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 investigate the effects of Zuogui Jiangtang Jieyu Formula (ZGJTJYF) on histone H3 lysine 18 lactylation (H3K18la) in the hippocampus of rats with diabetes mellitus complicated with depression (DD) and predict the regulatory genes of H3K18la. Methods: Male Sprague-Dawley rats were divided into control, model, and positive drug (metformin [0.18 g/kg] and fluoxetine [1.8 mg/kg]) groups, and the three groups were treated with high, medium, and low ZGJTJYF doses (20.52, 10.26, and 5.13 g/kg, respectively), with 10 rats per group. After treatment, the forced swimming and water maze tests were performed to assess depressive-like behaviors and cognitive function. An enzyme-linked immunosorbent assay was used to measure blood insulin, glycosylated hemoglobin, lactate levels, and lactate content in the hippocampus. Western blotting was used to detect H3K18la expression in the hippocampus. Cleavage Under Targets and lagmentation(CUT&Tag) experiments targeted hippocampal H3K18la epigenetic modification regions to analyze the transcription factors bound by H3K18la. Kyoto Encyclopedia of Genes and Genomes and Protein-Protein Interaction networks were constructed to identify key pathways and target genes regulated by H3K18la. Results: Compared with the normal group, the model group rats showed prolonged immobility time in the forced swim test, increased escape latency in the water maze experiment, decreased target quadrant distance ratio (P<0.01), increased serum lactate content, and decreased lactate content in hippocampal homogenate (P<0.01), as well as decreased H3K18la protein expression in the hippocampus (P<0.01). Compared with the model group, ZGJTJYF reduced the immobility time in the forced swim test and the escape latency in the water maze test (P<0.01), while the distance ratio in the target quadrant increased (P<0.01) in model rats. Lowered fasting blood glucose, insulin, and glycosylated hemoglobin levels (P<0.05, P<0.01) were also observed. ZGJTJYF also increased the lactate content and H3K18la protein expression in hippocampal homogenate (P<0.05, P<0.01). The DNA sequences bound by H3K18la were predominantly enriched at the transcription start sites. ZGJTJYF modulated H3K18la-associated pathways, including cell adhesion junctions, tumor growth factor-beta (TGF-β) signaling, stem cell pluripotency regulation, mitogen-activated protein kinase(MAPK) signaling pathway, and insulin resistance, leading to the identification of 12 target genes. Conclusion ZGJTJYF enhances hippocampal lactate levels and H3K18la modification in DD rats, which may regulate neural cell interactions, neurogenic stem cell function, TGF-β signaling, MAPK signaling, and insulin resistance pathways.

OBJECTIVE To analyze the etiological and clinical characteristics of the neonates with early-onset and late-onset purulent meningitis.METHODS A total of 140 neonates who were diagnosed with purulent meningitis and were hospitalized in neonatal intensive care unit(NICU)of Xuzhou Children's Hospital Affiliated to Xuzhou Medical University from Jan.2018 to Dec.2022 were recruited as the research subjects and were divided into the early-onset group with 32 cases and the late-onset group with 108 cases according to the onset time.The clinical data were collected from the enrolled neonates and were retrospectively analyzed.The etiological and clinical char-acteristics of the neonates with purulent meningitis were observed.RESULTS Totally 140 neonates with purulent meningitis were included in the study,the total morbidity rate was 1.03％(140/13644),and it was more common among the male neonates and full-term neonates,dominated by late-onset cases.The incidence rates of perinatal infection,premature rupture of fetal membranes,lethargy/irritability,cyanosis,abnormal muscle tone and septic shock were higher in the early-onset group than in the late-onset group(P＜0.05).There were significant differ-ences in serum PCT,cerebrospinal fluid cell counts,percentage of neutrophils and proteins between the early-on-set group and the late-onset group(P＜0.05).The positive rate of etiological culture of the early-onset group was 43.75％(14/32),higher than 20.37％(22/108)of the late-onset group(P＜0.05);Escherichia coli was the pre-dominant species of pathogen isolated from the two groups.The total proportion of the neonates with abnormal imaging findings was 22.85％among the two groups of neonates;the intracranial hemorrhage,subdural effusion and ventricular enlargement/hydrocephalus were the major abnormal types;the proportion of the neonates with abnormal imaging findings of the early-onset group was 43.75％,higher than 16.67％of the late-onset group(P＜0.05).CONCLUSIONS The neonates with late-onset purulent meningitis are dominant among the neonates with purulent meningitis enrolled in the study.The neonates with early-onset purulent meningitis present with more se-vere clinical manifestations and higher proportion of abnormal imaging findings;there is significant difference in the clinical characteristics between the early-onset neonates and the late-onset neonates.The result of etiological culture shows that E.coli is the predominant species of pathogen among both the early-onset neonates and the late-onset children.

