A 42-year-old male with chest tightness and dyspnea was admitted to the hospital. Chest CT indicated diffuse interstitial lung infiltration. Despite receiving anti-infective therapy, glucocorticoid therapy, and immunosuppressive agents, the patient developed refractory hypoxaemia. Endotracheal intubation and invasive mechanical ventilation failed to improve oxygenation. Therefore the patient was diagnosed with rapidly progressive interstitial lung disease (RP-ILD) accompanied by type Ⅰ respiratory failure. Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) was initiated, and oxygenation improved in this patient. The patient subsequently underwent bilateral lung transplantation with veno-arterio-venous (VAV) ECMO support. ECMO machine was withdrawn on day 1, and extubation was achieved on day 9 after surgery. Histopathology revealed fibrotic nonspecific interstitial pneumonia (NSIP) with hyaline membrane formation. The patient developed ICU-acquired myasthenia and received early rehabilitation, with gradual recovery of muscle strength. During follow-up, graft lung function remained stable. This case demonstrates that ECMO can serve as a bridge to lung transplantation in RP-ILD patients.

ObjectiveTo identify the main chemical constituents of Anmeidan （AMD） and to explore the mechanism of AMD in regulating the extracellular signal-regulated kinase 1/2 （ERK1/2）/mitogen-activated protein kinase （MAPK）-interacting serine/threonine-protein kinase （MNK）/eukaryotic translation initiation factor 4E （eIF4E） signaling pathway to improve circadian rhythm disturbances in insomnia rats. MethodsThe main chemical constituents of AMD were identified using ultra-high-performance liquid chromatography-linear ion trap-electrostatic orbital trap mass spectrometry （UPLC-LTQ/Orbitrap/MS） in combination with reference standards. Sixty male Sprague-Dawley （SD） rats were randomly divided into control， model， melatonin， and AMD low-， medium-， and high-dose groups， with 10 rats in each group. Except for the control group， all rats were administered p-chlorophenylalanine via intraperitoneal injection to establish an insomnia model. The activity-rest rhythm of rats was assessed using the open field test and circadian rhythm test. Hematoxylin-eosin （HE） staining and Nissl staining were used to observe structural changes in hypothalamic neurons. Immunofluorescence， real-time quantitative polymerase chain reaction （Real-time PCR）， and Western blot analysis were employed to detect mRNA and protein expression levels of ERK1/2， MNK， and eIF4E in the hypothalamus. ResultsA total of 50 chemical components， including flavonoids， phenylpropanoids， triterpenoid saponins， alkaloids， and lignans， were identified in AMD. Compared with the control group， the model group exhibited significantly increased total distance traveled， average speed， central area residence time， and cumulative rearing time （P<0.01）， as well as prolonged cumulative activity time and total activity time in both light and dark phases （P<0.01）. Hypothalamic neurons in the model group were sparsely arranged， reduced in number， and exhibited nuclear disappearance or nucleolar rupture， with a significantly increased apoptosis index （P<0.01）. The cytoplasm appeared turbid， Nissl body staining was lighter， and the Nissl body apoptosis index was significantly increased （P<0.01）. The mRNA expression levels of ERK1/2， MNK， and eIF4E were significantly decreased （P<0.01）， along with a significant reduction in protein expression levels of ERK1/2， phosphorylated ERK1/2 （p-ERK1/2）， MNK， phosphorylated MNK （p-MNK）， eIF4E， and phosphorylated eIF4E （p-eIF4E） （P<0.01）. Compared with the model group， the total distance， average speed， central area residence time and body upright cumulative time of the AMD high-dose group were significantly reduced （P<0.01）. The total distance， average speed and body upright cumulative time of the AMD medium-dose group were significantly reduced （P<0.01）. The cumulative time of light activity and total time of activity in each dose group of AMD were significantly shortened （P<0.01）. The cumulative time of dark activity in the high-dose group of AMD was prolonged （P<0.01）. The neurons in the middle and high dose groups of AMD were closely arranged， the number of neurons increased， and the apoptosis index of hypothalamic cells decreased significantly （P<0.05， P<0.01）. The cytoplasm of the low， middle and high dose groups of AMD was clear， the color of Nissl body became darker， and the apoptosis index of Nissl body decreased significantly （P<0.01）. The expression of ERK1/2， MNK and eIF4E mRNA and protein in the hypothalamus of the middle and high dose groups of AMD increased significantly （P<0.05， P<0.01）. ConclusionAMD primarily contains 50 chemical constituents， including flavonoids， phenylpropanoids， and triterpenoid saponins. It exhibits a "synergistic enhancement" effect through multiple components and multiple pathways to improve insomnia. AMD ameliorates circadian rhythm disturbances in p-chlorophenylalanine-induced insomnia rats by upregulating ERK1/2/MNK/eIF4E signaling pathway-related proteins.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc), primarily manifesting as motor dysfunctions such as resting tremor, muscle rigidity, and bradykinesia. According to the classical model of basal ganglia motor control, approximately half of the medium spiny neurons (MSNs) in the striatum are D1-MSNs, which constitute the direct pathway. These neurons express D₁-dopamine receptor (D₁R) and substance P, and they mainly participate in the selection, initiation, and execution of movements. The other half are D2-MSNs, which constitute the indirect pathway. These neurons express D₂-dopamine receptor (D₂R) and adenosine 2A receptors and are involved in inhibiting unnecessary movements or terminating ongoing movements, thereby adjusting movement sequences to perform more precise motor behaviors. The direct pathway in the striatum modulates the activity of motor cortex neurons by exciting D1-MSNs through neurotransmitters such as glutamate (Glu), allowing the motor cortex to send signals more freely to the motor system, thus facilitating the generation and execution of specific motor behaviors. Studies using D1-Cre and D2-Cre mice with neurons labeled for D₁R and D₂R have shown that both types of neurons are involved in the execution of movements, with D1-MSNs participating in movement initiation and D2-MSNs in inhibiting actions unrelated to the target movement. These findings suggest that the structural and functional plasticity of D1-MSNs and D2-MSNs in the basal ganglia circuitry enables motor learning and behavioral regulation. Additionally, when SNpc DA neurons begin to degenerate, D1-MSNs are initially affected but do not immediately cause motor impairments. In contrast, when D2-MSNs undergo pathological changes, they are first activated by upstream projecting neurons, leading to the inhibition of most motor behaviors and resulting in motor dysfunction. Therefore, it is hypothesized that motor impairments such as bradykinesia and initiation difficulties are more closely related to the functional activity of D2-MSNs. The extracellular signal-regulated kinase (Erk)/mitogen-activated protein kinase (MAPK) signaling pathway has been identified as a critical modulator in the pathophysiology of PD. Recent findings indicate that Erk/MAPK signaling pathway can mediate DA and Glu signaling in the central nervous system, maintaining normal functional activity of striatal MSNs and influencing the transmission of motor control signals. Within this complex regulatory network, the Erk/MAPK signaling pathway plays a key role in transmitting motor information to downstream neurons, regulating normal movements, avoiding unnecessary movements, and finely tuning motor behaviors. Our laboratory’s previous research found that 4 weeks of aerobic exercise intervention improved motor dysfunction in PD mice by inhibiting the Erk1/2 signaling upstream of striatal MSNs, primarily involving the Erk1/2 signaling in D2-MSNs rather than D1-MSNs. This review summarizes the neurobiological mechanisms of Erk/MAPK signaling pathway in D2-MSNs for the prevention and treatment of motor dysfunction in PD. By exploring the role of this signaling pathway in regulating motor abnormalities and preventing motor dysfunction in the central nervous system of PD, this review provides new theoretical perspectives for related mechanistic research and therapeutic strategies.

