ObjectiveTo predict the mechanism through which Shasheng Maidong Tang enhances the efficacy of chemotherapy for lung cancer via network pharmacology and validate the prediction results in animal experiments. MethodsThe potential mechanism through which Shasheng Maidong Tang enhances the efficacy of chemotherapy for lung cancer was predicted by network pharmacology， liquid chromatography-mass spectrometry （LC-MS）， and molecular docking methods. C57/BL6 mice were assigned into normal， model， cisplatin， and Shasheng Maidong Tang+cisplatin groups. In addition to the normal group， the remaining groups were injected subcutaneously with 0.2 mL of 1×10⁷ cells·mL^-1 Lewis lung cancer cells to establish the Lewis lung cancer model. The daily gavage dose of Shasheng Maidong Tang was 3.58 g·kg^-1， and the concentration of cisplatin intraperitoneally injected on every other day was 2 mg·kg^-1. Drugs were administered for 14 d. The changes in the tumor volume and the rate of tumor suppression were monitored， and the tumor histopathological changes were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay was employed to measure the interleukin （IL）-6 and interferon （IFN）-γ levels in peripheral blood. Real-time PCR was performed to quantify the mRNA levels of Janus kinase 2 （JAK2）， signal transducer and activator of transcription 1 （STAT1）， and signal transducer and activator of transcription 3 （STAT3） in the tumor tissue of mice. Western blot was employed to determine the protein levels of JAK2， STAT3， B-cell lymphoma-2 （Bcl-2）， cysteinyl aspartate-specific proteinase-3 （Caspase-3）， and Pim-1 proto1 （PIM1） in the tumor tissue. Immunohistochemistry was employed to detect the expression of Bcl-2 and PIM1 in the tumor tissue. ResultsNetwork pharmacological predictions indicated that Shasheng Maidong Tang might enhance the efficacy of chemotherapy for lung cancer by regulating nitrogen metabolism， AGE-RAGE signaling pathway， cancer pathway， and JAK/STAT signaling pathway. The experimental results demonstrated that tumor volume in the cisplatin group and Shasheng Maidong Tang+cisplatin group was reduced compared with the model group， with statistically distinct differences observed on days 14， 17， 20 post modeling （P<0.05）. Notably， the Shasheng Maidong Tang+cisplatin therapy further decreased tumor volume compared with the cisplatin group， showing marked reductions on days 17 and 20 （P<0.05）， consistent with trends visualized in tumor volume comparison charts. The Shasheng Maidong Tang+cisplatin group exhibited higher tumor inhibition rate than the cisplatin group （P<0.05）. Histopathological analysis via HE staining revealed that the tumors in the model group displayed frequent nuclear mitosis， densely arranged cells， hyperchromatic nuclei， and no necrosis. Cisplatin treatment induced partial necrosis and vacuolization， while the Shasheng Maidong Tang+cisplatin group exhibited extensive necrotic regions， maximal vacuolization， disarranged tumor cells， and minimal mitotic activity. Compared with the model group， the cisplatin group and the Shasheng Maidong Tang+cisplatin group showed elevated level of IFN-γ （P<0.01） and declined level of IL-6 （P<0.01） in the peripheral blood. Compared with the cisplatin group， the Shasheng Maidong Tang+cisplatin group presented elevated level of IFN-γ （P<0.01） and lowered level of IL-6 （P<0.01） in the peripheral blood. Compared with the model group， the cisplatin group and the Shasheng Maidong Tang+cisplatin groups showed down-regulated mRNA levels of JAK2 and STAT3 （P<0.01） and up-regulated mRNA level STAT1 （P<0.01）. Compared with the cisplatin group， the Shasheng Maidong Tang+cisplatin group presented down-regulated mRNA levels of JAK2 and STAT3 （P<0.01） and up-regulated mRNA level of STAT1 （P<0.01）. Compared with the model group， the cisplatin group and the Shasheng Maidong Tang+cisplatin group showed down-regulated protein levels of JAK2 （P<0.01）， Bcl-2 （P<0.01）， PIM1 （P<0.01）， and STAT3 （P<0.05）， and up-regulated protein level of Caspase-3 （P<0.01）. Compared with the cisplatin group， Shasheng Maidong Tang+cisplatin group presented down-regulated protein levels of JAK2 （P<0.01）， Bcl-2 （P<0.01）， PIM1 （P<0.01）， STAT3 （P<0.05）， and up-regulated protein level of Caspase-3 （P<0.01）. The Bcl-2 and PIM1 expression results obtained by immunohistochemistry were consistent with those of Western blot. ConclusionShasheng Maidong Tang may enhance the efficacy of chemotherapy in the mouse model of Lewis lung cancer by regulating the JAK2/STAT3 signaling pathway.

