OBJECTIVE: To investigate the biomechanical characteristics of retrograde tibial nailing (RTN) and distal tibial L-shaped plating in the internal fixation of distal tibial fractures. METHODS: Fourteen fresh adult tibia specimens were selected, comprising 7 males and 7 females aged from 34 to 55 years old. The specimens were randomly divided into experimental group and control group by numerical table method with 7 specimens in each group. RTN was used for internal fixation of distal tibial fractures in the experimental group, and L-shaped plate was used for internal fixation of distal tibial fractures in the control group. The axial compression properties of the two groups of specimens were tested under the pressure of 100, 200, 300, 400, and 500 N after operation, and torsional resistance at torque levels of 1.0, 2.0, 3.0, 4.0, 5.0 N·m. The anti-fatigue performance of the specimens was tested at 500 N pressure for 3 000 and 10 000 cycles. X-ray fluoroscopy was performed to observe whether the the internal fixator was deformed and whether the screw was loosened or broken. RESULTS: When the pressure was 400 N and 500 N, the axial compression displacement of the experimental group was (1.11±0.06) mm and (1.24±0.05) mm, which were smaller than those of the control group (1.21±0.08) mm and (1.37±0.11) mm, and the differences were statistically signific (P<0.05). Under the pressure of 500 N, the axial compression stiffness of the experimental group was (389.24±17.79) N·mm^-1, which was significantly higher than that of the control group (362.37±14.44) N·mm^-1(P<0.05). When the torque was 4 and 5 N·m, the torsion angles of the experimental group were (2.97±0.23) ° and (3.41±0.17) °, which were smaller than those of the control group (3.31±0.28) ° and (3.76±0.20) °, and the differences were statistically significant (P<0.05). When the torque was 5 N·m, the torsional stiffness of the experimental group was (1.48±0.07) N·m per degree, which was higher than that of the control group (1.36±0.06) N·m per degree, and the difference was statistically significant (P<0.05). For the intragroup comparison of fatigue resistance, the differences in axial compression displacement between the two groups were not statistically significant at 3 000 and 10 000 cycles (all P>0.05). When 3 000 times and 10 000 times of compression, the axial compression displacement of the experimental group was (1.38±0.08), (1.43±0.07) mm, which was smaller than that of the control group (1.51±0.10), (1.54±0.08) mm, the differences were statistically significant (P<0.05). In the experimental group, no screw loosening, fracture or internal fixation deformation was found, while in the control group, locking screw loosening occurred in 2 models after 10 000 pressures. CONCLUSION The biomechanical performance of RTN is obviously better than that of the distal tibial L-shaped plate, which provides biomechanical data support for the clinical application of RTN.
Humans ; Female ; Male ; Adult ; Tibial Fractures/physiopathology* ; Middle Aged ; Biomechanical Phenomena ; Bone Plates ; Fracture Fixation, Internal/instrumentation* ; Bone Nails ; Tibia/surgery*

Objective:To explore the predictive value of positive lymph node ratio (LNR) for tumor specific mortality in cervical cancer patients after surgery for 5 years.Methods:A total of 120 patients with cervical cancer with lymph node metastasis admitted to the Affiliated Hospital of Jining Medical University from January 2017 to December 2018 were retrospectively selected. The patients were followed up for 5 years and divided into a death group (48 cases) and a control group (72 cases) according to whether tumor-specific death occurred after surgery. The main clinical features and LNR differences between the two groups were compared. The predictive value of LNR for tumor-specific death was analyzed by receiver operating characteristic(ROC) curve, and the risk factors for tumor-specific death in patients with cervical cancer at 5 years after surgery were analyzed by multivariate Logistic retrospective analysis.Results:The low differentiation rate and the rate of periuterine invasion, the rate of pelvic invasion, the number of lymph node metastasis and LNR in the death group were higher than those in the control group: 47.92%(23/48) vs.16.67%(12/72), 58.33%(28/48) vs. 27.78%(20/72), 29.17%(14/48) vs. 9.72%(7/72), (9.35 ± 4.04) nodes vs. (5.07 ± 2.74) nodes, (46.01 ± 19.66)% vs.(23.04 ± 13.76)%, there were statistical differences ( P<0.05). The results of ROC curve analysis showed that LNR was valuable in predicting the tumor specific mortality in cervical cancer patients after surgery within 5 years, with areas under the curve of 0.832 (95% CI 0.760 - 0.905). The results of multivariate Logistic retrospective analysis showed that LNR>30.43%, poorly differentiated cancer, parametrial infiltration and pelvic infiltration were independent risk factors for tumor specific death in cervical cancer patients at 5 years after surgery ( P<0.05). Conclusions:The LNR has a high predictive value for tumor specific mortality in cervical cancer patients after 5 years of surgery, and can be used as a predictive indicator for patient's prognosis.

