Objective:To investigate the potential of praeruptorin A (PA) in alleviating inflammatory damage in sepsis through the inhibition of ferritin expression.Methods:C57BL/6 mice were intraperitoneally injected with lipopolysaccharide (LPS) to establish the model of sepsis. After 6 and 12 h of PA intervention, serum levels of inflammatory cytokines IL-6 and TNF-α were measured by ELISA. Kidney tissues were collected at 72 h for HE staining to assess inflammatory cell infiltration and tissue damage. Human neutrophils were divided into four groups: control, LPS, ferritin, and LPS+ ferritin groups. After 12 h of intervention, qRT-PCR was used to detect the expression of IL-6 and TNF-α mRNA. In order to observe the effect of PA on the expression of inflammatory cytokines and ferritin, human neutrophils were grouped into control, LPS, and LPS+ PA (2/3/4 μmol/L) groups. After 12 h of intervention, qRT-PCR was performed to measure the expression of IL-1β, IL-6, TNF-α, and ferritin mRNA; ELISA was used to quantify the levels of IL-1β, IL-6, and TNF-α in culture supernatants; Western blot was used to analyze the expression of ferritin. Molecular docking was conducted to verify interactions between PA and ferritin.Results:Significant inflammatory cell recruitment, tissue damage, and elevated serum levels of IL-6 and TNF-α ( P<0.01) were observed in mice with LPS-induced sepsis. PA significantly inhibited cytokine secretion ( P<0.01) and alleviated tissue injury in sepsis mice. In human neutrophil models, ferritin upregulated the expression of IL-6 and TNF-α mRNA ( P<0.01); LPS stimulation alone increased the expression of IL-1β, IL-6, TNF-α, and ferritin at both mRNA and protein levels ( P<0.01), while co-stimulation with PA (3/4 μmol/L) significantly reversed the aforementioned results ( P<0.01). Molecular docking confirmed there were interaction sites between PA and ferritin. Conclusion:PA inhibits the release of inflammatory cytokines and alleviates tissue damage in sepsis, and the potential mechanism may involve modulating ferritin expression to suppress inflammatory responses.

OBJECTIVE To investigate the effects of ginsenosides as P-glycoprotein(P-gp)substrates in combination with paclitaxel on the proliferation and migration of colon cancer Caco-2 cells.METHODS Bio-layer interferometry(BLI)technology was used to detect the constants of ginsenosides and P-gp.Network molecular docking was adopted to predict the binding affinity energy of ginsenosides and P-gp.Caco-2 cells were divided into paclitaxel 0,6.25,12.5,25,50,100 and 200 mg·L-1 groups,ginsenoside Rg3 0,6.25,12.5,25,50,100 and 200 mg·L-1 groups,and paclitaxel 5 mg·L-1+ginsenoside Rg3 0,25,50,100 and 200 mg·L-1 groups.After 48 h of incubation,the growth inhibition rate of Caco-2 cells was detected by MTT assay,and the interaction between the two drugs was quantitatively evaluated using the"one-belt,one-line"modle.Caco-2 cells were divided into the cell control group,paclitaxel 5 mg·L-1 group,ginsenoside Rg3 50 and 100 mg·L-1 groups,and paclitaxel 5 mg·L-1+ginsenoside Rg3 50 and 100 mg·L-1 groups.After 24 h of incubation,the proliferation and migration ability of the cells were detected by colony assay and Transwell migration assay.Caco-2 cells were then divided into the cell control group,quinidine 12.5 mg·L-1 group,and ginsenoside Rg3 6.25 and 12.5 mg·L-1 groups.After 4 h of incubation,the expression levels of P-gp and total protein were detected by ELISA.RESULTS The affinity constants of ginsenoside Rb1,Rg3,Rg5 with P-gp were all less than 10-3 mol·L-1,while that of ginsenoside CK with P-gp was 10-2 mol·L-1.There was no typical binding dissociation curve between ginsenoside Re and P-gp.The absolute binding affinities of ginsenosides Rg3 and Rg5 to P-gp were determined to be 8.5 kcal·mol-1 and 7.6 kcal·mol-1,respectively.Ginsenosides mixed with PTX 5 mg·L-1 inhibited the growth of colon cancer cells through synergy and addition,and the dose range of the syner-gistic effect was[0+5,43.15+5]mg·L-1;[164.51+5,200+5]mg·L-1,the additive effect dose ranged from[43.15+5,164.51+5]mg·L-1.The combination of the two drugs could significantly reduce the proliferation and migration ability of Caco-2 cells(P<0.01).The ELISA results showed a decrease in total protein and P-gp content in both the ginsenoside and quinidine groups(P<0.05).CONCLUSION Ginsenoside bind to and inhibit the activity of P-gp,synergizing with paclitaxel to reduce the proliferative and migratory abili-ties of Caco-2 cells.The combination of ginsenosides and paclitaxel enhances the sensitivity of Caco-2 cells to paclitaxel induced inhibition.The combined use of these two substances is expected to achieve better anticancer effects compared to paclitaxel alone.

