Objective To explore the mechanism of modified maimendong decoction (MMD) in inhibiting lung cancer metastasis from the perspective of immune regulation. Methods CTC-TJH-01 and LLC cells were intervened with different concentrations of modified maimendong decoction. The cell proliferation was detected with a CCK-8 kit, apoptosis was detected with an Annexin V-FITC/PI kit, and cell migration was detected through Transwell assays. A lung metastasis model was established through the tail vein injection of LLC cells into C57BL/6 mice, and body weight change and lung tumor metastasis in the mice were evaluated after continuous gavage intervention with MMD. HE staining, immunohistochemistry, and immunofluorescence were employed to observe the histomorphology, Ki-67 protein level, and NK and T cell levels of metastatic lesions. The levels of NK and T cells in the peripheral blood of mice were detected throughflow cytometry. Results MMD had no significant inhibitory effect on the proliferation, apoptosis, and migration of CTC-TJH-01 and LLC cells in vitro. In mice, MMD could significantly inhibit the lung metastasis of LLC cells, increase the proportion of NK and CD8⁺ T cells in peripheral blood and tumor microenvironment (P<0.05), and reduce the expression of Ki-67 protein in metastatic tumor tissues (P<0.05). Conclusion MMD may inhibit the growth of metastatic tumors by upregulating the expression levels of NK and CD8⁺ T cells in peripheral blood to promote the elimination of circulating tumor cells, and regulating the infiltration of NK and CD8⁺ T cells in the immune microenvironment of metastatic tumors, then play an antimetastatic role in lung cancer.

Objective To observe the protective effect of modified Baishile Decoction on hippocampal neuronal cells cultured in vitro;To explore its mechanism of treating post-stroke depression.Methods Hippocampal neuronal cells from mammary rats were isolated and cultured in vitro,cell injury was induced by oxygen glucose deprivation combined with lipopolysaccharide.The cells were divided into normal group,model group,blank serum group(10%)and modified Baishile Decoction containing serum group(10%).Invertedmicroscope was used to observe cell morphological changes,CCK-8 method was used to detect cell survival rate,Hoechst33342 staining was used to observe apoptosis,ELISA was used to detect Glu,5-HT,TNF-α,IL-1β,and IL-6 contents in cell supernatant,the expressions of purinergic P2X7 receptor(P2X7R)and NOD-like receptor protein 3(NLRP3)were detected by immunofluorescence staining.Results Compared with the normal group,the hippocampal neurons in the model group showed significant changes in cell morphology,the cell survival rate significantly decreased(P<0.01),the cell apoptosis increased(P<0.01);Glu,TNF-α,IL-1β,IL-6 contents in cell supernatant significantly increased(P<0.05,P<0.01),5-HT content significantly decreased(P<0.01),P2X7R and NLRP3 expressions in hippocampal neuronal cells significantly increased(P<0.01).Compared with the model group,the morphology of hippocampal neurons in modified Baishile Decoction containing serum group was significantly improved,the cell survival rate significantly increased(P<0.01),the cell apoptosis reduced(P<0.01);Glu,TNF-α and IL-1β content in cell supernatant significantly reduced(P<0.05,P<0.01),5-HT content significantly increased(P<0.01),and P2X7R and NLRP3 expressions in hippocampal neuronal cells significantly decreased(P<0.01).Conclusion Modified Baishile Decoction may exert a protective effect on oxidative glucose deprivation combined with lipopolysaccharide induced hippocampal neuronal inflammation damage by inhibiting the P2X7R/NLRP3 signaling pathway,regulating neurotransmitter secretion,and inhibiting inflammatory factor release,thus treating post-stroke depression.

