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.

Objective: To compare the effects of immediate versus delayed post-space preparation on the bond strength of fiber posts and the fracture resistance of roots after root canal obturation using iRoot SP and the single-cone technique, and to provide an experimental basis for the selection of the timing of clinical post-space preparation. Methods: This study was approved by the Medical Ethics Committee of the institution, and written informed consent was obtained from all participants. Seventy-two extracted human single-rooted premolars were randomly divided into two groups (n = 36 each): the immediate post-space preparation group (post-space preparation performed immediately after root canal obturation) and the delayed post-space preparation group (post-space preparation performed 1 week after root canal obturation). Cleanliness of the root canal walls was assessed with a dental microscope after preparation in both groups; the ultrastructural characteristics of the dentinal surface were examined via scanning electron microscopy; the fracture resistance of roots was measured with root fracture resistance tests; the bond strength of the fiber posts was measured with the thin-slice push-out test; and the bond failure modes were observed and analyzed under a stereomicroscope. Results: Under dental microscopy, the dentin surface of the immediate post-space preparation group appeared cleaner than that of the delayed post-space preparation group. Scanning electron microscopy revealed that most dentinal tubules remained open in the immediate post-space preparation group, while the tubules in the delayed post-space preparation group showed incomplete patency. The fracture resistance of the immediate post-space preparation group was (2 872 ± 241.5) N and that of the delayed post-space preparation group was (2 934 ± 353.1) N, with no statistically significant difference (t = -0.328, P = 0.751). The push-out bond strength of the immediate post-space preparation group (10.310 ± 2.907) MPa was significantly higher than that of the delayed post-space preparation group (7.917 ± 2.429) MPa, with a statistically significant difference (t = 4.457, P < 0.001). Analysis of failure modes showed that adhesive-to-dental interface failure was the predominant mode in both groups. Conclusion Following root canal obturation with iRoot SP using the single-cone technique, immediate post-space preparation yields superior fiber post bond strength compared to delayed post-space preparation, without compromising root fracture resistance.

Objective To analyze the pollution characteristics of PM_2.5-bound polycyclic aromatic hydrocarbons (PAHs) during the non-heating period, heating period, and haze period in Harbin, and infer their possible sources, and to evaluate their impact on population carcinogenesis. Methods From 2020 to 2022, sampling points were set up in different districts of Harbin. PM_2.5 samples were regularly collected every month to analyze the contents of 10 types of PM_2.5-bound 4-6 rings PAHs. The pollution characteristics of PAHs were analyzed during different monitoring periods (non-heating period, heating period, and haze period). The excess carcinogenesis risks of PM_2.5-bound PAHs were assessed according to the Technical Specifications for Health Risk Assessment of Ambient Air Pollution and the U. S. Environmental Protection Agency (US EPA) risk assessment method. The characteristic ratio method and the positive matrix factorization (PMF) model were used to infer the sources of PAHs. Results The median mass concentrations of ambient PM_2.5-bound 4-6 rings PAHs (ΣPAHs) during the non-heating period, heating period, and haze period were 6.44 ng/m³, 37.85 ng/m³, and 106.79 ng/m³, respectively. During the heating season and haze period, the concentrations of benzo[a]anthracene, benzo[k]fluoranthene, pyrene and fluoranthene were relatively high. The excess carcinogenic risks for ASF_>16, ASF_2-16 and ASF_<2 caused by exposure to PM_2.5-bound 4-6rings PAHs during the heating season were 2.34×10^-6, 1.82×10^-6, and 0.88×10^-6, respectively, while the excess carcinogenic risks for the whole population during the heating season and haze period were 5.05×10^-6 and 1.75×10^-6, respectively. The results of the two source methods showed that the main characteristic elements during the heating season were fluoranthene, pyrene, benzo[a]anthracene, benzo[b]fluoranthene, benzo[k]fluoranthene, and benzo[a]pyrene. According to the emission source standards, it was determined that the sources were mainly coal and biomass combustion, accompanied by traffic source emissions. Conclusion In Harbin, the PM_2.5-bound 4-6 rings PAHs during the haze period is significantly higher than that during the heating period. The pollution is mainly from coal combustion emissions, accompanied by continuous traffic source pollution. The exposure to PAHs during the heating period poses a potential carcinogenic risk to the population.