Objective:To explore the clinical efficacy of Wenshen Chushi Decoction combined with low intensity pulsed ultra-sound(LIPUS)on erectile dysfunction(ED)caused by renal deficiency and phlegm-dampness syndrome.Methods:One hundred and twenty ED patients were included from the Department of Andrology in the First Hospital of Hunan University of Traditional Chinese Medicine.The patients in control group were treated with Wenshen Chushi Decoction.While the patients in observation group were trea-ted with Wenshen Chushi Decoction combined with LIPUS for 8 consecutive weeks.After the treatment,the efficacy was evaluated using the International Index of Erectile Function-5(IIEF-5)score,Penile Flow Index(PFI),Traditional Chinese Medicine Syndrome Score,Self-Rating Depression Scale(SDS)score,and Self-Rating Anxiety Scale(SAS)score.Safety was also observed.And the ef-ficacy was followed up 4 weeks after the end of treatment.Results:Fifty-seven cases were enrolled into control group finally with 55 cases in the treatment group.After the treatment,all the patients in both of groups showed an improvement in IIEF-5 scores(P＜0.01).Compared with the control group(19.09±2.22),the IIEF-5 score in observation group(20.42±2.39)increased signifi-cantly(P＜0.01).After the treatment,the scores of PFI,TCM syndrome and SDS in both groups decreased(P＜0.01,P＜0.05,P＜0.01).Compared with the control group([3.77±1.21],[9.91±1.71]and[39.88±2.63]points),the observation group([2.92±1.08],[4.78±1.45],and[34.51±2.09]points)showed a more significant decrease(P＜0.01).There was no significant difference in total effective rate between the two groups(P＞0.05).During follow-up,the IIEF-5 scores of both groups of patients were higher than those before(P＜0.05,P＜0.01),and the observation group score was higher than that in the control group([17.15±3.37]vs[13.63±1.96],P＜0.01).No adverse reaction and abnormality of indicators occurred in both of two groups.Conclusion:Wenshen Chushi Decoction has a significant therapeutic effect on ED caused by renal deficiency and phlegm-dampness syndrome.It can not only improve the quality of erection,but also improve the physical and mental symptoms associated with ED,which makes therapeutic effect lasting longer.