ObjectiveTo explore and verify the key pathway of Zuogui Jiangtang Jieyu prescription in the treatment of diabetes with depression by means of gene set enrichment analysis （GSEA） and short time-series expression miner （STEM）. MethodSD rats were randomly divided into six groups， including a normal group， a model group， high， medium， and low dose groups of Zuogui Jiangtang Jieyu prescription， and a positive drug group. The model of diabetes with depression was established by high-fat feeding， streptozotocin （STZ） injection， and chronic mild unpredictable stress. The high， medium， and low dose groups of Zuogui Jiangtang Jieyu prescription were orally administered at 20.52， 10.26， and 5.13 g·kg^-1 respectively. The positive drug group was orally administered 0.18 g·kg^-1 metformin and 1.8 g·kg^-1 fluoxetine. The rats in the normal group and model group were administered with an equal volume of distilled water. After 28 days， the animals were tested for depressive-like behaviors and cognitive function using the forced swimming test and Morris water maze. Fasting blood glucose was measured using blood glucose test strips. Cholesterol and triglyceride levels were measured using enzyme-linked immunosorbent assay （ELISA）. Three hippocampus samples were randomly selected from the normal group， the model group， the high dose group of Zuogui Jiangtang Jieyu prescription for high-throughput transcriptome sequencing. Differential gene analysis， GSEA analysis， and STEM analysis were used to screen the key pathways and target genes of Zuogui Jiangtang Jieyu prescription in the treatment of diabetes with depression. Key target genes were validated using real-time fluorescence quantitative PCR （Real-time PCR）. The expression of the signal protein mediated by the target genes was detected by Western blot. ResultCompared with the results in the normal group， the fasting blood glucose， cholesterol， and triglyceride levels in the model group were significantly increased （P<0.01）. Moreover， the immobility time in the forced swimming test was significantly increased， while the time to climb the platform was significantly prolonged， and the search distance in the target quadrant was significantly reduced in the Morris water maze test （P<0.05，P<0.01）. Compared with the model group， the high dose of Zuogui Jiangtang Jieyu prescription significantly reduced the levels of blood glucose， cholesterol， and triglycerides in rats with diabetes with depression （P<0.05，P<0.01）， reduced the immobility time in the forced swimming test， shortened the stage time in the Morris water maze test， and increased the search distance ratio in the target area （P<0.05，P<0.01）. Transcriptome sequencing differential analysis showed that the normal group had 1 366 differentially expressed genes compared to the model group， while the model group had 1 149 differentially expressed genes compared to the high dose group of Zuogui Jiangtang Jieyu prescription， with 581 intersecting genes. The GSEA results showed that there were 9 sets of differentially expressed genes between the normal group and the model group， and 43 sets of differentially expressed genes between the model group and the high dose group of Zuogui Jiangtang Jieyu prescription， with 7 intersecting gene sets. STEM analysis showed that according to the analysis order of the normal group， model group， and high dose group of Zuogui Jiangtang Jieyu prescription， two significantly different trend clustering groups were obtained. One key gene set for axonal guidance， as well as key target signal elements Sema3c， Sema7a， Robo3， Epha8， and Epha7， were identified through synthesizing the three analysis results. Real-time PCR validated that compared with the results in the normal group， the mRNA expression of Robo3， Sema7a， and Epha7 in the hippocampus of the model rats was significantly reduced （P<0.05， P<0.01）. Compared with the model group， the high dose of Zuogui Jiangtang Jieyu prescription significantly increased the mRNA expression of Robo3， Sema7a， and Epha7 （P<0.05， P<0.01）. Western blot results showed that compared with the results in the normal group， the Sema7a， ITGB1， and FAK protein expression in the hippocampus of the model group was significantly reduced （P<0.01）. Compared with the model group， the high dose of Zuogui Jiangtang Jieyu prescription significantly increased the protein expression of Sema7a， ITGB1， and FAK in the hippocampus （P<0.05，P<0.01）. ConclusionZuogui Jiangtang Jieyu prescription may treat diabetes with depression by regulating axonal guidance based on the Sema7a/ITGB1 signaling pathway.

