Neurological disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), cerebral ischemia, and multiple sclerosis (MS), impose an escalating global health burden and remain largely incurable. These disorders arise from multifactorial and interconnected pathological processes, such as chronic neuroinflammation, oxidative stress, protein misfolding and aggregation, demyelination, and neurovascular dysfunction. Despite substantial advances in elucidating disease-associated molecular mechanisms, current therapeutic strategies are predominantly symptomatic and fail to effectively halt or reverse disease progression. This limitation highlights the urgent need to identify endogenous regulatory molecules capable of coordinating neuronal survival, synaptic maintenance, inflammatory control, and tissue repair within the central nervous system (CNS). Pleiotrophin (PTN) is a heparin-binding, growth-associated cytokine that has emerged as a key regulator of neural development, plasticity, and regeneration. Structurally, PTN contains multiple high-affinity heparin-binding domains that facilitate interactions with extracellular matrix components and cell surface proteoglycans, enabling spatially restricted and context-dependent signaling. Through these molecular properties, PTN functions as a multifunctional organizer of neural growth, plasticity, and tissue remodeling across developmental and adult stages. Its diverse biological effects are executed through a multi-receptor signaling system that integrates extracellular cues with intracellular programs governing cellular survival, migration, and differentiation. Notably, PTN displays a highly dynamic and cell type-specific expression pattern in the central nervous system, being enriched in neural progenitor cells during development and later restricted to discrete neuronal populations, neural stem cells, and non-neuronal niche cells—including astrocytes, pericytes, and vascular endothelial cells—which serve as critical sources of PTN under physiological and pathological conditions. PTN expression is tightly regulated during development and exhibits pronounced plasticity in response to pathological stimuli. Under physiological conditions, PTN is transiently expressed during critical windows of neural growth and synaptogenesis, supporting neuron-glia interactions and myelin formation. In contrast, in pathological contexts such as amyloid β-protein (Aβ) accumulation in AD, dopaminergic neuron degeneration in PD, demyelination in MS, and ischemic brain injury, PTN expression is frequently dysregulated, suggesting an active role in disease-associated remodeling rather than a passive bystander effect. Importantly, accumulating evidence indicates that PTN exerts a dual and context-dependent influence on neurological disorders. On the one hand, aberrant PTN signaling may contribute to maladaptive responses, including sustained glial activation, dysregulated neuroinflammation, extracellular matrix remodeling, and enhanced Aβ deposition. On the other hand, PTN displays robust neuroprotective and reparative functions by promoting neuronal survival, enhancing oligodendrocyte maturation and remyelination, and stimulating post-injury angiogenesis, thereby facilitating tissue repair and functional recovery. At the mechanistic level, PTN signaling is characterized by extensive cross-talk among receptor-dependent pathways. Activation of anaplastic lymphoma kinase (ALK) triggers canonical PI3K-AKT-mTOR and MAPK cascades that support neuronal survival and axonal integrity. PTN binding to protein tyrosine phosphatase receptor type Z1 (PTPRZ1) induces conformational inhibition of its phosphatase activity, resulting in increased phosphorylation of downstream effectors such as β-catenin, Fyn, and Src, which regulate neuronal migration and synaptic stabilization. Syndecan-3 (SDC3) functions as both a co-receptor and an independent signaling mediator by capturing extracellular PTN, amplifying ALK- and PTPRZ1-dependent signaling, and directly modulating cytoskeletal dynamics through PKC and ERK pathways. In parallel, PTN interaction with αVβ3 integrin contributes to remodeling of the neurovascular niche, linking angiogenesis with neurogenesis and neural repair. From a translational perspective, therapeutic strategies targeting PTN can be broadly classified into 3 categories: direct enhancement of PTN signaling through exogenous protein supplementation or gene therapy-mediated upregulation, pharmacological modulation of PTN-associated receptor pathways and downstream signaling nodes, and exploitation of PTN as a dynamic biomarker to inform disease stratification and therapeutic responsiveness. These complementary approaches underscore the growing interest in PTN-centered interventions across a spectrum of neurological disorders. In summary, PTN functions not merely as a classical trophic factor but as a central signaling hub integrating inflammatory regulation, neural regeneration, and vascular remodeling within the CNS. This review aims to synthesize current insights into PTN’s molecular architecture, multi-receptor signaling mechanisms, and disease-specific functions, and to highlight emerging therapeutic strategies targeting PTN. By conceptualizing PTN as a dynamic modulator of neuronal resilience rather than a static biomarker, we propose that precise modulation of PTN signaling may offer promising avenues for therapeutic development in neurodegenerative and neuroinflammatory diseases.