OBJECTIVE: To observe the effects of Tiaoshu Anshen (regulating the hinge and calming the mind) acupuncture on sleep quality and serum levels of 5-hydroxytryptamine (5-HT) and dopamine (DA) in patients with chronic insomnia. METHODS: A total of 58 patients with chronic insomnia were randomly divided into an acupuncture group and a medication group, 29 cases in each group. Tiaoshu Anshen acupuncture was applied at Baihui (GV20) and bilateral Shenmen (HT7), Sanyinjiao (SP6), Benshen (GB13) in the acupuncture group, once a day, 1-day interval was taken after 6 consecutive days of treatment. Estazolam tablet was given orally before bed in the medication group, 1 mg each time. The 4-week treatment was required in both groups. Before and after treatment, the sleep quality was assessed by Pittsburgh sleep quality index (PSQI) and polysomnography (PSG), the serum levels of 5-HT and DA were detected by ELISA. RESULTS: After treatment, the item scores and total scores of PSQI were decreased compared with those before treatment in the two groups (P<0.05); in the acupuncture group, the scores of sleep quality, sleep latency, sleep time, sleep efficiency, sleep disorders and total score of PSQI were lower than those in the medication group (P<0.05). After treatment, the total sleep time (TST) was prolonged (P<0.05), the sleep latency (SL) and wake after sleep onset (WASO) were shortened (P<0.05), the sleep efficiency (SE%), percentage of non-rapid eye movement stage 3 (N3%), percentage of rapid eye movement stage (REM%) and serum levels of 5-HT were increased (P<0.05) compared with those before treatment; the percentage of non-rapid eye movement stage 1 (N1%), percentage of non-rapid eye movement stage 2 (N2%) and serum levels of DA were decreased (P<0.05) compared with those before treatment in the two groups. After treatment, in the acupuncture group, TST was longer, while SL and WASO were shorter than those in the medication group (P<0.05), SE%, N3%, REM% and serum level of 5-HT were higher, while N1%, N2% and serum level of DA were lower than those in the medication group (P<0.05). CONCLUSION Tiaoshu Anshen acupuncture may improve the sleep quality by regulating the serum neurotransmitter levels i.e. 5-HT and DA in patients with chronic insomnia.
Humans ; Sleep Initiation and Maintenance Disorders/physiopathology* ; Male ; Acupuncture Therapy ; Female ; Middle Aged ; Adult ; Serotonin/blood* ; Sleep Quality ; Acupuncture Points ; Dopamine/blood* ; Aged ; Neurotransmitter Agents/blood* ; Young Adult

Following the release of the Technical Requirements on Quality Control and Standard Establishment of Traditional Chinese Medicine Formula Granules by the National Medical Products Administration in 2021, Chinese Pharmacopoeia Commission has promulgated 296 national drug standards so far, and most provinces have started the work of establishing provincial standards as supplements. The promulgation of standards fostered high-quality development of the industry. Since the implementation of national and provincial standards for more than three years, enterprises have gained deep understanding and hands-on experiences on the characteristics, technical requirements, production process, and quality control of traditional Chinese medicine(TCM) formula granules. Meanwhile, challenges have emerged restricting the high-quality development of this industry, including how to formulate quality control strategies for medicinal materials and decoction pieces, how to reduce manufacturing costs, and how to improve the pass rate and product stability under high standards. Based on the work experiences from standard management and process research, this article analyzed the distribution of sources, processing methods, dry extract rate ranges, process requirements for volatile oil-containing decoction pieces, control measures of safety indices, characteristics and trends of setting characteristic chromatograms or fingerprints, characteristics and trends of setting content ranges, and main differences between national standards and provincial standards. On the one hand, this article aims to present main characteristics for deeply understanding different indicators in standards and provide basic ideas for establishing quality and process control systems. On the other hand, from the perspective of industrial practice, suggestions are put forward on the important aspects that need to be focused on in the quality and process control of TCM formula granules.
Drugs, Chinese Herbal/chemistry* ; Quality Control ; Medicine, Chinese Traditional/standards* ; China ; Drug Industry/standards*

