ObjectiveTo investigate the effect and mechanism of polysaccharide in water extract of Cyclocarya paliurus （CPWP） in inhibiting benign prostatic hyperplasia （BPH）. MethodsCPWP was obtained by heating reflux， aqueous extraction， alcohol precipitation， and freeze drying. The chemical composition and structural properties of CPWP were analyzed by high performance liquid chromatography with 1-pheny-3-methyl-5-pyrazolone pre-column derivatization and infrared spectroscopy. Male SD rats were randomly assigned into control， model， finasteride （ig 5 mg·kg^-1）， and low-， medium-， and high-dose （ig 50， 75， 100 mg·kg^-1） CPWP groups， with 8 rats in each group. The BPH model was established by subcutaneously injecting propionate testosterone in castrated rats. The rats in the drug intervention groups were administrated with corresponding drugs， and those in the control group were administrated with an equal volume of normal saline each day. After 30 consecutive days， the rats were sacrificed， and the prostate tissue was separated and weighed. The effects of drug interventions on the body weight， prostate wet weight， and prostate index of rats were examined. The prostate tissue was stained with hematoxylin-eosin （HE） for observation of pathological changes. Enzyme-linked immunosorbent assay was employed to measure the level of dihydrotestosterone （DHT）， and immunohistochemical staining was used to detect the expression of steroid 5 alpha-reductase 2 （SRD5A2） and Ki67 in the prostate tissue. ResultsCPWP was identified as a saccharide， with characteristic absorption peaks of saccharides. CPWP showed the total sugar content of 44.15% and molecular weight within the range of 5.5-78.8 kDa， being composed of mannose， rhamnose， galacturonic acid， glucose， galactose， xylose， and arabinose. Compared with the control group， the model group had significantly increased prostate wet weight and prostate index （P<0.01）， thick and tall prostate epithelial cells， increased internal wrinkles， papillary expansion into the cavity， an elevation in DHT level in the serum， and up-regulated expression of SRD5A2 and Ki67 in the prostate tissue （P<0.05， P<0.01）. Compared with the model group， both the finasteride and CPWP groups showed decreases in prostate wet weight and prostate index （P<0.05， P<0.01）， thinned prostate epithelial cells， with only a small portion of internal wrinkles and papillary expansion into the cavity， shortened papillary protrusions， lowered DHT level in the serum， and down-regulated expression of SRD5A2 and Ki67 in the prostate tissue （P<0.01）. Moreover， CPWP exerted effects in a dose-dependent manner. ConclusionCPWP inhibits BPH by regulating the expression of SRD5A2.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

ObjectiveTraditional Chinese medicine (TCM) constitutes a valuable cultural heritage and an important source of antitumor compounds. Poria (Poria cocos (Schw.) Wolf), the dried sclerotium of a polyporaceae fungus, was first documented in Shennong’s Classic of Materia Medica and has been used therapeutically and dietarily in China for millennia. Traditionally recognized for its diuretic, spleen-tonifying, and sedative properties, modern pharmacological studies confirm that Poria exhibits antioxidant, anti-inflammatory, antibacterial, and antitumor activities. Pachymic acid (PA; a triterpenoid with the chemical structure 3β-acetyloxy-16α-hydroxy-lanosta-8,24(31)-dien-21-oic acid), isolated from Poria, is a principal bioactive constituent. Emerging evidence indicates PA exerts antitumor effects through multiple mechanisms, though these remain incompletely characterized. Neuroblastoma (NB), a highly malignant pediatric extracranial solid tumor accounting for 15% of childhood cancer deaths, urgently requires safer therapeutics due to the limitations of current treatments. Although PA shows multi-mechanistic antitumor potential, its efficacy against NB remains uncharacterized. This study systematically investigated the potential molecular targets and mechanisms underlying the anti-NB effects of PA by integrating network pharmacology-based target prediction with experimental validation of multi-target interactions through molecular docking, dynamic simulations, and in vitro assays, aimed to establish a novel perspective on PA’s antitumor activity and explore its potential clinical implications for NB treatment by integrating computational predictions with biological assays. MethodsThis study employed network pharmacology to identify potential targets of PA in NB, followed by validation using molecular docking, molecular dynamics (MD) simulations, MM/PBSA free energy analysis, RT-qPCR and Western blot experiments. Network pharmacology analysis included target screening via TCMSP, GeneCards, DisGeNET, SwissTargetPrediction, SuperPred, and PharmMapper. Subsequently, potential targets were predicted by intersecting the results from these databases via Venn analysis. Following target prediction, topological analysis was performed to identify key targets using Cytoscape