Based on LI Gao's Academic Thought， focusing on the process of qi transformation and taking the regulation and restoration of metabolism and immunity as the entry point， a "source-pivot-convergence" diagnostic and therapeutic model for malignant tumors is constructed. In this model， spleen and stomach internal injury is the source of malignant tumor occurrence， while the disorder of ascending and descending is the pivot of the disease development， and the generation of yin fire is the convergence of malignant tumor progression. Based on this， the three major therapeutic methods of clearing the source， harmonizing the pivot， and resolving the convergence are established. To fortify spleen and boost qi， consolidate the root and clear the source， modified Buzhong Yiqi Decoction（补中益气汤）can be used. To raise the clear and direct the turbid downward， regulate qi and harmonize the pivot， modified Shengyang Yiwei Decoction （升阳益胃汤） is suggested. To restore balance and promote circulation， disperse accumulation and resolve convergence， modified Shengyang Sanhuo Decoction （升阳散火汤） is selected. In clinical practice， these formulas can be used in combination according to the complexity of the pathogenesis， and further adapted with prescriptions for promoting dispersion and penetrating pathogenic factors， resolving phlegm and promoting circulation， activating blood and eliminating concretions， which can provide a reference for the prevention and treatment of tumor diseases.

Based on LI Gao's Academic Thought， focusing on the process of qi transformation and taking the regulation and restoration of metabolism and immunity as the entry point， a "source-pivot-convergence" diagnostic and therapeutic model for malignant tumors is constructed. In this model， spleen and stomach internal injury is the source of malignant tumor occurrence， while the disorder of ascending and descending is the pivot of the disease development， and the generation of yin fire is the convergence of malignant tumor progression. Based on this， the three major therapeutic methods of clearing the source， harmonizing the pivot， and resolving the convergence are established. To fortify spleen and boost qi， consolidate the root and clear the source， modified Buzhong Yiqi Decoction（补中益气汤）can be used. To raise the clear and direct the turbid downward， regulate qi and harmonize the pivot， modified Shengyang Yiwei Decoction （升阳益胃汤） is suggested. To restore balance and promote circulation， disperse accumulation and resolve convergence， modified Shengyang Sanhuo Decoction （升阳散火汤） is selected. In clinical practice， these formulas can be used in combination according to the complexity of the pathogenesis， and further adapted with prescriptions for promoting dispersion and penetrating pathogenic factors， resolving phlegm and promoting circulation， activating blood and eliminating concretions， which can provide a reference for the prevention and treatment of tumor diseases.