Objective To investigate the clinical effect of elastic fixation of Endobutton plate with loop in the treatment of lower tibiofibular combined injury.Methods A total of 326 patients with lower tibiofibular joint injury combined with ankle fracture underwent surgical treatment from June 2019 to June 2021 were randomly divided into experimental group(163 cases)and control group(163 cases)by using a random number table.The control group was fixed with traditional steel plate screw,and the experimental group was fixed with elastic steel plate with loop Endobutton.Hospitalization and operation related indexes were compared between the two groups.The American Association of Foot and Ankle Surgery Ankle Function Score(AOFAS)was performed on the two groups at 2 and 6 months after surgery,respectively,and the reseparation rate of the lower tibiofibular union was evaluated and compared between the two groups at 6 months after surgery.Results There were no significant differences in operation time,blood loss,incision length,getting out of bed time and hospital stay between experimental group and control group(P＞0.05).The incidence of postoperative complications in experimental group was 2.45％,lower than that in control group(7.98％),and the difference between the two groups was statistically significant(P＜0.05).The incidence of postoperative complications in experimental group was 2.45％,lower than that in control group(7.98％),and the difference was statistically significant between the two groups(P＜0.05).The AOFAS scores of control group were(74.5±9.2)and(81.3±4.3)at 2 months and 6 months,respectively,and the excellent and good rate was 76.0％.AOFAS of experimental group were(82.3±5.3)points and(91.2±3.8)points at 2 months and 6 months after surgery,respectively,and the excellent and good rate was 93.2％,the above indexes of experimental group were higher than those of control group,and the difference between the two groups was statistically significant(P＜0.05).Reexamination 6 months after surgery the reseparation rate of lower tibiofibular combination was 12.8％in the control group and 2.4％in the experimental group,and the risk of reseparation in the experimental group was lower than that in the control group,with statistical significance(P＜0.05).Conclusion Elastic fixation using Endobutton plate with loop could be used in the treatment of ankle fracture with distal tibiofibular syndesmosis injury,which has a better effect of traditional internal fixation with plate and screws.

