The paper reviews the evolution of the theory related to meridians and zangfu organs during the Warring States, Qin and Han dynasties, so as to reveal the rules and value of its development. By analyzing historical documents, especially Zubi Shiyimai Jiujing (Moxibustion Classics of Eleven Meridians of Legs and Arms), Yinyang Shiyimai Jiujing (Moxibustion Classic on Eleven Yin and Yang Meridians), Laoguanshan bamboo medical slips of Han Dynasty and lacquer figure of meridian points, the evolutionary stages, i.e. the germination, development, and maturity of meridian-zangfu theory, are explored. In the time of the Warring States, Qin and Han dynasties, the meridian-zangfu related theory was developed from the germination to the maturity. In the classics of the early time, Zubi Shiyimai Jiujing and Yinyang Shiyimai Jiujing demonstrated the preliminary relationship between meridians and zangfu organs, focusing on the physiological connection and pathogenesis of three yin meridians of foot and zangfu organs. In the literature of Laoguanshan bamboo medical slips of Han Dynasty and lacquer figure of meridian points, the physiological connection between the yin meridians of hand and foot, and five zang organs, as well as the related diseases were further clarified; additionally, the meridian-zangfu theory had been developed in the field of diagnosis and treatment. In the era of Chapter of Meridians in Lingshu (Miraculous Pivot), there were up to 31 descriptions relevant with the connection of meridian distribution and zangfu physiological functions. It marks the construction of the "circular" flow of meridians and the interior-exterior communication of zang and fu organs; and enriches the knowledge in diseases, diagnosis and treatment with meridians and zangfu organs involved. The review on the evolution of the meridian-zangfu theory is conductive to supplementing and improving the development history of this theory of early time, and further recognizing its development rules and value. The maturity of this theoretical system not only links the meridians with the five zang and six fu organs, but also provides an important theoretical basis for the diagnosis and treatment of traditional Chinese medicine.
Meridians ; Humans ; History, Ancient ; China ; History, Medieval ; History, 19th Century ; History, 20th Century ; History, 18th Century ; History, 17th Century ; History, 16th Century ; Medicine, Chinese Traditional/history*

Objective To establish a prognostic model that predicts the survival and prognosis of gastric adenocarcinoma patients by studying the LncRNAs related to iron death in gastric cancer cells,thereby providing a theoretical basis for the development of their biomarkers and therapeutic targets.Methods The transcript sequencing data of gastric adenocarcinoma patients in the TCGA database were analyzed and intersected with iron death-related genes,which were screened for iron death-related LncRNAs by co-expression and differential analysis methods.One-way and multifactorial Cox regression analyses were used to screen out the prognostic-related LncRNAs in gastric adenocarcinoma patients,so as to establish the prognostic scoring models.On this basis,risk values were calculated for each sample,and the reliability of the model was fully verified.According to the model results,differences in the immune infiltration and immune response between the high-and low-risk groups were analyzed.Results Tumor tissues were screened for 503 LncRNAs(431 up-regulated and 72 down-regulated)associated with iron death compared to the normal tissues;univariate Cox regression analysis yielded 33 LncRNAs that could be used as the independent risk factors,whereas multivariate Cox regression analysis constructed a predictive model consisting of 17 LncRNAs.Survival curves indicated that patients with the high risk had the significantly lower survival rates than those with the low risk(P<0.001).Unifactorial and multifactorial independent prognostic analyses showed that age,stage,and risk value were independent risk factors for patients;Time-dependent ROC curves suggested that the predicted AUC values of the model's 1-,2-,and 3-year survival rates were 0.751,0.799,and 0.779 respectively,proving that the model was reliable and stable.There were significant differences in multiple immune activation responses,the degree of immune cell infiltration,and the expression levels of immune check points between the high-and low-risk groups.Conclusion The established prognostic prediction model based on iron death-related lncRNAs for gastric adenocarcinoma patients can better assess the prognosis of patients,and the lncRNAs included in the model have the feasibility of being developed into biomarkers and therapeutic targets.

Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure

AIM:To investigate the effect and mechanism of Shen-Huang granule(SHG)on Aβ25-35-induced ferroptosis in HT22 cells.METHODS:An in vitro model of Alzheimer disease(AD)was established by treating HT22 cells with Aβ25-35.The cells were divided into the following groups:control group,model group(Aβ25-35 group),ferroptosis inhibitor ferrostatin-1(Fer-1)group,low-dose SHG(SHG-L)group,and high-dose SHG(SHG-H)group.Cell viability was assessed using the Cell Counting Kit-8(CCK-8)assay.Ultrastructural changes in each group were observed via trans-mission electron microscopy.The intracellular levels of reactive oxygen species(ROS)were measured by flow cytometry.Iron deposition and lipid peroxidation levels were evaluated by examining Fe2+,total superoxide dismutase(SOD),and malondialdehyde(MDA)levels.Western blot analysis was employed to detect the protein expression of cyclooxygenase 2(TfR1),ferritin heavy chain 1(FTH1),nuclear factor E2-related factor 2(Nrf2),and heme oxygenase-1(HO-1).RE-SULTS:Compared to the control group,the model group exhibited mitochondrial shrinkage,increased membrane densi-ty,and decreased cristae.Levels of ROS,Fe2+,and MDA were significantly elevated,while SOD levels were markedly re-duced.The protein expression of SLC7A11,GPX4,FTH1,Nrf2,and HO-1 was significantly down-regulated,whereas the expression of COX2 and TfR1 was significantly up-regulated.In comparison to the model group,the morphology and structure of mitochondria improved in the Fer-1,low-dose SHG,and high-dose SHG groups.ROS,Fe2+,and MDA levels decreased while SOD levels increased.Furthermore,the expression of SLC7A11,GPX4,FTH1,Nrf2,and HO-1 was sig-nificantly up-regulated,while COX2 and TfR1 expression was significantly down-regulated.CONCLUSION:Shen-Huang granule can inhibit Aβ25-35-induced ferroptosis in HT22 cells,and the underlying mechanism may involve the Nrf2/HO-1/GPX4 signaling pathway.

Objective:To investigate the relationship between visual recovery and non-treponemal serologic test titers [tolulized red unheated serum test (TRUST) or rapid plasma reagin (RPR)] in patients with isolated ocular syphilis and those with ocular syphilis combined with neurosyphilis.Methods:A total of 35 ocular syphilis patients treated at the Department of Ophthalmology, the First Affiliated Hospital of Soochow University, and the Department of Dermatology, the Fifth People′s Hospital of Suzhou between 2016 and 2024 were enrolled. Pre-treatment serum TRUST/RPR and treponema pallidum particle agglutination (TPPA) assay results were collected for all 35 patients. Cerebrospinal fluid (CSF) biochemical, routine, TRUST/RPR, and TPPA results were obtained for 29 patients. Visual acuity (logMAR) before and after treatment was recorded for 21 patients (34 eyes). Pearson or Spearman correlation analysis was used to assess the relationship between pre-and post-treatment visual acuity, degree of visual recovery, and serum titers.Results:No significant differences in titer distribution were observed among the 35 ocular syphilis patients based on age or sex ( P>0.05). Among the 29 patients who underwent lumbar puncture, 17(58.62%) were diagnosed with ocular syphilis combined with neurosyphilis, while 12(41.38%) had isolated ocular syphilis. The proportion of patients with high pre-treatment serum titers did not differ significantly between the two groups ( P=0.294). The degree of post-treatment visual recovery showed a positive correlation with pre-treatment serum titers, indicating that higher initial titers were associated with better visual recovery (34 eyes, r=-0.302, P=0.081). Post-treatment visual acuity was positively correlated with pre-treatment visual acuity (34 eyes, r=0.547, P=0.001), suggesting that patients with poor baseline vision had worse post-treatment visual outcomes. The median visual improvement was logMAR 0.560 in the isolated ocular syphilis group and logMAR 0.202 in the neurosyphilis-combined group, with no significant difference between the two ( P=0.322). Conclusions:Ocular syphilis patients with higher pre-treatment titers exhibit better visual recovery, while poor post-treatment visual outcomes are associated with low baseline visual acuity.