ObjectiveTo observe the mechanism of Guihuang formula in regulating the activation of NOD-like receptor protein 3 （NLRP3） inflammasome and inhibiting pyroptosis in the treatment of type Ⅲ prostatitis. Methods（1） In an animal experiment， 50 Sprague Dawley （SD） rats were randomly divided into a blank group， a model group， and low-dose， medium-dose， and high-dose groups of Guihuang formula， with 10 rats in each group. Except for the blank group， the type Ⅲ prostatitis rat model was prepared for the other four groups.After the modeling was successful， the blank group and the model group were given normal saline intragastrically， and the low-dose， medium-dose， and high-dose groups of Guihuang formula were given intragastrically with Guihuang formula （4.9， 9.8， 19.6 g·kg^-1）. After 30 days of intragastrical administration， samples were taken for detection. Inflammatory cell infiltration in prostate tissue was observed by hematoxylin-eosin （HE） staining， and serum IL-1β and IL-18 levels were measured by enzyme-linked immunosorbent assay （ELISA）. Serum malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px） levels were determined by biochemistry. NLRP3 expression in prostate tissue was assessed by immunohistochemistry， and the expression of NLRP3， cysteine-aspartic acid protease-1 （Caspase-1）， and gasdermin D （GSDMD） in prostate tissue was measured by Western blot. （2） In a cell experiment， human normal prostate epithelial cells （RWPE-1 cells） were divided into a blank group， a model group， a Guihuang formula group， and an NLRP3 inhibitor group （MCC950 group）. Except for the blank group， the other three groups were stimulated by 100 μg·L^-1 lipopolysaccharide （LPS） for 4 h and 5 mol·L^-1 adenosine triphosphate （ATP） for 30 min to prepare the pyroptosis model. After successful modeling， blank serum was given to the blank group and the model group. 6.25 μg·mL^-1 Guihuang formula drug-containing serum was added to the Guihuang formula group， and MCC950 was added to the MCC950 group on the basis of the model group. Propidium iodide （PI） uptake and Caspase-1 expression were detected by flow cytometry， and lactate dehydrogenase （LDH） level in the cell supernatant was measured by biochemistry. Interleukin （IL）-1β and IL-18 levels of the cell supernatant were determined by ELISA， and the expression of NLRP3， Caspase-1， and GSDMD was detected in Western blot. Results（1） For the animal experiment， compared with the blank group， the model group showed significant infiltration of inflammatory cells in prostate tissue， while the low-dose， medium-dose， and high-dose groups of Guihuang formula showed reduced infiltration of acinar inflammatory cells， reduced degree of glandular epithelial degeneration and interstitial edema， and significantly reduced degree of damage. Compared with those in the blank group， the levels of IL-1β and IL-18 in the serum of the model group were significantly increased （P<0.01）. Compared with the model group， the low-dose， medium-dose， and high-dose groups of Guihuang formula showed a significant decrease in serum IL-1β and IL-18 levels （P<0.01）. Compared with that in the blank group， the serum MDA level in the model group significantly increased （P<0.01）. Compared with that in the model group， the MDA level in the low-dose， medium-dose， and high-dose groups of Guihuang formula was significantly reduced （P<0.01）. Compared with those in the blank group， the levels of SOD and GSH-Px in the serum of the model group significantly decreased （P<0.05）. Compared with the model group， the low-dose， medium-dose， and high-dose groups of Guihuang formula showed a significantly increase in SOD （P<0.01）. Compared with the model group， the low-dose， medium-dose， and high-dose groups of Guihuang formula showed a significantly increase in GSH-Px （P<0.05）. Immunohistochemistry showed that compared with the blank group， the model group had high expression of NLRP3 molecule in prostate tissue. The expression of NLRP3 in the low-dose， medium-dose， and high-dose groups of Guihuang formula was significantly lower than that in the model group. Compared with those in the blank group， the expression levels of NLRP3， Caspase-1， and GSDMD proteins in the prostate tissue of the model group were significantly increased （P<0.01）. Compared with those in the model group， the expression levels of NLRP3， Caspase-1， and GSDMD proteins in the low-dose， medium-dose， and high-dose groups of Guihuang formula were significantly inhibited （P<0.01）. （2） For the cell experiment， compared with that in the blank group， the PI uptake rate of RWPE-1 cells in the model group significantly increased （P<0.01）. Compared with that in the model group， the PI uptake rate of the Guihuang formula group and the inhibitor group significantly decreased （P<0.01）. Compared with that in the blank group， the expression of Caspase-1 in the model group was significantly higher （P<0.01）. Compared with that in the model group， the Caspase-1 in the Guihuang formula group and the inhibitor group significantly decreased （P<0.01）. Compared with the blank group， the model group showed an increase in LDH release （P<0.01）. Compared with the model group， the Guihuang formula group and the inhibitor group showed a significantly decrease in LDH release （P<0.01）. Compared with those in the blank group， the levels of IL-1β and IL-18 in the supernatant of the model group were significantly increased （P<0.01）. Compared with the model group， the Guihuang formula group and the inhibitor group showed a significantly decrease in the levels of IL-1β and IL-18 （P<0.01）. Compared with those in the blank group， the expression levels of NLRP3， Caspase-1， and GSDMD proteins significantly increased in the model group （P<0.01）. Compared with those in the model group， the protein expression levels of NLRP3， Caspase-1， and GSDMD were significantly reduced in the Guihuang formula group and inhibitor group （P<0.01）. ConclusionGuihuang formula can inhibit the activation of Caspase-1， prevent GSDMD cleavation and lysis， and inhibit cell pyrodeath in the treatment of type Ⅲ prostatitis by inhibiting the activation of NLRP3 inflammasome.