This study aimed to explore the effects and mechanisms of total extracts from Anthriscus sylvestris on pulmonary hypertension in rats. Sixty male SD rats were divided into normal(NC) group, model(M) group, positive drug sildenafil(Y) group, low-dose A. sylvestris(ES-L) group, medium-dose A. sylvestris(ES-M) group, and high-dose A. sylvestris(ES-H) group. On day 1, rats were intraperitoneally injected with monocrotaline(60 mg·kg~(-1)) to induce pulmonary hypertension, and the rat model was established on day 28. From days 15 to 28, intragastric administration of the respective treatments was performed. After modeling and treatment, small animal echocardiography was used to detect the right heart function of the rats. Arterial blood gas was measured using a blood gas analyzer. Hematoxylin and eosin(HE) staining and Masson staining were performed to observe cardiopulmonary pathological damage. Flow cytometry was used to detect apoptosis in the lung and myocardial tissues and reactive oxygen species(ROS) levels. Western blot was applied to detect the expression levels of transforming growth factor-β1(TGF-β1), phosphorylated mothers against decapentaplegic homolog 3(p-Smad3), Smad3, tissue plasminogen activator(t-PA), and plasminogen activator inhibitor-1(PAI-1) in lung tissue. A blood routine analyzer was used to measure inflammatory immune cell levels in the blood. Enzyme-linked immunosorbent assay(ELISA) was used to detect the expression levels of P-selectin and thromboxane A2(TXA2) in plasma. The results showed that, compared with the NC group, right heart hypertrophy index, right ventricular free wall thickness, right heart internal diameter, partial carbon dioxide pressure(PaCO_2), apoptosis in cardiopulmonary tissue, and ROS levels were significantly increased in the M group. In contrast, the ratio of pulmonary blood flow acceleration time(PAT)/ejection time(PET), right cardiac output, change rate of right ventricular systolic area, systolic displacement of the tricuspid ring, oxygen partial pressure(PaO_2), and blood oxygen saturation(SaO_2) were significantly decreased in the M group. After administration of the total extract of A. sylvestris, right heart function and blood gas levels were significantly improved, while apoptosis in cardiopulmonary tissue and ROS levels significantly decreased. Further testing revealed that the total extract of A. sylvestris significantly decreased the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and PAI-1 proteins in lung tissue, while increasing the expression of t-PA. Additionally, the extract reduced the levels of inflammatory cells such as leukocytes, lymphocytes, granulocytes, and monocytes in the blood, as well as the levels of P-selectin and TXA2 in plasma. Metabolomics results showed that the total extract of A. sylvestris significantly affected metabolic pathways, including arginine biosynthesis, tyrosine metabolism, and taurine and hypotaurine metabolism. In conclusion, the total extract of A. sylvestris may exert an anti-pulmonary hypertension effect by inhibiting the TGF-β1/Smad3 signaling pathway, thereby alleviating immune-inflammatory responses and thrombosis.
Animals ; Male ; Smad3 Protein/metabolism* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Rats ; Signal Transduction/drug effects* ; Hypertension, Pulmonary/genetics* ; Thrombosis/immunology* ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Apoptosis/drug effects*