Objective:To investigate the relationship between visual recovery and non-treponemal serologic test titers [tolulized red unheated serum test (TRUST) or rapid plasma reagin (RPR)] in patients with isolated ocular syphilis and those with ocular syphilis combined with neurosyphilis.Methods:A total of 35 ocular syphilis patients treated at the Department of Ophthalmology, the First Affiliated Hospital of Soochow University, and the Department of Dermatology, the Fifth People′s Hospital of Suzhou between 2016 and 2024 were enrolled. Pre-treatment serum TRUST/RPR and treponema pallidum particle agglutination (TPPA) assay results were collected for all 35 patients. Cerebrospinal fluid (CSF) biochemical, routine, TRUST/RPR, and TPPA results were obtained for 29 patients. Visual acuity (logMAR) before and after treatment was recorded for 21 patients (34 eyes). Pearson or Spearman correlation analysis was used to assess the relationship between pre-and post-treatment visual acuity, degree of visual recovery, and serum titers.Results:No significant differences in titer distribution were observed among the 35 ocular syphilis patients based on age or sex ( P>0.05). Among the 29 patients who underwent lumbar puncture, 17(58.62%) were diagnosed with ocular syphilis combined with neurosyphilis, while 12(41.38%) had isolated ocular syphilis. The proportion of patients with high pre-treatment serum titers did not differ significantly between the two groups ( P=0.294). The degree of post-treatment visual recovery showed a positive correlation with pre-treatment serum titers, indicating that higher initial titers were associated with better visual recovery (34 eyes, r=-0.302, P=0.081). Post-treatment visual acuity was positively correlated with pre-treatment visual acuity (34 eyes, r=0.547, P=0.001), suggesting that patients with poor baseline vision had worse post-treatment visual outcomes. The median visual improvement was logMAR 0.560 in the isolated ocular syphilis group and logMAR 0.202 in the neurosyphilis-combined group, with no significant difference between the two ( P=0.322). Conclusions:Ocular syphilis patients with higher pre-treatment titers exhibit better visual recovery, while poor post-treatment visual outcomes are associated with low baseline visual acuity.

AIM:To investigate the effect and mechanism of Shen-Huang granule(SHG)on Aβ25-35-induced ferroptosis in HT22 cells.METHODS:An in vitro model of Alzheimer disease(AD)was established by treating HT22 cells with Aβ25-35.The cells were divided into the following groups:control group,model group(Aβ25-35 group),ferroptosis inhibitor ferrostatin-1(Fer-1)group,low-dose SHG(SHG-L)group,and high-dose SHG(SHG-H)group.Cell viability was assessed using the Cell Counting Kit-8(CCK-8)assay.Ultrastructural changes in each group were observed via trans-mission electron microscopy.The intracellular levels of reactive oxygen species(ROS)were measured by flow cytometry.Iron deposition and lipid peroxidation levels were evaluated by examining Fe2+,total superoxide dismutase(SOD),and malondialdehyde(MDA)levels.Western blot analysis was employed to detect the protein expression of cyclooxygenase 2(TfR1),ferritin heavy chain 1(FTH1),nuclear factor E2-related factor 2(Nrf2),and heme oxygenase-1(HO-1).RE-SULTS:Compared to the control group,the model group exhibited mitochondrial shrinkage,increased membrane densi-ty,and decreased cristae.Levels of ROS,Fe2+,and MDA were significantly elevated,while SOD levels were markedly re-duced.The protein expression of SLC7A11,GPX4,FTH1,Nrf2,and HO-1 was significantly down-regulated,whereas the expression of COX2 and TfR1 was significantly up-regulated.In comparison to the model group,the morphology and structure of mitochondria improved in the Fer-1,low-dose SHG,and high-dose SHG groups.ROS,Fe2+,and MDA levels decreased while SOD levels increased.Furthermore,the expression of SLC7A11,GPX4,FTH1,Nrf2,and HO-1 was sig-nificantly up-regulated,while COX2 and TfR1 expression was significantly down-regulated.CONCLUSION:Shen-Huang granule can inhibit Aβ25-35-induced ferroptosis in HT22 cells,and the underlying mechanism may involve the Nrf2/HO-1/GPX4 signaling pathway.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population of myeloid origin with immunosuppressive function. MDSCs can inhibit the normal immune response of the host to tumor by inhibiting the activity of T cells, natural killer cells, macrophage, B cells, and promoting the proliferation of Treg and other mechanisms. Therefore, MDSCs are potential targets for tumor immunotherapy. However, whether immunotherapy or other treatments, the effectiveness of monotherapy is limited, so immunotherapy combined with other treatments is a breakthrough combination. In recent years, immunotherapy combined with other treatments has shown initial results, with better results than monotherapy. It has become a research hotspot in tumor treatment and a new treatment method in the future. This article summarized the research progress on the effects of immunotherapy combined with chemotherapy, radiotherapy, Chinese herbal extract and Immunotherapy combination on MDSCs, in order to provide theoretical support for the clinical application of immunotherapy based combined tumor treatment measures.

