OBJECTIVE:To evaluate the clinical efficacy of the transverse V-Y advancement mucosal flap for reconstruction of small- to medium-sized lip mucosal defects. METHODS:Clinical data from 17 patients who underwent reconstruction of lip mucosal defects following resection of benign or early-stage malignant lip lesions between June 2017 and October 2025 were reviewed. Triangular mucosal flaps were designed on 1 or both sides of the defect while preserving a deep tissue pedicle ∼1.0 cm in width. The mucosal flaps were advanced horizontally toward the center of the defect and inset using V-Y closure, while the donor sites were closed primarily. Flap survival, postoperative complications, and functional and aesthetic outcomes during follow-up were evaluated. RESULTS:All 17 transverse V-Y advancement mucosal flaps survived, and all wounds achieved primary healing. The defect sizes ranged from 1.5×1.5 cm to 2.0×2.5 cm. The median follow-up duration was 15 months (6-28 mo), during which no recurrence was observed. All patients achieved satisfactory postoperative lip symmetry, with normal mouth opening and preserved lip mobility. The flaps showed excellent tissue integration, demonstrating satisfactory color and texture match, and no obvious complications, such as scar contracture, were observed. CONCLUSION:The transverse V-Y advancement mucosal flap is a reliable reconstructive technique characterized by flexible design, technical simplicity, minimal donor-site morbidity, and robust vascularity. It effectively uses adjacent redundant mucosal tissues to avoid dog-ear deformity and additional tissue injury. Therefore, it represents an effective and reliable option for reconstruction of small- to medium-sized partial-thickness mucosal defects of the lip.

Platelets play a critical role in tumor immunity, particularly in promoting cancer progression. Numerous studies suggest that platelets could serve as a novel target for cancer immunotherapy, however, no comprehensive reviews have yet summarized and discussed this potential. Our review provides an in-depth discussion of the roles and mechanisms of platelets within both the immunosuppressive tumor microenvironment and the anti-tumor immune microenvironment. Additionally, we summarize the key therapeutic targets and approaches for clinical translation. This work offers essential insights for reprogramming platelets to shift their function from tumor promotion to tumor suppression, providing a foundation for the development of novel immunotherapeutic strategies and related research.

The prognosis for traumatic brain injury (TBI) depends largely on prompt hemostasis and effective pharmacologic interventions. Natural all-small-molecule self-gelling powder, integrating the advantages of self-assembled small-molecule hydrogels and powders, is expected to provide timely and effective prehospital management of TBI. However, the synthesis and application of natural all-small-molecule self-gelling powder is still uncharted territory. In this study, an all-small-molecule co-assembled MGF-H3BO3-RUT (MBR) self-gelling powder is fabricated through the co-assembly of mangiferin (MGF) and rutin (RUT) in H3BO3/NaOH aqueous solution. Both compounds can bind with boric acid, leading to co-assembling into hydrogels through hydrogen-bonding interactions and pi-pi stacking. MBR self-gelling powder is then obtained by drying the as-prepared hydrogels, thus integrating hemostasis and pharmacodynamics into one. Remarkably, it displays robust regeneration capabilities, while retaining excellent self-healing properties and injectability after drying-hydration cycles. Moreover, MBR self-gelling powder not only achieves rapid effective hemostasis but also attenuates conspicuously cerebral edema and inflammatory response after TBI by in situ spraying, exhibiting notable neuroprotective effects without discernible toxic side effects. This study provides a novel assembly strategy and application form for self-assembled gel materials originating from natural small molecules, offering promising avenues for the treatment of TBI in the acute phase. An all-small-molecule co-assembled self-gelling powder is fabricated based on mangiferin and rutin, which can regenerate into a gel state with good self-healing ability and injectability after hydration. It can be used in prehospital emergency management of traumatic brain injury, and attenuates conspicuously cerebral edema and inflammatory response by in situ spraying, exhibiting notable neuroprotective effects without discernible toxic side effects. image