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.

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.

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.

Objective To explore the effects of home-based exercise rehabilitation on cardiac structure, valvular function, and exercise capacity in patients with severe aortic stenosis (AS) after transcatheter aortic valve replacement (TAVR). Methods 49 patients with severe AS who underwent TAVR at Zhongshan Hospital, Fudan University, from January 2024 to February 2025 were enrolled. They were divided into an exercise group (n＝25) or a non-exercise group (n＝24) based on participating or not in home-based rehabilitation after TAVR. The exercise group received 12 weeks of home-based exercise training (aerobic exercise plus resistance training every week); the non-exercise group received routine care. Transthoracic echocardiography (TTE) was used to assess cardiac structural parameters before discharge (T0) and after 12 weeks of exercise (T1). Functional outcomes including the 6-minute walk test (6MWT), Duke Activity Status Index (DASI), and Short Physical Performance Battery (SPPB) were compared between the two groups. A linear mixed-effects model was used to analyze the effect of home-based rehabilitation on echocardiographic parameters. Patients were stratified by baseline 6MWT (＜240 m as low-function subgroup, ≥240 m as high-function subgroup) to compare exercise-related outcomes between subgroups. Results At T1, the exercise group had a longer 6MWT distance than the non-exercise group (P＝0.012). The linear mixed-effects model showed that after 12 weeks of exercise, the left ventricular end-diastolic diameter (LVEDD) decreased in the exercise group but slightly increased in the non-exercise group, with a significant difference in changes over time between the two groups (P_interaction＝0.030). The exercise group also showed greater improvement in effective orifice area index (P_interaction＝0.028) and effective orifice area (P_interaction＝0.042) than the non-exercise group. Subgroup analysis revealed that in the low-function subgroup, the exercise group showed greater improvement in the 6MWT (P_interaction＝0.035) and the effective orifice area index (P_interaction＝0.046) compared to the non-exercise group; in the high-function subgroup, the exercise group showed greater improvement only in LVEDD compared to the non-exercise group (P_interaction＝0.046). Conclusions Home-based exercise rehabilitation improves exercise capacity, optimizes left ventricular remodeling, and enhances valvular function in patients with severe AS after TAVR, with greater benefits observed in patients with lower baseline 6MWT.

Objective To investigate the therapeutic mechanism of Gandou Bushen Decoction(GDBSD)for improving reproductive disorders in male mouse models of Wilson disease(WD).Methods Sixty male homozygous TX mice were randomized equally into 4 groups and treated with daily gavage of saline(WD model group),penicillamine(0.09 g/kg),or GDBSD(0.2 mL/10 g),or with intraperitoneal injection of U0126(20 mg/kg)in addition to GDBSD gavage,with 15 male DL mice as control.After 4 weeks of treatment,copper content in testicular tissue of the mice was detected,and histopathology of the testes and epididymis was examined using HE staining and electron microscopy.TUNEL staining was used to identify apoptotic cells in the testes.The protein expressions of Bcl-2,Cytc,caspase-3,ERK,and p-ERK in the testicular tissue were evaluated with Western blotting,and BrdU-positive cells were detected with immunohistochemical labeling.Sperm density,viability,malformation rate and fertility levels of male mice were studied.Results Treatment with penicillamine and GDBSD obviously improved pathological changes of the testis,increased sperm density and motility,lowered sperm abnormality rate,fertility levels and increased testicular JOHNSEN score of TK mice,but the therapeutic effect of GDBSD was blocked by U0126.GDBSD treatment significantly lowered Cytc and caspase-3 expressions and increased Bcl-2 expression in the testicular tissue of TX mice(P<0.05),while U0126 treatment significantly lowered testicular Bcl-2 expression level.No significant differences were found in total protein expression levels of ERK1/2 among the 5 groups,but p-ERK protein expression was significantly reduced in WD and U0126 groups and increased in penicillamine and GDBSD groups.Conclusion GDBSD can improve spermatogenesis and enhance fertility of male TX mice with WD possibly by activating the ERK signaling pathway to enhance proliferation and reduce apoptosis of the spermatogenic cells.

