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.

Objective To evaluate the molluscicidal effect and cost of spraying molluscicides with drones against Oncomelania hupensis snails in marshland and lake areas, so as to provide new insights into field snail control in China. Methods A marshland and lake setting measuring approximately 12 000 m² was selected in Wanzhi District, Wuhu City on June 2023 as the test field, and assigned to four groups, of 3 000 m² in each group. Environmental cleaning was not conducted in groups A or B, which were given 5% niclosamide ethanolamine salt granules sprayed with knapsack-type sprayers and drones at a dose of 40 g/m², and environmental cleaning was conducted in groups C and D, which were given 5% niclosamide ethanolamine salt granules sprayed with drones and knapsack-type sprayers at a dose of 40 g/m², respectively. O. hupensis snails were surveyed before chemical treatment and 1, 3, 5, 7, 14 days post-treatment. The uniformity of chemicals was determined on the day of treatment, and the snail mortality, corrected snail mortality and density of living snails were calculated and compared among groups. The cost of molluscicides, labor fees of environmental cleaning and chemical treatment and cost of equipment were calculated, and the cost for a 1% reduction in the mean density of living snails was calculated 14 days post-treatment. Results The mean densities of living snails and mortality rates of snails were 1.82 to 2.85 snails/0.1 m² and 1.41% to 2.94% in groups A, B, C and D before chemical treatment, and the mortality and corrected mortality of snails were 55.75%, 49.32%, 85.94% and 87.50%, and 55.00%, 48.47%, 85.70% and 87.29% in groups A, B, C and D 14 days post-treatment. There was a significant difference in the mortality of snails among the four groups 14 days post-treatment (χ² = 38.735, P < 0.005), and there was a higher snail mortality in Group D than in Group A (χ² = 16.876, P < 0.005), and higher in Group C than in Group B (χ² = 20.508, P < 0.005). The density of living snails reduced by 55.00%, 43.94%, 90.43% and 87.14% 14 days post-treatment relative to pre-treatment in groups A, B, C and D, respectively. The test for uniformity of chemicals showed that the mean dose of molluscicides were 57.34, 55.21, 40.19 g/m² and 32.37 g/m² in groups A, B, C and D, respectively, and the minimal standard deviation (7.07) and coefficient of variation (0.18) of mean doses were seen in Group C. The costs for chemical treatment were 0.33 Yuan in groups A and B and 1.53 Yuan in groups C and D, respectively. The costs for a 1% reduction in the mean density of living snails were 17.82, 22.47, 50.73 Yuan and 52.56 Yuan in groups A, B, C, and D 14 days post-treatment, respectively. Conclusions The molluscicidal effect and cost of spraying 5% niclosamide ethanolamine salt granules with drones are comparable to manual spraying, and chemical treatment with drones are high in uniformity of molluscicides, time- and labor-saving, and feasible for applications in complex environments, which deserves widespread applications in the field of snail control.

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.

Patchoulol is an important sesquiterpenoid in the volatile oil of Pogostemon cablin, and is also considered to be the main contributing component to the pharmacological efficacy and fragrance of P. cablin oil, which has antibacterial, antitumor, antioxidant, and other biological activities. Currently, patchoulol and its essential oil blends are in high demand worldwide, but the traditional plant extraction method has many problems such as wasting land and polluting the environment. Therefore, there is an urgent need for a new method to produce patchoulol efficiently and at low cost. To broaden the production method of patchouli and achieve the heterologous production of patchoulol in Saccharomyces cerevisiae, the patchoulol synthase(PS) gene from P. cablin was codon optimized and placed under the inducible strong promoter GAL1 to transfer into the yeast platform strain YTT-T5, thereby obtaining strain PS00 with the production of(4.0±0.3) mg·L~(-1) patchoulol. To improve the conversion rate, this study used protein fusion method to fuse SmFPS gene from Salvia miltiorrhiza with PS gene, leading to increase the yield of patchoulol to(100.9±7.4) mg·L~(-1) by 25-folds. By further optimizing the copy number of the fusion gene, the yield of patchoulol was increased by 90% to(191.1±32.7) mg·L~(-1). By optimizing the fermentation process, the strain was able to achieve a patchouli yield of 2.1 g·L~(-1) in a high-density fermentation system, which was the highest yield so far. This study provides an important basis for the green production of patchoulol.
Saccharomyces cerevisiae/metabolism* ; Sesquiterpenes/metabolism* ; Pogostemon ; Oils, Volatile/metabolism*