AIM:To investigate the effect of apoptosis stimulation protein 2(ASPP2)on the development of traumatic proliferative vitreoretinopathy(PVR)in a rabbit model.METHODS:A total of 30 New Zealand white rabbits were selected, and the right eyes of all rabbits were inflicted with a scleral penetrating wound of approximately 6 mm. Then rabbits were randomly and evenly divided into experimental and control group. The experimental group received an intravitreal injection of 0.1 mL of ARPE-19 cell suspension transfected with lentivirus-ASPP2, while the control group received an intravitreal injection of 0.1 mL of ARPE-19 cell suspension transfected with negative control lentivirus. At 1, 2, 3, and 4 wk after PVR modeling, a handheld tonometer was used to measure the intraocular pressure. Moreover, fundus photography and ocular ultrasound examination were performed to detect the retinal proliferation. At 4 wk after modeling, hematoxylin-eosin staining was used to observe the morphological retinal changes, and Western blot was used to determine the protein expressions of ASPP2 and the epithelial-mesenchymal transition(EMT)marker Vimentin in the rabbit retinas.RESULTS:At 1, 2, 3, and 4 wk after modeling, there were no significant changes in intraocular pressure within the experimental and control group of rabbit eyes, either before or after PVR modeling, the success rate of PVR modeling in the experimental group was lower than that in the control group(P<0.05), and the retinal proliferation and structural disorder was less severe in the experimental group. At 4 wk after modeling, the retinal protein expression level of ASPP2 in the experimental group was significantly higher than that in the control group(t=3.193, P=0.033), while the Vimentin protein expression level was significantly lower in the experimental group(t=-3.599, P=0.023).CONCLUSION:ASPP2 may be involved in regulating the process of EMT in retinal pigment epithelial cells, thereby delaying the development and progression of traumatic PVR in rabbit eyes.

Age-related macular degeneration(ARMD)is a progressive visual impairment fundus disease that frequently occurs in individuals aged >55 years. The main risk factors are aging, long-term smoking, genetics, and racial differences. Pathogenesis includes abnormal function of the retinal pigment epithelium, damaged blood-retinal barrier, and abnormal immune function. Currently, intravitreal injection(IVI)of anti-vascular endothelial growth factor(VEGF)drugs is the preferred treatment option for ARMD in clinical practice. However, it also faces challenges such as repeated treatments, high medical costs, and poor patient compliance. The predicament in the treatment of ARMD has given rise to several new treatment options. This article aims to review the treatment methods and progress of dry ARMD and wet ARMD, providing new ideas for addressing the limitations of the current clinical anti-VEGF treatment.

