ObjectiveTo explore the efficacy and mechanisms of Sini San in the treatment of depression and liver injury based on gut microbiota. MethodsThirty-two male Sprague-Dawley （SD） rats were randomly divided into a normal group， model group （M）， Sini San group （MS， 2.5 g·kg^-1）， and fluoxetine group （MF， 2 mg·kg^-1）. Except for the normal group， rats in the other three groups were subjected to chronic unpredictable mild stress （CUMS）. After 8 weeks， the open-field test and sucrose preference test were conducted. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum corticosterone （CORT）， adrenocorticotropic hormone （ACTH）， corticotropin-releasing factor （CRF）， lipopolysaccharide （LPS）， Zonulin， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， γ-aminobutyric acid （GABA） levels in the hippocampus and prefrontal cortex， and brain-derived neurotrophic factor （BDNF） levels in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect hippocampal BDNF mRNA expression. Serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured using the ultraviolet lactate dehydrogenase method. The ultrastructure of the intestinal epithelium was observed by electron microscopy， and gut microbiota in rat feces were analyzed using 16S rDNA high-throughput sequencing. ResultsCompared with the normal group， the sucrose preference of rats in the model group was significantly reduced （P0.01）， whereas it was significantly increased in the Sini San group compared with the model group （P0.05）. Compared with the normal group， hippocampal GABA protein levels and BDNF mRNA expression in the model group were significantly decreased （P0.05）， and compared with the model group， both were significantly increased in the Sini San group （P0.05， P0.01）. Compared with the normal group， serum LPS and Zonulin levels in the model group were significantly increased （P0.05， P0.01）， and compared with the model group， Zonulin levels in the Sini San group were significantly decreased （P0.05）. No obvious changes were observed in the ultrastructure of the jejunal mucosa among groups. Compared with the normal group， widened and blurred tight junctions， sparse and shortened microvilli， and mitochondrial swelling with cristae disruption in epithelial cells were observed in the ileal and colonic mucosa of the model group， which were markedly improved in the Sini San and fluoxetine groups. The results of 16S rDNA high-throughput sequencing showed that Sini San improved CUMS-induced dysbiosis of Bacteroidetes and Proteobacteria. Correlation analysis indicated that Bacteroidetes and Proteobacteria were significantly correlated with depression-related indicators， liver function， and intestinal mucosal permeability. ConclusionSini San exerts antidepressant and hepatoprotective effects by improving Bacteroidetes and Proteobacteria and inhibiting the increase in intestinal mucosal permeability in CUMS rats.

ObjectiveTo explore the efficacy and mechanisms of Sini San in the treatment of depression and liver injury based on gut microbiota. MethodsThirty-two male Sprague-Dawley （SD） rats were randomly divided into a normal group， model group （M）， Sini San group （MS， 2.5 g·kg^-1）， and fluoxetine group （MF， 2 mg·kg^-1）. Except for the normal group， rats in the other three groups were subjected to chronic unpredictable mild stress （CUMS）. After 8 weeks， the open-field test and sucrose preference test were conducted. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum corticosterone （CORT）， adrenocorticotropic hormone （ACTH）， corticotropin-releasing factor （CRF）， lipopolysaccharide （LPS）， Zonulin， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， γ-aminobutyric acid （GABA） levels in the hippocampus and prefrontal cortex， and brain-derived neurotrophic factor （BDNF） levels in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect hippocampal BDNF mRNA expression. Serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured using the ultraviolet lactate dehydrogenase method. The ultrastructure of the intestinal epithelium was observed by electron microscopy， and gut microbiota in rat feces were analyzed using 16S rDNA high-throughput sequencing. ResultsCompared with the normal group， the sucrose preference of rats in the model group was significantly reduced （P<0.01）， whereas it was significantly increased in the Sini San group compared with the model group （P<0.05）. Compared with the normal group， hippocampal GABA protein levels and BDNF mRNA expression in the model group were significantly decreased （P<0.05）， and compared with the model group， both were significantly increased in the Sini San group （P<0.05， P<0.01）. Compared with the normal group， serum LPS and Zonulin levels in the model group were significantly increased （P<0.05， P<0.01）， and compared with the model group， Zonulin levels in the Sini San group were significantly decreased （P<0.05）. No obvious changes were observed in the ultrastructure of the jejunal mucosa among groups. Compared with the normal group， widened and blurred tight junctions， sparse and shortened microvilli， and mitochondrial swelling with cristae disruption in epithelial cells were observed in the ileal and colonic mucosa of the model group， which were markedly improved in the Sini San and fluoxetine groups. The results of 16S rDNA high-throughput sequencing showed that Sini San improved CUMS-induced dysbiosis of Bacteroidetes and Proteobacteria. Correlation analysis indicated that Bacteroidetes and Proteobacteria were significantly correlated with depression-related indicators， liver function， and intestinal mucosal permeability. ConclusionSini San exerts antidepressant and hepatoprotective effects by improving Bacteroidetes and Proteobacteria and inhibiting the increase in intestinal mucosal permeability in CUMS rats.