This paper analyzed the legal issues existing on the medical side in 20 medical damage cases in obstetrics from January 2020 to June 2022 in China Judgment Documents Network， and hoped to explore the paths that the medical side can use for reference in building a harmonious doctor-patient relationship in the legal context. Firstly， medical institutions should establish rescue evaluation systems and early warning mechanisms for critical pregnancy and maternal， so as to ensure the health and safety of life of pregnant women and newborns， as well as prevent the occurrence of adverse obstetric events. Secondly， strengthening the cultivation of the humanistic quality among obstetric medical practitioners is the basis of the harmonious obstetrical doctor-patient relationship. Thirdly， the training and learning of relevant laws and regulations such as the Civil Code of the People’s Republic of China and the Physician Law of the People’s Republic of China should be strengthened. Fourthly， the patients’ informed consent should be respected， the process and procedures of fulfilling informed consent should be standardized by the systems， and the forms for fulfilling informed consent should be further explored. Fifthly， the medical risk-sharing mechanism should be explored and this paper suggested that postpartum women purchase obstetric accident insurance to reasonably share medical risks. Sixthly， medical social workers should be introduced， doctor-patient communication should be strengthened， and the obstetric risk awareness of the whole society should be enhanced.

ObjectiveTo explore the potential mechanism of Zuogui Jiangtang Jieyu Formula （左归降糖解郁方， ZJJF） for diabetic rats with depression. MethodsSixty rats were randomly divided into normal group， model group， wingless MMTV integration site family member 5a （Wnt5a） agonist group， ZJJF group， and ZJJF plus Wnt5a inhibitor group， with 12 rats in each group. Except for the normal group， the rats were fed with high-fat chow， streptozotocin injection， and chronic mild unpredictable stress combination， to establish model of diabetes mellitus complicated with depression. After successful modelling， rats in the Wnt5a agonist group were given bilateral hippocampal stereotactic injections of Wnt5a agonist Foxy-5 with 5 μl each for 7 consecutive days； rats in ZJJF group were given 20.52 g/（kg·d） of ZJJF by gavage； rats in ZJJF plus Wnt5a inhibitor group were given the drug by gavage， and bilateral hippocampal stereotactic injections of Wnt5a inhibitors Box5， with the same dosage and injection method as above. The normal group and model group were given 10 ml/（kg·d） of normal saline by gavage. All groups were gavaged for 4 consecutive weeks. At the end of the intervention， the depression-like behaviour of rats was evaluated using the forced swimming experiment （immobility time） and the absent field experiment （number of activities）； the blood glucose and insulin levels of rats were measured and the insulin resistance index was calculated； the dendritic morphology of dentate gyrus neurons in the hippocampus was observed using Golgi staining； the level of dentate gyrus neuron proliferation was measured using 5-bromodeoxyuracil nucleoside （Brdu） injection and immunofluorescence； RT-qPCR and Western blot were used to detect the mRNA and protein expression of Wnt5a， Ras homologue genomic member A （RhoA） and Rho homologue-associated coiled-coil protein kinase 1 （ROCK1） in the dentate gyrus. ResultsCompared with the normal group， rats in the model group had significantly higher blood glucose， insulin and insulin resistance indices， longer immobility time， fewer activities， lower Brdu integral optical density values and Wnt5a， RhoA， ROCK1 protein and mRNA expression in the dentate gyrus of the hippocampus （P＜0.05 or P＜ 0.01）； the dendritic branches of rat hippocampal dentate gyrus neurons could be seen to be significantly reduced or broken， and their length shortened. Compared with the model group， the blood glucose， insulin and insulin resistance indices of rats in ZJJF group and the ZJJF plus Wnt5a inhibitor group significantly reduced （P＜0.05 or P＜0.01）； the immobility time of rats in the Wnt5a agonist group and ZJJF group was significantly shortened， the number of activities increased， the Brdu integral optical density values elevated， and the Wnt5a， RhoA， ROCK1 protein and mRNA expression elevated （P＜0.05 or P＜0.01）， and the number of dendritic branches of hippocampal dentate gyrus neurons significantly increased， the length lengthened， and the complexity of dendrites increased. Compared with the Wnt5a agonist group， rats in the ZJJF group showed significant decrease in blood glucose， insulin and insulin resistance indices， prolongation of immobilisation time， reduction in the number of activities， and reduction in the Brdu integral optical density value； except for the Wnt5a mRNA in ZJJF group， Wnt5a， RhoA， ROCK1 protein and mRNA expression reduced in both ZJJF group and ZJJF plus Wnt5a inhibitor group （P＜0.05 or P＜0.01）. Compared with ZJJF group， Wnt5a， RhoA， ROCK1 protein and mRNA expression were reduced in ZJJF plus Wnt5a inhibitor group （P＜0.05 or P＜0.01）. ConclusionZJJF can improve hyperglycemia and depressive-like behaviours in rat models of diabetes with depression， and its antidepressant effects may be related to the activation of hippocampal Wnt5a/RhoA signaling and promotion of dentate gyrus neuron dendritic growth.