Meibomian gland dysfunction(MGD)and dry eye disease(DED)are prevalent ocular surface disorders, with MGD being a primary cause of DED. Although multiple observational studies, systematic reviews, and Meta-analysis have found that dyslipidemia may be associated with the rising risk of DED and MGD, the mechanisms remain unclear, and these findings have been not yet fully incorporated into Chinese expert consensus on dry eye and MGD. The article begins by comparing the similarities and differences between meibum and blood lipids in terms of composition, and their age-related trends, noting that changes in meibum composition are more likely a result of MGD rather than alterations in blood lipids. Then we systematically review epidemiological evidence revealing the association between dyslipidemia and MGD/DED, delving into the underlying pathophysiological mechanisms. Finally, we evaluate the treatment prospects as well as controversies of lipid-lowering agents on their dual mechanisms of lipid-lowering and anti-inflammatory effects. This review aims to systemically integrate current research findings, elucidate gaps and contradictions, and provide a theoretical foundation for future exploration of blood lipids' role in ocular surface homeostasis, thereby advancing systemic prevention and treatment strategies for DED and MGD.

ObjectivePolygoni Multiflori Radix is a commonly used tonic traditional Chinese medicine （TCM） in clinical practice， but liver injury has often been reported in recent years. Some related preparations containing Polygoni Multiflori Radix have been reported by the National Medical Products Administration many times for the risk of liver injury. This has caused extensive discussion on the potential toxicity of TCM in China and abroad， which has limited the clinical use of Polygoni Multiflori Radix to some extent. To understand the adverse reactions of Polygoni Multiflori Radix， the safe and rational use of Polygoni Multiflori Radix in clinical practice was discussed. MethodsThe pharmacovigilance thought of modern Chinese medicine and the TCM pharmacovigilance system framework of ''identification of poison， use of poison， anti-poison， and detoxification'' were employed to mine the relevant toxicity records， usage and dosage， processing compatibility， and contraindication of taking Polygoni Multiflori Radix in ancient books. The drug safety information of Polygoni Multiflori Radix was summarized by comparing with modern reports. ResultsA total of 74 ancient books related to Polygoni Multiflori Radix were included， suggesting that the toxicity of Polygoni Multiflori Radix was recognized in ancient times. The main chemical components of Polygoni Multiflori Radix had both efficacy and toxicity， and the adverse reactions may be related to long-term use， excessive use， and individual differences. The results showed that the toxic components of Polygoni Multiflori Radix could be reduced by peeling， steaming with black beans， and processing without iron tools. The toxic effects of Polygoni Multiflori Radix could be reduced by the compatibility of Polygoni Multiflori Radix with Poria， Psoraleae Fructus， and Cistanches Herba. ConclusionReasonable dosage， standard processing， correct compatibility， and syndrome differentiation are the key points to standardize the use of Polygoni Multiflori Radix and reduce the incidence of adverse reactions. Clinically， the toxicity classification of TCM should be strengthened， and the susceptible population should be prioritized. The detection indicators and early warning mechanisms should be improved， and precise drug dosage and course of treatment should be guaranteed. These measures can ensure the safe use of Polygoni Multiflori Radix.

ObjectivePolygoni Multiflori Radix is a commonly used tonic traditional Chinese medicine （TCM） in clinical practice， but liver injury has often been reported in recent years. Some related preparations containing Polygoni Multiflori Radix have been reported by the National Medical Products Administration many times for the risk of liver injury. This has caused extensive discussion on the potential toxicity of TCM in China and abroad， which has limited the clinical use of Polygoni Multiflori Radix to some extent. To understand the adverse reactions of Polygoni Multiflori Radix， the safe and rational use of Polygoni Multiflori Radix in clinical practice was discussed. MethodsThe pharmacovigilance thought of modern Chinese medicine and the TCM pharmacovigilance system framework of ''identification of poison， use of poison， anti-poison， and detoxification'' were employed to mine the relevant toxicity records， usage and dosage， processing compatibility， and contraindication of taking Polygoni Multiflori Radix in ancient books. The drug safety information of Polygoni Multiflori Radix was summarized by comparing with modern reports. ResultsA total of 74 ancient books related to Polygoni Multiflori Radix were included， suggesting that the toxicity of Polygoni Multiflori Radix was recognized in ancient times. The main chemical components of Polygoni Multiflori Radix had both efficacy and toxicity， and the adverse reactions may be related to long-term use， excessive use， and individual differences. The results showed that the toxic components of Polygoni Multiflori Radix could be reduced by peeling， steaming with black beans， and processing without iron tools. The toxic effects of Polygoni Multiflori Radix could be reduced by the compatibility of Polygoni Multiflori Radix with Poria， Psoraleae Fructus， and Cistanches Herba. ConclusionReasonable dosage， standard processing， correct compatibility， and syndrome differentiation are the key points to standardize the use of Polygoni Multiflori Radix and reduce the incidence of adverse reactions. Clinically， the toxicity classification of TCM should be strengthened， and the susceptible population should be prioritized. The detection indicators and early warning mechanisms should be improved， and precise drug dosage and course of treatment should be guaranteed. These measures can ensure the safe use of Polygoni Multiflori Radix.