ObjectiveTo observe the changes in the levels of different subtypes of epidermal growth factor receptor （ErbB）， namely ErbB1， ErbB2， ErbB3， and ErbB4， in the spinal dorsal horn of inflammatory pain model rats， and to explore their mechanism of mediating hyperalgesia as well as the intervention mechanism of electroacupuncture at "Zusanli （ST 36）" and "Kunlun （BL 60）". MethodsThe study was divided into five parts. In experiment 1， 14 Sprague Dawley （SD） rats were randomly divided into control and inflammatory pain group （7 rats each group） to observe the pain behavior and the protein expression of different ErbB receptor subtypes in the spinal dorsal horn. In experiment 2， 30 rats were randomly divided into control group 1， inflammatory pain group 1， and low-， medium-， and high-concentration TX1-85-1 groups， with 6 rats in each group， to observe the effect of inhibiting spinal ErbB3 on inflammatory pain. In experiment 3， 12 rats were randomly divided into control virus group and ErbB3 knockdown virus group， with 6 rats in each group， to observe the effect of knocking down ErbB3 in the spinal dorsal horn on inflammatory pain. In experiment 4， 44 rats were randomly divided into control group 2， inflammatory pain group 2， electroacupuncture group， and sham electroacupuncture group， with 11 rats in each group， to observe the effect of electroacupuncture. In experiment 5， 40 rats were randomly divided into control group 3， inflammatory pain group 3， electroacupuncture group 1， and electroacupuncture + NRG1 group， with 10 rats in each group， to observe the effect of activating ErbB3 on electroacupuncture. A rat model of inflammatory pain was established by subcutaneous injection of 100 μl of complete Freund's adjuvant into the sole of the unilateral hind foot of SD rats. Rats in the low-， medium-， and high-concentration TX1-85-1 groups were intrathecally injected with ErbB3 inhibitor TX1-85-1 on day 5 to day 7 after modeling. Rats in the ErbB3 knockdown virus group were injected with ErbB3 knockdown virus packaged with adenovirus vector-based short hairpin RNA （shRNA） into the spinal dorsal horn in situ 3 weeks before modeling. Rats in each electroacupuncture group received electroacupuncture at bilateral "Zusanli （ST 36）" and "Kunlun （BL 60）" from day 1 to day 7 after modeling， with dense-sparse waves at a frequency of 2 Hz/100 Hz and a current of 0.5-1.5 mA for 30 minutes once a day. Rats in the electroacupuncture + NRG1 group were intrathecally injected with ErbB3 ligand recombinant human neuregulin-1 （NRG1） after electroacupuncture intervention from day 5 to day 7 after modeling. The mechanical withdrawal threshold and thermal withdrawal latency of rats were measured on day 1， 3， 5， and 7 after modeling to evaluate behavior， and Western Blot was used to detect the protein and phosphorylation levels of each ErbB subtype in the spinal dorsal horn. ResultsCompared with the control group， rats in the inflammatory pain group showed decreased mechanical withdrawal threshold and thermal withdrawal latency of rats， and increased expression of phosphorylated ErbB3 （p-ErbB3） protein in the spinal dorsal horn on days 1， 3， 5， and 7 after modeling （P＜0.01）. On day 5 and day 7 after modeling， compared with the inflammatory pain group 1， the mecha-nical withdrawal threshold and thermal withdrawal latency of rats in the medium- and high-concentration TX1-85-1 groups increased， and the expression of p-ErbB3 protein decreased （P＜0.05）. On day 1， 3， 5， and 7 after modeling， compared with the control virus group， the mechanical withdrawal threshold and thermal withdrawal latency of rats in the ErbB3 knockdown virus group increased （P＜0.05）. On day 5 