Lung cancer is the most common malignant tumor worldwide, ranking first in both incidence and mortality rates. According to the latest statistics from the International Agency for Research on Cancer (IARC), approximately 2.5 million new cases and around 1.8 million deaths from lung cancer occurred in 2022, placing a tremendous burden on global healthcare systems. The high mortality rate of lung cancer is closely linked to its subtle early symptoms, which often lead to diagnosis at advanced stages. This not only complicates treatment but also results in substantial economic losses. Current treatment options for lung cancer include surgery, radiotherapy, chemotherapy, targeted drug therapy, and immunotherapy. Among these, immunotherapy has emerged as the most groundbreaking advancement in recent years, owing to its unique antitumor mechanisms and impressive clinical benefits. Unlike traditional therapies such as radiotherapy and chemotherapy, immunotherapy activates or enhances the patient’s immune system to recognize and eliminate tumor cells. It offers advantages such as more durable therapeutic effects and relatively fewer toxic side effects. The main approaches to lung cancer immunotherapy include immune checkpoint inhibitors, tumor-specific antigen-targeted therapies, adoptive cell therapies, cancer vaccines, and oncolytic virus therapies. Among these, immune checkpoint inhibitors and tumor-specific antigen-targeted therapies have received approval from the U.S. Food and Drug Administration (FDA) for clinical use in lung cancer, significantly improving outcomes for patients with advanced non-small cell lung cancer. Although other immunotherapy strategies are still in clinical trials, they show great potential in improving treatment precision and efficacy. This article systematically reviews the latest research progress in lung cancer immunotherapy, including the development of novel immune checkpoint molecules, optimization of treatment strategies, identification of predictive biomarkers, and findings from recent clinical trials. It also discusses the current challenges in the field and outlines future directions, such as the development of next-generation immunotherapeutic agents, exploration of more effective combination regimens, and the establishment of precise efficacy prediction systems. The aim is to provide a valuable reference for the continued advancement of lung cancer immunotherapy.

