OBJECTIVE To explore the effects of Lycium barbarum polysaccharides on the proliferation， migration， and immune escape of oral cancer cells by regulating the T cell immunoglobulin and mucin domain-containing protein 3 （TIM3）/ galectin-9 （Gal-9） signaling pathway. METHODS Human oral cancer cells KB and CAL27 were assigned to control group， L. barbarum polysaccharides low-concentration group （200 μg/mL）， L. barbarum polysaccharides high-concentration group （400 μg/mL）， pcDNA-NC group （transfection of pcDNA-NC plasmid）， pcDNA-TIM3 group （transfection of pcDNA-TIM3 plasmid）， high concentration of L. barbarum polysaccharides+pcDNA-NC group （400 μg/mL L. barbarum polysaccharides + transfection of pcDNA-NC plasmid）， and high concentration of L. barbarum polysaccharides+pcDNA-TIM3 group （400 μg/mL L. barbarum polysaccharides + transfection of pcDNA-TIM3 plasmid）. The proliferation， migration and invasion abilities of the cells， T cell killing rate as well as the levels of interferon-γ （IFN-γ） and interleukin-2 （IL-2） in the cell supernatant were measured. mRNA expressions of TIM3 and Gal-9 and protein expressions of indoleamine 2，3-dioxygenase 1 （IDO1）， programmed death-ligand 1 （PD-L1）， TIM3 and Gal-9 in the cells were also determined. RESULTS Compared with control group， the clone formation rate， scratch healing rate， the number of invasive cells， protein expressions of IDO1 and PD-L1， mRNA and protein expressions of TIM3 and Gal-9 in both cell types of L. barbarum polysaccharide low- and high-concentration groups were decreased significantly （P＜0.05）， while the proliferation inhibition rate， T cell killing rate， and the levels of IFN-γ and IL-2 were significantly increased （P＜0.05）. Compared with control group and pcDNA-NC group， the clone formation rate， scratch healing rate， the number of invasive cells， and protein expressions of IDO1 and PD-L1， mRNA and protein expressions of TIM3 and Gal-9 in both cell types of the pcDNA-TIM3 group were all significantly increased （P＜0.05）， while the proliferation inhibition rate， T cell killing rate， IFN-γ and IL-2 levels were significantly decreased （P＜0.05）. Compared with L. barbarum polysaccharides high-concentration group and high concentration of L. barbarum polysaccharides+pcDNA-NC group， the clone formation rate， scratch healing rate， the number of invasive cells， and protein expressions of IDO1 and PD-L1， mRNA and protein expressions of TIM3 and Gal-9 in both cell types of high concentration of L. barbarum polysaccharides+pcDNA-TIM3 group were significantly increased （P＜0.05）， while the proliferation inhibition rate， T cell killing rate， and the levels of IFN-γ and IL-2 were significantly decreased （P＜0.05）. CONCLUSIONS L. barbarum polysaccharides may inhibit the proliferation， migration， and immune escape of oral cancer cells by suppressing TIM3/Gal-9 signaling pathway.

The integrated medical and elderly care model provides comprehensive medical and elderly care services by establishing medical facilities in elderly care institutions or forming close cooperative relationships with surrounding medical institutions. Currently， there are 87，000 paired partnerships established nationwide between medical and health institutions and elderly care service institutions， and more than 7，800 integrated medical and elderly care institutions have obtained the qualifications of medical and health institutions and completed elderly care service registration. This model not only meets the elderly’s healthcare needs but also provides life care， psychological support， and social activities， thereby improving their quality of life. However， the integrated medical and elderly care model also faces numerous ethical dilemmas in practice. This paper aimed to explore in depth the ethical dilemmas and countermeasures optimization in the work of elderly care institutions under this model， to promote the improvement of service quality， comprehensively guarantee the rights and interests of the elderly， and promote the healthy development of this model in practice. Under this model， the elderly care institutions not only bear the responsibility of providing long-term care and life services but also need to cooperate with medical institutions to provide healthcare and health management services for the elderly. By exploring the practical paths for elderly care institutions to address the ethical dilemmas faced with this model， feasible solutions were proposed to enhance the welfare of the elderly and promote the harmonious development of society.

