Chen Wei, He Lei, Yin Ming, Wan Tao, Tang You-Qing, Wang Ai-Ping, Li Yang, Yu Wan-Xian, Emergency Branch of Chinese Medical Rescue Association, Emergency Medical Equipment Society of China Association of Medical Equipment, Integrated Rehabilitation Medicine Branch of Chinese Medical Rescue Association, Pre-Hospital Emergency Care Working Committee of Chinese Aging Well Association
摘要:Hypothermia is a clinical syndrome characterized by core body temperature <35 ℃, caused by significant heat loss from body surface in cold environment. As a systemic cold injury, it can be lethal if treatment is delayed. Emergent diagnosis and treatment of hypothermia are expected to improve the prognosis of patients. In 2005, the U.S. Army Research Institute of Environmental Medicine (USARIEM) issued guidelines for the prevention and management of cold injuries, but there has been no corresponding standard in China. Therefore, Emergency Branch of Chinese Medical Rescue Association, Emergency Medical Equipment Society of China Association of Medical Equipment, Integrated Rehabilitation Medical Branch of Chinese Medical Rescue Association, and Pre-Hospital Emergency Care Working Committee of Chinese Aging Well Association jointly developed the Chinese Expert Consensus on Emergent Treatment of Hypothermia (2025 edition). The consensus covers the pathophysiology, etiology and epidemiology, diagnosis and severity grading, prehospital treatment, and in-hospital treatment of hypothermia, including 15 recommendations in total, aiming to provide guidance for the relevant clinical rescue work.
摘要:ObjectiveTo analyze the effect of Hsa-circ-0101216 on gemcitabine (GEM) chemotherapy resistance in pancreatic cancer and its mechanism.MethodsDifferentially expressed circRNAs between GEM-resistant pancreatic cancer cells and parent cells were screened using the GEO database. Pancreatic cancer GEM resistant cell lines (BxPC-3-GEM and Capan-1-GEM) were constructed by intermittent concentration gradient method. qRT-PCR was used to detect the expression of Hsa-circ-0101216 in cells. GEM resistant pancreatic cancer cell lines were taken and divided into sh-circ-0101216 group (knockdown of circ-0101216), sh-NC group (transfected with sh-NC), and blank control group (untreated). CCK-8 assay and EdU proliferation assay were used to detect the half inhibitory concentration (IC50) of GEM and proliferation ability of cells in each group. Western blotting was performed to detect the expression of multidrug resistance-related protein 1 (MRP1), breast cancer resistance protein (BCRP), and human equilibrative nucleoside transporter-1 (hENT-1). A subcutaneous xenograft tumor model of human pancreatic cancer in nude mice was constructed, and sh-NC+GEM group and sh-circ-0101216+GEM group (n=6) were set up. The volume and weight of xenograft tumor in nude mice were compared between the two groups. Western blotting and immunohistochemistry were used to detect the expression of MRP1, BCRP, and hENT-1 proteins in xenograft tumor tissues, and EDU proliferation assay was used to detect the proliferation ability of tumor cells.ResultsThe GEO database screening showed that Hsa-circ-0101216 was up-regulated in GEM-resistant pancreatic cancer cell lines. Pancreatic cancer GEM-resistant cell lines were successfully constructed, and the expression levels of Hsa-circ-0101216 and the IC50 value in GEM-resistant pancreatic cancer cells BxPC-3-GEM and Capan-1-GEM were significantly higher than those in parental cells (P<0.05). In sh-circ-0101216 group, the IC50 values of GEM, cell viability, EdU positivity rate, and the expression levels of MRP1 and BCRP proteins in GEM-resistant pancreatic cancer cells BxPC-3-GEM and Capan-1-GEM were significantly lower than those in blank control group and sh-NC group, while the expression level of hENT-1 protein was significantly higher (P<0.05 or P<0.001). In sh-circ-0101216+GEM group, the weight and volume of subcutaneous xenograft tumors in nude mice, the expression levels and positive expression rates of MRP1 and BCRP proteins in tumor tissues, and the EdU positive rate were significantly lower than those in sh-NC+GEM group, while the expression level and positive expression rate of hENT-1 protein were significantly higher (P<0.05).ConclusionsHsa-circ-0101216 is highly expressed in GEM-resistant pancreatic cancer cell lines. Its knockdown can inhibit the proliferation of pancreatic cancer cells and enhance the chemosensitivity of pancreatic cancer cells to GEM. The mechanism may be related to the regulation of transmembrane transporter protein expression.