software. Molecular docking was conducted using AutoDock Vina, with the binding pocket defined based on crystal structures. MD simulations were performed for 100 ns using GROMACS, and RMSD, RMSF, SASA, and hydrogen bonding dynamics were analyzed. MM/PBSA calculations were carried out to estimate the binding free energy of each protein-ligand complex. In vitro validation included RT-qPCR and Western blot, with GAPDH used as an internal control. ResultsThe CCK-8 assay demonstrated a concentration-dependent inhibitory effect of PA on NB cell viability. GO analysis suggested that the anti-NB activity of PA might involve cellular response to chemical stress, vesicle lumen, and protein tyrosine kinase activity. KEGG pathway enrichment analysis suggested that the anti-NB activity of PA might involve the PI3K/AKT, MAPK, and Ras signaling pathways. Molecular docking and MD simulations revealed stable binding interactions between PA and the core target proteins AKT1, EGFR, SRC, and HSP90AA1. RT-qPCR and Western blot analyses further confirmed that PA treatment significantly decreased the mRNA and protein expression of AKT1, EGFR, and SRC while increasing the HSP90AA1 mRNA and protein levels. ConclusionIt was suggested that PA may exert its anti-NB effects by inhibiting AKT1, EGFR, and SRC expression, potentially modulating the PI3K/AKT signaling pathway. These findings provide crucial evidence supporting PA’s development as a therapeutic candidate for NB.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Sleep-wake disorder is one of the most common nonmotor symptoms of Parkinson's disease (PD). Melatonin has the potential to improve sleep-wake disorder, but its mechanism of action is still unclear. Our data showed that melatonin only improved the motor and sleep-wake behavior of a zebrafish PD model when melatonin receptor 1 was present. Thus, we explored the underlying mechanisms by applying a rotenone model. After the PD zebrafish model was induced by 10 nmol/L rotenone, the motor and sleep-wake behavior were assessed. In situ hybridization and real-time quantitative PCR were used to detect the expression of melatonin receptors and lipid-metabolism-related genes. In the PD model, we found abnormal lipid metabolism, which was reversed by melatonin. This may be one of the main pathways for improving PD sleep-wake disorder.
Animals ; Zebrafish ; Melatonin/pharmacology* ; Lipid Metabolism/drug effects* ; Disease Models, Animal ; Rotenone/pharmacology* ; Sleep Wake Disorders/metabolism* ; Parkinson Disease/metabolism* ; Motor Activity/drug effects* ; Sleep/drug effects*

Objective To explore the efficacy and safety of modified meibomian gland massage combined with ultrasonic atomization and drug therapy for dry eye in high-altitude military personnel.Methods A total of 180 patients(360 eyes)with dry eye who were diagnosed and treated by the medical team of General Hospital of Central Theater Command of Chinese PLA from July to October 2022 in Linzhi,Tibet(average altitude of 3100 meters)were selected as the research subjects.Patients were divided into four block groups based on the course of the disease:＜1 month,1-3 months,3-6 months,and≥6 months,and each block group was randomly assigned to control group,traditional group and modified group by random number table method,with 60 cases in each group.Control group received routine treatment(artificial tear drops and atomization fumigation);on the basis of routine treatment,traditional group underwent traditional meibomian gland massage,and modified group underwent modified meibomian gland massage.After 3 months of treatment,the scores of symptoms and signs,total effective rate,duration of treatment and incidence of adverse events were compared among the 3 groups.Results In the intra-group comparison before and after treatment,except for control group's symptom scores difference which was not statistically significant(P＞0.05),all other scores decreased significantly(P＜0.05).In the inter-group comparison after treatment,the scores of both traditional group and modified group were significantly better than those of control group(P＜0.05),but no significant difference was observed in symptom and sign scores between traditional and modified groups(P＞0.05).Compared with control group,the total effective rates of traditional group and modified group both significantly increased(P＜0.01),but there was no significant difference in total effective rate between traditional and modified groups(P＞0.05).The treatment time in modified group was significantly longer than that in control group(P＜0.05),but significantly shorter than that in traditional group(P＜0.05).The incidence of adverse events was significantly lower in modified group than that in traditional group(P＜0.001).Conclusion In high-altitude areas,modified meibomian gland massage combined with ultrasonic atomization and local drug therapy for dry eye is safe and effective,non-invasiveness and easy to perform,and suitable for promoting and application in military field training.