OBJECTIVE To investigate the effects and potential mechanism of curcumin on neurological injury in neonatal rats with bacterial meningitis based on the signal transducer and activator of transcription 1（ STAT1）/ nucleotide-binding domain leucine- rich repeat and pyrin domain-containing receptor 3 （NLRP3） signaling pathway. METHODS Neonatal rats， with an equal number of males and females， were randomly divided into control group， model group， curcumin low-dose （Cur-L）， medium-dose （Cur- M） and high-dose （Cur-H） groups， and Cur-H+STAT1 transcription enhancer [2-（1，8-naphthyridin-2-yl）phenol] group （Cur-H+2- NP group）， with 15 rats in each group. Except for the control group， rats in other groups were injected with a suspension of group B Streptococcus （1×104 cfu/mL， 10 μL） into the cerebellomedullary cistern to establish a bacterial meningitis model. After successful model establishment， rats in Cur-L， Cur-M and Cur-H groups were intraperitoneally injected with 1.25， 2.5 and 5 mg/kg curcumin， respectively， and those in the Cur-H+2-NP group were intraperitoneally injected with 5 mg/kg curcumin and 0.5 mg/kg 2- NP， once a day， for 3 consecutive weeks. After the last administration， modified Loeffler score was conducted， white blood cells （WBC） count in cerebrospinal fluid as well as the contents of inflammatory factors [tumor necrosis factor-α， interleukin-6 （IL-6）， IL-1β and IL-18]， brain water content and blood-brain barrier permeability were detected； the histopathological changes of hippocampus and cortex tissues were observed. The percentage of apoptosis in hippocampal/cortical tissue cells， the positive expression of ionized calcium-binding adapter molecule-1 （Iba-1）， the co-localization of Iba-1 and NLRP3， as well as the expressions of proteins related to the STAT1/NLRP3 signaling pathway （phosphorylated STAT1， NLRP3， apoptosis-associated speck-like protein containing a CARD， gasdermin D， caspase-1， IL-1β and IL-18） were examined. RESULTS Compared with the control group， the neurons in the hippocampal/cortical tissues of rats in the model group exhibited significant morphological abnormalities， accompanied by neuronal edema and necrosis， as well as infiltration of inflammatory cells. The modified Loeffler score and the number of Nissl bodies were significantly decreased/reduced in the model group， while the WBC count， levels of inflammatory factors， brain water content， blood-brain barrier permeability， HE staining score， number of degenerated neurons， percentage of apoptotic cells， positive expression of Iba-1， percentage of Iba-1 and NLRP3 co-localization- positive cells， and expressions of pathway-related proteins were all significantly rose/increased/upregulated （P＜0.05）. Compared with the model group， the histopathological changes in the hippocampal/cortical tissues of rats in all curcumin dosage groups were alleviated to varying degrees， with significant improvements in all quantitative indicators （P＜0.05）； conversely， 2-NP significantly reversed the ameliorative effects of curcumin on these quantitative indicators （P＜0.05）. CONCLUSIONS Curcumin can alleviate cerebral edema and blood-brain barrier damage， reduce neuroinflammation， inhibit cell apoptosis and pyroptosis， and thereby alleviate neuronal injury in neonatal rats with bacterial meningitis. The underlying mechanism may be related to the inhibition of the STAT1/NLRP3 signaling pathway.