摘要:Pancreatic cancer is characterized by significant drug resistance, and despite continuous advancements in treatment regimens, the 5-year survival rate of patients remains low. The nuclear factor-κB (NF-κB) signaling pathway, frequently mutated in tumors, has been identified as a critical factor in triggering drug resistance. Multiple studies have demonstrated that strategies targeting NF-κB signaling transduction exhibit promising outcomes in pancreatic cancer treatment. Therefore, exploring the relationship between the NF-κB signaling pathway and drug resistance in pancreatic cancer has become a research hotspot in pancreatic cancer treatment. This review summarizes recent advances in the relationship between NF-κB signaling pathway and tumor drug resistance, as well as its role in pancreatic cancer treatment. Specifically, the mechanisms by which the NF-κB signaling pathway mediates drug resistance in pancreatic cancer are elaborated from two perspectives: chemotherapy and immunotherapy, aiming to provide insights for pancreatic cancer treatment and future research.
摘要:Research on immune checkpoints such as programmed death protein-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) has provided new directions for tumor treatment. V-domain immunoglobulin suppressor of T-cell activation (VISTA) is an emerging immune checkpoint within the B7 family. Functioning as both a ligand and a receptor, VISTA is an inhibitory immune checkpoint molecule expressed in tumor cells, myeloid cells and T lymphocytes. It plays a crucial role in regulating autoimmunity, inflammatory response and tumor immunity. The non-redundant interactions between VISTA and other immune checkpoints, such as PD-1, may offer new therapeutic strategies and serve as a new target for overcoming immunotherapy resistance. This review summarizes the recent research progress on VISTA in hematological tumors, aiming to provide new insights into its application in the treatment of these malignancies.
关键词:V-domain immunoglobulin suppressor of T-cell activation;immune checkpoint;hematological tumor;immunotherapy
摘要:Programmed death ligand-1 (PD-L1), which is expressed on the surface of tumor cells, can bind to programmed death receptor-1 (PD-1) on T cells. The interaction between PD-1 and PD-L1 can activate negative regulatory signal of T cells and inhibit their activation and proliferation, thus promoting tumor immune escape. PD-L1 is mainly expressed on the tumor cell membrane, but is also distributed in the nucleus, cytoplasm, and exosomes. Different spatial distribution of PD-L1 has different effects on tumors, among which the dynamic transformation and spatial heterogeneity expression of PD-L1 in tumors is the main reason for the unsatisfactory efficacy of PD-L1 antibodies. This article aims to introduce the spatial heterogeneity of PD-L1, and review the research progress on PD-L1 dynamic transformation in tumor cells, so as to provide new ideas for antitumor therapy based on PD-L1 antibody.
关键词:tumor cells;programmed death ligand-1;spatial heterogeneity;exosomes
摘要:ObjectiveTo assess the efficacy of a novel inguinal tourniquet in healthy individuals and to investigate the relationship between localized inguinal compression and femoral artery blood flow occlusion.MethodsA self-controlled study was conducted. From November 9 to November 30, 2024, 11 volunteers were recruited at the Third Medical Center of Chinese PLA General Hospital. Three compression methods -- finger pressure, a novel groin tourniquet, and a SAM junction tourniquet (SJT)—were applied bilaterally to the inguinal region until distal blood flow signals disappeared. Each compression method was tested in 22 trials with a 5-minute interval between operations. Differences in hemostatic efficacy between bilateral inguinal regions and across compression methods were compared. Subsequently, the novel tourniquet was incrementally pressurized in 120 mmHg multiples using an integrated pressure device to analyze trends in popliteal artery blood flow velocity. Observational indicators included the internal pressure of the tourniquet pressurization device, peak systolic velocity (PSV) of popliteal artery, inguinal surface pressure magnitude, inguinal surface pressure distribution, and pain scores (assessed using a single-dimensional numerical rating scale).ResultsNo statistically significant difference was observed in the minimum pressure required to occlude femoral artery blood flow bilaterally (P>0.05). The success rates of femoral artery blood flow occlusion at the inguinal region were 100% for the novel inguinal tourniquet, SJT, and finger pressure. The novel inguinal tourniquet induced the highest pain scores, ranging from 5 to 8. A significant reduction in PSV of popliteal artery was noted when the intra-tourniquet pressure reached 360 mmHg and 480 mmHg (P<0.05), with a 95% hemostasis efficacy observed within the range of 360-600 mmHg. No significant association was observed between the recovery of popliteal artery blood flow after limb movement and inguinal pressure distribution (P>0.05). The PSV of popliteal artery exhibited the strongest negative correlation with the average pressure within the inguinal compression area (r=-0.79, P<0.001), with a linear regression fitting line of y=69.69-0.13x (P<0.001, R2=0.58).ConclusionsThe novel inguinal tourniquet effectively occludes femoral artery blood flow within a pressure range of 360-600 mmHg, accompanied by moderate-to-severe pain. Its hemostatic mechanism mainly relies on increasing the mean pressure within the inguinal compression area.