Objective To evaluate the effectiveness of active screening in improving the detection rate of carbape-nem-resistant Enterobacterales(CRE)in the intensive care units(ICUs).Methods From July 2023 to June 2024,active screening of rectal swab CRE was conducted on ICU patients in 10 hospitals.ICU patients who underwent ac-tive screening from July 2023 to June 2024 were selected as the study group,while those who did not undergo active screening from July 2022 to June 2023 were selected as the control group.Difference in CRE detection rates between the two groups of patients was compared.Results A total of 7 803 ICU patients were included in the study group,744 CRE strains were detected,with a detection rate of 9.53％,out of which 304 CRE strains were detected through routine detection(detection rate 3.90％),3 707 patients underwent active screen,440 CRE strains were detected(detection rate 11.87％).7 561 ICU patients were included in the control group,out of which 250 CRE strains were detected through routine detection,with a detection rate of 3.31％.There was a statistically significant difference in the overall detection rate of CRE between two groups of patients(x2=246.18,P＜0.001).In the study group,CRE detection rate of active screening(11.87％)was higher than that of routine detection(3.90％),with statistically significant difference(x2=264.26,P＜0.001).A total of 17 CRE strains were detected from the study group.The proportions of Klebsiella pneumoniae(80.92％vs 73.41％)and Serratia marcescens(2.30％vs0.23％)in the routine detection group were both higher than in the active screening group,while the proportion of Escherichia coli in the routine detection group was lower(8.22％vs 19.55％),all with statistically significant differences(all P＜0.05).Conclusion The prevalence of CRE in ICUs is relatively high,with a wide range of bac-terial species.Active screening can improve the detection rate of CRE.

Enhancer of zeste homolog 2(EZH2)is a histone methyltransferase It mediates trimethylation of lysine 27 on histone H3,thereby facilitating the epigenetic silencing of downstream genes.In conjunc-tion with SUZ12,EED,and other components,it constitutes the polycomb repressive complex 2(PRC2)complex.While EZH2 is intricately involved in cellular proliferation and cardiac development,the chan-ges in its expression during cardiac terminal differentiation remain elusive.In this study,we employed differential gene expression analysis of embryonic and adult myocardial cells using the GEO database,and found that EZH2 is highly expressed in embryonic myocardium,but is present at very low levels in adult myocardium(P＜0.0001).Conversely,the expression changes of PRC2 members SUZ12 and EED are not as pronounced.Online analysis through the Tabula Muris database indicates that under physiological conditions,various cell subpopulations in the adult mouse heart exhibit negligible expression of EZH2.Immunohistochemical staining of mouse cardiac tissues shows that EZH2 is highly expressed in embryonic and neonatal myocardium but declines progressively from the first day after birth(P＜0.0001),becoming almost undetectable by the third day.Western blotting further confirms the rapid disappearance of EZH2 expression post-birth(P＜0.05),with EZH1 compensating for the downregulation of EZH2 to maintain H3K27me3 modification levels.Additionally,using the P19 teratocarcinoma stem cell model for cardio-myocyte differentiation,it is observed that EZH2 is significantly upregulated during the transition from cardiac progenitor cells to spontaneously beating cardiomyocytes,correlating with the expression of the cardiomyocyte transcription factor Gata4(P＜0.01).Targeted degradation of EZH2 using the small mole-cule drug MS1943 significantly inhibits the proliferation of induced cardiomyocytes,as evidenced by 5-e-thynyl-2'-deoxyuridine(EdU)incorporation assays(P＜0.01),and RT-qPCR reveals a marked in-crease in the expression of the proliferation inhibitor CDKN1A(P＜0.01).In summary,the high expres-sion of EZH2 in embryonic myocardial cells is associated with enhanced cell proliferation.The rapid loss of EZH2 expression postnatally correlates with the loss of proliferative capacity in cardiomyocytes,mark-ing it as a key indicator of cardiac terminal differentiation.

