS-STING-mediated type Ⅰ interferons and the interferon-stimulated genes production by dual-luciferase reporter assay system and real-time quantitative PCR. The results of co-immunoprecipitation assay and confocal microscopy showed that pI226R interacted with cGAS. Furthermore, pI226R promoted cGAS degradation through autophagy-lysosome pathway. Moreover, we found that pI226R decreased the binding of cGAS to E3 ligase tripartite motif protein 56 (TRIM56), resulting in the weakened monoubiquitination of cGAS, thus inhibiting the activation of cGAS and cGAS-STING signaling. In conclusion, ASFV pI226R suppresses the antiviral innate immune response by antagonizing cGAS, which contributes to an in-depth understanding of the immune escape mechanism of ASFV and provides a theoretical basis for the development of vaccines.
Animals ; Swine ; African Swine Fever Virus/metabolism* ; Membrane Proteins/metabolism* ; Immunity, Innate ; Nucleotidyltransferases/metabolism* ; Signal Transduction/genetics*