Objective To identify clinicopathological parameters that differentiate between very high-risk and ordinary high-risk gas-trointestinal stromal tumors(GISTs)to provide guidance for clinical treatment and follow-up monitoring.Methods A retrospective cohort study was conducted,collecting 174 cases of high-risk GISTs initially diagnosed and surgically resected at Tianjin Medical University Cancer Institute and Hospital between January 1st,2011,and December 31st,2019.Based on long-term follow-up data,the X-tile software was used to identify key parameters for screening very high-risk GISTs from ordinary high-risk GISTs,and the results were validated by using high-risk GIST cases from the cBioPortal database.Results Among the 174 high-risk GIST cases,the X-tile software indicat-ed that the maximum tumor diameter of 14 cm,the mitotic count of 14/5 mm2,and the Ki-67 proliferation index of 10%were the optimal cutoff values for distinguishing very high-risk GISTs from ordinary high-risk GISTs.Univariate survival analysis confirmed that these cutoff values were associated with progression free survival(PFS,all P<0.05).Multivariate survival analysis confirmed that the maximum tumor diameter≥14 cm(HR=5.727,P<0.01),mitotic count≥14/5 mm2(HR=2.454,P=0.047),and Ki-67 proliferation index≥10%(HR=2.275,P=0.047)were independent risk factors for tumor progression in high-risk GIST patients.High-risk GISTs with any one of the three parameters more than or equal to its optimal cutoff value were defined as very high-risk GISTs,and the other GISTs were defined as ordinary high-risk GISTs.Compared to very high-risk GIST patients,the ordinary high-risk GIST patients had superior PFS(P<0.01),and a trend toward better overall survival(OS,P=0.082).Stratified analysis showed that,in subgroups of patients with gastric or non-gas-tric primary tumors,those receiving or not receiving adjuvant therapy,and those with KIT proto-oncogene,receptor tyrosine kinase(KIT)gene mutations,ordinary high-risk GIST patients all exhibited superior PFS compared to very high-risk GIST patients(all P<0.05).Both PFS and OS of ordinary high-risk GIST patients in the cBioPortal database were better than those of very high-risk GIST patients(both P=0.001).Stratified analysis of the cBioPortal database data showed that,in subgroups of patients with gastric or non-gastric primary tu-mors,those who received adjuvant therapy,and those with KIT gene mutations,ordinary high-risk GIST patients all exhibited superior PFS compared to very high-risk GIST patients(all P<0.05);conversely,among patients who did not receive adjuvant therapy,very high-risk GIST patients showed a trend toward poorer PFS(P=0.366).Conclusions This study has established a method utilizing commonly used clinical parameters to distinguish very high-risk GISTs in clinical practice.However,further validation through multicenter studies with larger sample sizes is still required.

Objective:To investigate the preventive and therapeutic effects and mechanisms of Dachaihu decoction(DCD)on dextran sodium sulfate(DSS)-induced ulcerative colitis(UC)and liver injury in mice,as well as the association between DCD benefits and gut microbiota modulation.Methods:Mice were treated with DCD(20.10 and 10.05 g/kg)for 2 weeks,with free access to drinking water containing 3%DSS in the second week to induce UC.Histopathological examination,RT-qPCR and 16S rRNA sequencing were used to investigate the effect of DCD on UC mice.Results:DCD pretreatment significantly alleviated weight loss,bloody diarrhea with mucus,histopathological abnormalities of the colon,and colon shortening in mice with DSS-induced UC.In addition,DCD pretreat-ment significantly upregulated the levels of Occludin,ZO-1,and MUC-2 in the colon and protected the intestinal barrier of mice.DCD pretreatment also alleviated inflammatory cell infiltration in the colon and the liver and significantly reduced the expression levels of the proinflammatory factors such as IL-1β,IL-6,TNF-α,iNOS,COX-2,and NLRP3,thereby exerting a protective effect against UC and liver injury.It should be noted that DCD corrected gut micro-biota imbalance in UC mice by enriching probiotic bacteria such as Lactobacillus and Bifidobacterium and reducing harmful bacteria such as Norank_f_Desulfovibrionaceae and Escherichia-Shigella.Conclusion:DCD can alleviate DSS-induced UC and exert a liver-protecting effect by protecting intestinal barrier,inhibiting inflam-mation,and regulating gut microbiota.

