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.

Surgical treatment is one of the key approaches for non-small cell lung cancer (NSCLC). Regular postoperative follow-up is crucial for early detection and timely management of tumor recurrence, metastasis, or second primary tumors. A scientifically sound and reasonable follow-up strategy not only extends patient survival but also significantly improves quality of life, thereby enhancing overall prognosis. This consensus aims to build upon the previous version by incorporating the latest clinical research advancements and refining postoperative follow-up protocols for early-stage NSCLC patients based on different treatment modalities. It provides a scientific and practical reference for clinicians involved in the postoperative follow-up management of NSCLC. By optimizing follow-up strategies, this consensus seeks to promote the standardization and normalization of lung cancer diagnosis and treatment in China, helping more patients receive high-quality care and long-term management. Additionally, the release of this consensus is expected to provide insights for related research and clinical practice both domestically and internationally, driving continuous development and innovation in the field of postoperative management for NSCLC.

Objective: To explore the clinical manifestations, diagnosis, differential diagnosis, and treatment of granulomatous cheilitis complications after treatment in patients with upper lip venous malformations, as well as to provide a reference for their clinical diagnosis and treatment. Methods: This report provides details on the clinical manifestations, diagnosis, differential diagnosis, and treatment of a case of granulomatous cheilitis after the treatment of upper lip venous malformation, and then analyzes granulomatous cheilitis alongside the related literature. The patient, a 30-year old male, was first seen in the dermatology department of another hospital with bright red spots on his lips, diagnosed with allergic dermatitis and received symptomatic treatment, and the erythema did not improve. He was diagnosed with ‘cavernous hemangioma’ and was treated with polydocanol and bleomycin injections. The bright red spots on his lips improved, but the swelling worsened for more than half a year. He then sought treatment at the oral mucosal department of our hospital. At the time of consultation, the swelling of the upper lip and perilabial skin was obvious, and there was a red patch on the right side of the upper lip, that was congested with blood. The upper lip was tough, with hard nodules, unclear borders, and poor mobility. Pathological examination showed epithelial hyperplasia of the upper lip mucosa, surface hyperkeratosis, subepithelial fibrous tissue hyperplasia, and chronic inflammation of the mucosa and minor salivary glands. Focal histiocyte, lymphocyte, and plasma cell infiltration was seen in the submucosal layer, with granulomatous inflammatory manifestations. Based on the patient's medical history, clinical manifestations, and histopathological manifestations, the diagnosis of granulomatous cheilitis was made. Tretinoin 0.3 mL (40 mg/mL, 1 mL/vial) was injected into the deep layer of the mucosa of the right and left upper lips for local block treatment. Prednisone acetate tablets (10 mg/Qd) were taken orally, and after 1 week of follow-up, the symptoms improved, so the original treatment was continued. After 2 weeks of follow-up, the swelling of the lips improved significantly, and the oral prednisone acetate tablets were adjusted to 5 mg/Qd. After 4 weeks of follow-up, the shape of the lips was largely back to normal, and the color and suppleness of the lips had improved significantly. The local block treatment and oral medication were stopped, and the patient was instructed to apply the topical tretinoin ointment Bid on the upper lip. Results: The patient had a follow-up visit 8 weeks later, at which their lip color, shape, and texture remained normal, and the patient was instructed to stop the medication and follow up. A review of the literature suggests that the etiology of granulomatous cheilitis is unknown and that it is associated with genetic predisposition, odontogenic infections, allergic factors, microbial infections, and immunological factors. It needs to be clinically differentiated from diseases such as lip venous malformations, lip angioneurotic oedema, Crohn's disease, and tuberculosis. At present, the clinical treatment of granulomatous cheilitis is still based on local glucocorticoid block therapy or a combination of oral glucocorticoid drugs. In this case, the area of erythema on the lips decreased in size, but swelling occurred and continued to worsen after polydocanol and bleomycin injection treatment. Pre-existing venous malformation should be considered as a complication associated with injectable drugs that can produce granulomatous cheilitis. Conclusion The injection-based treatment of lip venous malformation may be complicated by granulomatous cheilitis, and in the process of clinical diagnosis and treatment, it is necessary to be aware to the existence of drug-related factors in the occurrence and development of granulomatous diseases.