OBJECTIVES:The repair of small and medium-sized defects in the oral has always been a challenge, free skin flap and distal pedicled tissue flaps are difficult to meet clinical needs, and the traditional under-chin flap has the risk of donor-area injury. This study aims to investigate the efficacy of V-shaped folded submental flap in the repair of small-sized and medium-sized oral defects.METHODS:The clinical data of 28 patients with oral defect lesions, who were hospitalized in the Department of Stomatology, Third Xiangya Hospital of Central South University from March 2019 to December 2022, were retrospectively analyzed. Patients were divided into a V-shaped folded group (17 cases) and a conventional group (11 cases) according to different surgical methods. The V-shaped folded group was treated with a V-shaped folded submental flap for postoperative soft tissue repair, while the conventional group was treated with a conventional submental flap for repair. The postoperative follow-up time was 6-48 months. The survival status, repair time, and repair effect of the 2 groups were compared.RESULTS:There was no significant difference in flap survival rate, flap size, flap preparation time, repair surgery time, and postoperative hospital stay between the 2 groups (all P>0.05). At 6 months after the surgery, the V-shaped folded group had no difficulty in raising the head or everting the lower lip, no "cat ear" deformity in the submental skin. Scars in the V-shaped folding group were hidden at the lower edge of the mandible. The wound aesthetics and functional scores in the V-shaped folded group were significantly higher than those in the conventional group (both P<0.05).CONCLUSIONS:The V-shaped foldable submental flap has the advantages of flexible design, simple preparation, reliable blood supply, and protection of the donor area, which can effectively protect the appearance of the chin and avoid functional disorders.

Gallbladder cancer (GBC) is an aggressive cancer with poor prognosis. PARP inhibitors (PARPi) target PARP enzymes and have shown efficacy in patients with breast cancer gene (BRCA) mutations. Immunotherapy, especially immune checkpoint inhibitors (ICIs), has transformed cancer treatment. However, the combined impact of PARPi and ICIs in GBC remains unclear. We present a groundbreaking case of a GBC patient with BRCA2 mutations who received combination therapy with PARPi and ICIs after failing multiple lines of treatment. Next-generation sequencing (NGS-Seq) identified BRCA gene mutations. To further investigate potential mechanisms, we developed a PARP1-BRCA1-BRCA2 pathway-related risk score (PBscore) system to evaluate the impact of PARPi on the tumor immune microenvironment via RNA-Seq data. Gene expression and functional analysis identified potential mechanisms associated with the PBscore. Experimental validation assessed the impact of the combination therapy on the tumor microenvironment using multiplexed immunofluorescence imaging and immunohistochemistry in patients with BRCA gene wild type or mutations. RNA-Seq analysis revealed correlations between PBscore, immune checkpoint levels, tumor-infiltrating immune cells (TIICs), and the cancer-immunity cycle. Multiplexed immunofluorescence imaging validated that low PBscore patients might have an active tumor microenvironment. Furthermore, upon drug resistance, we observed an upregulation of negative immune checkpoints such as CEACAM1, indicating that the tumor immune microenvironment becomes suppressed after resistance. Our study revealed that PBscore could serve as a biomarker to predict immunotherapy efficacy, offering a promising alternative for BRCA2-mutated GBC patients.