Objective:To investigate the potential of praeruptorin A (PA) in alleviating inflammatory damage in sepsis through the inhibition of ferritin expression.Methods:C57BL/6 mice were intraperitoneally injected with lipopolysaccharide (LPS) to establish the model of sepsis. After 6 and 12 h of PA intervention, serum levels of inflammatory cytokines IL-6 and TNF-α were measured by ELISA. Kidney tissues were collected at 72 h for HE staining to assess inflammatory cell infiltration and tissue damage. Human neutrophils were divided into four groups: control, LPS, ferritin, and LPS+ ferritin groups. After 12 h of intervention, qRT-PCR was used to detect the expression of IL-6 and TNF-α mRNA. In order to observe the effect of PA on the expression of inflammatory cytokines and ferritin, human neutrophils were grouped into control, LPS, and LPS+ PA (2/3/4 μmol/L) groups. After 12 h of intervention, qRT-PCR was performed to measure the expression of IL-1β, IL-6, TNF-α, and ferritin mRNA; ELISA was used to quantify the levels of IL-1β, IL-6, and TNF-α in culture supernatants; Western blot was used to analyze the expression of ferritin. Molecular docking was conducted to verify interactions between PA and ferritin.Results:Significant inflammatory cell recruitment, tissue damage, and elevated serum levels of IL-6 and TNF-α ( P<0.01) were observed in mice with LPS-induced sepsis. PA significantly inhibited cytokine secretion ( P<0.01) and alleviated tissue injury in sepsis mice. In human neutrophil models, ferritin upregulated the expression of IL-6 and TNF-α mRNA ( P<0.01); LPS stimulation alone increased the expression of IL-1β, IL-6, TNF-α, and ferritin at both mRNA and protein levels ( P<0.01), while co-stimulation with PA (3/4 μmol/L) significantly reversed the aforementioned results ( P<0.01). Molecular docking confirmed there were interaction sites between PA and ferritin. Conclusion:PA inhibits the release of inflammatory cytokines and alleviates tissue damage in sepsis, and the potential mechanism may involve modulating ferritin expression to suppress inflammatory responses.

OBJECTIVE To investigate the effects of ginsenosides as P-glycoprotein(P-gp)substrates in combination with paclitaxel on the proliferation and migration of colon cancer Caco-2 cells.METHODS Bio-layer interferometry(BLI)technology was used to detect the constants of ginsenosides and P-gp.Network molecular docking was adopted to predict the binding affinity energy of ginsenosides and P-gp.Caco-2 cells were divided into paclitaxel 0,6.25,12.5,25,50,100 and 200 mg·L-1 groups,ginsenoside Rg3 0,6.25,12.5,25,50,100 and 200 mg·L-1 groups,and paclitaxel 5 mg·L-1+ginsenoside Rg3 0,25,50,100 and 200 mg·L-1 groups.After 48 h of incubation,the growth inhibition rate of Caco-2 cells was detected by MTT assay,and the interaction between the two drugs was quantitatively evaluated using the"one-belt,one-line"modle.Caco-2 cells were divided into the cell control group,paclitaxel 5 mg·L-1 group,ginsenoside Rg3 50 and 100 mg·L-1 groups,and paclitaxel 5 mg·L-1+ginsenoside Rg3 50 and 100 mg·L-1 groups.After 24 h of incubation,the proliferation and migration ability of the cells were detected by colony assay and Transwell migration assay.Caco-2 cells were then divided into the cell control group,quinidine 12.5 mg·L-1 group,and ginsenoside Rg3 6.25 and 12.5 mg·L-1 groups.After 4 h of incubation,the expression levels of P-gp and total protein were detected by ELISA.RESULTS The affinity constants of ginsenoside Rb1,Rg3,Rg5 with P-gp were all less than 10-3 mol·L-1,while that of ginsenoside CK with P-gp was 10-2 mol·L-1.There was no typical binding dissociation curve between ginsenoside Re and P-gp.The absolute binding affinities of ginsenosides Rg3 and Rg5 to P-gp were determined to be 8.5 kcal·mol-1 and 7.6 kcal·mol-1,respectively.Ginsenosides mixed with PTX 5 mg·L-1 inhibited the growth of colon cancer cells through synergy and addition,and the dose range of the syner-gistic effect was[0+5,43.15+5]mg·L-1;[164.51+5,200+5]mg·L-1,the additive effect dose ranged from[43.15+5,164.51+5]mg·L-1.The combination of the two drugs could significantly reduce the proliferation and migration ability of Caco-2 cells(P<0.01).The ELISA results showed a decrease in total protein and P-gp content in both the ginsenoside and quinidine groups(P<0.05).CONCLUSION Ginsenoside bind to and inhibit the activity of P-gp,synergizing with paclitaxel to reduce the proliferative and migratory abili-ties of Caco-2 cells.The combination of ginsenosides and paclitaxel enhances the sensitivity of Caco-2 cells to paclitaxel induced inhibition.The combined use of these two substances is expected to achieve better anticancer effects compared to paclitaxel alone.