This research aims to construct a stable epithelial cell senescence model for screening and e-valuation of senolytics.We explored the optimal conditions for doxorubicin-induced senescence of non-transformed epithelial cells MCF 10A,including the optimal induction concentration,the optimal inter-vention time,and the optimal senescence duration,and confirmed the feasibility of MCF 10A as an epi-thelial senescence model by multiple ways.The optimal condition for Doxorubicin-induced senescence of MCF 10A cells was treatment with 0.6 μmol/L Doxorubicin for 16 h to achieve the best senescence state on the 8th day.Under the optimal induction conditions,the positive rate of senescence-associated β-gal-actosidase(SA-β-gal)staining in the treated group reached 97％.At the same time,biochemical results of detecting the expression of mRNA,proteins,and immunofluorescence demonstrated that the expression levels of senescence-associated secretory phenotype(SASP),p16,p21 and p53 in the treated group were significantly higher than those in the control cells,and Lamin B1 was significantly decreased(P＜0.001),which were consistent with the specific characteristics of senescence.In summary,an epithelial senescence model was successfully induced in MCF 10A cells by Doxorubicin in this study,which will promote the screening of senolytics for senescent epithelial cells.

Objective To explore the neurophysiological signatures of auditory event-related potentials(AERP)during propofol-induced graded sedation depths,and their correlations with sedation levels and behavioral responsiveness,and further to evaluate the feasibility of AERP components as potential biomarkers for quantifying consciousness states.Methods An auditory Oddball paradigm was used to evoke AERP responses in healthy volunteers under propofol-induced graded sedation.Linear mixed model was applied to explore the relationships between the mean amplitudes of AERP components[mismatch negativity(MMN);P300]and both sedation-induced conscious states[Modified Observer's Assessment of Alertness/sedation Scale(MOAA/S)scores]and behavioral performance(response accuracy).Results Twenty-two healthy volunteers were included.Data analysis revealed significant negative correlations between the mean amplitudes of MMN components[MMN-Dev:β=-0.62(-2.70--0.07),P=0.04;MMN-Nov:β=-0.15(-0.27--0.03),P=0.02]and MOAA/S scores during propofol sedation.Novel stimulus-evoked MMN amplitudes also correlated with response accuracy[MMN-Nov:β=-5.08(-7.78--2.37),P<0.01].There was a weak positive correlation between novel stimulus-evoked P300 amplitudes and MOAA/S scores[β=0.16(0.04-0.39),P=0.04],however,the correlation was no significant difference after adjusting for confounding factors including age,education level,and cognitive level.Conclusion The mean amplitude of MMN component elicited during auditory tasks was correlated with conscious states and behavioral accuracy under propofol-induced graded sedation.MMN holds promise as a potential neurophysiological indicator for quantifying conscious states or behavioral responsiveness during sedation.