ObjectiveTo investigate the current status of emergency management for severe mental disorders in Shanghai, and to provide countermeasures and suggestions for the establishment of a sound emergency management system for severe mental disorders and the enhancement of emergency management capability. MethodsA questionnaire survey and qualitative interviews were used to conduct an investigation into the emergency management in 17 district-level mental illness prevention and control institutions in Shanghai, which includes the basic situation of emergency management for severe mental disorders, the construction of emergency response teams and personnel, emergency preparedness drills and training, emergency management plans and rules and regulations, and problems encountered in emergency management. ResultsIn terms of emergency management mechanism and basic situation, resources such as personnel allocation, security funds and green channel were well equipped in each district-level mental illness prevention and control institution in Shanghai. However, the equipment of some hardware facilities was still insufficient to some extent. Therefore, further improvement on the emergency management mechanism for severe mental disorders was needed. With regard to the construction of emergency team and personnel allocation, the majority were those aged between 35‒<45 years old, with a bachelor’s degree, and more than 10 years of working experience. For example, 90.27% staff in district-level mental illness prevention and control institution had a bachelor’s degree or above, which was higher than that among the staff in community-level (73.60%); staff majored in clinical medicine in district-level institution accounted for the proportion at 52.71%, higher than that among the staff in community-level (28.86%); 57.24% staff in district-level institution had an intermediate professional title, higher than that among the staff in community-level (42.28%); and 69.90% staff in district-level institution had more than 10 years of working experience, higher than that among the staff in community-level (43.62%). In the aspect of emergency drills and training, all district-level mental illness prevention and control institutions in Shanghai had a high demand for emergency training, and the weak aspects mainly focused on lack of emergency service protocols, skills of addressing technical challenges, and construction of effectiveness evaluation system. Moreover, the teaching methods were primarily centered on case analysis, simulation drills, interactive discussions, and so forth. Concerning emergency management plans and rules and regulations, all districts in Shanghai had relatively established well-developed systems for emergency response plans, emergency response leadership groups, and emergency response operational task forces for severe mental disorders. About half of the institutions had established other rules and regulations related to emergency management of severe mental disorders in addition to emergency plans. ConclusionShanghai has initially established an emergency management system for severe mental disorders, but it is still fragile in specialized training for emergency management of severe mental disorders, construction of emergency management mechanisms, and the building-up of grassroots emergency teams. Further priorities should include strengthening emergency management training, enhancing the construction of emergency management personnel teams, and gradually establishing a more comprehensive and integrated emergency management mechanism for severe mental disorders.

Objective: To investigate the predictive value of EZH2 expression for malignant transformation in oral leukoplakia (OLK) and to provide a reference for clinical practice. Methods: This study was approved by the institutional ethics committee, and informed consent was obtained from all participants. A total of 114 patients diagnosed with OLK by pathological examination and treated at our hospital between November 2020 and July 2022 were initially enrolled. After excluding those with incomplete data or follow-up, 105 participants were included in the final analysis, comprising 14 in the high EZH2 expression group and 91 in the low EZH2 expression group. Histopathological examination of oral mucosa and immunohistochemical detection of EZH2 protein expression were performed. The follow-up period was 30 months; participants were followed until malignant transformation occurred or until the end of follow-up, at which point they were withdrawn from the study. The exposure factor was the level of EZH2 protein expression, and the outcome was the malignant transformation rate of OLK. Differences in EZH2 expression levels and transformation outcomes were analyzed. Results: There were no statistically significant differences between the high and low EZH2 expression groups in terms of age, sex, history of systemic disease, lifestyle habits, psychological status, diet, and sleep conditions (P > 0.05). Lesions in the high EZH2 expression group were mainly located on the ventral tongue, while in the low EZH2 expression group, they were more commonly found on the dorsal tongue and buccal mucosa. The malignant transformation rate was 28.6% (4/14) in the high expression group and 8.8% (8/91) in the low expression group; these differences were not statistically significant (P=0.053). In univariate Cox regression analysis, the risk of malignant transformation in the high EZH2 expression group was 3.647 times that of the low EZH2 expression group (HR = 3.647, 95% CI: 1.097-12.120, P<0.05). Kaplan-Meier survival analysis showed that over the 30-month follow-up period, the cancer-free survival rate in the high EZH2 expression group was 19.8% lower than in the low expression group, and the difference was statistically significant (P<0.05). In multivariate Cox regression analysis, only moderate and severe epithelial dysplasia were identified as independent risk factors for malignant transformation. The risk of malignant transformation in the moderate and severe dysplasia groups was 10.695 and 13.623 times higher, respectively, than in the mild dysplasia group (HR = 10.695, 95% CI: 2.270-50.396, P<0.05; HR=13.623, 95% CI: 1.918-96.774, P<0.05). EZH2 high expression was not an independent risk factor in the multivariate model (HR= 2.528, 95% CI: 0.752-8.500, P = 0.134). Conclusion High EZH2 protein expression is a risk factor for the malignant transformation of OLK but does not have independent predictive value.