Background and Aims:Totally implantable venous access port(TIVAP)are widely used for chemotherapy,blood transfusion,and nutritional support in patients with malignancies.Among them,upper arm port(UAP)are increasingly recommended in clinical practice due to their advantages in avoiding thoracic complications and providing more concealed incisions.Currently,two main implantation techniques are used for UAP:the tunnel needle-transverse incision technique and the puncture point-transverse incision technique.This study aims to compare the clinical outcomes of these two techniques in patients with hematological malignancies,focusing on safety and cosmetic appearance,to provide evidence for clinical decision-making.Methods:A retrospective analysis was conducted on 412 patients with hematological malignancies who underwent UAP implantation at Xiangya Hospital of Central South University between December 2021 and December 2024.Based on the implantation method,patients were divided into the tunnel needle-transverse incision group(n=200)and the puncture point-transverse incision group(n=212).Intraoperative variables(operative time,intraoperative pain score,catheter kinking at the pocket,intraoperative blood loss)and postoperative indicators(incidence of complications and incision aesthetic satisfaction)were compared between the two groups.Results:There were no significant differences in baseline characteristics between the two groups(all P>0.05),indicating comparability.The puncture point-transverse incision group showed superior performance in operative time[(32.99±4.91)min vs.(41.42±5.35)min],catheter kinking rate(1.4％vs.8.5％),and incision aesthetic satisfaction(7.99±0.58 vs.6.26±0.86)compared with the tunnel needle-transverse incision group(all P<0.05).Although the puncture point group had slightly more intraoperative bleeding[(4.52±1.02)mL vs.(4.16±0.83)mL],the difference,while statistically significant,was of limited clinical relevance.No significant differences were observed between the two groups in intraoperative pain scores or incidence of postoperative complications(both P>0.05).Conclusion:The puncture point-transverse incision technique offers significant advantages in terms of operative efficiency,reduced catheter kinking,and improved incision aesthetics,without compromising safety.It represents a promising alternative to the traditional tunnel needle-transverse incision method and has strong potential for broader clinical adoption.The puncture point-transverse incision technique offers advantages such as shorter operative time,lower catheter kinking rate,and higher incision aesthetic satisfaction.It is a promising alternative to the traditional tunnel needle-transverse incision technique and has good potential for clinical application and promotion.

Background and Aims:Totally implantable venous access ports(TIVAP)are widely used in patients requiring long-term intravenous therapy.Traditional butterfly needle puncture fixation methods have limitations,including low success rates,increased pain,and risk of needle-stick injury.This study aimed to design an adjustable puncture protection kit for butterfly needles and evaluate its clinical utility using a simulated device.Methods:A prospective randomized controlled trial was conducted with 70 patients implanted with upper arm ports in the Hematology Department of Xiangya Hospital,Central South University,from January to December 2024.The patients were divided into a study group and a control group,with 35 cases in each,using a randomized block design.The study group underwent puncture with the simulated adjustable protection kit,while the control group used the traditional finger fixation method.Outcomes compared included first-attempt success rate,vertical puncture rate,pain score,puncture time,and complication rate.Results:The baseline characteristics of the two groups were balanced.The study group had significantly higher first-attempt puncture success rate and vertical puncture rate than the control group(94.3%vs.77.1%;91.4%vs.57.1%,both P<0.05).In the experimental group compared with the control group,pain scores were lower(1.80±1.13 vs.2.94±1.33,P<0.05),and puncture time was shorter[(31.31±9.05)s vs.(41.80±23.97)s,P<0.05].There was no significant difference in the incidence of puncture-related complications between the two groups(2.9%vs.14.3%,P>0.05).Conclusion:The simulated adjustable butterfly needle puncture protection kit effectively improves puncture success,enhances efficiency,reduces patient pain,and demonstrates good clinical safety.This innovative design provides a promising solution for reducing needle-stick injury risks and optimizing port puncture procedures,although larger,multicenter,and long-term studies are warranted.

