ObjectiveTo study the clinical characteristics and influencing factors of rheumatoid arthritis （RA） in the patients with cold dampness obstruction syndrome. MethodsThe RA patients treated in the Department of Traditional Chinese Medicine and Rheumatology of the China-Japan Friendship Hospital from August 2022 to June 2024 were selected. The demographic information， clinical data， laboratory test results， and traditional Chinese medicine （TCM） symptom information were collected for syndrome differentiation， on the basis of which the characteristics and influencing factors of cold dampness obstruction syndrome were analyzed. ResultsA total of 258 RA patients were selected in this study， including 88 （34.1%） patients with cold dampness obstruction syndrome， 53 （20.5%） patients with dampness and heat obstruction syndrome， 31 （12.0%） patients with wind dampness obstruction syndrome， 29 （11.2%） patients with liver-kidney deficiency syndrome， 19 （7.4%） patients with Qi-blood deficiency syndrome， 14 （5.4%） patients with phlegm-stasis obstruction syndrome， 15 （5.8%） patients with stasis obstructing collateral syndrome and 9 （3.5%） patients with Qi-Yin deficiency syndrome. The patients were assigned into two groups of cold dampness obstruction syndrome and other syndromes. The group of cold dampness obstruction syndrome had lower joint fever， 28-tender joint count （TJC28）， and 28-joint disease activity score （DAS28）-C-reactive protein （CRP） and higher central sensitization， cold feeling of joints， fear of wind and cold， cold limbs， and abdominal distention than the group of other syndromes （P<0.05）. The binary logistic regression analysis showed that central sensitization （OR 5.749， 95%CI 2.116-15.616， P<0.001） and DAS28-CRP （OR 0.600， 95% CI 0.418-0.862， P=0.006） were the independent factors influencing cold dampness obstruction syndrome in RA. ConclusionCold dampness obstruction syndrome is a common syndrome in RA patients. It is associated with central sensitization， cold feeling of joints， abdominal distension and may be a clinical syndrome associated with central sensitization.

Malignant tumor metastasis is the key factor leading to poor prognosis of patients， and it is a difficult problem to be overcome in the field of tumor therapy. Metabolic reprogramming， as a key link in the regulation of tumor metastasis activity， affects the growth， invasion， and metastasis of tumor cells by changing the metabolic pathways of intracellular substances （such as glucose， amino acids， lipids， and nucleotides）. In particular， metabolic reprogramming plays a key role in the multistage linked steps related to tumor metastasis and can play a crucial role in several key stages of tumor tissue dissociation in situ， hematogenous metastasis， and remote colonization. Malignant tumor cells can selectively adjust their own metabolic state to adapt to the growth conditions of different metastatic microenvironments and colonization sites and then choose the most favorable growth and metabolism strategy. According to the holistic concept of traditional Chinese medicine （TCM）， the metastasis of malignant tumors is generally closely related to the metabolic state of the whole body. One of the advantages of TCM in the treatment of malignant tumors is systemic regulation. With its multi-pathway， multi-target， and multi-component therapeutic characteristics， TCM can effectively control the metastasis of malignant tumors by regulating the degradation of tumor epithelial mesenchymal transformation （EMT） and extracellular matrix （ECM）， anchoring the independent growth of tumor cells and the tumor microenvironment. In this paper， the potential regulatory effects of metabolic reprogramming on the metastasis of malignant tumors were discussed， and the latest research progress of the regulation of metabolic reprogramming by TCM on tumor metastasis was reviewed. At the same time， the key targets of TCM and its bioactive components in the process of tumor metastasis intervention were reviewed. This study aims to provide a more valuable basis and clearer idea for the treatment of malignant tumor metastasis by regulating metabolic reprogramming with TCM.