Objective:To investigate the clinicopathological features and prognosis of patients with penile cancer.Methods:The clinical data of 362 patients with penile cancer who underwent surgery in Fudan University Shanghai Cancer Center from January 2005 to December 2020 were retrospectively analyzed. The mean age was (57.0±0.7) years. According to the clinical N stage classification, 239 patients were in N 0 stage, 57 patients in N 1 stage, 37 patients in N 2 stage, and 29 patients in N 3 stage. All these patients had no metastasis. Based on tumor size and location, 50 patients underwent extended circumcision, 283 patients underwent partial penectomy, and 29 patients underwent total penectomy. One hundred and eighty-three patients underwent inguinal lymphadenectomy and 47 patients underwent pelvic lymphadenectomy. Tumor pathology, tumor size, HPV subtype, postoperative pathological stage, overall survival (OS) and prognosis were analyzed. The Kaplan-Meier analysis and multivariate Cox regression analysis were used to analyse the factors which could affect the survival of patients. 5-year OS rate of these patients were also calculated. Results:In the pathological T classification, 137 cases were in T 1a stage, 24 cases in T 1b stage, 51 cases in T 2 stage, 136 cases in T 3 stage, and 14 cases in T 4 stage. In the pathological N classification, 235 cases were in N 0 stage, 54 cases in N 1 stage, 31 cases in N 2 stage and 42 cases in N 3 stage. The most common tumor type was squamous cell carcinoma (300 cases, 83%), followed by verrucous carcinoma (40 cases, 11%), sarcomatoid carcinoma(7 cases), carcinoma in situ (6 cases), basal-like carcinoma (6 cases), and adenosquamous carcinoma (3 cases). The most common tumor grade was mild (160 cases, 44%), followed by moderate differentiation (130 cases, 36%), poor differentiation (46 cases, 13%), and unclear differentiation (26 cases). The tumor sizes were < 3 cm in 135 patients and ≥ 3 cm in 142 patients. The tumor size was unclear in 85 patients. 173 cases (48%) were HPV positive and 189 cases (52%) were HPV negative. The Kaplan-Meier analysis showed the 5-year OS rate of HPV-positive group was higher than that of HPV-negative group (79% vs. 72%) but no significant difference was found ( P=0.09). The 5-year OS rate of patients whose tumor ≥ 3 cm (69%) was lower than those tumor < 3 cm (85%) and significant difference could be found ( P = 0.02). The 5-year OS rate of wild and moderate and poor grade were 85%, 70% and 58%, and significant difference could be found in the three groups ( P<0.01). The 5-year OS rates of patients with stage T 1a, T 1b, T 2, T 3and T 4 were 90%, 67%, 71%, 68% and 37% respectively( P<0.01). The 5-year OS rates of patients with stage N 0, N 1, N 2, and N 3 were 91%, 62%, 57%, and 30%, respectively( P<0.01). N stage could significantly affect the prognosis. The 5-year OS rate of T 1b patients was lower than that of T 1a and T 2 stage (67% vs. 90% vs. 71%, P=0.003). Of the 24 patients with T 1b stage, 17 cases received inguinal lymphadenectomy and 7 cases not. The 5-year OS rate of T 1b who received lymphadenectomy, who not and T 2 group were 73%, 57% and 71% respectively ( P=0.22). Multivariate Cox analysis showed that N stage ( HR =4.55, 95% CI 2.64-7.85, P<0.01) and tumor grade ( HR =2.09, 95% CI 1.09-4.02, P=0.03) were independent factors which could affect the prognosis. Conclusions:N stage and tumor grade were independent factors which could affect the prognosis. The poorer the tumor grade, the worse the prognosis. Inguinal lymphadenectomy could improve the prognosis of patients with T 1b stage.

