ObjectiveTo investigate the differences in clinical features and outcomes between patients with hepatic Wilson's disease （WD） presenting with the syndrome of combined phlegm and stasis and the syndrome of dampness-heat internal accumulation. MethodsA retrospective cohort study was conducted by consecutively recruiting patients with hepatic WD from the Encephalopathy Center of the First Affiliated Hospital of Anhui University of Chinese Medicine between January 2022 and August 2025. According to traditional Chinese medicine （TCM） syndrome differentiation， the patients were assigned into a combined phlegm and stasis group and a dampness-heat internal accumulation group. All the patients received standard treatment. Baseline data， laboratory indicators， complications， Model for End-Stage Liver Disease （MELD） score， Child-Turcotte-Pugh （CTP） score， and Chronic Liver Failure-Sequential Organ Failure Assessment （CLIF-SOFA） score were recorded. The clinical features and outcomes of the two groups of patients were compared by t-test， U-test and multivariate logistic regression. ResultsA total of 141 patients with hepatic WD were included. The combined phlegm and stasis group comprised 68 patients with an average age of （28.22±10.47） years， including 43 males and 25 females. The dampness-heat internal accumulation group comprised 73 patients with an average age of （30.22±8.79） years， including 44 males and 29 females. Univariate analysis showed no statistically significant differences in age or gender between the two groups. The combined phlegm and stasis group had lower platelet （PLT）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， creatine （CRE）， total cholesterol （TC）， and triglycerides （TG） levels （P<0.05 or P<0.01） and higher total bilirubin （TBIL） and prothrombin time （PT） （P<0.05） than the dampness-heat internal accumulation group. There were no statistically significant differences in the incidence of hepatic encephalopathy， infection， spontaneous bacterial peritonitis， ascites， or gastrointestinal bleeding between the two groups. The incidence of splenomegaly and the MELD score were higher in the combined phlegm and stasis group （P<0.05）. The CTP and CLIF-SOFA scores were also higher in the combined phlegm and stasis group， while these differences were not statistically significant. Eleven patients in the combined phlegm and stasis group and 9 patients in the dampness-heat internal accumulation group developed liver failure. Multivariate logistic regression analysis showed that PT （OR=1.794， 95%CI 1.249-2.576）， TBIL （OR=1.111， 95%CI 1.026-1.203）， ALT （OR=1.053， 95%CI 1.004-1.105）， and TCM syndrome （OR=5.420， 95%CI 1.384-21.227） were independent risk factors for the development of liver failure in hepatic WD. ConclusionCompared with the hepatic WD patients with the syndrome of dampness-heat internal accumulation， those with the syndrome of combined phlegm and stasis exhibit severe liver function impairment and disease conditions. Furthermore， TCM syndrome serves as an independent predictive factor for the occurrence of liver failure in patients with hepatic WD.

ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription （BSTDP）. MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-LIT-Orbitrap-MS）. Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction （PPI） network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg （mpx： GFP）. At three days post-fertilization （3 dpf）， larvae of zebrafish were randomly assigned to blank group， model group， positive drug dexamethasone acetate group （75 μmol·L^-1）， and BSTDP groups with low， medium， and high doses （500， 1 000， and 2 000 mg·L^-1）. The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa-B （NF-κB） signaling pathway and inflammatory factors including interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsA total of 120 chemical components were identified in BSTDP， among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis （RA） and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine， vomicine， sinapine， rehmannioside， cinnamyl alcohol glycoside， and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 （Akt1）， signal transducer and activator of transcription 3 （STAT3）， tumor necrosis factor （TNF）， TLR4， mitogen-activated protein kinase 14 （MAPK14）， and phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit α （PIK3CA）， thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L^-1. Compared to those in the blank group， zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region （P<0.01） and rising mRNA levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β （P<0.01）. Compared to that in the model group， the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses， as well as the dexamethasone acetate group （P<0.05， P<0.01）. There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β were significantly down-regulated （P<0.05， P<0.01）. ConclusionThis paper identifies the material basis of the efficacy of BSTDP， demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.