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

Objective: To establish a dynamic syndromic surveillance system in the border areas of Yunnan Province based on information technology, evaluate its effectiveness and timeliness in the response to common communicable disease epidemics and improve the communicable disease prevention and control in border areas. Methods: Three border counties were selected for full coverage as study areas, and dynamic surveillance for 14 symptoms and 6 syndromes were conducted in medical institutions, the daily collection of information about students' school absence in primary schools and febrile illness in inbound people at border ports were conducted in these counties from January 2016 to February 2018 to establish an early warning system based on mobile phone and computer platform for a field experimental study. Results: With syndromes of rash, influenza-like illness and the numbers of primary school absence, the most common communicable disease events, such as hand foot and mouth disease, influenza and chickenpox, can be identified 1-5 days in advance by using EARS-3C and Kulldorff time-space scanning models with high sensitivity and specificity. The system is easy to use with strong security and feasibility. All the information and the warning alerts are released in the form of interactive charts and visual maps, which can facilitate the timely response. Conclusions: This system is highly effective and easy to operate in the detection of possible outbreaks of common communicable diseases in border areas in real time, so the timely and effective intervention can be conducted to reduce the risk of local and cross-border communicable disease outbreaks. It has practical application value.
Humans ; Influenza, Human ; Sentinel Surveillance ; Syndrome ; China ; Cell Phone

Objective: To analyze and compare the efficacy and safety of pingyangmycin fibrin glue composite (PFG) and pingyangmycin dexamethasone composite (PD) in the treatment of pharyngolaryngeal venous malformation (VM). Methods: The clinical data of 98 patients with pharyngolaryngeal VM who underwent sclerotherapy with pingyangmycin composite in the First Affiliated Hospital of Sun Yat-sen University from June 2013 to November 2022 were retrospectively analyzed. According to their treatment, patients were divided into PFG group (n=34) and PD group (n=64), among those patients there were 54 males and 44 females, aged 1-77(37.06±18.86)years. The lesion size, total treatment times and adverse events were recorded before and after treatment. And the efficacy was divided into three grades: recovery, effective and invalid. According to the length of VM, all patients were divided into three subgroups, to compare the differences in efficacy and treatment times between each two groups.And finally the adverse events and their treatments were analyzed. SPSS 25.0 software was used for statistical analysis. Results: The efficacy of PFG group was 94.11%(32/34), the recovery rate was 85.29%(29/34).And the efficacy of PD group was 93.75%(60/64), the recovery rate was 64.06%(41/64). No serious adverse eventst occurred in subgroup comparison, there was no statistical difference between the two groups in efficacy and the times of treatments when the length was≤3 cm (Z_efficacy=1.04, t_{treatment times}=2.18, P>0.05); when the length was 3-5 cm, there was no significant efficacy difference between the two groups(Z_efficacy=1.17, P>0.05), but the treatment times of PFG were less (t_{treatment times}=4.87, P<0.01); when the length≥5 cm, efficacy of PFG was significantly better than PD (Z_efficacy=2.94, P<0.01), and had fewer treatments times (t_{treatment times}=2.16, P<0.01). There were no serious adverse events in either group during treatment and follow-up. Conclusion: Both PFG and PD are safe and effective composite sclerotherapy agent for the treatment of laryngeal VM, but PFG has a higher cure rate and fewer treatment times for massive lesions.
Male ; Female ; Humans ; Fibrin Tissue Adhesive/therapeutic use* ; Retrospective Studies ; Bleomycin/adverse effects* ; Vascular Malformations/therapy* ; Dexamethasone/therapeutic use* ; Treatment Outcome

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

Primary signet ring cell carcinoma (SRCC) of the prostate is a rare neoplasm. However, its potential tumorigenic mechanism, clinicopathological features, and prognostic outcome have not been systematically described. To determine the pathogenic mechanism, we detected distributions of programmed cell death-ligand 1 (PD-L1), programmed death 1 (PD-1), and cellular components in the tumor microenvironment, including tumor-infiltrating lymphocytes (CD4 and CD8), tumor-associated macrophages (TAMs; CD163 and CD68), and tumor-associated fibroblasts (vimentin and alpha-smooth muscle actin [α-SMA]), in tumor tissues from four patients with primary prostatic SRCC compared with corresponding adjacent tissues and tumor tissues from 30 patients with prostate adenocarcinoma (PCa) by immunohistochemical staining. We found higher expression of PD-L1, CD163, and CD68 in primary SRCC specimens than that in both corresponding adjacent nontumor specimens and PCa specimens with different Gleason scores, indicating that TAMs may participate in the malignant biological behavior of primary SRCC of the prostate. For further analysis, we searched electronic journal databases and Surveillance, Epidemiology, and End Results (SEER) to identify 200 eligible patients including our four cases. According to Kaplan-Meier survival curve analysis, patients <68 years old, with radical prostatectomy (RP), Gleason score of 7-8, and lower clinical stage had longer overall survival (OS). Moreover, Cox multivariate analysis indicated that race (hazard ratio [HR] = 1.422), surgical approach (HR = 1.654), and Gleason score (HR = 2.162) were independent prognostic factors for OS. Therefore, primary SRCC of the prostate represents a distinct and aggressive subtype of prostate cancer associated with a higher distribution of PD-L1 and TAMs, which warrants further clinical investigation.
Aged ; B7-H1 Antigen ; Carcinoma, Signet Ring Cell ; Humans ; Lymphocytes, Tumor-Infiltrating ; Male ; Prognosis ; Prostate ; Prostatic Neoplasms ; Tumor Microenvironment