摘要:ObjectiveTo explore the predictive value of automated breast ultrasound (ABUS) features combined with Ki-67 in predicting pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC).MethodsA retrospective analysis was conducted on 127 female TNBC patients treated at Xijing Hospital, Air Force Medical University from March 2019 to December 2023. All patients underwent NAC and surgical treatment after ABUS examination. Based on postoperative pathological results, patients were divided into pCR group (n=60) and non-pathological complete response (npCR) group (n=67). Differences in various parameters before NAC were compared between the two groups. LASSO regression was used to identify independent factors influencing pCR after NAC in TNBC patients, and a predictive model was constructed using multivariate logistic regression. The prediction model was internally validated using the Bootstrap method (1000 resamples). The discriminative ability of the model was evaluated using receiver operating characteristic (ROC) curves, and the area under the curves (AUCs) of different prediction models were compared using De-long's test. The accuracy of the model was assessed using calibration curves, and the clinical benefit of the model was evaluated using clinical decision curve analysis (DCA).ResultsSignificant differences were observed between two groups in terms of age, Ki-67, menopausal status, tumor type, posterior echo, coronal plane convergence sign, coronal plane skip sign, and coronal plane white wall sign before NAC (P<0.05). LASSO regression analysis showed that Ki-67, coronal plane convergence sign, and coronal plane white wall sign were independent influencing factors of pCR after NAC in TNBC patients (P<0.05). The AUC of the multivariate logistic regression model based on Ki-67 was 0.733 (95%CI 0.646-0.819), the AUC of ABUS model was 0.777 (95%CI 0.695-0.858), and the AUC of ABUS combined with Ki-67 model was 0.816 (95%CI 0.741-0.890). De-long's test showed that the AUC of the combined model was higher than those of ABUS feature model and Ki-67 model, with statistically significant differences (P<0.05). There was no significant difference in the AUC between ABUS feature model and Ki-67 model (P=0.40). Hosmer-Lemeshow test indicated that the combined model had a good fit (P=0.304). Internal validation results showed that the combined model had a good stability with a consistency index (C-index) of 0.820 (95%CI 0.726-0.879). The calibration curve demonstrated good consistency between the predicted and actual probabilities of the combined prediction model, and the DCA curve indicated that the model had favorable clinical benefit.ConclusionThe combined ABUS feature and Ki-67 model can be used to predict the probability of pCR after NAC in TNBC patients, providing a reference for the formulation of clinical treatment plans in TNBC patients.
关键词:automatic breast ultrasound;Ki-67;neoadjuvant chemotherapy;triple negative breast cancer;pathological complete response
摘要:ObjectiveTo investigate the correlation between sleep duration and chest pain in the Chinese population.MethodsA cross-sectional analysis was conducted using data on chest pain and sleep duration from 7942 participants in the 2018 China Health and Retirement Longitudinal Study (CHARLS). Among them, 1239 had chest pain and 6703 did not; 2645 were aged>65 years and 5297 were aged ≤65 years. All participants were categorized into three groups based on sleep duration: ≤6 h (n=3123), 6-8 h (n=2959), and >8 h (n=1860). Differences in characteristics such as gender, age, marital status, education level, diabetes, and hypertension were compared across these groups. Multivariate logistic regression analysis, curve fitting, and threshold effect analysis were further employed to explore the correlation between sleep duration and chest pain.ResultsA total of 7942 participants were finally included in the study. Among the three groups with sleep duration >8 h, 6-8 h and ≤6 h, the incidences of chest pain were 12.6%, 13.0%, and 19.8%, respectively. Multivariate logistic regression analysis demonstrated that with the increase in sleep duration, the incidence of chest pain showed a decreasing trend [odds ratio (OR)=0.88, 95% confidence interval (CI) 0.86-0.91, P<0.001]. Curve fitting and threshold effect analysis indicated a U-shaped relationship between sleep duration and the risk of chest pain. In the population aged ≤65 years, the inflection point for sleep duration was 8.5 h, beyond which the risk of chest pain did not decrease; in the population aged >65 years, the inflection point was 7.7 h, beyond which the risk of chest pain significantly increased (P<0.05).ConclusionsThere is a U-shape relationship between sleep duration and the risk of chest pain. In the age group ≤65 years old, 8.5 h is the turning point; in the population >65 years old, 7.7 h is the turning point. When the sleep duration is below the turning point, prolonging the sleep time can help reduce the risk of chest pain. It is recommended to maintain an appropriate sleep duration of 6-8 h to reduce the risk of chest pain.