Objective To investigate the effect of Angelica polysaccharide(APS)on the differentiation and function of M2 macrophages and underlying molecular mechanism.Methods Mouse bone marrow derived macrophages(BMDM)and M2 macrophages were induced and treated with APS(0,80,160,320 μg/mL);Mouse peritoneal macrophages were isolated and treated with APS(0,160 μg/mL).Flow cytometry(FCM)was used to detect mannose receptor(MR),CD11b,F4/80,CD163,and ARG-1 expression levels,apoptosis,and phagocytic ability of M2 macrophages and peritoneal macrophages.Mice were randomly divided into APS gavage group and control group,APS was intragastrically administered to mice,and macrophage MR expression level in blood and spleen were detected by FCM.Fluorescence microscopy was used to observe the morphology of BMDM-differentiated M2 macrophages.RT-qPCR was employed to detect the mRNA expression levels of MR and ARG-1 in M2 macrophages.Immunofluorescence assay was performed to detect the expression of the proteins related to molecular mechanism of differentiation and function of M2 macrophages.Results Compared with the 0 μg/mL APS group,the MR expression level in the M2 macrophages was decreased with the increase of APS concentration within a certain concentration range(80～320 μg/mL),and the MR expression level in peritoneal macrophages was also decreased in the 160 μg/mL APS treatment group(P＜0.01).The expression level of macrophage MR was also significantly decreased in peripheral blood and spleen in the APS gavage mice than the control group(P＜0.05).Compared with the 0 μg/mL APS group,the expression levels of CD11b,F4/80,and CD163 in the macrophages were increased in the 80～320 μg/mL APS treatment groups(P＜0.01).The morphology of macrophage had changed,from mostly spindle-shaped and pseudopodia to mostly round or irregular,and even a few cells with pseudopodia.APS induced apoptosis in M2 macrophages(P＜0.05).Compared with the 0 μg/mL APS group,M2 macrophages treated with 160 μg/mL APS had an increased ability to phagocytose fluorescent microspheres(P＜0.01),but the expression level of ARG-1 was decreased(P＜0.01).The mRNA expression of MR and ARG-1 in M2 macrophages was decreased(P＜0.05).The mean fluorescence intensity of phosphate acidified-signal transducers and activators of transcription 6(p-STAT6)-positive signals in M2 macrophages was significantly reduced in the 160 μg/mL APS-treated group(P＜0.05).Conclusion APS has bidirectional regulation on the differentiation and function of M2 macrophages,which may be associated with its downregulation of signal transducers and activators of transcription 6(STAT6)signaling pathway.

【Objective】 To explore the causal association between the onset of gastroesophageal reflux disease (GERD) and migraine and to provide genetic evidence, a two-sample bidirectional Mendelian randomization (MR) method was used in this study. 【Methods】 Single nucleotide polymorphism (SNP) information for both samples was obtained from publicly available genome-wide association study (GWAS) databases, in which the appropriate SNPs were selected as instrumental variables, and then bidirectional MR analysis used five MR analysis methods including inverse variance weighting (IVW), MR-Egger regression, weighted median, weighted mode and simple mode methods, followed by sensitivity analysis. 【Results】 IVW showed positive results of forward MR analysis with GERD as exposure [OR=1.398 7, 95%CI (1.181 7-1.655 6), P=9.59×10^-5] , while no positive significance of reverse MR analysis results with migraine as exposure (P>0.05). The same results were obtained in methods other than MR-Egger method. Meanwhile, none of the instrumental variables were found to be horizontally polytomous (P=0.92, P=0.64), and the results were robust after the leave-one-out method to exclude single SNPs. 【Conclusion】 There may be a unidirectional causal association between GERD and migraine, and GERD is a risk factor for migraine development.