AIM: To investigate the differences in morphological structure and retinal blood perfusion between the affected eye and the contralateral healthy eye using optical coherence tomography angiography(OCTA)in patients with idiopathic macular epiretinal membrane(IMEM)before and after surgery, and to evaluate the association of these parameters with functional and anatomical outcomes to inform prognostic assessment. METHODS:A prospective study was conducted at Zhejiang Provincial People's Hospital between January 2023 and December 2024. Consecutive patients diagnosed with unilateral IMEM were enrolled; the fellow eye served as an internal control. All participants underwent standardized ophthalmic evaluations, including optical coherence tomography(OCT), OCTA, and color fundus photography. Key quantitative parameters assessed included best-corrected visual acuity(BCVA), central macular thickness(CMT), foveal avascular zone(FAZ)area, vessel density in the inner capillary plexus(ICP), superficial capillary plexus(SCP), deep capillary plexus(DCP), and choroidal capillary perfusion area(CCPA). Measurements were obtained preoperatively and at 1 and 3 mo postoperatively. Correlation analyses were performed between the above parameters and postoperative BCVA and CMT.RESULTS: This study enrolled 30 patients(60 eyes)diagnosed with IMEM, comprising 14 males and 16 females, with a mean age of 65.4±10.8 y.At baseline, IMEM-affected eyes demonstrated significantly reduced BCVA, DCP density, and FAZ area, alongside significantly increased CMT and CCPA, compared with contralateral controls. Following vitrectomy with membrane peeling, CMT decreased significantly at both 1 and 3 mo(both P<0.05)postoperatively; DCP density and BCVA showed significant improvement(both P<0.05). No significant change in FAZ area was observed postoperatively(P>0.05). At 3 mo postoperatively, BCVA of the affected eye was negatively correlated with CMT(r=-0.549, P=0.022). At 1 mo postoperatively, CMT was negatively correlated with preoperative DCP and FAZ, positively correlated with preoperative CMT, and positively correlated with ICP and SCP at 1 mo postoperatively, and negatively correlated with FAZ at 1 mo postoperatively(all P<0.05). Furthermore, CMT at 3 mo postoperatively was negatively correlated with preoperative DCP(r=-0.498,P=0.042).CONCLUSION:In patients with IMEM, the affected eyes exhibit significantly reduced DCP density and FAZ area, alongside increased CMT and CCPA. Following vitrectomy with membrane peeling, CMT decreased progressively, DCP density demonstrated partial restoration, and vision improved gradually. Preoperatively, smaller CMT larger DCP, and FAZ were associated with more favorable surgical outcomes; postoperatively, smaller ICP and SCP densities—combined with a larger FAZ—also correlated with better functional recovery.

ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription （BSTDP）. MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-LIT-Orbitrap-MS）. Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction （PPI） network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg （mpx： GFP）. At three days post-fertilization （3 dpf）， larvae of zebrafish were randomly assigned to blank group， model group， positive drug dexamethasone acetate group （75 μmol·L^-1）， and BSTDP groups with low， medium， and high doses （500， 1 000， and 2 000 mg·L^-1）. The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa-B （NF-κB） signaling pathway and inflammatory factors including interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsA total of 120 chemical components were identified in BSTDP， among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis （RA） and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine， vomicine， sinapine， rehmannioside， cinnamyl alcohol glycoside， and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 （Akt1）， signal transducer and activator of transcription 3 （STAT3）， tumor necrosis factor （TNF）， TLR4， mitogen-activated protein kinase 14 （MAPK14）， and phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit α （PIK3CA）， thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L^-1. Compared to those in the blank group， zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region （P<0.01） and rising mRNA levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β （P<0.01）. Compared to that in the model group， the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses， as well as the dexamethasone acetate group （P<0.05， P<0.01）. There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β were significantly down-regulated （P<0.05， P<0.01）. ConclusionThis paper identifies the material basis of the efficacy of BSTDP， demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.

