Objective: To prepare the erythrocyte-liposome drug delivery system to enhance the therapeutic effect of drugs on tumors and inhibit tumor metastasis. Methods: This study prepared and characterized paclitaxel (PTX)-plerixafor (AMD3100) liposomes (Lips), developed the erythrocyte-liposome drug delivery system, and evaluated its targeting efficiency and therapeutic efficacy through a series of in vitro cellular and in vivo animal experiments. Results: The particle size of PTX-AMD-Lips was (186.4±0.83) nm. Drug encapsulation efficiency of PTX-AMD-Lips was (75.50±5.27)% for PTX and (88.31±2.45)% for AMD. The Binding efficiency between RBC and liposomes in the drug delivery system was (69.93±2.55)%. Vitro cellular experiments revealed that PTX-AMD-Lips significantly inhibited tumor cell migration. In vivo animal experiments, the erythrocyte-liposome drug delivery system significantly increased drug accumulation in the lungs. At the experimental endpoint, the quantitative fluorescence signal of tumor size measured (4.04±0.44)×10 for the PTX-Lips group, and (5.14±3.40)×10 for the RBC-PTX-AMD-Lips group. Conclusion: The erythrocyte-liposome drug delivery system could enhance the lung-specific targeting capability of liposomes, kill tumor cells and suppress further metastasis effectively.

Objective: To develop a depression recognition model by integrating the spirit-expression diagnostic framework of traditional Chinese medicine (TCM) with machine learning algorithms. The proposed model seeks to establish a TCM-informed tool for early depression screening, thereby bridging traditional diagnostic principles with modern computational approaches. Methods: The study included patients with depression who visited the Shanghai Pudong New Area Mental Health Center from October 1, 2022 to October 1, 2023, as well as students and teachers from Shanghai University of Traditional Chinese Medicine during the same period as the healthy control group. Videos of 3 – 10 s were captured using a Xiaomi Pad 5, and the TCM spirit and expressions were determined by TCM experts (at least 3 out of 5 experts agreed to determine the category of TCM spirit and expressions). Basic information, facial images, and interview information were collected through a portable TCM intelligent analysis and diagnosis device, and facial diagnosis features were extracted using the Open CV computer vision library technology. Statistical analysis methods such as parametric and non-parametric tests were used to analyze the baseline data, TCM spirit and expression features, and facial diagnosis feature parameters of the two groups, to compare the differences in TCM spirit and expression and facial features. Five machine learning algorithms, including extreme gradient boosting (XGBoost), decision tree (DT), Bernoulli naive Bayes (BernoulliNB), support vector machine (SVM), and k-nearest neighbor (KNN) classification, were used to construct a depression recognition model based on the fusion of TCM spirit and expression features. The performance of the model was evaluated using metrics such as accuracy, precision, and the area under the receiver operating characteristic (ROC) curve (AUC). The model results were explained using the Shapley Additive exPlanations (SHAP). Results: A total of 93 depression patients and 87 healthy individuals were ultimately included in this study. There was no statistically significant difference in the baseline characteristics between the two groups (P > 0.05). The differences in the characteristics of the spirit and expressions in TCM and facial features between the two groups were shown as follows. (i) Quantispirit facial analysis revealed that depression patients exhibited significantly reduced facial spirit and luminance compared with healthy controls (P < 0.05), with characteristic features such as sad expressions, facial erythema, and changes in the lip color ranging from erythematous to cyanotic. (ii) Depressed patients exhibited significantly lower values in facial complexion L, lip L, and a values, and gloss index, but higher values in facial complexion a and b, lip b, low gloss index, and matte index (all P < 0.05). (iii) The results of multiple models show that the XGBoost-based depression recognition model, integrating the TCM “spirit-expression” diagnostic framework, achieved an accuracy of 98.61% and significantly outperformed four benchmark algorithms—DT, BernoulliNB, SVM, and KNN (P < 0.01). (iv) The SHAP visualization results show that in the recognition model constructed by the XGBoost algorithm, the complexion b value, categories of facial spirit, high gloss index, low gloss index, categories of facial expression and texture features have significant contribution to the model. Conclusion This study demonstrates that integrating TCM spirit-expression diagnostic features with machine learning enables the construction of a high-precision depression detection model, offering a novel paradigm for objective depression diagnosis.