OBJECTIVE: To observe the effects of moxibustion at "Shenque" (CV8) on urodynamics and the expression of brain-derived neurotrophic factor (BDNF) and immediate early gene (c-fos) in pontine micturition center (PMC), periaqueductal gray (PAG), medial prefrontal cortex (mPFC) of neurogenic bladder (NB) rats after spinal cord injury. METHODS: Twenty-four SPF female SD rats were randomly divided into a sham-operation group (6 rats) and a modeling group (18 rats). In the modeling group, T₉ complete spinal cord transection method was used to establish a neurogenic detrusor overactivity model, and the 12 rats with successful modeling were randomized into a model group and a moxibustion group, with 6 rats in each group. The rats in the moxibustion group were treated with ginger/salt-insulated moxibustion at "Shenque" (CV8), and 4 consecutive moxa cones were delivered in one intervention. Moxibustion was operated once daily and for 14 days. After intervention completion, the urodynamic indexes of rats in each group were detected. Fluorescence quantitative PCR was used to detect the mRNA expression of BDNF and c-fos in PMC, PAG and mPFC in rats. Western blot was used to detect the protein expression of BDNF and c-fos in PMC, PAG and mPFC. RESULTS: The rats in the sham-operation group did not show phasic detrusor contraction during bladder filling. Compared with the model group, the frequency and amplitude of the phasic detrusor contraction were reduced 5 min before urine leakage in the rats of the moxibustion group (P<0.05), and the duration of the first phasic detrusor contraction during bladder filling was prolonged (P<0.05). Compared with the sham-operation group, the mRNA and protein expression of BDNF and c-fos in PMC, PAG and mPFC increased in the model group (P<0.05). Compared with the model group, the mRNA and protein expression of BDNF and c-fos in PMC, PAG and mPFC decreased in the moxibustion group (P<0.05). CONCLUSION Moxibustion at "Shenque" (CV8) can improve the phasic contraction during bladder filling in NB rats after spinal cord injury, possibly by down-regulating the mRNA and protein expression of BDNF and c-fos in PMC, PAG, and mPFC.
Animals ; Moxibustion ; Female ; Rats ; Brain-Derived Neurotrophic Factor/metabolism* ; Rats, Sprague-Dawley ; Acupuncture Points ; Spinal Cord Injuries/metabolism* ; Urinary Bladder, Neurogenic/etiology* ; Proto-Oncogene Proteins c-fos/metabolism* ; Humans ; Urinary Bladder/physiopathology* ; Brain/metabolism* ; Urination

ObjectiveTo explore the potential mechanism of action of the combination of Sanguisorbae Radix-Sophorae Flos （DH） in the treatment of ulcerative colitis （UC） using network pharmacology methods and molecular docking technology. MethodsNetwork pharmacology analysis was utilized to predict the potential targets of DH for the treatment of UC. The therapeutic effects were experimentally validated by inducing a UC model in mice with 3% dextran sulfate sodium （DSS）. The experimental groups were the normal group， the model group， the salazosulfapyridine group （100 mg·kg^-1）， and the low， medium， and high dose groups of DH （1.2， 2.4， and 4.8 g·kg^-1）. The efficacy of the treatment was assessed through the general condition of the mice， histopathological examination， and the expression levels of inflammatory markers in the colon. The effect of DH on angiogenesis was explored by messenger RNA （mRNA） detection of colonic angiogenesis-related mediators， vascular endothelial growth factor （VEGF） immunohistochemistry， microvessel density （MVD） detection， and transmission electron microscopy. The phosphatidylinositol-3-kinase （PI3K）-protein kinase B （Akt） signaling pathway proteins were quantitatively analyzed through Western blot to assess whether the suppression of pathological angiogenesis by DH is associated with this pathway. ResultsNetwork pharmacological analysis yielded 112 potential core therapeutic targets for the treatment of UC with DH， of which the core targets were tumor protein 53 （TP53）， JUN， interleukin （IL）-6， Akt1， and tumor necrosis factor （TNF）. Compared with the normal group， mice in the model group showed significant weight loss， colon shortening， and high DAI score， increased expression of inflammatory factors IL-6， IL-1β， and TNF-α， as well as increased mRNA expression levels of angiogenesis-related mediators VEGF， vascular cell adhesion molecule 1 （VCAM1）， angiotensin 1 （Ang1）， matrix metalloproteinase （MMP）-1， MMP-2， and MMP-9. The positive expression of CD31 and VEGF in colonic tissue increased， and the protein expression of the PI3K/Akt pathway was increased （P<0.05）. The endothelial cells of the colonic mucosa and the colonic vasculature were severely damaged. Compared with the model group， mice in the DH groups had significantly reduced weight loss and colon shortening， lower DAI scores， and a significant decrease in mRNA expression of inflammatory factors and angiogenesis-related mediators. In addition， there was decreased positive expression of CD31 and VEGF in colonic tissue and decreased protein expression of the PI3K/Akt pathway （P<0.05）. ConclusionNetwork pharmacology， molecular docking， and experimental validation are applied to explore the mechanism of action of DH in the treatment of UC， and it is found that DH is able to improve the symptoms of colitis and inhibit the pathological angiogenesis in UC mice. Its action might be related to affecting the PI3K/Akt pathway.