摘要:ObjectiveTo investigate the causal relationship between cathepsin (CTS) and thyroid cancer by using Mendelian randomization (MR).MethodsAggregate data for CTS GWAS was obtained from the IEU Open Genome-wide Association Study (GWAS) database (https://gwas.mrcieu.ac.uk/), and thyroid cancer GWAS data was obtained from the EBI database (https://www.ebi.ac.uk/). Five different MR analysis methods were utilized, with the inverse variance-weighted method (IVW) as the main approach, complemented by the weighted median method, MR-Egger regression, simple mode method and weighted majority method. These methods were employed to analyze the relationship between 9 CTS genes and thyroid cancer through 9 double-sample analyses. MR-Egger intercept, MR-PRESSO for gene pleiotropy detection, Cochran Q test, and leave-one-out method were applied to assess pleiotropy and sensitivity, followed by reverse MR analysis.ResultsMR analysis showed that elevated level of CTS B was positively correlated with the risk of thyroid cancer (IVW OR=1.60, 95%CI 1.12-2.30, P=0.01), while elevated CTS O level was negatively correlated with the risk of thyroid cancer (IVW OR=0.65, 95%CI 0.45-0.95, P=0.02). Reverse MR analysis revealed no significant causal relationship between thyroid cancer and CTS B and CTS O (P>0.05).ConclusionCTS B may promote the development of thyroid cancer, whereas CTS O may inhibit its progression.
摘要:ObjectiveTo investigate the impact of different antibiotic courses on intestinal floras and immune function in 28-day-old premature infants.MethodsA retrospective analysis was conducted on 120 premature infants admitted to the First People's Hospital of Nanyang City between March 2021 and March 2024. According to different courses of antibiotics, they were divided into short-course group (n=82, antibiotics use ≤3 d) and long-course group (n=38, antibiotics use ≥7 d). General data were collected, and intestinal floras and immune function were assessed at 28 days of age. Shannon and Simpson indexes of intestinal flora α-diversity, bacterial phylum and genus distribution of intestinal floras, and peripheral blood CD8+, CD4+ T cell percentages, and CD4+/CD8+ ratio were compared between the two groups. Pearson correlation analysis was used to explore the relationship between intestinal floras and immune function, and adverse outcomes were recorded.ResultsThe Shannon and Simpson indexes of intestinal flora α-diversity in long-course group were lower than those in short-course group (P<0.05). No significant differences were found between the two groups in the distribution of Actinobacteria, Bacteroidetes, Firmicutes or Proteobacteria at the bacterial phylum level and Bacteroides, Enterococcus, or Veillonella at genus distribution level (P>0.05). However, the long-course group had lower proportions of Clostridioides, Clostridium sensu stricto 1, Escherichia and Klebsiella, and higher proportions of Enterococcus, Robinsoniella and Streptococcus than those in short-course group (P<0.05). After antibiotics use, levels of CD4+ and CD4+/CD8+ were decreased (P<0.05), while CD8+ was increased in both groups (P<0.05). Compared with short-course group, levels of CD4+ and CD4+/CD8+ were lower, while CD8+ was higher in short-course group (P<0.05). Pearson correlation analysis revealed that Clostridioides, Clostridium sensu stricto 1, Escherichia, Klebsiella were positively correlated with CD4+ and CD4+/CD8+, while negatively correlated with CD8+ (P<0.05). Conversely, Enterococcus, Robinsoniella and Streptococcus were negatively correlated with CD4+ and CD4+/CD8+, while positively correlated with CD8+ (P<0.05). No adverse outcomes occurred in two groups.ConclusionCompared with short-term antibiotic use, long-term use affects the colonization and diversity of intestinal floras in premature infants, and cause intestinal flora disturbance, potentially impairing immune function.
关键词:antibiotic;course of treatment;premature infant;intestinal flora;immune function
摘要:ObjectiveTo explore the risk factors of venous thromboembolism (VTE) following laparoscopic urological surgery and to construct a predictive model.MethodsA retrospective analysis was conducted on the clinical data from 846 laparoscopic surgery patients admitted to the Urology Department of Hainan Cancer Hospital from January 2020 to January 2023. Patients were divided into VTE group (n=64) and non-VTE group (n=782) based on postoperative VTE confirmed by imaging examination. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for VTE after laparoscopic urological surgery. A predictive model was developed using regression coefficients from the multivariate analysis, and its predictive accuracy was assessed using a nomogram. Additionally, its sensitivity and specificity were evaluated through the construction of a receiver operating characteristic (ROC) curve and a calibration curve. The clinical application of predictive model was evaluated using a decision curve analysis.ResultsThe incidence of VTE after laparoscopic urological surgery was 7.6%(64/864). Significant differences were observed between two groups in age, body mass index (BMI), hypertension, diabetes, malignant tumor, history of abdominal surgery, previous VTE, operation time≥4 h, preoperative fibrinogen levels, preoperative prothrombin time, postoperative D-dimer (D-D) levels, Caprini score and postoperative immobilization time (P<0.05). Increasing age, higher BMI, history of malignancy, abdominal surgery, and previous VTE, longer operation and postoperative immobilization time, and higher postoperative D-D levels and Caprini score were identified as independent risk factors for the development of VTE after urological laparoscopy (P<0.05). Based on the regression coefficients between independent risk factors, a predictive model was constructed as P=ex/(1+ex), where X=0.054×age+0.105×BMI+0.902×history of abdominal surgery+1.172×previous VTE+0.787×operation time+1.546×malignant tumor+0.867×postoperative D-D+1.303×Caprini score+0.544×postoperative immobilization time-13.888. The model demonstrated a discriminant evaluation C-index of 0.827, and the area under the ROC curve for the combined independent risk factors is 0.827 (95%CI 0.776-0.878), with a sensitivity of 64.1%, and specificity of 87.7%. Calibration and decision curves indicated that high predictive accuracy and clinical application of the model.ConclusionsIncreasing age, higher BMI, history of malignancy, abdominal surgery, and previous VTE, longer operation and postoperative immobilization time, and higher postoperative D-D and Caprini score are independent risk factors for the development of VTE after urological laparoscopy.