e15621 Background: The recurrence rate of locally advanced colon cancer (T3-4 or N+, M0) after surgery is significantly high. Emerging data indicate that the combination of immunotherapy and chemotherapy demonstrates synergistic effects in other solid tumors. Consequently, a combination of immunotherapy and chemotherapy holds the potential to benefit patients with MSS and pMMR colon cancer. We have designed a prospective trial to investigate whether the immune checkpoint inhibitor (ICI) in combination with chemotherapy represents a safe and beneficial treatment approach for locally advanced colon cancer. Methods: Inclusive Criteria: Patients with locally advanced colon cancer (T3-4 or N+, M0) confirmed through pathological biopsy, with confirmed indications for neoadjuvant/adjuvant chemotherapy by the multidisciplinary team. Patients must be eligible for surgery, and a measurable mass must be identified according to RECIST version 1.1. All individuals aged over 18 years, with an estimated life expectancy of over one year and an ECOG score within 0-1, are eligible. The neoadjuvant chemoimmunotherapy group (NACI) includes mFOLFOX 6 (Q2W) and the anti-PD-1 monoclonal antibody (Toripalimab) (3mg/kg, Q2W), while the neoadjuvant chemotherapy group (NAC) receives only mFOLFOX 6 for neoadjuvant/adjuvant therapy (a total of 12 cycles, 6 cycles pre-surgery and 6 cycles post-surgery). The primary endpoint is the pathological complete response (pCR) rate. Results: From 2019 to 2022, a total of 22 patients were enrolled in the study, with 13 in the NACI group and 9 in the NAC group. The research findings indicate that in the NACI group, over 30% (4/13) of patients achieved a pathological complete response (pCR), whereas none of the patients in the NAC group reached pCR (0/9). Among the pCR patients, one was identified as MSI-H/dMMR, two as MSS/pMMR, and one had an unknown status. Tumor regression grade (TRG) levels also revealed that all patients in the NACI group were below grade 2, significantly outperforming the NAC group (P < 0.05), with statistically significant differences. However, no significant differences were observed between the NAC and NACI groups in terms of CT regression percentage, R0 resection, vascular cancer emboli, and the level of neural invasion. Adverse reactions did not show significant differences between the two groups. Conclusions: The combination of immunotherapy and chemotherapy exhibits a synergistic effect in treating locally advanced colorectal cancer. Tolerable adverse reactions suggest that neoadjuvant chemoimmunotherapy could potentially serve as a novel therapeutic option. Clinical trial information: NCT03985891 .

OBJECTIVES:The repair of small- and medium-sized defects in the oral tongue has always been a challenge, and the effect of free flap and distal pedicle flap is still far from satisfactory. Tongue flap is an ideal choice for repairing small- and medium-sized defects. However, the disadvantages such as poor local morphology restricts the development of this operation.This study aims to investigate the efficacy of double V-Y advancement mucosal flap in repair of small- and medium-sized defects of the tongue defect.METHODS:The clinical data of 15 patients with tongue defect lesions who were hospitalized in the Department of Stomatology, Third Xiangya Hospital of Central South University from March 2019 to May 2022 were retrospectively analyzed. After the lesions were completely excised, the mucosa and part of the tongue defect were left. One V-Y advancement mucosal flap was designed anteriorly and posteriorly to the defect. The superficial mucosa was incised gradually all around, preserving the deep median muscle tip. The 2 flaps were freed toward the middle of the defect, and the anterior and posterior flaps were sutured together at the middle of the defect, with the donor area directly pulled together and sutured.RESULTS:The double V-Y advancement mucosal flap survived in 15 patients, and the wounds healed at stage I. The postoperative follow-up time was 12-22 months, and the patients had no recurrence, with symmetrical tongue shape, and no traction and deformation in the affected tongue organs. Meanwhile, the intraoral flap was thin and flat, and healed well with the surrounding mucosa, without obvious flap contracture or tongue bite.CONCLUSIONS:Double V-Y advancement mucosal flap has the advantages of flexible design, simple preparation, reliable blood supply, and good protection of the donor site, which may be one of the effective methods for repairing small- and medium-sized defects in the anterior tongue mucosa.