OBJECTIVE To investigate the effects of imperatorin （IMP-SD） on malignant biological behavior of gastric cancer （GC） cells by regulating zinc finger and BTB domain 7B （ThPOK）. METHODS Human GC cells MKN-7 were used as the research object and then divided into control group （no treatment）， IMP-SD low-， medium- and high-concentration groups （40， 80 and 160 μmol/L IMP-SD）， si-ThPOK and si-NC group [treated with 160 μmol/L IMP-SD and then transfected with ThPOK small interfering RNA （si-ThPOK） or its negative control （si-NC）]. After treatment， cell clone formation， migration and invasion abilities and apoptosis of MKN-7 cells were detected； the killing activity of NK cells， T cells classification， the protein expressions of ThPOK， programmed death-1 （PD-1） and programmed death-ligand 1 （PD-L1） were all determined. RESULTS Compared with the control group， the number of cell clones， migration number， invasion number， and the protein expressions of PD-1 and PD-L1 were decreased or down-regulated significantly in IMP-SD groups， while the cell apoptotic rate， NK cell killing activity， CD4+ T proportion， the ratio of CD4+ T proportion and CD8+ T proportion （CD4+ T/CD8+ T）， and the protein expression of ThPOK were increased or up-regulated significantly， in a concentration-dependent manner （P＜0.05）. Compared with IMP-SD high-concentration group and si-NC group， the number of cell clones， migration number， invasion number， and the protein expressions of PD-1 and PD-L1 were increased or up-regulated significantly in si-ThPOK group， while the cell apoptotic rate， NK cell killing activity， CD4+ T proportion， CD4+ T/CD8+ T， and the protein expression of ThPOK were decreased or down-regulated significantly （P＜0.05）. CONCLUSIONS IMP-SD may reduce the clonal formation， migration and invasion abilities of GC cells， promote their apoptosis and inhibit their immune escape by promoting ThPOK expression.

OBJECTIVE To investigate the effects of imperatorin （IMP-SD） on malignant biological behavior of gastric cancer （GC） cells by regulating zinc finger and BTB domain 7B （ThPOK）. METHODS Human GC cells MKN-7 were used as the research object and then divided into control group （no treatment）， IMP-SD low-， medium- and high-concentration groups （40， 80 and 160 μmol/L IMP-SD）， si-ThPOK and si-NC group [treated with 160 μmol/L IMP-SD and then transfected with ThPOK small interfering RNA （si-ThPOK） or its negative control （si-NC）]. After treatment， cell clone formation， migration and invasion abilities and apoptosis of MKN-7 cells were detected； the killing activity of NK cells， T cells classification， the protein expressions of ThPOK， programmed death-1 （PD-1） and programmed death-ligand 1 （PD-L1） were all determined. RESULTS Compared with the control group， the number of cell clones， migration number， invasion number， and the protein expressions of PD-1 and PD-L1 were decreased or down-regulated significantly in IMP-SD groups， while the cell apoptotic rate， NK cell killing activity， CD4+ T proportion， the ratio of CD4+ T proportion and CD8+ T proportion （CD4+ T/CD8+ T）， and the protein expression of ThPOK were increased or up-regulated significantly， in a concentration-dependent manner （P＜0.05）. Compared with IMP-SD high-concentration group and si-NC group， the number of cell clones， migration number， invasion number， and the protein expressions of PD-1 and PD-L1 were increased or up-regulated significantly in si-ThPOK group， while the cell apoptotic rate， NK cell killing activity， CD4+ T proportion， CD4+ T/CD8+ T， and the protein expression of ThPOK were decreased or down-regulated significantly （P＜0.05）. CONCLUSIONS IMP-SD may reduce the clonal formation， migration and invasion abilities of GC cells， promote their apoptosis and inhibit their immune escape by promoting ThPOK expression.