and day 7 after modeling， compared with the inflammatory pain group 2 and the sham electroacupuncture group， the mechanical withdrawal threshold and thermal withdrawal latency of rats in the electroacupuncture group increased， and the expression of p-ErbB3 protein decreased （P＜0.05）. On day 5 and day 7 after modeling， compared with the electroacupuncture + NRG1 group， the mechanical withdrawal threshold and thermal withdrawal latency of rats in the electroacupuncture group 1 increased （P＜0.05）. ConclusionThe p-ErbB3 in the spinal dorsal horn involved in hyperalgesia in rats with inflammatory pain， and electroacupuncture at "Zusanli （ST 36）" and "Kunlun （BL 60）" can alleviate inflammatory pain by inhibiting the expression of p-ErbB3 protein in the spinal dorsal horn of rats.

Objective: To investigate the barrier membrane fixation performance and enhanced guided bone regeneration (GBR) capability of a thermosensitive adhesive containing bioactive glass nanoparticles in order to provide a novel solution for membrane fixation during GBR procedures. Methods: M2NP@BGN (methoxyethyl acrylate-co-N-isopropylacrylamide-co-protocatechuic acid@Bioactive glass nanoparticle), a thermosensitive adhesive, was synthesized via free radical polymerization by compositing methoxyethyl acrylate, N-isopropylacrylamide, and protocatechuic acid into a basic adhesive that was modified with bioactive glass nanoparticle (BGN). The successful fabrication of basic adhesive M2NP was characterized by attenuated total reflection-Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The thermosensitive adhesive M2NP@BGN (BGN concentration of 1 mg/mL) was characterized by scanning electron microscopy and a rheometer. By adjusting the BGN concentration (0.1 mg/mL, 0.5 mg/mL, 1 mg/mL, and 2 mg/mL), the adhesive and mechanical strengths were investigated with a universal testing machine. Biocompatibility was evaluated with a cell counting kit-8 assay and hemolysis test to identify the optimal formulation. The optimal material’s extract was co-cultured with mouse bone marrow mesenchymal stem cells, and its osteogenic activity was examined in vitro by quantitative real-time PCR, alkaline phosphatase, and alizarin red S staining. The rat mandibular defect model was established, filled with bone graft, and divided into 3 groups based on membrane fixation method: M2NP@BGN (BGN concentration of 1 mg/mL) fixation group (M2NP@BGN), titanium nail fixation group (Nail), and unfixed control group (Negative). Bone regeneration was analyzed after 8 weeks by micro computed tomography and histological staining. Results: M2NP@BGN (BGN concentration of 1 mg/mL) was successfully synthesized and demonstrated rapid gelation under warm, humid conditions. The adhesive with a BGN concentration of 1 mg/mL exhibited the highest adhesive strength (P < 0.001) and significantly enhanced mechanical strength (P < 0.001) under 37℃ wet conditions. All formulations showed excellent biocompatibility, with cell viability > 80% and hemolysis ratio < 5%. M2NP@BGN (BGN concentration of 1 mg/mL) significantly upregulated the expression of Runx2 and Col I (P < 0.001) and enhanced the activity of osteogenic differentiation markers (P < 0.05). In the animal model, the M2NP@BGN group (BGN concentration of 1 mg/mL) achieved significantly higher bone volume fraction and better bone maturity compared to the negative and nail groups (P < 0.05). Conclusion M2NP@BGN (BGN concentration of 1 mg/mL) combines excellent wet adhesion with potent osteogenic activity, enhances the bone augmentation efficacy of membranes, and presents a novel fixation strategy with significant clinical translation potential for GBR therapy.