Objective:To investigate the clinicopathological features and prognosis of patients with penile cancer.Methods:The clinical data of 362 patients with penile cancer who underwent surgery in Fudan University Shanghai Cancer Center from January 2005 to December 2020 were retrospectively analyzed. The mean age was (57.0±0.7) years. According to the clinical N stage classification, 239 patients were in N 0 stage, 57 patients in N 1 stage, 37 patients in N 2 stage, and 29 patients in N 3 stage. All these patients had no metastasis. Based on tumor size and location, 50 patients underwent extended circumcision, 283 patients underwent partial penectomy, and 29 patients underwent total penectomy. One hundred and eighty-three patients underwent inguinal lymphadenectomy and 47 patients underwent pelvic lymphadenectomy. Tumor pathology, tumor size, HPV subtype, postoperative pathological stage, overall survival (OS) and prognosis were analyzed. The Kaplan-Meier analysis and multivariate Cox regression analysis were used to analyse the factors which could affect the survival of patients. 5-year OS rate of these patients were also calculated. Results:In the pathological T classification, 137 cases were in T 1a stage, 24 cases in T 1b stage, 51 cases in T 2 stage, 136 cases in T 3 stage, and 14 cases in T 4 stage. In the pathological N classification, 235 cases were in N 0 stage, 54 cases in N 1 stage, 31 cases in N 2 stage and 42 cases in N 3 stage. The most common tumor type was squamous cell carcinoma (300 cases, 83%), followed by verrucous carcinoma (40 cases, 11%), sarcomatoid carcinoma(7 cases), carcinoma in situ (6 cases), basal-like carcinoma (6 cases), and adenosquamous carcinoma (3 cases). The most common tumor grade was mild (160 cases, 44%), followed by moderate differentiation (130 cases, 36%), poor differentiation (46 cases, 13%), and unclear differentiation (26 cases). The tumor sizes were < 3 cm in 135 patients and ≥ 3 cm in 142 patients. The tumor size was unclear in 85 patients. 173 cases (48%) were HPV positive and 189 cases (52%) were HPV negative. The Kaplan-Meier analysis showed the 5-year OS rate of HPV-positive group was higher than that of HPV-negative group (79% vs. 72%) but no significant difference was found ( P=0.09). The 5-year OS rate of patients whose tumor ≥ 3 cm (69%) was lower than those tumor < 3 cm (85%) and significant difference could be found ( P = 0.02). The 5-year OS rate of wild and moderate and poor grade were 85%, 70% and 58%, and significant difference could be found in the three groups ( P<0.01). The 5-year OS rates of patients with stage T 1a, T 1b, T 2, T 3and T 4 were 90%, 67%, 71%, 68% and 37% respectively( P<0.01). The 5-year OS rates of patients with stage N 0, N 1, N 2, and N 3 were 91%, 62%, 57%, and 30%, respectively( P<0.01). N stage could significantly affect the prognosis. The 5-year OS rate of T 1b patients was lower than that of T 1a and T 2 stage (67% vs. 90% vs. 71%, P=0.003). Of the 24 patients with T 1b stage, 17 cases received inguinal lymphadenectomy and 7 cases not. The 5-year OS rate of T 1b who received lymphadenectomy, who not and T 2 group were 73%, 57% and 71% respectively ( P=0.22). Multivariate Cox analysis showed that N stage ( HR =4.55, 95% CI 2.64-7.85, P<0.01) and tumor grade ( HR =2.09, 95% CI 1.09-4.02, P=0.03) were independent factors which could affect the prognosis. Conclusions:N stage and tumor grade were independent factors which could affect the prognosis. The poorer the tumor grade, the worse the prognosis. Inguinal lymphadenectomy could improve the prognosis of patients with T 1b stage.

Valencene, a kind of sesquiterpenoid with a citrus flavor, is mainly found in Valencia orange and is commonly used in cosmetics and food additives, as well as industrial synthetic nootkatone. In this study, synthetic biology was used to create a Saccharomyces cerevisiae cell factory to produce valencene. Fistly, valencene synthase gene (CnVS) from Callitropsis nootkatensis was inserted into the chromosome of the chassis strain YTT-T5. The resulting strain VAL-01 could produce 1.1 mg·L^-1 valencene. Protein fusion technique was used, different valencene synthases were compared and the copy number of key genes was adjusted, yielding valencene to 436.4 mg·L^-1. Then, knocking-out the transcription factor ROX1 resulted in valencene improvement by 17.4%. Moreover, the induction system of galactose was regulated, transcription factor PDR3 and INO2 were overexpressed. The engineered strain VAL-10 could produce 2 798.6 mg·L^-1 valencene by high cell density fermentation method (nearly 2 500 times higher than VAL-01). This study provides a basis for green production of valencene.