Objective: To investigate the mechanism of action of Prim-O-glucosylcimifugin (POG) to improve cholesterol metabolism in osteoarthritic (OA) chondrocytes based on the long noncoding RNA nuclear-enriched transcript 1 (lncRNA NEAT1)/microRNA-128-3p (miR-128-3p) pathway. Methods: For in vivo experiments, 60 mice were divided into the normal, sham operation, model, and POG groups using the random number table method, with 15 mice per group. The osteoarthritis mouse model was constructed using the modified Hulth method in the model and POG groups. Mice in the POG group were administered 30 mg/(kg·d)POG by gavage. The other groups were administered an equal amount of normal saline for 8 weeks. The cartilage tissue structure of mice in each group was observed using hematoxylin and eosin staining. Real-time PCR was used to detect changes in the lncRNA NEAT1 and miR-128-3p mRNA expression levels in the cartilage tissues of mice. Western blotting was used to detect the protein expressions of ATP-binding cassette transporter A1 (ABCA1), liver X receptor β (LXRβ), matrix metalloprotein-3 (MMP-3), and B-lymphoblastoma-2-associated X protein (Bax) in articular cartilage of mice. An enzyme-linked immunosorbent assay was used to measure the tumor necrosis factor-α (TNF-α) content in the synovial fluid of mice. A biochemical microplate assay was used to measure the total cholesterol level in the synovial fluid of mice. The in vitro experiments were divided into the negative control, interleukin-1β(IL-1β), IL-1β+ POG, IL-1β+ oe-lncRNA NEAT1, IL-1β+ oe-lncRNA NEAT1 + POG, IL-1β + miR-128-3p inhibition, and IL-1β+ miR-128-3p inhibition+ POG groups. An OA model was established by inducing chondrocytes with IL-1β for 24 h, and 90 mg/L of POG and miR-128-3p inhibitor(50 nmol/L) were administered for 48 h as an intervention. lncRNA NEAT1 expression in chondrocytes was detected using fluorescence in situ hybridization. A dual luciferase assay was used to detect the targeting relationship between lncRNA NEAT1 and miR-128-3p. Lentiviral plasmids overexpressing lncRNA NEAT1 were used to transfect mouse chondrocytes. Real-time PCR was used to detect the effect of lncRNA NEAT1 overexpression on the mRNA level of miR-128-3p in chondrocytes. Western blotting was used to detect ABCA1, LXRβ, MMP-3, and Bax protein expression in chondrocytes after lncRNA NEAT1 overexpression and miR-128-3p inhibition. Results: POG significantly reduced OA cartilage tissue damage. Compared with the model group, the lncRNA NEAT1 mRNA level decreased, whereas the miR-128-3p mRNA level increased in the cartilage tissue of the POG group (P<0.05). Compared with the model group, ABCA1 and LXRβ protein expression increased in the POG group, whereas MMP-3 and Bax protein expression decreased (P<0.05). The TNF-α levels decreased in the POG group compared to the model group (P<0.05). Compared with the model group, the total cholesterol level in the synovial fluid of the joint of mice in the POG group decreased (P<0.05). The mean fluorescence intensity of lncRNA NEAT1 in the IL-1β+ POG group decreased compared with the IL-1β group (P<0.05). The relative luciferase activity in the miR-128-3p mimics group bound to the lncRNA NEAT1-WT plasmid decreased compared with the miR-128-3p negative control group (P<0.05). The lncRNA NEAT1 mRNA levels decreased, whereas the miR-128-3p mRNA levels increased in the IL-1β+ oe-lncRNA NEAT1 + POG group compared with the IL-1β+ oe-lncRNA NEAT1 group (P<0.05). Compared with the IL-1β+ POG group, ABCA1 and LXRβ protein expression decreased, whereas MMP-3 and Bax protein expression increased (P<0.05). Conclusion POG mediates lncRNA NEAT1/miR-128-3p to improve cholesterol metabolism in OA chondrocytes.