关键词:urology;venous thromboembolism;laparoscopic surgery;risk factors;prediction model
摘要:ObjectiveTo explore the diagnostic value of 68Ga-PSMA-11 PET/CT combined with abnormal prothrombin (PIVKA-Ⅱ) in the diagnosis of different tumors.MethodsA total of 200 patients with suspected cancer who underwent examinations in the Affiliated Hospital of Southwest Medical University from September 2021 to December 2023 were retrospectively selected, including 51 suspected liver cancer, 49 suspected pancreatic cancer, 52 suspected rectal cancer and 48 suspected prostate cancer. All patients underwent both serum PIVKA-Ⅱ testing and 68Ga-PSMA-11 PET/CT imaging. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of 68Ga-PSMA-11 PET/CT and serum PIVKA-Ⅱ for liver cancer, pancreatic cancer, rectal cancer and prostate cancer.ResultsNo significant differences were found in general data of 4 suspected tumor groups (P>0.05) except for age. Serum PIVKA-Ⅱ levels were significantly higher in patients with suspected liver cancer and rectal cancer compared with those with suspected pancreatic cancer and prostate cancer (P<0.05). No significant difference was observed in the serum PIVKA-Ⅱ levels between suspected pancreatic cancer group and suspected prostate cancer group (P>0.05). The positive rates of 68Ga-PSMA-11 PET/CT and serum PIVKA-Ⅱ for diagnosing liver, pancreatic, rectal, and prostate cancers were significantly lower than those of pathological examination (49.0% vs. 47.1% vs. 92.2%, 57.1% vs. 55.1% vs. 87.8%, 48.1% vs. 44.2% vs. 92.3%, 64.6% vs. 62.5% vs. 89.6%, respectively, P<0.05). ROC curve analysis showed that serum PIVKA-Ⅱ had a sensitivity of 79.06%, specificity of 72.02%, area under ROC curve (AUC) of 0.822, and Youden index of 0.512. For 68Ga-PSMA-11 PET/CT, the sensitivity was 79.11%, specificity 72.07%, AUC 0.829, and Youden index 0.510. The combined use of 68Ga-PSMA-11 PET/CT and serum PIVKA-Ⅱ achieved higher diagnostic accuracy, with a sensitivity of 93.28%, specificity of 81.15%, AUC of 0.924 and Youden index of 0.744, all surpassing the single index.ConclusionBoth 68Ga-PSMA-11 PET/CT and serum PIVKA-Ⅱ are effective diagnostic tools for liver, pancreatic, rectal, and prostate cancers, with the combined approach yielding superior diagnostic performance.