ObjectiveTo explore the potential mechanism of action of the combination of Sanguisorbae Radix-Sophorae Flos （DH） in the treatment of ulcerative colitis （UC） using network pharmacology methods and molecular docking technology. MethodsNetwork pharmacology analysis was utilized to predict the potential targets of DH for the treatment of UC. The therapeutic effects were experimentally validated by inducing a UC model in mice with 3% dextran sulfate sodium （DSS）. The experimental groups were the normal group， the model group， the salazosulfapyridine group （100 mg·kg^-1）， and the low， medium， and high dose groups of DH （1.2， 2.4， and 4.8 g·kg^-1）. The efficacy of the treatment was assessed through the general condition of the mice， histopathological examination， and the expression levels of inflammatory markers in the colon. The effect of DH on angiogenesis was explored by messenger RNA （mRNA） detection of colonic angiogenesis-related mediators， vascular endothelial growth factor （VEGF） immunohistochemistry， microvessel density （MVD） detection， and transmission electron microscopy. The phosphatidylinositol-3-kinase （PI3K）-protein kinase B （Akt） signaling pathway proteins were quantitatively analyzed through Western blot to assess whether the suppression of pathological angiogenesis by DH is associated with this pathway. ResultsNetwork pharmacological analysis yielded 112 potential core therapeutic targets for the treatment of UC with DH， of which the core targets were tumor protein 53 （TP53）， JUN， interleukin （IL）-6， Akt1， and tumor necrosis factor （TNF）. Compared with the normal group， mice in the model group showed significant weight loss， colon shortening， and high DAI score， increased expression of inflammatory factors IL-6， IL-1β， and TNF-α， as well as increased mRNA expression levels of angiogenesis-related mediators VEGF， vascular cell adhesion molecule 1 （VCAM1）， angiotensin 1 （Ang1）， matrix metalloproteinase （MMP）-1， MMP-2， and MMP-9. The positive expression of CD31 and VEGF in colonic tissue increased， and the protein expression of the PI3K/Akt pathway was increased （P<0.05）. The endothelial cells of the colonic mucosa and the colonic vasculature were severely damaged. Compared with the model group， mice in the DH groups had significantly reduced weight loss and colon shortening， lower DAI scores， and a significant decrease in mRNA expression of inflammatory factors and angiogenesis-related mediators. In addition， there was decreased positive expression of CD31 and VEGF in colonic tissue and decreased protein expression of the PI3K/Akt pathway （P<0.05）. ConclusionNetwork pharmacology， molecular docking， and experimental validation are applied to explore the mechanism of action of DH in the treatment of UC， and it is found that DH is able to improve the symptoms of colitis and inhibit the pathological angiogenesis in UC mice. Its action might be related to affecting the PI3K/Akt pathway.

Objective:To explore the changes of brain excitation/inhibition balance and gray matter volume (GMV) and their correlations with clinical features in benign childhood epilepsy with centrotemporal spikes (BECTS).Methods:A cross-sectional study was performed; 83 BECTS children enrolled from Department of Diagnostic Radiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2015 to January 2024 were selected as BECTS group. During the same period, 101 age- and gender-matched healthy children were recruited as healthy control group through advertisements in local primary schools. Data of conventional MRI and resting-state functional MRI (rs-fMRI) of the two groups were collected. Whole brain GMV was analyzed by voxel-based morphometry (VBM), and Hurst index was calculated based on time series data of blood oxygen level dependent (BOLD) signal of rs-fMRI. Correlations of GMV and Hurst index with disease duration and onset age in children with BECTS were explored by Pearson correlation analysis.Results:Compared with the healthy control group, the BECTS group had significantly increased GMV and decreased Hurst index in the bilateral Rolandic region ( P<0.05). Pearson correlation analysis showed that in the BECTS group, GMV in bilateral Rolandic region was negatively correlated with onset age ( r=-0.267, P=0.015) and positively correlated with disease course ( r=0.267, P=0.015); Hurst index in bilateral Rolandic region was positively correlated with onset age ( r=0.323, P=0.003) and negatively correlated with disease course ( r=-0.240, P=0.029); Hurst index was negatively correlated with GMV in bilateral Rolandic region ( r=-0.328, P=0.003). Conclusion:BECTS children have excitation/inhibition imbalance in epilepsy-related regions and cortical structural delay, and both of them are related to onset age and disease course.