Objective To construct a glioma microfluidic chip model to simulate tumor microenvironment for evaluating the medicinal efficacy of anti-glioma traditional Chinese medicines. Methods Glioblastoma cells U251 were seeded into microfluidic chips with different culture modes, and the cell viability and tumour microenvironment within the constructed model were characterized. Fluorescence staining was used to evaluate the effects of the positive drugs temozolomide （TMZ） and docetaxel （DOC） on the cell activity and apoptosis within the model, which was applied to evaluate the medicinal efficacy of the extracts of the herb Scutellaria barbata on gliomas. Results The cells in the constructed U251 microfluidic chip model displayed high viability and were able to mimic the hypoxic microenvironment of tumor to a certain extent. The viability of the U251 cells in the microfluidic chips decreased with the increasing of the concentration of the positive drug, and the viability of the 3D cultured U251 cells was higher than that in the 2D condition （P<0.05）. The intracellular mitochondrial membrane potential decreased with the increasing of the concentration of the positive drug. And the 2 mg/ml Scutellaria barbata extract killed U251 cells to a certain extent and reduced the mitochondrial membrane potential of the cells in the model. Conclusion This study successfully constructed a microfluidic chip model of glioma that could effectively simulate the tumor microenvironment and rapidly evaluate the anti-tumor medicinal efficacy, which provided a new strategy for the medicinal efficacy evaluation and active components screening of anti-glioma traditional Chinese medicines.

[摘 要] 目的：探讨iSEND免疫评分联合肺癌免疫治疗预后指数（LIPI）在评估非小细胞肺癌（NSCLC）接受免疫治疗预后中的价值。方法：通过回顾性分析2018年2月至2023年2月期间100例接受免疫治疗的晚期NSCLC患者的临床资料，收集并整理患者的iSEND免疫评分和LIPI数据，根据iSEND免疫评分和LIPI分别将患者分为3组（不良组、中等组和良好组），运用Kaplan-Meier方法绘制生存曲线分析所有患者和不同组别患者的无进展生存期（PFS），运用Cox回归分析评估影响患者预后的风险因素。结果：在接受免疫治疗后，NSCLC患者的ORR为42.00%（42/100），DCR为82.00%（82/100）。iSEND免疫评分和LIPI不良组ORR和DCR均最低，良好组均最高，不同组别ORR和DCR比较均有统计学意义（均P < 0.01）。100例NSCLC患者的中位PFS为7.63个月[95% CI（7.23, 8.05）]，iSEND免疫评分不良组、中等组和良好组的中位PFS分别为4.69、6.58和8.99个月，iSEND免疫评分良好组的PFS最长，其次为中等组，不良组最短（χ2=125.391，P < 0.000 1）。LIPI不良组、中等组和良好组的中位PFS分别为4.54、6.39和8.49个月，以LIPI良好组的PFS最长，其次为中等组（χ2 = 115.707，P < 0.000 1）。Cox多因素分析提示，ECOG PS > 1、远处转移、iSEND免疫评分≥ 2分和LIPI ≥ 2分是影响患者独立预后的风险因素。结论：iSEND免疫评分和LIPI可作为评估NSCLC免疫治疗预后的良好指标，具有一定的临床价值。

ObjectiveTo investigate whether the effect of Taohong Siwutang on cerebral ischemia-reperfusion （CIRI） injury in rats is related to the regulation of astrocyte polarization and explore the related mechanism. MethodsEighty-four male SD rats were randomly assigned to the following groups： A sham operation group， a model group， Taohong Siwutang treatment groups （low dose， medium dose， and high dose）， ligustrazine phosphate tablet （LPT） group， and AG490 group. All groups， except for the sham operation group， underwent middle cerebral artery occlusion/reperfusion （MCAO/R） modeling and were treated for seven days. The neurological impairment was evaluated using the Longa score. The volume of cerebral infarction was assessed through 2，3，5-triphenyltetrazolium chloride （TTC） staining. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot analyses were performed to analyze the mRNA and protein expression levels of cortical complement 3 （C3）， S100 calcium-binding protein A10 （S100A10）， Janus kinase 2 （JAK2）， and signal transducer and activator of transcription 3 （STAT3）. Additionally， protein expression levels of vascular endothelial growth factor-A （VEGF-A） were assessed， and the mRNA expression levels of inflammatory factors， including interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）， were evaluated. Glial fibrillary acidic protein （GFAP） and C3， S100A10 and Co-localization was detected via immunofluorescence double staining. Lastly， VEGF expression levels were measured using enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham operation group， the model group showed a significant increase in cerebral infarction volume and neurological impairment （P<0.01）. C3 protein levels were elevated， while S100A10 levels were decreased. Pathway-related markers were significantly upregulated （P<0.05， P<0.01）， and VEGF-A protein levels were significantly reduced （P<0.01）. The mRNA expression of inflammatory factors was significantly upregulated （P<0.01）. Co-localization analysis showed significantly increased GFAP and C3 fluorescence intensity （P<0.01） and greatly decreased GFAP and S100A10 fluorescence intensity （P<0.01）. Additionally， VEGF content was significantly elevated （P<0.01）. Compared with the model group， medium- and high-dose Taohong