Objective: To investigate the efficacy of implantable neuromuscular electrical stimulation system on stress urinary incontinence (SUI) model in female rats. Methods: A total of 21 female infertile SD rats were randomly divided into the control，sham stimulation，and stimulation groups，with 7 rats in each group.All rats received vaginal dilation (VD) to simulate postpartum SUI.One week after VD，the control group was given normal feeding，stimulators were implanted in the pelvic floor muscles of the sham stimulation and stimulation groups.The sham stimulation group received normal feeding for 2 weeks，and the stimulation group received pelvic floor electrical stimulation (PFES) for 2 consecutive weeks.The leak point pressure (LPP) of each rat was measured with cystometry before VD (baseline value)，1 week after VD，and 2 weeks after PFES. Results: In the control group and sham stimulation group，LPP increased after 2 weeks of treatment compared with that after 1 week of VD，but it still did not return to the baseline level (P<0.001).In the stimulation group，after 2 consecutive weeks of PFES，LPP increased significantly compared with that 1 week after VD，and returned to the baseline value (P>0.05).There was no significant difference in the LPP baseline values and levels after 1 week of VD among the 3 groups (P>0.05).The LPP in the stimulation group after 2 weeks of PFES was significantly higher than that in the sham stimulation group and stimulation group (P<0.001). Conclusion: The implantable neuromuscular electrical stimulation system is effective in short-term intervention of SUI in female rats，the further studies are needed to confirm the long-term efficacy and safety of the system，the optimal stimulation sites，optimal stimulation parameters，and potential mechanisms of action.

Cancer is the result of evolving crosstalk between neoplastic cell and its immune microenvironment. In recent years, immune therapeutics targeting T lymphocytes, such as immune checkpoint blockade (ICB) and CAR-T, have made significant progress in cancer treatment and validated targeting immune cells as a promising approach to fight human cancers. However, responsiveness to the current immune therapeutic agents is limited to only a small proportion of solid cancer patients. As major components of most solid tumors, myeloid cells played critical roles in regulating the initiation and sustentation of adaptive immunity, thus determining tumor progression as well as therapeutic responses. In this review, we discuss emerging data on the diverse functions of myeloid cells in tumor progression through their direct effects or interactions with other immune cells. We explain how different metabolic reprogramming impacts the characteristics and functions of tumor myeloid cells, and discuss recent progress in revealing different mechanisms-chemotaxis, proliferation, survival, and alternative sources-involved in the infiltration and accumulation of myeloid cells within tumors. Further understanding of the function and regulation of myeloid cells is important for the development of novel strategies for therapeutic exploitation in cancer.
Humans ; Tumor Microenvironment/immunology* ; Myeloid Cells/immunology* ; Neoplasms/therapy* ; Animals

Children， as a special group， frequently experience of off-label drug use worldwide. Common reasons for off-label drug use in children include the lack of data on pediatric patients during the clinical trial stage of drug development， delayed updates to drug instructions， and the non-standard professional behavior of some doctors. Off-label drug use in children is a double-edged sword. It could save lives and provide a way to explore additional functions of drugs， while it may also lead to the phenomenon of hyper-indication abuse， increasing the risk of adverse drug events. Regulating off-label drug use in children can safeguard the best treatment rights and interests of children. It is recommended to encourage pharmaceutical enterprises to conduct research and development of pediatric new drugs， simplify the approval process for drug instructions amendments， accumulate evidence-based medical evidence for off-label drug use in children， standardize the process of off-label drug use in children in medical institutions， continuously improve the standardized diagnosis and treatment capabilities of pediatricians， and actively cooperate with the families of pediatric patients in diagnosis and treatment， so as to comprehensively safeguard the rights and interests of both doctors and patients.

Mitochondria, ubiquitous energy-producing organelles in eukaryotic cells, can have their normal functions disrupted by bacterial infections, leading to mitochondrial dysfunction. This dysfunction is closely associated with inflammatory diseases. Periodontitis, a chronic inflammatory disorder of periodontal tissues caused by pathogenic microorganisms, has been increasingly linked to mitochondrial dysfunction in its pathogenesis and progression. Compared to healthy periodontal tissues, inflammatory lesions exhibit more pronounced mitochondrial dysfunction—a pathological process that is strongly correlated with periodontal pathogen infection. Studies reveal that these pathogens disrupt mitochondrial homeostasis in host cells (e.g., gingival epithelial cells and fibroblasts) through multiple mechanisms, including disrupting mitochondrial biogenesis, altering mitochondrial dynamics (promoting excessive fission), inhibiting mitophagy, impairing mitochondrial dysfunction-associated apoptosis, and inducing endogenous oxidative stress, which upregulates pro-inflammatory cytokines. Collectively, these processes drive the establishment and persistence of an inflammatory microenvironment. This review explores how periodontal pathogens affect mitochondrial function and their mechanistic contributions to periodontitis progression, with the goal of providing novel insights for developing mitochondria-targeted therapeutic strategies.