This study elucidated the structure-activity relationships (SAR) of three distinct opioid ligand series at the μ-opioid receptor (μ-OR) and investigated the ligand-dependent role of arrestin in downstream signaling. Radioligand binding assays across 13 compounds revealed that high-affinity μ-OR binding is not restricted to a single chemical scaffold. For fentanyl analogs, SAR analysis identified four key structural determinants: the N-phenethyl group (R1) is essential for μ-OR binding, the piperidine 4-position (R2) is sterically constrained and tolerates only small substituents such as carbomethoxy, the acyl side chain (R3) tolerates diverse chemical modifications including alkyl, alkoxy, and heteroaryl groups without substantial loss of affinity, and para-substitution on the phenethyl ring (R4) with electron-withdrawing groups like fluorine is well-tolerated. Analysis of non-fentanyl scaffolds (2-Methyl AP-237, W-15, and brorphine) demonstrated that specific side-chain functionalization, rather than core scaffold architecture, primarily determines binding potency. Comparison of classical opioids further revealed that structural flexibility, exemplified by methadone, can confer superior binding affinity compared to the rigid morphine scaffold. Consistent with this structural diversity, the contribution of arrestins to ERK activation varied substantially across compounds, suggesting that μ-OR-biased signaling is not dictated exclusively by intrinsic receptor properties but emerges from the interplay between receptor conformation and ligandspecific structural features. Collectively, our results provide a molecular framework for understanding opioid pharmacology with important implications for rational drug design aimed at minimizing adverse effects while maintaining analgesic efficacy.

Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

Objective To compare the dosimetric differences, plan complexity, verification pass rate, and execution efficiency of volumetric modulated arc therapy (VMAT) plans designed for post-mastectomy radiotherapy of breast cancer using Halcyon 2.0 and VitalBeam accelerators in flattening filter-free mode. Methods A retrospective analysis was conducted on imaging data from 87 female breast cancer patients aged 29 to 75 (49.9 ± 9.9) years who underwent modified radical mastectomy followed by radiotherapy. VMAT plans were designed using both VitalBeam and Halcyon accelerators in flattening filter-free mode. The dosimetric parameters, plan complexity, verification pass rate, and execution efficiency were compared between the plans designed for both accelerators, with a significance level of P<0.05. Results In terms of target volume parameters, Halcyon 2.0 plans demonstrated superior homogeneity index and conformity index. For organs at risk, the Halcyon 2.0 plans showed lower doses for the lungs (D_20% and D_mean) and heart (D_mean) compared to the VitalBeam plans (all P<0.05). Regarding plan complexity, Halcyon 2.0 plans exhibited better median average aperture area variation (0.35 ± 0.02), smaller aperture score, and larger median plan aperture area than VitalBeam plans (all P<0.05). However, VitalBeam plans had a superior median modulation complexity score (0.28 ± 0.01) compared to Halcyon 2.0 plans (P<0.05). Patient plans were assessed using the ArcCHECK phantom, revealing higher pass rates and significantly shorter execution time for Halcyon plans compared to VitalBeam plans (P<0.05). Conclusion Both Halcyon 2.0 and VitalBeam accelerators can provide high-quality VMAT plans for postoperative radiotherapy of breast cancer, with excellent verification pass rates ensuring treatment accuracy and efficacy. However, Halcyon 2.0 offers lower plan complexity, simplifies the treatment planning process, and reduces execution time, thereby achieving higher treatment efficiency and demonstrating greater advantages in clinical applications.

ObjectiveTo explore the function and related molecular mechanisms of magnoflorine against colon cancer via network pharmacology， molecular docking， and in vitro cell experiments. MethodsIn this study， the canonical SMILES of magnoflorine was obtained from the PubChem database， and the potential targets of magnoflorine were predicted by the Swiss Target Prediction database， while the disease targets of colon cancer were obtained from the DisGeNET， GeneCards and OMIM databases. The intersecting targets between magnoflorine's predicted targets and colon cancer disease targets were taken， and a protein-protein interaction （PPI） network was constructed and analyzed. The DAVID online database was employed to conduct Gene Ontology （GO） and KEGG pathway enrichment analyses on core targets. The top five key targets screened were docked with magnoflorine using AutoDock software. Finally， cellular experiments including CCK-8 assays， EdU experiments， cell scratch assays， and Transwell assays were conducted to validate the results from network pharmacology and molecular docking. Results44 key targets of magnoflorine in resisting colon cancer were acquired. The molecular docking results showed that magnoflorine had a strong binding activity with the core target signal transducer and activator of transcription 3 （STAT3） in the top five of the PPI network. Cellular experiments confirmed that magnoflorine could inhibit the proliferation and migration of colon cancer cells by suppressing the JAK/STAT3 signaling pathway. ConclusionMagnoflorine may inhibit the proliferation and migration of colon cancer cells by regulating the JAK/STAT3 signaling pathway.