Siwutang and LPT groups exhibited a significant reduction in cerebral infarction volume and neurological impairment （P<0.01）. Groups treated with low， medium， and high doses of Taohong Siwutang and LPT group exhibited a decrease in C3 protein expression levels and an increase in S100A10 expression levels （P<0.01）. In the high-dose Taohong Siwutang and AG490 groups， both protein and mRNA expression of C3 and pathway-related markers were significantly downregulated （P<0.05， P<0.01）， while S100A10 expression and VEGF-A protein levels were significantly increased （P<0.01）. Additionally， the mRNA expression levels of inflammatory factors were significantly reduced （P<0.01）. The co-localization fluorescence intensity of GFAP and C3 significantly decreased （P<0.01）， while that of GFAP and S100A10 greatly increased （P<0.01）. Furthermore， VEGF content exhibited a marked elevation （P<0.01）. ConclusionTaohong Siwutang exerts a protective effect in rats with cerebral CIRI injury. The underlying mechanism is associated with the downregulation of the JAK2/STAT3 signaling pathway， promotion of A2-type astrocyte polarization， reduction of inflammatory factor release， and enhancement of VEGF production.

ObjectiveTo investigate whether the effect of Taohong Siwutang on cerebral ischemia-reperfusion （CIRI） injury in rats is related to the regulation of astrocyte polarization and explore the related mechanism. MethodsEighty-four male SD rats were randomly assigned to the following groups： A sham operation group， a model group， Taohong Siwutang treatment groups （low dose， medium dose， and high dose）， ligustrazine phosphate tablet （LPT） group， and AG490 group. All groups， except for the sham operation group， underwent middle cerebral artery occlusion/reperfusion （MCAO/R） modeling and were treated for seven days. The neurological impairment was evaluated using the Longa score. The volume of cerebral infarction was assessed through 2，3，5-triphenyltetrazolium chloride （TTC） staining. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot analyses were performed to analyze the mRNA and protein expression levels of cortical complement 3 （C3）， S100 calcium-binding protein A10 （S100A10）， Janus kinase 2 （JAK2）， and signal transducer and activator of transcription 3 （STAT3）. Additionally， protein expression levels of vascular endothelial growth factor-A （VEGF-A） were assessed， and the mRNA expression levels of inflammatory factors， including interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）， were evaluated. Glial fibrillary acidic protein （GFAP） and C3， S100A10 and Co-localization was detected via immunofluorescence double staining. Lastly， VEGF expression levels were measured using enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham operation group， the model group showed a significant increase in cerebral infarction volume and neurological impairment （P<0.01）. C3 protein levels were elevated， while S100A10 levels were decreased. Pathway-related markers were significantly upregulated （P<0.05， P<0.01）， and VEGF-A protein levels were significantly reduced （P<0.01）. The mRNA expression of inflammatory factors was significantly upregulated （P<0.01）. Co-localization analysis showed significantly increased GFAP and C3 fluorescence intensity （P<0.01） and greatly decreased GFAP and S100A10 fluorescence intensity （P<0.01）. Additionally， VEGF content was significantly elevated （P<0.01）. Compared with the model group， medium- and high-dose Taohong Siwutang and LPT groups exhibited a significant reduction in cerebral infarction volume and neurological impairment （P<0.01）. Groups treated with low， medium， and high doses of Taohong Siwutang and LPT group exhibited a decrease in C3 protein expression levels and an increase in S100A10 expression levels （P<0.01）. In the high-dose Taohong Siwutang and AG490 groups， both protein and mRNA expression of C3 and pathway-related markers were significantly downregulated （P<0.05， P<0.01）， while S100A10 expression and VEGF-A protein levels were significantly increased （P<0.01）. Additionally， the mRNA expression levels of inflammatory factors were significantly reduced （P<0.01）. The co-localization fluorescence intensity of GFAP and C3 significantly decreased （P<0.01）， while that of GFAP and S100A10 greatly increased （P<0.01）. Furthermore， VEGF content exhibited a marked elevation （P<0.01）. ConclusionTaohong Siwutang exerts a protective effect in rats with cerebral CIRI injury. The underlying mechanism is associated with the downregulation of the JAK2/STAT3 signaling pathway， promotion of A2-type astrocyte polarization， reduction of inflammatory factor release， and enhancement of VEGF production.