Yun Peng1, Jun Cao2, Xiao-Yi Yao3, Jian-Xin Wang4, Mei-Zuo Zhong3, Ping-Ping Gan3 and Jian-Huang Li3 1International Medical Center, Xiangya Hospital, Central South University, Changsha 410008, P.R. China 2Department of Medical Oncology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410008, P.R. China 3Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, P.R. China 4School of Information Science and Engineering, Central South University, Changsha 410008, P.R. China

Background. Traumatic brain injury (TBI) is one of the most common neurosurgical diseases and refers to brain function impairment or brain pathological changes induced by external causes. A traditional Chinese medicine, Xuefu-Zhuyu Decoction (XFZYD), has been indicated to harbor therapeutic properties against TBI. Transfer RNA (tRNA)-derived small RNAs, that is, tsRNAs (a group of small RNAs derived from tRNAs), are multifunctional regulatory noncoding RNAs generated under pressure and implicated in the progression of TBI. Methods. A TBI model was successfully constructed using rats. We further performed sequencing and omics analyses to identify novel tsRNAs as drug targets for XFZYD therapy against TBI in the rat hippocampus. qPCR assays were used to further verify the experimental results. Gene Ontology (GO) was used to analyze the signaling pathways of downstream target genes of tsRNAs in the XFZYD-regulated TBI model. qPCR was used to detect the influence of overexpressed tsRNA mimics/inhibitors on their target genes in PC12 cells. Results. Our RNA-Seq data illustrate that 11 tsRNAs were mediated by XFZYD. The experimental data revealed AS-tDR-002004 and AS-tDR-002583 as potential targets for XFZYD therapy and showed that they influenced TBI via the cadherin signaling pathway, cocaine addiction, circadian entrainment, and the nicotine pharmacodynamics pathway. We also confirmed that Pi4kb, Mlh3, Pcdh9, and Ppp1cb were target genes of 2 XFZYD-regulated tsRNAs in the hippocampus of a rat model and PC12 cells. Furthermore, biological function analysis revealed the potential therapeutic effects of tsRNAs, and the results showed that Mapk1 and Gnai1 were related genes for XFZYD therapy against TBI. Conclusion. Our work successfully illuminates the efficiency of XFZYD in the treatment of TBI. The experimental data revealed AS-tDR-002004 and AS-tDR-002583 as potential targets for XFZYD therapy and showed that they influenced TBI via the cadherin signaling pathway, cocaine addiction, circadian entrainment, and the nicotine pharmacodynamics pathway in a TBI rat model.

Purpose:Paclitaxel-induced peripheral neuropathy (PIPN) is increasingly becoming one of the most widespread adverse effects in the treatment of cancer patients, and further precipitate neuroinflammation in the nervous system. Interestingly, Shaoyao Gancao Decoction (SGD), a traditional Chinese analgesic prescription, has emerged as a primary adjuvant to chemotherapy in relieving side effects, especially in the case of PIPN. However, the underlying mechanism of SGD functioning in PIPN remains elusive. Accordingly, the current study set out to explore the potential axis implicated in the functioning of SGD in PIPN.Methods:First, network pharmacology was adopted to predict the role of the transient receptor potential vanilloid type 1 (TRPV1) protein in treating PIPN with SGD. Subsequently, the effects of SGD treatment on mechanical allodynia and thermal hyperalgesia were evaluated in rat PIPN models. Based on the bioinformatics information and current literature, paclitaxel activates toll-like receptor 4 (TLR4) induces the sensitization of TRPV1 mechanistically. Thereafter, TLR4-myeloid-differentiation response gene 88 (MyD88) signaling and TRPV1 expression patterns in dorsal root ganglias (DRGs) were measured by means of Western blotting, qPCR and immunofluorescence.Results:Initial bioinformatics reared a total of 105 bioactive compounds and 1075 target genes from SGD. In addition, 40 target genes intersected with PIPN were considered as potential therapeutic genes. Based on the network analysis, SGD was found to exert its analgesic effect by reducing the expression of TRPV1. Further experimentation validated that SGD exerted an analgesic effect on thermal hyperalgesia in PIPN models, such that this protective effect was associated with the suppression of TRPV1 and TLR4-MyD88 Signaling over-expression.Conclusion:Collectively, our findings indicated that SGD ameliorates PIPN by inhibiting the over-expression of TLR4-MyD88 Signaling and TRPV1, and further highlights the use of SGD as a potential alternative treatment for PIPN.