Dysphagia is a common complication of stroke. Combining the principles of traditional Chinese medicine with modern research findings， it is proposed that "latent pathogen in the cerebral collaterals" constitutes the core pathogenesis of post-stroke dysphagia （PSD）. In clinical practice， treatment is tailored according to the location of PSD. During the oral stage， when the pathogen invades the face and mouth， resulting in excessive salivation， acupoints are primarily selected from the foot shaoyin （少阴） kidney channel， in combination with ren mai （任脉） ， du mai （督脉）， chong mai （冲脉） and the spleen channel， to replenish essence and fill the marrow， dispel dampness and unblock the channels. In the pharyngeal stage， as the pathogen obstructs the throat， disrupting normal swallowing， the therapy emphasizes dredging the shaoyang （少阳） channel and warming and tonifying the jueyin （厥阴） channel， by taking acupoints mainly from the hand and foot shaoyang channels， along with the jueyin channels， so as to soothe the liver and promote bile secretion， regulate and harmonize qi and blood. During the esophageal stage， where the pathogen damages the esophagus， impeding food passage， the treatment emphasizes activating the yangming （阳明） channels and regulating taiyin （太阴） channels； acupoints are mainly selected from the foot yangming stomach channel， along with the taiyin channels， aiming to warm yang， unblock the channels and dispel stasis.

Objective:To investigate the expression of placenta expressed transcript 1(Plet1)in ovarian tissue of the letrozole-induced model rats of polycystic ovary syndrome(PCOS)and its effect on the proliferation of rat ovarian granulosa cells,and to clarify the possible mechanism by which Plet1 may contribute to the pathogenesis of PCOS.Methods:The ovarian tissue samples from the rats collected in previous studies were used and divided into control and PCOS groups.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods were used to detect the expression levels of Plet1 mRNA and protein in ovarian tissue of the rat in two groups.Additionally,twenty-four rats underwent vaginal smear cytology were divided into four groups by estrous cycle phase:proestrus,estrus,metestrus and diestrus.RT-qPCR was used to detect the expression level of Plet1 mRNA in ovarian tissue of the rats in various groups,and immunohistochemistry(IHC)method was used to detect the location of Plet1 expression in the rat ovarian tissue in various groups.The rat ovarian granulosa cells were transfected and divided into control group,si-Plet1-rat-266 group,si-Plet1-rat-383 group,and si-Plet1-rat-554 group.Cell counting kit-8(CCK-8)method was used to assess the cell proliferation activities of rat ovarian granulosa cells in various groups,and RT-qPCR method was used to detect the expression levels of cyclin-d epend ent kinase 6(CDK6)and P53 mRNA in rat ovarian granulosa cells in various groups.Results:The RT-qPCR results revealed that Plet1 mRNA was expressed in the ovaries of normal rats,while no statistically significant difference was observed across estrous cycle phases(P＞0.05).The immunohistochemistry results showed that the expression of Plet1 protein was mainly localized in ovarian granulosa cells and luteal cells in the rat ovarian tissue.Compared with control group,the expression levels of Plet1 mRNA and protein in ovarian tissue of the rats in PCOS group were significantly decreased(P＜0.05).The RT-qPCR results showed that compared with control group,the expression level of Plet1 mRNA in ovarian granulosa cells in si-Plet1-rat-383 group was decreased(P＜0.01),exhibiting the most pronounced reduction.Compared with control group,the proliferation activity of rat ovarian granulosa cells in si-Plet1-rat-383 group was decreased(P＜0.05).Compared with control group,the expression levels of CDK6 and P53 mRNA in rat ovarian granulosa cells in si-Plet1-rat-383 group were significantly decreased(P＜0.05 or P＜0.01).Conclusion:Plet1 protein is predominantly expressed and localized in granulosa cells and luteal cells in normal rat ovarian tissue.Its expression is downregulated in the ovarian tissue of PCOS model rats,and interference with Plet1 gene expression may inhibit the proliferation of rat ovarian granulosa cells.