Objective To evaluate the effectiveness of active screening in improving the detection rate of carbape-nem-resistant Enterobacterales(CRE)in the intensive care units(ICUs).Methods From July 2023 to June 2024,active screening of rectal swab CRE was conducted on ICU patients in 10 hospitals.ICU patients who underwent ac-tive screening from July 2023 to June 2024 were selected as the study group,while those who did not undergo active screening from July 2022 to June 2023 were selected as the control group.Difference in CRE detection rates between the two groups of patients was compared.Results A total of 7 803 ICU patients were included in the study group,744 CRE strains were detected,with a detection rate of 9.53％,out of which 304 CRE strains were detected through routine detection(detection rate 3.90％),3 707 patients underwent active screen,440 CRE strains were detected(detection rate 11.87％).7 561 ICU patients were included in the control group,out of which 250 CRE strains were detected through routine detection,with a detection rate of 3.31％.There was a statistically significant difference in the overall detection rate of CRE between two groups of patients(x2=246.18,P＜0.001).In the study group,CRE detection rate of active screening(11.87％)was higher than that of routine detection(3.90％),with statistically significant difference(x2=264.26,P＜0.001).A total of 17 CRE strains were detected from the study group.The proportions of Klebsiella pneumoniae(80.92％vs 73.41％)and Serratia marcescens(2.30％vs0.23％)in the routine detection group were both higher than in the active screening group,while the proportion of Escherichia coli in the routine detection group was lower(8.22％vs 19.55％),all with statistically significant differences(all P＜0.05).Conclusion The prevalence of CRE in ICUs is relatively high,with a wide range of bac-terial species.Active screening can improve the detection rate of CRE.

Enhancer of zeste homolog 2(EZH2)is a histone methyltransferase It mediates trimethylation of lysine 27 on histone H3,thereby facilitating the epigenetic silencing of downstream genes.In conjunc-tion with SUZ12,EED,and other components,it constitutes the polycomb repressive complex 2(PRC2)complex.While EZH2 is intricately involved in cellular proliferation and cardiac development,the chan-ges in its expression during cardiac terminal differentiation remain elusive.In this study,we employed differential gene expression analysis of embryonic and adult myocardial cells using the GEO database,and found that EZH2 is highly expressed in embryonic myocardium,but is present at very low levels in adult myocardium(P＜0.0001).Conversely,the expression changes of PRC2 members SUZ12 and EED are not as pronounced.Online analysis through the Tabula Muris database indicates that under physiological conditions,various cell subpopulations in the adult mouse heart exhibit negligible expression of EZH2.Immunohistochemical staining of mouse cardiac tissues shows that EZH2 is highly expressed in embryonic and neonatal myocardium but declines progressively from the first day after birth(P＜0.0001),becoming almost undetectable by the third day.Western blotting further confirms the rapid disappearance of EZH2 expression post-birth(P＜0.05),with EZH1 compensating for the downregulation of EZH2 to maintain H3K27me3 modification levels.Additionally,using the P19 teratocarcinoma stem cell model for cardio-myocyte differentiation,it is observed that EZH2 is significantly upregulated during the transition from cardiac progenitor cells to spontaneously beating cardiomyocytes,correlating with the expression of the cardiomyocyte transcription factor Gata4(P＜0.01).Targeted degradation of EZH2 using the small mole-cule drug MS1943 significantly inhibits the proliferation of induced cardiomyocytes,as evidenced by 5-e-thynyl-2'-deoxyuridine(EdU)incorporation assays(P＜0.01),and RT-qPCR reveals a marked in-crease in the expression of the proliferation inhibitor CDKN1A(P＜0.01).In summary,the high expres-sion of EZH2 in embryonic myocardial cells is associated with enhanced cell proliferation.The rapid loss of EZH2 expression postnatally correlates with the loss of proliferative capacity in cardiomyocytes,mark-ing it as a key indicator of cardiac terminal differentiation.