Objective To explore the diagnostic value of 68Ga-PSMA-11 PET/CT combined with abnormal prothrombin(PIVKA-Ⅱ)in the diagnosis of different tumors.Methods A total of 200 patients with suspected cancer who underwent examinations in the Affiliated Hospital of Southwest Medical University from September 2021 to December 2023 were retrospectively selected,including 51 suspected liver cancer,49 suspected pancreatic cancer,52 suspected rectal cancer and 48 suspected prostate cancer.All patients underwent both serum PIVKA-Ⅱ testing and 68Ga-PSMA-11 PET/CT imaging.Receiver operating characteristic(ROC)curve analysis was used to assess the diagnostic performance of 68Ga-PSMA-11 PET/CT and serum PIVKA-Ⅱ for liver cancer,pancreatic cancer,rectal cancer and prostate cancer.Results No significant differences were found in general data of 4 suspected tumor groups(P>0.05)except for age.Serum PIVKA-Ⅱ levels were significantly higher in patients with suspected liver cancer and rectal cancer compared with those with suspected pancreatic cancer and prostate cancer(P<0.05).No significant difference was observed in the serum PIVKA-Ⅱ levels between suspected pancreatic cancer group and suspected prostate cancer group(P>0.05).The positive rates of 68Ga-PSMA-11 PET/CT and serum PIVKA-Ⅱ for diagnosing liver,pancreatic,rectal,and prostate cancers were significantly lower than those of pathological examination(49.0%vs.47.1%vs.92.2%,57.1%vs.55.1%vs.87.8%,48.1%vs.44.2%vs.92.3%,64.6%vs.62.5%vs.89.6%,respectively,P<0.05).ROC curve analysis showed that serum PIVKA-Ⅱ had a sensitivity of 79.06%,specificity of 72.02%,area under ROC curve(AUC)of 0.822,and Youden index of 0.512.For 68Ga-PSMA-11 PET/CT,the sensitivity was 79.11%,specificity 72.07%,AUC 0.829,and Youden index 0.510.The combined use of 68Ga-PSMA-11 PET/CT and serum PIVKA-Ⅱ achieved higher diagnostic accuracy,with a sensitivity of 93.28%,specificity of 81.15%,AUC of 0.924 and Youden index of 0.744,all surpassing the single index.Conclusion Both 68Ga-PSMA-11 PET/CT and serum PIVKA-Ⅱ are effective diagnostic tools for liver,pancreatic,rectal,and prostate cancers,with the combined approach yielding superior diagnostic performance.

Integrins are transmembrane receptors that can coordinate signal transduction between cells and extracellular matrix or between cells.The abnormal function of integrins is one of the recognized mechanisms of tumor development.As an important regulatory mode,post-translational modification can change the conformation and physicochemical properties of proteins,thus affecting their activities,stability and functions.After the modification of the integrin,such as glycosylation and methylation,the corresponding signal transduction pathway changes,and then affects cell adhesion,migration,differentiation and other life activities,involving in diverse physiology and pathological processes.Post-translational modifications of integrins are abundant in tumor progression and play a key role in regulating the growth,metastasis and drug resistance of different tumor cells.In this review,the structure and function,post-translational modification of integrins,and their relationship with occurrence and development of tumors will be discussed,in order to provide more explorable targets for the treatment of cancer.

Objective:To investigatethe effects of different blood lead levels on indicators of immune function in occupationally lead-exposed populations.Methods:From October to December 2023, a total of 126 occupationally exposed lead workers of a company in Guizhou Province were selected, and their basic information was collected through questionnaires. Inductively coupled plasma mass spectrometry was used to detect blood lead levels in the study population. Workers were categorized into Group 1, Group 2 and Group 3 based on blood lead levels (blood lead levels <200 μg/L, 200~400 μg/L and >400 μg/L). Lymphocyte subpopulation marker leukocyte differentiation antigen (CD) in peripheral blood and interleukin (IL) -1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, tumor necrosis factor-alpha (TNF-α), and interferon (IFN) -γ in serum were examined by flow cytometry. Serum levels of immunoglobulin (Ig) A, IgG, IgM, and complement proteins (C3, C4) were measured by immunoscattering turbidimetry. Data were statistically analyzed using rank sum test, Chi-square test or Fisher exact probability method for multiple samples.Results:Compared with group 1, the percentage of CD3 +CD8 + and CD4 +CD25 + cells decreased ( P<0.05) and the percentage of CD4 + CD95 + cells increased in the lead-exposed populations in groups 2 and 3 ( P<0.05) ; however, the serum IL-1β, IL-2, IL- 5, IL-8, IL-12p70, and IFN-γ levels were decreased ( P<0.05) in group 3. Meanwhile, IgG ( P<0.05) and IgM levels in serum of lead-exposed population in group 2 and group 3 were reduced ( P<0.05) comparing with group 1. Spearman correlation analysis showed that blood lead levels of workers were negatively correlated with the percentage of peripheral blood CD8 +CD95 + cells, CD3 +CD8 + cells, CD3 -CD16 + CD56 + cells, IgG, IgM, and IgA ( rs=-0.20, -0.22, -0.23, -0.24, -0.26, -0.35, P<0.05), but was positively correlated with the level of CD3 +CD4 + cells ( rs= 0.18, P<0.05). Regression analysis revealed that blood lead level was a risk factor for the percentage of CD8 +CD95 + cells, CD3 +CD8 + cells, CD3 -CD16 + CD56 + cells, IgG, IgM, and IgA ( P<0.05) . Conclusion:Different lead loads can lead to abnormal changes in peripheral blood lymphocyte subsets, cytokines, and immunoglobulin levels in occupationally lead-exposed people. Lead exposure in occupationally lead-exposed populations may affect their immune function.