关键词:tumor;68Ga-PSMA-11 PET/CT;abnormal prothrombin;diagnostic value
摘要:ObjectiveTo investigate the effect of splenectomy on the repair of full-thickness skin tissue defects, as well as the impact of different recovery times after splenectomy on the healing of skin tissue defects.MethodsAccording to a random number table, 39 8-week-old female C57 mice were randomly divided into three groups: sham surgery group (sham group, n=13), splenectomy group with 3 days of recovery (Spx3d group, n=13), and splenectomy group with 3 weeks of recovery (Spx3w group, n=13). Full-thickness skin defects were created on the backs of the mice in each group. The wound healing conditions at different times after skin defects were observed, and the wound healing rates after the injury were calculated. Peripheral blood cell analysis was performed on day 14 after the defect, and tissue samples from the wound area were taken for hematoxylin and eosin (HE) staining to observe the granulation tissue thickness at the defect site and the re-epithelialization rate. Masson's trichrome staining was used to observe the proportion of collagen fibers.ResultsAfter splenectomy and sham surgery, the mice recovered well without significant discomfort. From 1 to 14 days after the skin defect modeling, the wound areas of the mice in all three groups gradually decreased. Compared with sham group, the wound areas were smaller in Spx3d and Spx3w groups at 3, 5 and 7 days after the injury, and the differences were statistically significant (P<0.05). The wound healing rates were also significantly higher (P<0.05). Moreover, at 3 days and 5 days after the injury, the wound healing rates of Spx3d group were significantly higher than those of Spx3w group (P<0.05 or P<0.01). The peripheral blood white blood cell (WBC) count in Spx3w group was significantly higher than that in sham group and Spx3d group (P<0.01). The platelet counts in both sham group and Spx3w group were significantly higher than that in Spx3d group (P<0.05). Additionally, the lymphocyte and neutrophil counts in Spx3w group were markedly higher than those in sham group (P<0.05). No statistically significant differences in red blood cell (RBC) counts were observed among the three groups (P>0.05). HE staining results showed that compared with sham group, the wound healing of the mice in Spx3d and Spx3w groups were better, and the thickness of the granulation tissue in Spx3d group were better than that in Spx3w group. At 7 days, the thickness of the granulation tissue in Spx3d and Spx3w groups was significantly higher than that in sham group (P<0.01, P<0.05) and the re-epithelialization rate in Spx3d group was significantly higher than that in sham group and Spx3w group (P<0.05). At 14 days, the re-epithelialization rates of Spx3d and Spx3w groups were significantly higher than those of sham group (P<0.05). The results of Masson's staining showed that the collagen fiber proportion in the wounds of Spx3d group at 7 and 14 days and that of Spx3w group at 14 days were significantly higher than that in sham group (P<0.05).ConclusionThe healing of skin defects in mice is accelerated after splenectomy, and the recovery time after splenectomy has a certain effect on the healing of skin defects.
摘要:ObjectiveTo investigate the inhibitory effect of antimicrobial peptide WK-13-3D on the proliferation of triple negative breast cancer MDA-MB-231 cells and its potential mechanism.p-eIF2α, and Bax proteins was significantly increased (P<0.05), with no significant change in eIF2α protein expression (P>0.05); Compared with si-BiP-592 group, si-BiP-592+WK-13-3D group showed a decrease in BiP protein expression (P<0.05) and an increase in PERK, p-eIF2α, and Bax protein expression (P<0.05 or P<0.01), with no significant change in eIF2α protein expression (P>0.05). Tumor volumes in mice treated with antimicrobial peptide WK-13-3D and TAX were significantly smaller than those in PBS groupMethodsThe effect of antimicrobial peptide WK-13-3D at concentrations of 0, 10, 15, 20, 25, 30, 35, and 40 μmol/L on MDA-MB-231 cells proliferation was assessed using the CCK-8 assay. A pull-down assay was conducted to identify interacting proteins of antimicrobial peptide WK-13-3D with MDA-MB-231 cells. MDA-MB-231 cells were obtained and divided into the following groups: (1) control group and treatment groups with 10 and 20 μmol/L antimicrobial peptide WK-13-3D. Apoptosis was evaluated using flow cytometry and Western blotting was conducted to detect the expression change of heavy chain binding protein (BiP), protein kinase R-like endoplasmic reticulum kinase (PERK), eukaryotic translation initiation factor 2α (eIF2α), phosphorylated eIF2α (p-eIF2α), and Bax proteins within the cells. (2) Control group (transfected with no-load plasmid), si-BiP-592 group (transfected with si-BiP-592 interference plasmid) and si-BiP-592+WK-13-3D group (co-treated with si-BiP-592 interference plasmid and 10 μmol/L antimicrobial peptide WK-13-3D). Western blotting was used to detect the expression changes of BiP, PERK, eIF2α, p-eIF2α and Bax proteins. Twelve BALB/c mice were randomly divided into PBS group (n=4), taxol (TAX) group (n=4) and WK-13-3D group (n=4). All mice were subcutaneously injected with MDA-MB-231 cells to establish a triple-negative breast cancer transplant tumor model. WK-13-3D group received local injections of antimicrobial peptide WK-13-3D [200 mg/(kg·d)], TAX group was administered TAX intraperitoneally at the same dose [200 mg/(kg·d)], and PBS group was injected with an equivalent volume of PBS. Two weeks post-injection, the mice were killed, and the tumor weight and volume were measured and photographed. Immunohistochemistry staining was performed to evaluate the expressions of BiP and Ki-67 proteins in the tumor tissues.ResultsCCK-8 assay showed a gradual decrease in MDA-MB-231 cell survival rates with increasing concentrations of WK-13-3D, with an inhibitory concentration 50 (IC50) of 19.82 μmol/L. The pull-down assay identified 268 interacting proteins of antimicrobial peptides and MDA-MB-231 cells, mainly including heavy-chain binding protein (BiP), heat shock protein 90 beta family member 1 (HSP90B1), valerin-containing protein (VCP), heat shock cognate 71 kD protein (HSPA8). Compared with control group, treatment with 10 and 20 μmol/L antimicrobial peptide WK-13-3D significantly increased the apoptosis rate of MDA-MB-231 cells (P<0.05 or P<0.01), decreased BiP protein expression (P<0.05), and increased the expression levels of PERK, p-eIF2α, and Bax (P<0.05 or P<0.01), with no significant change in eIF2α protein expression (P>0.05). Compared with control group, si-BiP-592 group showed BiP protein expression significantly decreased (P<0.05), and the expression of PERK,(P<0.05), and the immunohistochemical staining showed that the proportion of Ki-67 and BiP positive cells in tumor tissues of WK-13-3D treated mice was significantly lower than that in PBS group (P<0.01).ConclusionAntimicrobial peptide WK-13-3D could inhibit the proliferation of MDA-MB-231 cells and its mechanism may involve the activation of endoplasmic reticulum stress and the induction of cell apoptosis.