Objective To examine the safety, efficacy and durability of totally endoscopic minimally invasive (TEMI) mitral valve repair in Barlow’s disease (BD). Methods A retrospective study was performed on patients who underwent mitral valve repair for BD from January 2010 to June 2021 in the Guangdong Provincial People’s Hospital. The patients were divided into a MS group and a TEMI group according to the surgery approaches. A comparison of the clinical data between the two groups was conducted. Results A total of 196 patients were enrolled, including 133 males and 63 females aged (43.8±14.9) years. There were 103 patients in the MS group and 93 patients in the TEMI group. No hospital death was observed. There was a higher percentage of artificial chordae implantation in the TEMI group compared to the MS group (P=0.020), but there was no statistical difference between the two groups in the other repair techniques (P>0.05). Although the total operation time between the two groups was not statistically different (P=0.265), the TEMI group had longer cardiopulmonary bypass time (P<0.001) and aortic clamp time (P<0.001), and shorter mechanical ventilation time (P<0.001) and postoperative hospitalization time (P<0.001). No statistical difference between the two groups in the adverse perioperative complications (P>0.05). The follow-up rate was 94.2% (180/191) with a mean time of 0.2-12.4 (4.0±2.4) years. Two patients in the MS group died with non-cardiac reasons during the follow-up period. The 3-year, 5-year and 10-year overall survival rates of all patients were 100.0%, 99.2%, 99.2%, respectively. Compared with the MS group, there was no statistical difference in the survival rate, recurrence rate of mitral regurgitation, reoperation rate of mitral valve or adverse cardiovascular and cerebrovascular events in the TEMI group (P＞0.05). Conclusion TEMI approach is a safe, feasible and effective approach for BD with a satisfying long-term efficacy.

POEMS syndrome is a rare condition associated with plasma cell disorders， and it often involves multiple systems and has diverse clinical manifestations. This article reports two cases of POEMS syndrome with hepatosplenomegaly as the initial manifestation. During the course of the disease， the patients presented with lower limb weakness， hepatosplenomegaly， lymph node enlargement， ascites， hypothyroidism， positive M protein， and skin hyperpigmentation， and ¹⁸F-FDG PET-CT imaging revealed bone lesions mainly characterized by osteolytic changes and plasma cell tumors. There was an increase in the serum level of vascular endothelial growth factor. The patients were finally diagnosed with POEMS syndrome， and the symptoms were relieved after immunomodulatory treatment.

Aromatic inhalation therapy is a key traditional Chinese medicine （TCM） approach for preventing respiratory infectious diseases. Its foundational theory， "aromatics acting on the spleen"， is deeply rooted in TCM principles and supported by modern medical research. The theory posits that the aromatic properties of medicinals primarily act on the spleen， and the aromatic inhalation therapy achieved its protective effects by modulation of the spleen and spleen channel to enhance the regulation of wei qi， striae and interstices. In TCM， the spleen is considered the mother of the lungs， with the function of nurturing lung； it is also seen as the source of wei qi， responsible for external defense； and the root of healthy qi， forming the foundation of acquired （postnatal） constitution. Thus， preventive strategies for respiratory infectious diseases focus on strengthening the spleen. From a modern medical perspective， the spleen's role in regulating lung immune responses， the shared immune functions of the respiratory and gastrointestinal mucosa， and the spleen's overall immune modulation provide scientific evidence for using aromatic inhalation therapy to prevent respiratory infections. Additionally， aromatic inhalation therapy offers several advantages， including direct action， rapid onset， minimal side effects， controllable risks， convenience， and ease of dissemination， making it a practical and effective preventive measure for respiratory infectious diseases.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Clinical data of a patient with alveolar soft part sarcoma (ASPS) treated at Zhongshan Hospital, Fudan University were retrospectively analyzed. The patient was initially diagnosed with abdominal ASPS with multiple lung metastases. After 6 weeks of treatment with nivolumab and ipilimumab, the patient achieved stable disease (SD). In the 7th week, the treatment was changed to a combination of nivolumab (30 mg, d1, q3w), anlotinib (8 mg, d1-14, q3w) and ipilimumab (50 mg, d1, q6w). The patient remained SD at the 12th week. The patient then underwent iliac artery embolization and intensity-modulated radiation therapy for the lesion in the psoas major muscle, while continuing the combination treatment. By the 24th week, the evaluation showed partial remission (PR) of both primary tumor and lung metastases. The patient experienced mild adverse reactions during treatment.