Peptides are a particular molecule class with inherent attributes of some small-molecule drugs and macromolecular biologics, thereby inspiring continuous searches for peptides with therapeutic and/or agrochemical potentials. However, the success rate is decreasing, presumably because many interesting but less-abundant peptides are so scarce or labile that they are likely 'overlooked' during the characterization effort. Here, we present the biochemical characterization and druggability improvement of an unprecedented minor fungal RiPP (ribosomally synthesized and post-translationally modified peptide), named acalitide, by taking the relevant advantages of metabolomics approach and disulfide-bridged substructure which is more frequently imprinted in the marketed peptide drug molecules. Acalitide is biosynthetically unique in the macrotricyclization via two disulfide bridges and a protease (AcaB)-catalyzed lactamization of AcaA, an unprecedented precursor peptide. Such a biosynthetic logic was successfully re-edited for its sample supply renewal to facilitate the identification of the in vitro and in vivo antiparkinsonian efficacy of acalitide which was further confirmed safe and rendered brain-targetable by the liposome encapsulation strategy. Taken together, the work updates the mining strategy and biosynthetic complexity of RiPPs to unravel an antiparkinsonian drug candidate valuable for combating Parkinson's disease that is globally prevailing in an alarming manner.

Protein as the allergens could lead to allergy. In addition, a widespread class of allergens were known as glycans of N-glycoprotein. N-glycoprotein contained oligosaccharide linked by covalent bonds with protein. Recently,studies implicated that allergy was associated with glycans of heterologous N-glycoprotein found in food, inhalants, insect toxins, etc. The N-glycan structure of N-glycoprotein allergen has exerted an influence on the binding between allergens and IgE, while the recognition and presentation of allergens by antigen-presenting cells (APCs) were also affected. Some researches showed thatN-glycan structure of allergen was remodeled by N-glycosidase, such as cFase I, gpcXylase, as binding of allergen and IgE partly decreased. Thus, allergic problems caused by N-glycoproteins could potentially be solved by modifying or altering the structure ofN-glycoprotein allergens, addressing the root of the issue. Mechanism of N-glycans associated allergy could also be elaborated through glycosylation enzymes, alterations of host glycosylation. This article hopes to provide a separate insight for glycoimmunology perspective, and an alternative strategy for clinical prevention or therapy of allergic diseases.

Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (https://hlse.cn/), with the aim of synthesizing, evaluating, translating, and applying lifestyle-related evidence resources. This paper aims to introduce the functional module design of the evidence translation system, the system development process and testing, introduce the interface design and function demonstration, and explain the significance of constructing the HLSE.