Melanoma is an aggressive form of skin cancer characterized by rapid invasion and metastasis.CD147 is known to be functioning in cell invasion.In this study, we showed that CD147 was translocated from the cell membrane to the mitochondria in advanced melanoma.Melanoma patients with CD147 localized to the mitochondria confer a worse prognosis.The mitochondrial CD147 levels are correlated with the invasion potential of various melanoma cell lines as well as mitochondrial energy metabolism.Depletion of CD147 decreased the activity of mitochondrial complex V. STRING analysis for protein-protein interaction networks (PPIN) in CD147-depleted melanoma cells showed that mitochondrial proteins HSP60 and ATP5B, a subunit of mitochondrial complex V, were node proteins.HSP60 upregulation was correlated with a worse prognosis of melanoma patients.Co-immunoprecipitation (Co-IP) assay indicates that CD147 interacts with HSP60.These data suggested that mitochondrial CD147 may prompt HSP60 to activate ATP5B, thereby promoting the mitochondrial aerobic oxidation and the invasive abilities of melanoma cells.Correlation analysis of the data acquired from patients was helpful to draw a 5-year survival curve for patients who screened positive and negative for mitochondrial CD147.This study unravels the function of CD147 in tumor invasion and highlights it as a potential tumor therapeutic target.

e15076 Background: AKT1 is a key gene of the PI3K/AKT/mTOR signalling pathway. The recent development of ATK1 targeting drug has shown great promise. It is thus important to understand the genomic landscape of AKT1 in a specific population. Methods: Sequencing data of 11,813 tumor samples collected in China were analyzed for AKT1 mutation status. Concomitant genomic aberrations were further analyzed in tumors with AKT1 mutations. Results: AKT1 mutations were observed in 173 of 11,813 tumor samples (1.46%). The most common cancer types in our study included cervical (5.17%), breast (5.15%), osteosarcoma (3.51%), brain (3.14%), head and neck (2.22%) and colorectal (2.02%). We included only the cancer types with more than 50 cases for analysis. Higher frequencies of AKT1 mutation were observed in several common cancers, including brain glioma (1.38% vs 0.67%), breast (5.15% vs 2.92%), cervical (5.17% vs 2.93%), head and neck (2.22% vs 0.95%) cancer in our study than reported in TCGA, but showed no statistically significant difference. The main common type of variation was SNV/Indel (67.63%), amplification (20.81%), deletion (11.56%), fusion (1.16%). Among SNV/Indel, E17K accounted for 32.9% of AKT1 mutations, Q79K only accounted for 0.79%. AKT1 E17K was more commonly found in breast (3.09%), brain (1.96%) and cervical (1.72%) cancer. There is no significant difference between wild type and AKT1 mutated groups in age and gender. III/IV patients were identified in 85.71% of AKT1 mutated group, which were significantly higher than that of wild type group (73.76%; p<0.05).MSI-H patients were identified in 12.16% of AKT1 mutated group, which were significantly higher than that of wild type group (1.8%; p<0.001). Frequencies of specific concomitant aberrations varied between AKT1 mutated and wild type groups. In AKT1 mutated groups, 57 genes are more frequently altered, and mainly enriched in PI3K-Akt signaling pathway (26, q= 2.97E-20, MAPK signaling pathway (count:20, q= 9.74E-15), Central carbon metabolism in cancer (19, q= 5.01E-25), EGFR tyrosine kinase inhibitor resistance (19, q= 3.36E-24). Conclusions: Higher frequencies of AKT1 mutation were observed in several common cancers, including cervical, breast, osteosarcoma, brain, head and neck and colorectal in our study. AKT1 E17K was more commonly found in breast, brain and cervical cancer. Given the fact that III/IV patients are more common in AKT1 mutated group, it coincides with AKT inhibitors therapeutic prospects in a variety of advanced malignant tumors. MSI-H patients are more common in AKT1 mutated group, and it provides possibility for immune checkpoint inhibitors combined with targeted signaling pathway therapy. The enrichment results of the common co-occurring genes with AKT1 in this study, further investigations are still needed.