关键词:antimicrobial peptides;triple negative breast cancer;endoplasmic reticulum stress;apoptosis
摘要:ObjectiveTo analyze the effect of sodium cantharidinate and vitamin B6 injection (SCV) on four human hepatocellular carcinoma (HCC) cell lines (SMMC-7721, Bel-7402, Huh7, and HepG2) and explore its mechanism.P<0.01 or P<0.001). In addition, Transwell and wound healing assays revealed that SCV at different concentrations (2, 4, and 8 μmol/L) significantly inhibited the invasion and migration of HCC cells (P<0.05 or P<0.01 or P<0.001). In the above results, the inhibitory effect of SCV was concentration-dependent. Flow cytometry analysis indicated that SCV arrested cells in the G2/M phase (P<0.05 orMethodsNormal hepatic cell line L02 was treated with SCV at concentrations of 0 μmol/L (control), 0.5, 1, 2, 4, 8, 16, and 32 μmol/L, and the cytotoxicity of SCV on L02 cells was detected using CCK-8 assay. Human HCC cell lines (SMMC-7721, Bel-7402, Huh7, and HepG2) were cultured. SCV-untreated control group (0 μmol/L) and 2, 4, and 8 μmol/L SCV-treated groups were set up. CCK-8 assay, plate cloning formation assay, Transwell assay, wound healing assay, and flow cytometry were used to detect the effects of SCV on the growth and proliferation capacity, colony formation ability, invasion and migration capabilities, cell cycle, and apoptosis of the four hepatocellular carcinoma cell lines, respectively. Western blotting was performed to detect the expression levels of apoptosis-related proteins, including nuclear factor kappa-B subunit p65 (p65), B-cell lymphoma 2 (Bcl-2), and Caspase-3, and to preliminarily explore the underlying mechanism.ResultsThe CCK-8 assay showed that SCV at 0.5, 1, 2, 4, and 8 μmol/L had no significant cytotoxic effect on L02 cells compared with untreated control group, so 2, 4, and 8 μmol/L SCV were selected for subsequent experiments. Compared with the untreated control group (0 μmol/L), SCV at different concentrations (2, 4, and 8 μmol/L) significantly inhibited the proliferation of the four HCC cell lines (P<0.001). The plate cloning formation assay showed that SCV at different concentrations (2, 4, and 8 μmol/L) significantly reduced the colony formation ability of the four HCC cell lines (P<0.05 orP<0.01 or P<0.001) and significantly promoted cell apoptosis (P<0.05 or P<0.01 or P<0.001). Western blotting showed that SCV significantly down-regulated the expression of p65 (P<0.05 or P<0.01) and Bcl-2 (P<0.05), and up-regulated the expression of Caspase-3 (P<0.05 or P<0.01).ConclusionsSCV can significantly inhibit the proliferation, colony formation, invasion, and migration of multiple human HCC cell lines and arrest the cell cycle. SCV may inhibit the expression of p65 and Bcl-2, thereby lifting their inhibitory effect on the apoptotic pathway and activating Caspase-3 to promote apoptosis.