Objective : To study the effect and mechanism of action of Silibinin on the differentiation of 3T3-F442A preadipocytes in murine． Methods : The effects of 0－400 μmol / L Silibinin on the proliferation of 3T3-F442A adi- pocytes at 24，48 and 72 h were detected by 3-(4，5-dimethylthiazol-2) -2，5-diphenyltetrazolium bromide ( MTT) assay，and the effects of Silibinin on the adipogenesis of 3T3-F442A adipocytes were visualized by Oil Red O stai- ning ; RT-qPCR , Western blot and ELISA assays were used to detect the effects of Silibinin on 3T3-F442A adipo- cyte differentiation-associated transcription factor CCAAT / enhancer binding protein ( C / EBP) α , C / EBP β , per- oxisome proliferator-activated receptor γ cular endothelial growth factor (VEGF) -α and VEGF receptor 2 (VEGFR-2) ，matrix metalloproteinase (MMP) -2 and MMP-9，mitogen-activated protein kinase (MEK) and phosphorylated MEK (p-MEK) ，and extracellular regu- lated protein kinase (ERK) and phosphorylated ERK (p-ERK) expression. (PPARγ) ，adipocyte protein 2 (aP2) ，adipose generation-associated vas Results : MTT assay showed that the cell proliferation rate of 3T3-F442A preadipocytes decreased after 100，200，and 400 μmol /L Silibinin treatment compared with the control group (P＜0. 001) ; Oil Red O staining assay showed that the accumulation of red lipid droplets of the cells in the 160 μmol /L Silibinin assay group significantly decreased ; RT-qPCR assay showed that mRNA expression of C/EBPα , C/EBPβ , PPARγ , aP2，VEGF-α , VEGFR-2，MMP-2，and MMP-9 was down-reg- ulated in 3T3-F442A adipocytes treated with 160 μmol /L Silibinin compared with the control group (P＜0. 001) ; Western blot assay showed that protein expression of C /EBPα , C /EBPβ , PPARγ and aP2 was down-regulated in 3T3-F442A adipocytes treated with 160 μmol /L Silibinin (P＜0. 001) ，and the phosphorylation level of p-MEK/ MEK and p-ERK/ ERK proteins was down-regulated compared with the control group (P ＜0. 001) ; ELISA assay showed that the protein concentrations of MMP-2 and MMP-9 in the cell supernatant were down-regulated (P < 0. 001) in 3T3-F442A adipocytes treated with 160 μmol /L Silibinin． Conclusion Silibinin inhibited 3T3-F442A adipocyte differentiation and adipogenesis through inhibition of the MEK/ ERK pathway and matrix metalloproteinase activity.

[Abstract] [Objective] To investigate the therapeutic effect of platelet-rich plasma (PRP) subcutaneous injection combined with gypenosides (GPs) oral administration on BALB/c mouse psoriatic inflammation and explore its mechanism of action. [Methods] The 6-8 week-old female SPF BALB/c mice were randomly divided into five groups: control, model, PRP, GPs and PRP+GPs group, with 5 mice in each group. Imiquimod (IMQ) was used to induce psoriasis-like skin inflammation on the back of mice except the control group. The onset and severity of psoriasis-like inflammation in different treatment groups were evaluated by observing skin lesions, skin thickness and measuring PASI score. HE staining and Ki67 staining were used to evaluate the pathological changes and proliferation of keratinocytes in psoriasis-like skin lesions. Blood cell count, enzyme-linked immunosorbent assay and Western blot were used to explore the changes in circulating white blood cell count, cytokines IL-17A and TNF-α, and related signaling pathway proteins p-STAT3 and p-P38. [Results] At the end of the experiment (on day 6), scale scores of model, PRP, GPs and PRP+GPs group were 3.6±0.49, 1.8±0.75, 1.8±0.75, 1.2±0.40, respectively; the ratios of skin thickness (μm) were 0.86±0.18, 0.59±0.10, 0.56±0.07 and 0.42±0.09; PASI scores were 10.6±1.02, 4.0±0.63, 4.0±1.10 and 3.2±0.75. Compared with the model group, the number of scales (P<0.01), patch thickness (P<0.01) and PASI score decreased (P<0.0001) showed a certain therapeutic effect, and PRP+GPs group had the best effect. Pathological examination showed that both the epidermal layer thickness (P<0.01) and epidermal cell proliferation (P<0.05) decreased in all treatment groups; IL-17A expression levels were 9.02±2.54, 16.56±3.49, 10.01±1.83, 11.12±2.48 and 10.50±2.16, and TNF-α expression levels were 223.36±70.34, 377.36±58.47, 265.42±45.14, 262.94±33.29 and 268.94±26.80 respectively. The expression of skin tissue IL-17A (P<0.05) and TNF-α (P<0.05) decreased, along with the decreased expression of related signaling pathway proteins p-STAT3 and p-P38. [Conclusion] PRP combined with GPs can reduce the expression of IL-17A and TNF-α through the STAT3 and P38 signaling pathways, thereby alleviating inflammation and inhibiting the overproliferation of keratinocytes, thus improving psoriasis-like skin inflammation in BALB/c mice.