Objective: To investigate the predictive value of EZH2 expression for malignant transformation in oral leukoplakia (OLK) and to provide a reference for clinical practice. Methods: This study was approved by the institutional ethics committee, and informed consent was obtained from all participants. A total of 114 patients diagnosed with OLK by pathological examination and treated at our hospital between November 2020 and July 2022 were initially enrolled. After excluding those with incomplete data or follow-up, 105 participants were included in the final analysis, comprising 14 in the high EZH2 expression group and 91 in the low EZH2 expression group. Histopathological examination of oral mucosa and immunohistochemical detection of EZH2 protein expression were performed. The follow-up period was 30 months; participants were followed until malignant transformation occurred or until the end of follow-up, at which point they were withdrawn from the study. The exposure factor was the level of EZH2 protein expression, and the outcome was the malignant transformation rate of OLK. Differences in EZH2 expression levels and transformation outcomes were analyzed. Results: There were no statistically significant differences between the high and low EZH2 expression groups in terms of age, sex, history of systemic disease, lifestyle habits, psychological status, diet, and sleep conditions (P > 0.05). Lesions in the high EZH2 expression group were mainly located on the ventral tongue, while in the low EZH2 expression group, they were more commonly found on the dorsal tongue and buccal mucosa. The malignant transformation rate was 28.6% (4/14) in the high expression group and 8.8% (8/91) in the low expression group; these differences were not statistically significant (P=0.053). In univariate Cox regression analysis, the risk of malignant transformation in the high EZH2 expression group was 3.647 times that of the low EZH2 expression group (HR = 3.647, 95% CI: 1.097-12.120, P<0.05). Kaplan-Meier survival analysis showed that over the 30-month follow-up period, the cancer-free survival rate in the high EZH2 expression group was 19.8% lower than in the low expression group, and the difference was statistically significant (P<0.05). In multivariate Cox regression analysis, only moderate and severe epithelial dysplasia were identified as independent risk factors for malignant transformation. The risk of malignant transformation in the moderate and severe dysplasia groups was 10.695 and 13.623 times higher, respectively, than in the mild dysplasia group (HR = 10.695, 95% CI: 2.270-50.396, P<0.05; HR=13.623, 95% CI: 1.918-96.774, P<0.05). EZH2 high expression was not an independent risk factor in the multivariate model (HR= 2.528, 95% CI: 0.752-8.500, P = 0.134). Conclusion High EZH2 protein expression is a risk factor for the malignant transformation of OLK but does not have independent predictive value.

OBJECTIVE To explore the practice pathway and evaluate the effectiveness of the resident pharmacists stationed in the Drug Clinical Trial Institution Office （hereinafter referred to as the “GCP resident pharmacist”） in the management of dermatological drug clinical trials. METHODS The practical approach of GCP resident pharmacists participating in dermatological drug clinical trials at our hospital was introduced. A retrospective analysis was conducted on the data of dermatological drug clinical trials from 2021 to 2024， comparing efficiency and quality indicators between dermatological clinical trials and those of other specialties. RESULTS With the involvement of our hospital’s GCP resident pharmacists throughout, the process for dermatology drug clinical trials was constructed and optimized， a dedicated quality control system was established， and the acceleration strategy for subject enrollment was optimized. The number of dermatological drug clinical trials at our hospital showed a compound annual growth rate of 69.56% from 2021 to 2023. In terms of efficiency indicators， the approval waiting time for dermatological drug clinical trials was （12.31±4.99） days， which was significantly shorter than that of other specialties （[ 19.68±6.09） days， P＜0.05]. Regarding quality indicators， the enrollment rate for dermatological drug clinical trials was 75.71%（50.00%，114.48%）， which was significantly higher than that of other specialties [51.00%（25.00%，174.17%）， P＜0.05]. The numbers of first quality control issues （[ 8.31±3.25）items vs.（ 11.68±4.49）items] and protocol deviations [5.5（2.0，11.0）times vs. 11.0（5.5，17.5）times] were significantly lower than those of other specialties （P＜0.05）. CONCLUSIONS GCP resident pharmacists significantly enhance the overall efficiency of dermatological drug clinical trials， playing a crucial role in ensuring the reliability and authenticity of drug clinical trials， as well as safeguarding the rights and safety of trial subjects.