Objects To explore the effectiveness and safety of using the Cardio-O-Fix Plug occluder in the treatment of muscular ventricular septal defect(mVSD)in children.Methods 14 patients with mVSD were taken to the cardiology department of First Affiliated Hospital of Kunming Medical University from July 2015 to June 2021 as research subjects.They were divided into two groups:14 children who received Cardi-O-Fix Plug occluder as the experimental group,and 10 children who received Cardi-O-O-Fix mVSD occluder as the control group.Electrocardiogram and transthoracic echocardiography were used to evaluate the occlusive efficacy and incidence of complications 1 day after surgery and 1 month,3 months,and 6 months of follow-up.Results Among the 24 pediatric patients,22 cases were successfully occluded,and 2 cases were unsuccessful(1 in the experi-mental group and 1 in the control group).The success rate of the experimental group was 92.8%(13/14),while the success rate of the control group was 90.0%(9/10).The average surgical duration of the experimental group was(71.93±14.85)minutes,while the average surgical duration of the control group was(90.70±19.78)minutes.There was a significant statistical difference between the two groups(P<0.05).Both the experimental group and the control group did not experience serious complications during surgery and follow-up.There was no significant difference in cardiac ultrasound indicators(including left ventricular ejection fraction,left ventricular end-diastolic diameter,and pulmonary artery pressure)between the two groups at different time points(P>0.05).Conclusion Trans-catheter closure of mVSD using Cardi-O-Fix Plug occluder in children is both safe and effective.The incidence of arrhythmia is low in the short,medium and long term.

Objective:To explore the changes in acoustic features of 9-10-year-old primary school students with depressive symptoms, and based on these features and the random forest (RF) algorithm, construct a model for identifying depressive symptoms in primary school students, so as to provide an intelligent psychological health screening tool for schools and education departments.Methods:This was a case-control study.A total of 1 186 primary school students aged 9-10 from three primary schools in three regions of Jiangsu Province were selected as research subjects for psychological health screening from October 26, 2022 to February 13, 2023.Their demographic data, Depression-Anxiety-Stress Scale (DASS-21) scores, Insomnia Severity Index scores, and voice recordings were collected.Based on the DASS-21 scores, the participants were divided into a control group ( n=1 086) and a depression group ( n=100).Voice recordings were made using the neutral text " The North Wind and the Sun". openSMILE was used to extract 523 acoustic features from the pre-processed voice recordings.Group differences were assessed using independent-samples t-tests or chi-square tests.Pearson correlation analysis was conducted to examine the relationship between acoustic features and depression scores.Depressive symptoms were set as the dependent variable, and the correlated acoustic features were set as the independent variable to construct a classification model using the RF algorithm.The model performance was assessed using the receiver operating characteristic (ROC) curve, the area under the curve (AUC), precision, accuracy, recall, and F1 score. Results:Compared with the control group, the depression group showed significant differences in 105 acoustic features (44 spectral features, 49 source features, and 12 prosodic features) (all P<0.05).Correlation analysis showed that 12 acoustic features (7 spectral features, 4 source features, and 1 prosodic feature) were significantly correlated with the depression score (all P<0.05).Among the RF algorithm-based classification models, the spectral features demonstrated superior performance compared to source features and prosodic features (AUC=0.793), and the performance of the model based on the combination of these features was the best (AUC=0.818). Conclusions:Acoustic features may be an objective indicator to identify the depression of 9-10-year-old primary school students, and the classification model established based on acoustic features can identify the depressed primary school students.