Objective To investigate the therapeutic mechanism of Gandou Bushen Decoction(GDBSD)for improving reproductive disorders in male mouse models of Wilson disease(WD).Methods Sixty male homozygous TX mice were randomized equally into 4 groups and treated with daily gavage of saline(WD model group),penicillamine(0.09 g/kg),or GDBSD(0.2 mL/10 g),or with intraperitoneal injection of U0126(20 mg/kg)in addition to GDBSD gavage,with 15 male DL mice as control.After 4 weeks of treatment,copper content in testicular tissue of the mice was detected,and histopathology of the testes and epididymis was examined using HE staining and electron microscopy.TUNEL staining was used to identify apoptotic cells in the testes.The protein expressions of Bcl-2,Cytc,caspase-3,ERK,and p-ERK in the testicular tissue were evaluated with Western blotting,and BrdU-positive cells were detected with immunohistochemical labeling.Sperm density,viability,malformation rate and fertility levels of male mice were studied.Results Treatment with penicillamine and GDBSD obviously improved pathological changes of the testis,increased sperm density and motility,lowered sperm abnormality rate,fertility levels and increased testicular JOHNSEN score of TK mice,but the therapeutic effect of GDBSD was blocked by U0126.GDBSD treatment significantly lowered Cytc and caspase-3 expressions and increased Bcl-2 expression in the testicular tissue of TX mice(P<0.05),while U0126 treatment significantly lowered testicular Bcl-2 expression level.No significant differences were found in total protein expression levels of ERK1/2 among the 5 groups,but p-ERK protein expression was significantly reduced in WD and U0126 groups and increased in penicillamine and GDBSD groups.Conclusion GDBSD can improve spermatogenesis and enhance fertility of male TX mice with WD possibly by activating the ERK signaling pathway to enhance proliferation and reduce apoptosis of the spermatogenic cells.

ObjectiveUltra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS/MS） was used to investigate the metabolism and distribution of nardosinone in rats， then metabolic pathways were speculated. MethodRats were administered with 30 mg·kg^-1 of nardosinone suspension by gavage for 3 consecutive days， and plasma， urine， feces， and tissues of heart， liver， spleen， lung， kidney， brain， stomach， and intestine were collected at predetermined time points. After treatment， the samples were processed for UPLC-Q-Exactive Orbitrap MS/MS， and the MS data were analyzed using Xcalibur 2.2 software. The metabolites were searched by comparing the base peak chromatogram and extracted ion chromatogram between the treated group and blank group， and based on the relative retention time（t_R）， quasi-molecular ion peak， precise molecular mass， and fragment ions of MS/MS， the elemental composition were searched using databases such as SciFinder and PubChem， as well as referring to relevant literature， the possible metabolites were identified and the metabolic pathways were inferred. ResultA total of 30 metabolites of nardosinone were identified， including 15， 19， 12， 7， 4， 11， 8， 13， 13， 8 and 12 metabolites in urine， feces， plasma， brain， heart， liver， spleen， lung， kidney， stomach and intestine， respectively. The main metabolic pathways of nardosinone in rats were hydroxylation， dehydroxylation， reduction， dehydrogenation， hydration， dehydration， carboxylation， glucuronidation， and dehydroxy-isopropyl. ConclusionNardosinone can be metabolized by phase Ⅰ and phase Ⅱ metabolism in rats， and the metabolites are widely distributed in the major organs. The results of this study can provide a basis for further research on the pharmacodynamic material basis， pharmacological mechanism and clinical application of nardosinone.