Background At present, the treatment of silicosis is still limited, and no method is available to cure the disease. miRNAs are involved in the process of fibrosis at the transcriptional level by directly degrading target gene mRNA or inhibiting its translation. However, how miR-130a-3p regulates silicosis fibrosis has not been fully elucidated yet. Objective To investigate whether miR-130a-3p promotes epithelial-mesenchymal transition (EMT) by inhibiting peroxisome proliferators-activated receptors gamma (PPAR-γ), thereby pro-moting the process of silicotic fibrosis. To identify effective new targets for the treatment of silicotic fibrosis. Methods (1) Animal experiments: C57BL/6J mice were intratracheally injected with a one-time dose of 10 mg silica suspension (dissolved in 100 μL saline) as positive lung exposure. A silicosis model group was established 28 d after the exposure. A control group was injected with the same amount of normal saline into the trachea. Hematoxylin-eosin staining and Sirius red staining were used to observe the pathological changes and collagen deposition in lung tissues respectively. Realtime fluorescence-based quantitative polymerase chain reaction (RT-qPCR) was used to assay the expression of miR-130a-3p and PPAR-γ mRNA in lung tissues. Western blotting was used to detect the protein expression of PPAR-γ, transforming growth factor (TGF)-β1, E-cadherin, α-smooth muscle actin (α-SMA), and Collagen Ⅰ in lung tissues. (2) Cells experiments: Mouse lung epithelial cells (MLE-12) were induced with 5 µg·L⁻¹ TGF-β1 for different time (0, 12, 24, 48 h). RT-qPCR was used to detect the expression of miR-130a-3p and PPAR-γ mRNA in cells. The binding relationship between miR-130a-3p and PPAR-γ mRNA was verified by dual luciferase reporter gene assay. MLE-12 cells were stimulated by 5 µg·L⁻¹ TGF-β1 after transfection of miR-130a-3p inhibitor, and Western blotting was used to measure the protein expression of PPAR-γ, E-cadherin, and α-SMA in the TGF-β1-induced cells. Results In the silicosis model group, the alveolar septum was widened and the pulmonary nodules were formed. The Sirius red staining collagen deposition in pulmonary nodules indicated that a silicosis fibrosis model was successfully established. The expressions of TGF-β1, α-SMA, and Collagen Ⅰ proteins were increased, and the expressions of E-cadherin and PPAR-γ proteins were decreased in lung tissues of the silicosis group, compared with the control group (P<0.05 or P<0.01). The expression of miR-130a-3p was increased and the expression of PPAR-γ mRNA was decreased in lung tissues of the silicosis model (P<0.01). The expression of miR-130a-3p was significantly increased, while the expression of PPAR-γ mRNA was decreased in the TGF-β1 induced MLE-12 cells (P<0.05 or P<0.01). The dual luciferase reporter assay showed a direct relationship between miR-130a-3p and PPAR-γ mRNA in MLE-12 cells. The transfection of miR-130a-3p inhibitor in the TGF-β1 induced MLE-12 cells inhibited the decrease of PPAR-γ and E-cadherin proteins, and the increase of α-SMA protein in the MLE-12 cells induced by TGF-β1 (P<0.05 or P<0.01). Conclusion miR-130a-3p promotes the development of silicosis fibrosis by targeting PPAR-γ to increase pulmonary EMT.