Background: Inhalation-based combination therapy has gained increasing attention for local treatments. However, a key challenge remains in ensuring the sustained pulmonary release of multiple active ingredients, particularly in traditional Chinese medicine (TCM) formulations. Objective: This study investigates a novel PulmoSphere-based inhalable carrier designed for the sustained pulmonary release of multiple active ingredients, using Shuang-Huang-Lian as a model TCM formulation containing three chemical markers. Materials and methods: The carrier was developed using PulmoSphere technology, incorporating phospholipid complexes of the chemical markers and hyaluronic acid (HA) into spray-dried microparticles. The aerodynamic properties, release characteristics, pulmonary distribution, and anti-inflammatory efficacy of different formulations were evaluated in vitro and in mice. Results: The microparticles retained the excellent aerodynamic properties of conventional PulmoSphere particles, with a mass median aerodynamic diameter of approximately 3.1 μm and a fine particle fraction of approximately 55%. Compared to free Shuang-Huang-Lian or phospholipid complex-loaded PulmoSphere particles, the HA-containing particles prolonged the retention of chemical markers in the lung epithelial lining fluid, demonstrating sustained release in vivo. Additionally, the HA-containing formulation enhanced the exposure of the three chemical markers to immune cells and lung tissues, leading to improved and prolonged anti-inflammatory effects, even at decreased doses. Conclusion: This novel inhalable particle system represents a promising approach for sustained pulmonary co-delivery of multiple active ingredients, offering enhanced and extended local therapeutic efficacy.

Objective:To investigate the differences of the glymphatic system (GS) function between patients with mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) and healthy controls and between different seizure types by using diffusion tensor imaging along perivascular space (DTI-ALPS), and to analyze the correlation between GS function and the course of disease, as well as the efficacy of predicting the surgical outcome.Methods:This study was a cross-sectional study. A total of 171 patients with mTLE-HS (mTLE-HS group) and 75 healthy volunteers (HC group) were retrospectively enrolled from July 2009 to July 2021 at Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University. The general information of all subjects, such as seizure type (partial seizure, secondary generalized seizure), surgical outcome, etc., was analyzed. The 3D magnetization prepared rapid gradient echo T 1WI and DTI sequence images were collected. The VBM analysis method was used to segment cerebrospinal fluid and calculate the volume. The ALPS index of the bilateral brain was calculated using the Atlas-based DTI-ALPS method. Independent sample t-test or paired t test were used to compare the ALPS index between the mTLE-HS group and HC group, and between patients with different seizure types. Pearson correlation analysis was used to analyze the correlation between bilateral ALPS index and disease duration in mTLE-HS group. The predictive value of the ALPS index for surgical outcomes was evaluated by receiver operating characteristics curve and area under the curve. Results:Among the 171 mTLE-HS patients, 98 patients were mTLE with left-side HS (mTLE-LHS) and 73 patients were mTLE with right-side HS (mTLE-RHS); 37 patients underwent surgical treatment, including 27 with good prognosis and 10 with poor prognosis. Compared with the HC group, the left-side ALPS index of mTLE-LHS and mTLE-RHS were both decreased ( P<0.05). The right-side ALPS index in mTLE-RHS was lower than that in the HC group ( P<0.001). There was no significant difference in the right-side ALPS index between mTLE-LHS and HC group ( P=0.080). The ALPS index on the affected side of patients with secondary generalized seizures was significantly lower than that of patients with only partial seizures (all P<0.05), but the difference in ALPS index on the healthy side was not statistically significant( P>0.05). The left-side and right-side ALPS index in mTLE-LHS were negatively correlated with disease duration ( r=-0.272, P=0.007; r=-0.307, P=0.002), but no significant correlation was found between the left-side or right-side ALPS index in mTLE-RHS (all P>0.05). The DTI-ALPS index on the affected side in mTLE-HS patients exhibited good diagnostic accuracy for surgical outcome classification, with an area under the curve of 0.778. Conclusions:The patients with mTLE-HS exhibit dysfunction of the GS, and the degree of impairment is related to the type of seizure and the course of epilepsy. The ALPS index, which characterizes the function of GS, demonstrates good diagnostic accuracy for classifying surgical outcomes.

Sinopodophyllum hexandruma is a traditional Chinese medicine in China,which is mostly distributed in Gansu,Shaanxi,Sichuan,Qinghai,Yunnan and Xizang,etc.In recent years,with the gradual deepening of the research on the chemical composition and pharmacology-toxicology of Sinopodophyllum hexandruma,its antitumour and antiviral pharmacodynamic evaluation has increasingly become a research hotspot in the industry.Based on the chemical structure,pharmacological properties and the theoretical basis of quality markers(Q-markers),this paper presents an in-depth literature review and analysis of the chemical composition,pharmacological activities and Q-markers of Sinopodophyllum hexandruma,and systematically explores and predicts the Q-markers of Sinopodophyllum hexandruma.It is proposed that Podophyllotoxin,picropodophyllotoxin,podophyllotoxinone,quercetin,kaempferol,quercetin-3-O-β-glucoside can be used as the Q-marker of Sinopodophyllum hexandruma.In the later stage,these index components can be selected to control the whole quality of Sinopodophyllum hexandrum,and provide some data support and theoretical reference for the quality evaluation of Sinopodophyllum hexandrum.