Objective To investigate the clinical effect of elastic fixation of Endobutton plate with loop in the treatment of lower tibiofibular combined injury.Methods A total of 326 patients with lower tibiofibular joint injury combined with ankle fracture underwent surgical treatment from June 2019 to June 2021 were randomly divided into experimental group(163 cases)and control group(163 cases)by using a random number table.The control group was fixed with traditional steel plate screw,and the experimental group was fixed with elastic steel plate with loop Endobutton.Hospitalization and operation related indexes were compared between the two groups.The American Association of Foot and Ankle Surgery Ankle Function Score(AOFAS)was performed on the two groups at 2 and 6 months after surgery,respectively,and the reseparation rate of the lower tibiofibular union was evaluated and compared between the two groups at 6 months after surgery.Results There were no significant differences in operation time,blood loss,incision length,getting out of bed time and hospital stay between experimental group and control group(P＞0.05).The incidence of postoperative complications in experimental group was 2.45％,lower than that in control group(7.98％),and the difference between the two groups was statistically significant(P＜0.05).The incidence of postoperative complications in experimental group was 2.45％,lower than that in control group(7.98％),and the difference was statistically significant between the two groups(P＜0.05).The AOFAS scores of control group were(74.5±9.2)and(81.3±4.3)at 2 months and 6 months,respectively,and the excellent and good rate was 76.0％.AOFAS of experimental group were(82.3±5.3)points and(91.2±3.8)points at 2 months and 6 months after surgery,respectively,and the excellent and good rate was 93.2％,the above indexes of experimental group were higher than those of control group,and the difference between the two groups was statistically significant(P＜0.05).Reexamination 6 months after surgery the reseparation rate of lower tibiofibular combination was 12.8％in the control group and 2.4％in the experimental group,and the risk of reseparation in the experimental group was lower than that in the control group,with statistical significance(P＜0.05).Conclusion Elastic fixation using Endobutton plate with loop could be used in the treatment of ankle fracture with distal tibiofibular syndesmosis injury,which has a better effect of traditional internal fixation with plate and screws.

Objective To identify clinicopathological parameters that differentiate between very high-risk and ordinary high-risk gas-trointestinal stromal tumors(GISTs)to provide guidance for clinical treatment and follow-up monitoring.Methods A retrospective cohort study was conducted,collecting 174 cases of high-risk GISTs initially diagnosed and surgically resected at Tianjin Medical University Cancer Institute and Hospital between January 1st,2011,and December 31st,2019.Based on long-term follow-up data,the X-tile software was used to identify key parameters for screening very high-risk GISTs from ordinary high-risk GISTs,and the results were validated by using high-risk GIST cases from the cBioPortal database.Results Among the 174 high-risk GIST cases,the X-tile software indicat-ed that the maximum tumor diameter of 14 cm,the mitotic count of 14/5 mm2,and the Ki-67 proliferation index of 10%were the optimal cutoff values for distinguishing very high-risk GISTs from ordinary high-risk GISTs.Univariate survival analysis confirmed that these cutoff values were associated with progression free survival(PFS,all P<0.05).Multivariate survival analysis confirmed that the maximum tumor diameter≥14 cm(HR=5.727,P<0.01),mitotic count≥14/5 mm2(HR=2.454,P=0.047),and Ki-67 proliferation index≥10%(HR=2.275,P=0.047)were independent risk factors for tumor progression in high-risk GIST patients.High-risk GISTs with any one of the three parameters more than or equal to its optimal cutoff value were defined as very high-risk GISTs,and the other GISTs were defined as ordinary high-risk GISTs.Compared to very high-risk GIST patients,the ordinary high-risk GIST patients had superior PFS(P<0.01),and a trend toward better overall survival(OS,P=0.082).Stratified analysis showed that,in subgroups of patients with gastric or non-gas-tric primary tumors,those receiving or not receiving adjuvant therapy,and those with KIT proto-oncogene,receptor tyrosine kinase(KIT)gene mutations,ordinary high-risk GIST patients all exhibited superior PFS compared to very high-risk GIST patients(all P<0.05).Both PFS and OS of ordinary high-risk GIST patients in the cBioPortal database were better than those of very high-risk GIST patients(both P=0.001).Stratified analysis of the cBioPortal database data showed that,in subgroups of patients with gastric or non-gastric primary tu-mors,those who received adjuvant therapy,and those with KIT gene mutations,ordinary high-risk GIST patients all exhibited superior PFS compared to very high-risk GIST patients(all P<0.05);conversely,among patients who did not receive adjuvant therapy,very high-risk GIST patients showed a trend toward poorer PFS(P=0.366).Conclusions This study has established a method utilizing commonly used clinical parameters to distinguish very high-risk GISTs in clinical practice.However,further validation through multicenter studies with larger sample sizes is still required.