Background Salidroside (SAL) has a protective effect on multiple organ systems. Exposure to fine particulate matter (PM_2.5) in the atmosphere may lead to disruptions in gut microbiota and impact intestinal health. The regulatory effect of SAL on the gut microbiota of mice exposed to PM_2.5 requires further investigation. Objective To evaluate gut microbiota disruption in mice after being exposed to PM_2.5 and the potential effect of SAL. Methods Forty male C57BL/6 mice, aged 6 to 8 weeks, were randomly divided into four groups: a control group, an SAL group, a PM_2.5 group, and an SAL+PM_2.5 group, each containing 10 mice. In the SAL group and the SAL+PM_2.5 group, the mice were administered SAL (60 mg·kg⁻¹) by gavage, while in the control group and the PM_2.5 group, sterile saline (10 mL·kg⁻¹) was administered by gavage. In the PM_2.5 group and the SAL+PM_2.5 group, PM_2.5 suspension (8 mg·kg⁻¹) was intratracheally instilled, and in the control group and SAL group, sterile saline (1.5 mL·kg⁻¹) was intratracheally administered. Each experiment cycle spanned 2 d, with a total of 10 cycles conducted over 20 d. Histopathological changes in the ileum tissue of the mice were observed after HE staining. Colon contents were collected for gut microbiota sequencing and short-chain fatty acids (SCFAs) measurements. Results The PM_2.5 group showed infiltration of inflammatory cells in the ileum tissue, while the SAL+PM_2.5 group exhibited only a small amount of inflammatory cell infiltration. Compared to the control group, the PM_2.5 group showed decreased Shannon index (P<0.05) and increased Simpson index (P<0.05), indicating that the diversity of gut microbiota in this group was decreased; the SAL+PM_2.5 group showed increased Shannon index compared to the PM_2.5 group (P<0.05) and decreased Simpson index (P<0.05), indicating that the diversity of gut microbiota in mice intervened with SAL was increased. The principal coordinates analysis (PCoA) revealed a significant separation between the PM_2.5 group and the control group, while the separation trend was less evident among the control group, the SAL group, and the SAL+PM_2.5 group. The unweighted pair-group method with arithmetic means (UPGMA) clustering tree results showed that the control group and the SAL group clustered together first, followed by clustering with the SAL+PM_2.5 group, and finally, the three groups clustered with the PM_2.5 group. The PCoA and UPGMA clustering results indicated that the uniformity and similarity of the microbiota in the PM_2.5 group were significantly decreased. Compared to the control group, the PM_2.5 group showed decreased abundance of phylum Bacteroidetes and Candidatus_Saccharimonas (P<0.05) and increased abundance of phylum Proteobacteria, genus Escherichia, genus Bacteroides, genus Prevotella, genus Enterococcus, and genus Proteus (P<0.05). Compared to the PM_2.5 group, the SAL+PM_2.5 group showed decreased abundance of phylum Proteobacteria, phylum Actinobacteria, genus Prevotella, and genus Proteus (P<0.05), and increased abundance of Candidatus_Saccharimonas (P<0.05). The PM_2.5 group showed reduced levels of propionic acid, valeric acid, and hexanoic acid compared to the control group (P<0.05), while the SAL+PM_2.5 group showed increased levels of propionic acid, isobutyric acid, butyric acid, valeric acid, and hexanoic acid compared to the PM_2.5 group (P<0.05). Conclusion Exposure to PM_2.5 can cause pathological alterations, microbial dysbiosis, and disturbing production of SCFAs in intestinal tissue in mice. However, SAL can provide a certain degree of protective effect against these changes.