摘要:ObjectiveTo investigate the effects of varying durations of overwork on cardiomyocyte pyroptosis in mice.MethodsA total of 24 SPF KM mice were randomly divided into four groups (n=6) using a random number table: control group, 2-week overwork (W2) group, 4-week overwork (W4) group, and 6-week overwork (W6) group. Mice in control group were normally raised, while those in W2, W4, and W6 groups were forced to stand in water for 8 h and then restrained for 3 h daily for 2, 4, 6 weeks, respectively. The general condition and weekly weight changes of the mice were observed. After modeling, blood samples were collected, and hearts were excised. Myocardial histopathological changes were assessed using hematoxylin and eosin (HE) staining. The localization of gasdermin D (GSDMD) protein in myocardial tissue was detected through immunohistochemical staining, and the expression levels of pyroptosis-related proteins [NOD-like protein receptor 3 (NLRP3), Caspase-1, GSDMD] in myocardial tissue were analyzed using Western blotting. The contents of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in serum and myocardial tissues were measured using ELISA.Results(1) The weight of control group mice increased steadily within 2 weeks. In W2 group, there was no significant weight change within 2 weeks, while in W4 and W6 groups, the body weights were higher than their initial values from the 2nd to 6th week. Compared with control group, the body weights of W2, W4, and W6 groups were lower than those of control group in the 1st and 2nd week, with statistically significant differences (P<0.05). The activity levels of the mice in W2, W4, and W6 groups initially increased and then decreased, with their fur becoming dull and falling out, and their mental state deteriorating. (2) In control group, cardiomyocytes were neatly arranged, and the nuclear morphology was normal. Compared with control group, in W2 group, cardiomyocyte arrangement was less regular, and capillary congestion was increased. In W4 group, the vascular congestion in the myocardium was significantly increased, the interstitial tissue was hyperplastic, and vacuolization appeared around the nuclei. In W6 group, the myocardial interstitium was loose, fat infiltration was increased, vacuolization around the nuclei was increased, and myocardial fibers were swollen, and the arrangement was disordered. (3) GSDMD was mainly located in the cytoplasm of cardiomyocytes. Compared with control group, the expression levels of NLRP3, Caspase-1, and GSDMD proteins in W2, W4, and W6 groups were significantly increased, and the expression levels were in the order of W6 group >W4 group >W2 group, with significant differences (P<0.05). (4) Compared to control group, the levels of IL-1β in serum and myocardial tissues of W2, W4, and W6 groups were significantly increased. In serum, the level of IL-1β in W6 group was higher than those in W2 and W4 groups, and in myocardial tissue, the levels in W4 and W6 groups were higher than those in the W2 group, with significant differences (P<0.05). There were no significant differences in IL-1β levels in serum among W2 and W4 groups, nor were there significant differences in myocardial tissue between W4 and W6 groups (P>0.05). Compared with control group, the levels of IL-18 in serum and myocardial tissue of W4 and W6 groups were significantly increased (P<0.05). In serum, the levels of IL-18 in W4 and W6 groups were higher than that in W2 group, and in myocardial tissue, the level in W6 group was higher than those in W2 and W4 groups, with the differences being statistically significant (P<0.05).ConclusionsOverwork can cause structural damage to mouse myocardial tissue, increase the expression of pyroptosis proteins NLRP3, Caspase-1, GSDMD, and aggravate myocardial inflammatory responses in overworked mice. Cardiomyocyte pyroptosis may be one of the factors contributing to sudden cardiac death induced by overwork.
关键词:overwork;pyroptosis;NOD like protein receptor 3;heart;gasdermin D
摘要:Guillain-Barre syndrome (GBS) is an autoimmune-mediated peripheral nerve and nerve root disease with its cause not elucidated yet, which may be related to infection, surgery, vaccination, and other factors. With the deepening of understanding of the disease, its electromyographic characteristics have gradually attracted people's attention. This paper summarizes the advances in correlational research on various parameters of electromyography of GBS patients, such as motor and sensory nerve conductions, H reflex, F wave, conduction block, reversible conduction failure, temporal dispersion, sural preservation, and needle electrode electromyography, and analyzes their correlation with inducements and prognosis of GBS, thus being expected to improve understanding of the electromyography in patients with GBS and to provide reference for diagnosis of GBS.
摘要:Multiple sclerosis (MS) is a demyelinating disease of the central nervous system associated with autoimmunity. Its main pathological characteristics involve glial hyperplasia, demyelination and axonal damage accompanied by inflammatory infiltration of the central nervous system. Currently, it is believed that MS is related to multiple factors such as genetic susceptibility, environment, infection, lifestyle, and immunity. However, its exact etiology remains unclear. In recent years, studies have shown that both MS patients and experimental autoimmune encephalomyelitis animal models are closely associated with fungal infection. This review summarizes the research progress on the correlation between fungal infection and MS, and the role of fungi in the pathogenesis of MS, aiming to provide new insights for exploring the pathogenesis, clinical diagnosis and treatment of MS.
摘要:Deep venous thrombosis (DVT) has become one of the important diseases threatening human life and health due to its high incidence and mortality rates. The three generally recognized major risk factors for thrombosis are blood flow stasis, vascular wall injury, and hypercoagulability. However, the specific cellular mechanisms remain incompletely understood. In recent years, with the in-depth study of the pathogenesis of DVT, accumulating evidence has demonstrated that dysfunctional peripheral blood cells play an indispensable role in its pathogenesis. This review summarizes the impacts of neutrophils, monocytes, lymphocytes, platelets, and red blood cells in peripheral blood on the occurrence and development of DVT, and explores the potential mechanisms of these impacts, aiming to provide new non-anticoagulation targets for the prevention and treatment of DVT.