BACKGROUND:The pathogenesis of diabetic peripheral neuropathy has not yet been clarified,and TAM(Tyro3,Axl,and MerTK)receptor tyrosine kinases can control apoptotic cells and suppress inflammatory responses in the central nervous system. OBJECTIVE:To investigate the difference of Mer receptor tyrosine kinase(MerTK)levels in plasma and sciatic nerve tissue of Sprague-Dawley rats with type 2 diabetes and diabetic peripheral neuropathy,and to study the correlation between MerTK and diabetic peripheral neuropathy. METHODS:Forty male Sprague-Dawley were randomly divided into control group with 15 rats,type 2 diabetes group with 10 rats,and diabetic peripheral neuropathy group with 15 rats.The control group was fed with ordinary diet,while the experimental groups were fed with high-fat and high-sugar diet.After 6 weeks,intraperitoneal injection of streptozotocin at the minimum dose of 35 mg/kg was administered in the two experimental groups.After 14 days,tail vein blood was collected to detect blood glucose.If blood glucose≥16.7 mmol/L,the model of type 2 diabetes was successfully established.Rats in the diabetic peripheral neuropathy group continued to be fed with a high-sugar and high-fat diet for 8 weeks.The sciatic nerve conduction velocity of rats was detected through live isolation under anesthesia.Blood samples were collected from the abdominal aorta,and the sciatic nerve tissue was collected.Histological changes of nerve fibers in each group were observed under a light microscope to confirm the success of diabetic peripheral neuropathy modeling.ELISA was used to detect peripheral blood glucose,blood lipids and serum MerTK levels in rats;hematoxylin-eosin staining was used to observe the histological changes in the sciatic nerve;immunofluorescence,immunohistochemistry and western blot were used to detect the expression of MerTK in the sciatic nerve tissue. RESULTS AND CONCLUSION:The Sprague-Dawley rat models of type 2 diabetes and type 2 diabetes peripheral neuropathy were successfully constructed,and the modeling rate of diabetic peripheral neuropathy was 80%.Compared with the control group,the blood glucose levels of rats in the type 2 diabetes and diabetic peripheral neuropathy groups were significantly higher(P<0.000 1),while the blood glucose level in the diabetic peripheral neuropathy group was higher than that in the type 2 diabetes group;and the sciatic nerve conduction velocity was significantly decreased(P<0.05),which was lower in the diabetic peripheral neuropathy group than the type 2 diabetes group.Histological examination:Compared with the control group,the sciatic nerve nuclei were reduced in the type 2 diabetes group,with some vacuolar degeneration and phagocytosis;in the diabetic peripheral neuropathy group,the cell body was swollen,the nuclear spacing was increased,vacuolar degeneration was observed,and the myelin sheath was partitioned and unsmooth,and lattice-like axons appeared.Serum MerTK levels were significantly higher in the diabetic peripheral neuropathy group than the control group.Expression of MerTK in the sciatic nerve tissue was significantly upregulated in the diabetic peripheral neuropathy group compared with the control group(P<0.05).To conclude,elevated levels of MerTK in plasma and sciatic nerve tissue of rats with diabetic peripheral neuropathy are presumably related to its anti-inflammatory and immunomodulatory effects.