To promote the construction of first-class disciplines of "Double First-Class" universities in China, the construction of a comprehensive evaluation system was explored, so as to provide suggestions for the development of these disciplines.Essential Science Indicators (ESI), InCites and Derwent Innovation Index databases, together with range transformation method and entropy weight method, were employed to analyze the data in the field of pharmacology and toxicology from some universities; the construction approaches and index performance of the system were studied. The score performances of the sample universities in the index system are different from their ESI rankings, suggesting that the system has certain practical value.ESI rankings cannot fully reflect the development levels of disciplines, while the multi-dimensional index evaluation system can overcome this shortcoming to a certain extent.This paper establishes an evaluation system with published papers and granted patents as the main evaluation objects, covering as many multi-angle indicators of scientific research output as possible, and trying to overcome the disadvantages due to lack of information in a single or few index systems.It is suggested that universities should formulate their discipline development plans from the perspectives of publishing high-quality original research results, leading or widely participating in scientific research cooperation, strengthening university-enterprise cooperation, promoting the application of research results, promoting open science and encouraging open access.

Objective:This study examined the associations between the levels of bile acids in early pregnancy and the occurrence of overweight.Methods:From 2010 to 2012, 22 302 pregnant women were recruited by Tianjin Women and Children′s Health Center to investigate gestational diabetes. Two hundred and forty-three women with gestational diabetes mellitus provided overnight fasting blood samples in the first trimester, and 243 counterparts without gestational diabetes mellitus matched on age were selected randomly to establish a nested case-control study. The association between bile acids and overweight were evaluated by binary logistic regression with data from 166 overweight pregnant women (body mass index≥24.0 kg/m 2) and 320 normal weight subjects (body mass index <24.0 kg/m 2). Results:Compared to non-overweight group, the level of primary unconjugated bile acids in overweight group was significantly higher. After adjustment of confounding factors, the OR of cholic acid (CA)>0.086 nmol/mL for overweight was 2.09 (95% CI 1.14-3.80, adjusted P=0.040), and OR of chenodeoxycholic acid (CDCA)>0.043 nmol/mL was 2.15 (95% CI 1.22-3.78, adjusted P=0.040) compared with the lower groups. However, the significant associations between the other bile acids and overweight were not detected. Stepwise selection was used to identify significant bile acid species in logistic regression. We found that only CA was independently associated with overweight, and the OR of CA>0.086 nmol/mL vs≤0.086 nmol/mL was 2.03 (95% CI 1.11-3.74, P=0.022). Conclusion:CA and CDCA in early pregnancy maybe associated with overweight, and CA might be independently associated with overweight.

Objective:To explore the clinical application value of sentinel lymph node biopsy (SLNB) in patients with early breast cancer after local excision surgery.Methods:A total of 93 breast cancer patients with clinical stage T is/T 1-2N 0M 0 who underwent SLNB and were confirmed by using tumor mass excision biopsy from March 2012 to November 2018 in Shanxi Bethune Hospital were retrospectively analyzed. According to the postoperative paraffin pathology, the patients who were successfully detected sentinel lymph node (SLN) were divided into SLN-positive group with metastasis or SLN-negative group without metastasis. The clinicopathological data were used to analyze influencing factors of SLN metastasis and SLN detection number after excision biopsy of breast masses in the two groups. Results:A total of 87 out of 93 patients were successfully detected SLN and the detection rate was 93.5% (87/93). A total of 255 SLN were detected, and the average number was 2.93 in per patient. All were subjected to rapid intraoperative freezing pathological, and 11 cases with positive SLN were detected. There were 17 patients who underwent axillary lymph node dissection (ALND), including 11 cases with positive SLN and 6 cases with SLN undetected. The paraffin pathology showed that 14 patients were confirmed as positive SLN, including 13 macrometastasis and 1 micrometastasis. The SLN false negative rate was 2.1% (3/14) of intraoperative frozen diagnosis. Univariate analysis showed that histological grade and intravascular thrombus of carcinoma were associated with SLN metastasis after breast cancer local excision; the number of SLN detection was effected by body mass index and staining method; the methylene staining method combined with radionuclide method could improve the detection rate of SLN (all P < 0.05). Multivariate analysis showed that the SLN non-detection of obesity patients was 2.651 times as much as that of normal patients (95% CI 1.592-8.194, P=0.010). Conclusion:The SLNB and appropriate tracer method will have a high SLN detection rate and better clinical application value for early breast cancer patients after breast mass resection.