The present study aims to evaluate the feasibility, safety, and effects of the combined use of submandibular transcatheter perfusion with lingual nerve block and subcutaneous infiltration for anesthetic purposes during submandibular gland surgery. A total of 38 patients with benign tumors, who had undergone resection by submandibular gland surgery were randomly divided into 2 groups. Patients in group A were administered with submandibular anesthesia through catheter perfusion, lingual nerve block, and subcutaneous infiltration anesthesia. Patients in the group B were only treated with lingual nerve block and subcutaneous infiltration anesthesia. The submandibular gland surgery was performed within 5minutes following anesthesia administration, after which the numerical rating scale (NRS) was evaluated before surgery, during skin incision (T-1), during the pulling process of the submandibular gland (T-2), during the removal of the submandibular gland (T-3), and at 2, 6, 12, and 24hours post-surgery. The dosage of analgesic drugs was also measured after surgery. The findings revealed no significant difference in NRS before surgery, at T-1, 6, 12, and 24hours after surgery (P>0.01) while NRS was much lower in group A patients as observed at T-2, T-3, and 2hours after surgery when compared with group B (P<0.01). The combined application of submandibular transcatheter perfusion with lingual nerve block and subcutaneous infiltration can be used as an effective anesthetic method during submandibular gland surgery.

Background: We aimed to preserve parotid function in patients with buccal carcinoma by applying a new surgical protocol based on reconstruction of parotid ductal defect with submandibular gland ductal. Aims/Objectives: The aim of this study is to introduce the method of autologous submandibular gland duct reconstruction for the treatment of parotid duct defect in buccal carcinoma, and to evaluate its clinical application in follow-up. Material and methods: A total of 28 patients with buccal carcinoma who underwent buccal and neck combined with radical surgery and vascularized flap transplantation were enrolled. Function of the reconstructed duct was reviewed in 6 months after surgery. Results: Both groups achieved good short-term results within 1 month after surgery. The 6-month postoperative angiography examination of the submandibular gland duct showed that 6% of patients in the submandibular gland duct graft group had a blockage or was not smooth. At the same time, 45% of the patients in the vein graft group had failure or obstruction, and the VAS score of pain was higher than that of the submandibular gland ductal graft group (p < .05). Conclusion and significance: Compared with vein grafting, the reconstruction of parotid ductal defect with submandibular gland ductal graft has better long-term effects.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Cancer incidence is rising, and the efficacy of current available anticancer agents is limited by severe dose‐limiting toxicities and drug resistance problems. Nanoparticles are heralded as the next frontier in cancer treatment. Here, a pure physical method is used to efficiently fabricate very small silver particles even approaching the Ångstrom (Ång) dimension. Fructose is used as a dispersant and stabilizer to coat the Ång‐scale silver particles (AgÅPs). Functional and mechanistic studies demonstrate that fructose‐coated AgÅPs (F‐AgÅPs) can enter and accumulate in multiple cultured cancer cell lines to induce apoptotic death, whereas most normal cells are resistant to the efficacious dose of F‐AgÅPs; in vivo, intravenous administration of F‐AgÅPs potently inhibits the growth of pancreatic and lung cancer xenografts in nude mice, without inducing notable toxic effects on the healthy tissues. The results suggest the promising potential of F‐AgÅPs as a potent, safe, and broad‐spectrum agent for the cancer treatment.