Lung cancer is the leading cause of cancer-related deaths worldwide,with metastasis being the primary cause of mortality in lung cancer patients,and its prevention and control efficacy remain limited.In recent years,immunothera-py has emerged as a promising direction for overcoming the bottleneck of metastasis.Macrophages,as essential components of innate immunity,participate in the entire process of tumor initiation and progression.Tumor-associated macrophages(TAMs)represent the most abundant immune population in the tumor microenvironment(TME),displaying both anti-tumor M1-like and pro-tumor M2-like phenotypes.The latter promotes tumor invasion and metastasis,angiogenesis,lymphangiogenesis,immune suppression,and reactivation of dormant disseminated tumor cells(DTCs),thereby facilitating tumor metastasis.In recent years,traditional Chinese medicine(TCM)has shown significant efficacy in inhibiting tumor metastasis and has been extensively validated.It exerts anti-tumor effects by reducing the recruitment of TAMs,inhibiting M2-like polarization,and modulating cytokines and proteins in the TME.This paper reviews the relationship between TAMs and lung cancer metastasis,elucidates the targets and mechanisms of TCM in regulating TAMs to prevent and treat lung cancer metastasis,aiming to pro-vide insights into lung cancer prevention and treatment.

Thirty-five cases of medical damage liability disputes concerning orthopedic omission of diagnosis that were made public in the China Judgement and Documentation Network during 2021—2023 were analyzed.The basic situation of the cases,appraisal opinions,liability composition,damage consequences,and causes of omission of diagnosis are analyzed,statistical results are obtained,and the results are discussed and relevant suggestions are made.

Orthopedic joint replacement patients include a significant proportion of elderly individuals.Due to the physiological characteristics of the elderly,the incidence of patient harm during the diagnosis and treatment process is relatively high.Consequently,orthopedic joint replacement is also an area with a high rate of medical disputes in both domestic and international healthcare.The courts often hold the medical side more responsible in their judgments of such disputes.A retrospective analysis of 24 cases of orthopedic joint replacement dispute judgments was conducted to explore and summarize the causes of these cases,and to propose corresponding countermeasures and suggestions with the aim of reducing the incidence of such medical disputes.

Objective Th is aim of this review was to clarify the role of neutrophils in diabetes by summarizing the characterization studies,potential trends,and research hotspots relating to neutrophils in the diabetes research field.Methods 2998 relevant studies on neutrophils in the diabetes research field indexed in Web of Science from 2010 to 2023 were retrieved,and a visual analysis of the relevant literature was conducted using CiteSpace 6.1.R6.Results Since 2012,the number of publications on this topic has grown rapidly.Bayat Mohammad,Liu Tong,Amini Abdollah,and Zhang Rui are high-yield authors,with seven related articles published.China and Shanghai Jiao Tong University are the country and institution with the most published papers.The most influential journal in this field is"Nature Medicine".Literature co-citation analysis of topics related to diabetes showed that the greatest focus is currently on"extracellular trap"and"COVID-19 patient".Co-occurrence analysis,clustering analysis,and keyword burst analysis indicated that"lymphocyte ratio"(13.08)and"neutrophil extracellular trap"(7.2)are the most researched topics in the field of neutrophils and diabetes.Literature in this field mainly focuses on"myocardial infarction","endothelial","oxidative stress",and"apoptosis".Conclusions This article highlights the evolving trends in research into neutrophils in the diabetes field using CiteSpace,providing new insights for researchers aiming to conduct research in this area.