This paper aimed to explore the effects of Duzhong Decoction(DZD)-containing serum on the proliferation and osteoblast differentiation of MC3T3-E1 cells through L-type voltage-gated calcium channels(L-VGCCs). L-VGCCs inhibitors, nifedipine and verapamil, were used to block L-VGCCs in osteoblasts. MC3T3-E1 cells were divided into a control group, a low-dose DZD-containing serum(L-DZD) group, a medium-dose DZD-containing serum(M-DZD) group, a high-dose DZD-containing serum(H-DZD) group, a nifedipine group, a H-DZD + nifedipine group, verapamil group, and a H-DZD + verapamil group. The CCK-8 method was used for cell proliferation analysis, alkaline phosphatase(ALP) assay kits for intracellular ALP activity measurement, Western blot for protein expression level in cells, real-time fluorescence quantitative PCR technology for intracellular mRNA expression level determination, fluorescence spectrophotometer for free Ca~(2+) concentration determination in osteoblasts, and alizarin red staining(ARS) for mineralized nodule formation in osteoblasts. The experimental results show that compared to the control group, DZD groups can promote MC3T3-E1 cell proliferation, ALP activity, and mineralized nodule formation, increase intracellular Ca~(2+) concentrations, and upregulate the protein expression of bone morphogenetic protein 2(BMP2), collagen Ⅰ(COL1), α2 subunit protein of L-VGCCs(L-VGCCα2), and the mRNA expression of Runt-related transcription factor 2(RUNX2), and BMP2. After blocking L-VGCCs with nifedipine and verapamil, the intervention effects of DZD-containing serum were inhibited to varying degrees. Both nifedipine and verapamil could inhibit ALP activity, reduce mineralized nodule areas, and downregulate the expression of bone formation-related proteins. Moreover, the effects of DZD-containing serum on increasing MC3T3-E1 cell proliferation, osteoblast differentiation, and Ca~(2+) concentrations, upregulating the mRNA expression of osteoprotegerin(OPG) and protein expression of phosphorylated protein kinase B(p-Akt) and phosphorylated forkhead box protein O1(p-FOXO1), and upregulating phosphatase and tensin homolog(PTEN) expression were reversed by nifedipine. The results indicate that DZD-containing serum can increase the Ca~(2+) concentration in MC3T3-E1 cells to promote bone formation, which may be mediated by L-VGCCs and the PTEN/Akt/FoxO1 signaling pathway, providing a new perspective on the mechanism of DZD in treating osteoporosis.
Animals ; Osteoblasts/metabolism* ; Cell Proliferation/drug effects* ; Cell Differentiation/drug effects* ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Calcium Channels, L-Type/genetics* ; Alkaline Phosphatase/genetics* ; Serum/chemistry* ; Cell Line ; Osteogenesis/drug effects* ; Bone Morphogenetic Protein 2/genetics*

PURPOSE: To methodically assess the effectiveness of augmentative plating (AP) and exchange nailing (EN) in managing nonunion following intramedullary nailing for long bone fractures of the lower extremity. METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library were searched to gather clinical studies regarding the use of AP and EN techniques in the treatment of nonunion following intramedullary nailing of lower extremity long bones. The search was conducted up until May 2023. The original studies underwent an independent assessment of their quality, a process conducted utilizing the Newcastle-Ottawa scale. Data were retrieved from these studies, and meta-analysis was executed utilizing Review Manager 5.3. RESULTS: This meta-analysis included 8 studies involving 661 participants, with 305 in the AP group and 356 in the EN group. The results of the meta-analysis demonstrated that the AP group exhibited a higher rate of union (odds ratio: 8.61, 95% confidence intervals (CI): 4.12 - 17.99, p < 0.001), shorter union time (standardized mean difference (SMD): -1.08, 95% CI: -1.79 - -0.37, p = 0.003), reduced duration of the surgical procedure (SMD: -0.56, 95% CI: -0.93 - -0.19, p = 0.003), less bleeding (SMD: -1.5, 95% CI: -2.81 - -0.18, p = 0.03), and a lower incidence of complications (relative risk: -0.17, 95% CI: -0.27 - -0.06, p = 0.001). In the subgroup analysis, the time for union in the AP group in nonisthmal and isthmal nonunion of lower extremity long bones was shorter compared to the EN group (nonisthmal SMD: -1.94, 95% CI: -3.28 - -0.61, p < 0.001; isthmal SMD: -1.08, 95% CI: -1.64 - -0.52, p = 0.002). CONCLUSION In the treatment of nonunion in diaphyseal fractures of the long bones in the lower extremity, the AP approach is superior to EN, both intraoperatively (with reduced duration of the surgical procedure and diminished blood loss) and postoperatively (with an elevated union rate, shorter union time, and lower incidence of complications). Specifically, in the management of nonunion of lower extremity long bones with non-isthmal and isthmal intramedullary nails, AP demonstrated shorter union time in comparison to EN.
Humans ; Bone Nails/adverse effects* ; Bone Plates/adverse effects* ; Femoral Fractures/surgery* ; Fracture Fixation, Intramedullary/methods* ; Fractures, Ununited/surgery* ; Lower Extremity/injuries*