Cancer incidence is rising, and the efficacy of current available anticancer agents is limited by severe dose-limiting toxicities and drug resistance problems. Nanoparticles are heralded as the next frontier in cancer treatment. Here, a pure physical method is used to efficiently fabricate very small silver particles even approaching the Ångstrom (Ång) dimension. Fructose is used as a dispersant and stabilizer to coat the Ång-scale silver particles (AgÅPs). Functional and mechanistic studies demonstrate that fructose-coated AgÅPs (F-AgÅPs) can enter and accumulate in multiple cultured cancer cell lines to induce apoptotic death, whereas most normal cells are resistant to the efficacious dose of F-AgÅPs; in vivo, intravenous administration of F-AgÅPs potently inhibits the growth of pancreatic and lung cancer xenografts in nude mice, without inducing notable toxic effects on the healthy tissues. The results suggest the promising potential of F-AgÅPs as a potent, safe, and broad-spectrum agent for the cancer treatment.

Backgrounds. Chaihu-Shugan-San (CSS) is a classic traditional Chinese herbal prescription for treating depression. However, the underlying mechanism of the Chinese syndrome-specific efficacy of CSS is poorly understood. Aim of the Study. From traditional Chinese medicine and pharmacogenetics perspectives, the present study aimed to investigate the antidepressant effects of CSS on a mouse model of Liver-Qi Stagnation (LQS) syndrome and its underlying mechanisms. Methods and Materials. We used two main mouse models of depressive syndromes in the study, including LQS and liver stagnation and spleen deficiency (LSSD) syndrome. Tail suspension and forced swimming tests were used to evaluate the effects of CSS on animal behaviour. The expression level of the CYP450 enzyme from liver microsomes was analysed by western blot (WB) analysis and quantitative real-time polymerase chain reaction (qRT-PCR). More specifically, we analysed the key compounds of CSS that are responsible for CYP450 regulation via bioinformatics. Ultimately, luciferase assays were employed to confirm the prediction in vitro. Results. CSS remarkably reduced the immobile time in LQS rather than in LSSD mice. Although CSS significantly upregulated CYP2C9 in mice with both syndromes, activated translation of CYP3A4 induced by CSS was only observed in the LQS group. Bioinformatics analysis revealed that the unique regulation of CYP3A4 was responsible for the effects of glycyrrhetinic acid (GA) from CSS. Further luciferase assays confirmed the enhancement of CYP3A4 expression via the pregnane X receptor (PXR) pathway in vitro. Conclusions. CSS specifically upregulates the translation of CYP3A4 via the PXR pathway in depressed LQS mice. GA, a bioactive compound that originates from CSS, contributes to this activation. This work provides novel insight into Chinese syndrome-based therapy for depression.

Licorice is the dried roots and rhizomes of Glycyrrhiza uralensis Fisch (Leguminosae), which is often used with paclitaxel to alleviate paclitaxel-induced pain in clinics. However, the herb–drug interaction between licorice and paclitaxel is still unknown. Our study evaluates the effects of oral licorice on the paclitaxel in rats via pharmacokinetic studies. A simple and rapid ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to determine paclitaxel in rat. SD rats were randomly divided into 3 groups of 6 animals each as follows: two groups of rats that were pretreated with a daily gavage of licorice (3 g/kg) for 1 or 14 successive days; Control group that was administered distilled water. All rats were then intravenously administered with paclitaxel (3 mg/kg). The results showed that 14 days pretreatment of licorice could decrease the area under the curve (AUC0–t) (from 7483.08 ± 528.78 to 6679.12 ± 266.56 mg/L × h) (P < 0.01), and increase the total clearance (CL) (from 0.36 ± 0.02 to 0.39 ± 0.02 L/h/kg) of paclitaxel (P < 0.01). However, a single co-administration of licorice did not significantly alter the pharmacokinetic parameters of paclitaxel, such as AUC0–t (from 7483.08 ± 528.78 to 7201.24 ± 292.76 mg/L × h) (P > 0.05) and CL (from 0.36 ± 0.02 to 0.36 ± 0.01 L/h/kg) (P > 0.05). The results will contribute to better use of licorice in the adjunctive therapy and provide information to study the interaction between herbs and chemotherapy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.