AIM: Given the biofilm formation abili- ty of different ST-type Klebsiella pneumoniae, our study was aimed at exploring the inhibitory and clearance of azithromycin combined with levofloxacin on the biofilm of Klebsiella pneumoniae of different ST-types and providing a new strategy for the prevention of biofilm formation in the treatment of post-infectious Klebsiella pneumoniae. METHODS: 9 strains of Klebsiella pneumoniae from all susceptibility groups, 19 strains of Klebsiella pneumoniae producing extended-spectrum β - lactamases (ESBLs), and 37 strains of Carbapenem-resistant Klebsiella pneumoniae (CRKP) were randomly collected from the samples of patients hospitalized in the First Affiliated Hospital of Wannan Medical College from August 2019 to November 2021. The isolates were identified using VITEK MS IVD KB V3.2 and VITEK 2-Compact 60. Multilocus sequence typing (MLST) was performed to analyze the homology of each strain; crystal violet staining was used for semi -quantitative detection of biofilm to compare the differences in biofilm formation ability between different ST-type Klebsiella pneumoniae. Different ST-type strains were selected, and the partial inhibitory concentration index (FICI) was calculated by micro broth dilution method to judge the combination effect and select the optimal combination concentration; crystalline violet staining method was used to investigate the inhibition and clearance effect of azithromycin combined with levofloxacin on the biofilm of different ST-type Klebsiella pneumoniae; laser scanning confocal fluorescence microscopy was used to observe the structural changes of the biofilm of Klebsiella pneumoniae before and after the effect of the antibacterial drugs. RESULTS: MLST typing results showed that the sensitive group of Klebsiella pneumoniae strains had 8 sequences such as ST86, ST727, etc., the ESBLs group strains belonged to 14 sequence types such as ST15, ST37, ST11, etc., of which ST15 accounted for 26.32% (5 / 19). The CRKP group strains belonged to 9 sequence types such as ST11, ST15, ST656, etc., of which ST11 accounted for 48.65% (18/37), ST15 accounted for 27.03% (10/37); ST15 (ESBLs), ST11 (CRKP), ST15 (CRKP) type Klebsiella pneumoniae biofilms all reached maturity on the 5th day, the ST15 (ESBLs) group had a stronger ability to produce material to be membranous than the ST15 (CRKP) group. The ST11 (CRKP) group had a stronger ability to produce material to be membranous than the ST15 (CRKP) group (P<0.01); the results of azithromycin combined with levofloxacin drug sensitivity showed that it had an additive effect on different ST-type Klebsiella pneumoniae bacteria; in the inhibition of biofilm formation and clearance test, the 2×MIC azithromycin group and the combined concentration group had a stronger inhibition of biofilm formation of different ST-type Klebsiella pneumoniae bacteria, and the inhibitory ability of the combined group was better than that of the single-drug group, and the highest inhibition rate could reach 89.93%; the clearance effects were all combined drug group>azithromycin>levofloxacin, and the highest clearance rate was 44.79%. CONCLUSION: There are differences in biofilm formation ability between different ST-type Klebsiella pneumoniae, and azithromycin combined with levofloxacin has a better inhibitory effect on different ST-type Klebsiella pneumoniae biofilm, conbined application can be used in the treatment of biofilm infections early stage.