Objective　To analyze the clinical characteristics and prognostic factors for clinical cure in chronic hepatitis B virus (HBV) infected patients with pegylated interferon-α-2b (PEG-IFN-α-2b) based therapy. Methods　This is a retrospective study. Chronic HBV infected patients receiving PEG-IFN-α-2b therapy were enrolled in Yuncheng Central Hospital affiliated to Shanxi Medical University between August 2020 and November 2023. Treatment-naïve patients received PEG-IFN-α-2b monotherapy, while nucleoside (acid) analogs (NAs)-experienced patients received PEG-IFN-α-2b add-on therapy. The study endpoint was hepatitis B surface antigen (HBsAg) negative in accompany with HBV DNA below the detection limit (course of treatment < 48 weeks) or treatment for 48 weeks. The general characteristics, virological variables, blood routine test, and liver function of patients were collected at baseline and study endpoint. Student’s t test or Mann-Whitney U test was used for comparison. The prognostic factors of clinical cure were examined using univariate and multivariate stepwise logistic regression models. Results　A total of 61 chronic HBV infected patients were enrolled, including 39 males and 22 females. The age were (39.13±7.53) years. Twenty-one cases were treatment-naïve, while 40 patients were NAs-experienced. Nineteen cases were positive for HBV DNA at baseline. The baseline HBsAg levels were 211.30(50.93, 2 110.00) IU/mL. Thirty-four patients achieved clinical cure at the study endpoint with 25.50 weeks of median course of PEG-IFN-α-2b treatment. Twenty-seven patients did not achieve clinical cure at the study endpoint, and the course of treatment was 48 weeks. Clinical cure group had significant lower baseline HBsAg level when compared with non-clinical cure group [78.66(19.54, 204.60) IU/mL vs 2 078.00(442.20, 4 237.00) IU/mL, P<0.001]. At the study endpoint, the white blood cell, platelet, red blood cell, hemoglobin levels were lower than those in baseline (P<0.05), while alanine aminotransferase and asparatate aminotransferase levels were higher than those in baseline (P<0.05). There were no remarkable differences in blood routine tests or liver function between clinical cure and non-clinical cure group at either baseline or study endpoint (P>0.05). Baseline low HBsAg level was a predictor for clinical cure in patients receiving PEG-IFN-α-2b therapy (OR=0.998, 95%CI: 0.998-0.999). No severe adverse events were happened during therapy. Conclusion　PEG-IFN-α-2b-based therapy was well-tolerant, and could achieve high rate of clinical cure in chronic HBV-infected patients who had low baseline HBsAg level.

Background Existing studies have confirmed that fine particulate matter (PM_2.5)is one of the important factors inducing pulmonary fibrosis. Pulmonary fibrosis is the terminal stage of a major category of lung diseases characterized by the destruction of tissue structure, and eventually leading lung ventilation and ventilation dysfunction. No effective pulmonary fibrosis treatment is available yet. Objective To investigate the protective effect of salidroside on pulmonary fibrosis induced by the exposure of PM_2.5 and its molecular mechanism. Methods Seventy 7-week-old male C57BL/6 mice were randomly divided into four groups: control group (intratracheal instillation of normal saline + saline by gavage, n=25), Sal group (intratracheal instillation of normal saline + Sal 60 mg·kg⁻¹ by gavage, n=10), PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ + saline by gavage, n=10), and Sal + PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ +Sal 60 mg·kg⁻¹ by gavage, n=10). The mice were administered by gavage once daily, intratracheal instillation once every 3 d, and every 3 d constituted an experimental cycle. At the end of the 26-30th cycles, 3 mice in the control group and 3 mice in the PM_2.5 group were randomly sacrificed, and the lung tissues were collected for Masson staining to verify whether the pulmonary fibrosis model was successfully established. After 30 cycles, the model was successfully constructed. After 1 week of continuous observation, the mice were sacrificed, and the blood and lung tissues of the mice were collected to make lung tissue sections. Assay kits were correspondingly employed to detect oxidative stress indicators such as serum malondialdehyde (MDA) and superoxide dismutase (SOD). Western blotting was used to detect the expression of fibrosis-related proteins (Collagen-III, α-SMA), mitochondrial dynamics-related proteins (MFN1, Drp1), and mitophagy-related proteins (PINK1, Parkin, and LC3). Results Compared with the control group, the weight gain rate of the PM_2.5 group was slowed down (P<0.05), which was alleviated by the Sal intervention (P<0.05). The lung coefficient increased after the PM_2.5 exposure (P<0.05), which was alleviated by Sal intervention. Compared with the control group, the PM_2.5 group showed severe alveolar structure damage, inflammatory cell infiltration, and blue collagen deposition, and significantly increased the lung injury score, collagen volume fraction (CVF), Szapiel score, and Ashcroft score (P<0.05), as well as serum oxidative stress levels (P<0.05). The protein expression levels of Collagen-III, α-SMA, Drp1, PINK1, Parkin, and LC3 II/I were increased (P<0.05), and the expression of MFN1 was decreased (P<0.05). Compared with the PM_2.5 group, the Sal intervention alleviated lung injury, reduced inflammatory cell infiltration and collagen deposition, showing decreased lung injury score, CVF, Szapiel score, and Ashcroft score (P<0.05), and decreased serum oxidative stress levels (P<0.05); the protein expression levels of Collagen-III, α-SMA, PINK1, Parkin, and LC3 II/I were decreased (P<0.05), the expression level of Drp1 was decreased, and the expression level of MFN1 was increased. Conclusion In the process of pulmonary fibrosis induced by PM_2.5 exposure in mice, Sal may affect mitochondrial autophagy through PINK1/Parkin pathway and play a protective role. The specific mechanism needs to be further verified.