PURPOSE: To investigate the incidence and influencing factors of bone loss in patients with spinal cord injury (SCI). METHODS: A retrospective case-control study was conducted. Patients with SCI in our hospital from January 2019 to March 2023 were collected. According to the correlation between bone mineral density (BMD) at different sites, the patients were divided into the lumbar spine group and the hip joint group. According to the BMD value, the patients were divided into the normal bone mass group (t > -1.0 standard deviation) and the osteopenia group (t ≤ -1.0 standard deviation). The influencing factors accumulated as follows: gender, age, height, weight, cause of injury, injury segment, injury degree, time after injury, start time of rehabilitation, motor score, sensory score, spasticity, serum value of alkaline phosphatase, calcium, and phosphorus. The trend chart was drawn and the influencing factors were analyzed. SPSS 26.0 was used for statistical analysis. Correlation analysis was used to test the correlation between the BMD values of the lumbar spine and bilateral hips. Binary logistic regression analysis was used to explore the influencing factors of osteoporosis after SCI. p < 0.05 was considered statistically significant. RESULTS: The incidence of bone loss in patients with SCI was 66.3%. There was a low concordance between bone loss in the lumbar spine and the hip, and the hip was particularly susceptible to bone loss after SCI, with an upward trend in incidence (36% - 82%). In this study, patients with SCI were divided into the lumbar spine group (n = 100) and the hip group (n = 185) according to the BMD values of different sites. Then, the lumbar spine group was divided into the normal bone mass group (n = 53) and the osteopenia group (n = 47); the hip joint group was divided into the normal bone mass group (n = 83) and the osteopenia group (n = 102). Of these, lumbar bone loss after SCI is correlated with gender and weight (p = 0.032 and < 0.001, respectively), and hip bone loss is correlated with gender, height, weight, and time since injury (p < 0.001, p = 0.015, 0.009, and 0.012, respectively). CONCLUSIONS The incidence of bone loss after SCI was high, especially in the hip. The incidence and influencing factors of bone loss in the lumbar spine and hip were different. Patients with SCI who are male, low height, lightweight, and long time after injury were more likely to have bone loss.
Humans ; Spinal Cord Injuries/complications* ; Male ; Female ; Retrospective Studies ; Incidence ; Adult ; Bone Density ; Middle Aged ; Case-Control Studies ; Osteoporosis/etiology* ; Lumbar Vertebrae ; Bone Diseases, Metabolic/etiology* ; Aged ; Risk Factors

Children with bronchopulmonary dysplasia (BPD) often exhibit severe respiratory problems and significant pulmonary dysfunction during school age and adulthood. Exercise tests show a decline in cardiopulmonary function and physical performance in children with BPD, who also have a higher incidence of pulmonary hypertension. These children generally perform poorly in terms of intelligence, language, and motor development. As they age, the risk of neurodevelopmental disorders increases, and health-related quality of life is also affected. This article reviews the prognosis of the respiratory system, physical capacity, cardiovascular system, nervous system, and health-related quality of life in children with BPD, aiming to improve the management of these patients and enhance their subsequent quality of life.
Humans ; Bronchopulmonary Dysplasia/complications* ; Prognosis ; Quality of Life ; Child