Objective:To explore the predictive value of positive lymph node ratio (LNR) for tumor specific mortality in cervical cancer patients after surgery for 5 years.Methods:A total of 120 patients with cervical cancer with lymph node metastasis admitted to the Affiliated Hospital of Jining Medical University from January 2017 to December 2018 were retrospectively selected. The patients were followed up for 5 years and divided into a death group (48 cases) and a control group (72 cases) according to whether tumor-specific death occurred after surgery. The main clinical features and LNR differences between the two groups were compared. The predictive value of LNR for tumor-specific death was analyzed by receiver operating characteristic(ROC) curve, and the risk factors for tumor-specific death in patients with cervical cancer at 5 years after surgery were analyzed by multivariate Logistic retrospective analysis.Results:The low differentiation rate and the rate of periuterine invasion, the rate of pelvic invasion, the number of lymph node metastasis and LNR in the death group were higher than those in the control group: 47.92%(23/48) vs.16.67%(12/72), 58.33%(28/48) vs. 27.78%(20/72), 29.17%(14/48) vs. 9.72%(7/72), (9.35 ± 4.04) nodes vs. (5.07 ± 2.74) nodes, (46.01 ± 19.66)% vs.(23.04 ± 13.76)%, there were statistical differences ( P<0.05). The results of ROC curve analysis showed that LNR was valuable in predicting the tumor specific mortality in cervical cancer patients after surgery within 5 years, with areas under the curve of 0.832 (95% CI 0.760 - 0.905). The results of multivariate Logistic retrospective analysis showed that LNR>30.43%, poorly differentiated cancer, parametrial infiltration and pelvic infiltration were independent risk factors for tumor specific death in cervical cancer patients at 5 years after surgery ( P<0.05). Conclusions:The LNR has a high predictive value for tumor specific mortality in cervical cancer patients after 5 years of surgery, and can be used as a predictive indicator for patient's prognosis.

OBJECTIVE: Despite the combination of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang (SB-SD) being a recognized Chinese medicinal herbal pair that is commonly used in the treatment of ovarian cancer, there is a poor understanding of their pharmacological mechanisms. This study examines the antitumor properties and potential mechanisms of SB-SD on human ovarian cancer A2780 cells through a multi-omics approach, establishing a pharmacological basis for clinical utilization. METHODS: A range of mass ratios and reagents were used in the hot reflux extraction of SB-SD. The inhibitory effect of the SB-SD extracts on A2780 cell proliferation was assessed using the cell-counting kit 8 assay. A zebrafish tumor implantation model was used to evaluate the effects of SB-SD extracts on tumor growth and metastasis in vivo. Transcriptomics and proteomics were used to investigate alterations in biological pathways in A2780 cells after treatment with different concentrations of SB-SD extract. Cell cycle, cell apoptosis, intracellular free iron concentration, intracellular reactive oxygen species (ROS) concentration, malondialdehyde (MDA), and mitochondrial membrane potential were measured. Real-time quantitative reverse transcription polymerase chain reaction and Western blotting were utilized to investigate the effects of heme catabolism and ferritinophagy on ferroptosis induced by SB-SD extract in A2780 cells. RESULTS: The 70% ethanol extract of SB-SD (a mass ratio of 4:1) inhibited A2780 cell proliferation significantly with a half maximal inhibitory concentration of 660 μg/mL in a concentration- and time-dependent manner. Moreover, it effectively suppressed tumor growth and metastasis in a zebrafish tumor implantation model. SB-SD extract induced the accumulation of free iron, ROS, MDA, and mitochondrial damage in A2780 cells. The mechanisms might involve the upregulated expression of ferritinophagy-related genes microtubule-associated protein 1 light chain 3, autophagy-related gene 5, and nuclear receptor coactivator 4. CONCLUSION SB-SD extract effectively inhibited the development of ovarian cancer both in vitro and in vivo. Its mechanism of action involved inducing ferroptosis by facilitating heme catabolism and ferritinophagy. This herbal pair holds promise as a potential therapeutic option for ovarian cancer treatment and may be utilized in combination with routine treatment to improve the treatment outcomes of ovarian cancer patients. Please cite this article as: Wang Z, Liu M, Li GX, Zhang L, Ding KY, Li SQ, Gao BQ, Chen P, Choe HC, Xia LY, Yang YT, Liu Y, Sui X, Ma JN, Zhang L. A herbal pair of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang induced ferroptosis in ovarian cancer A2780 cells via inducing heme catabolism and ferritinophagy. J Integr Med. 2024; 22(6): 666-683.
Ferroptosis/drug effects* ; Female ; Humans ; Animals ; Scutellaria/chemistry* ; Ovarian Neoplasms/genetics* ; Zebrafish ; Cell Line, Tumor ; Ferritins/genetics* ; Plant Extracts/pharmacology* ; Heme/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Cell Proliferation/drug effects* ; Reactive Oxygen Species/metabolism* ; Antineoplastic Agents, Phytogenic/pharmacology* ; Autophagy/drug effects* ; Apoptosis/drug effects*

Objective:To investigate the efficacy and safety of a treatment regimen based on daratumumab in patients with high-risk relapsed refractory multiple myeloma(MM)with mSMART 3.0 score.Methods:Clinical data were collected from 16 patients with mSMART3.0 score high-risk relapsed refractory MM treated at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from May 2020 to May 2023,all of whom received daltezumab-based regimen(regimen drugs including dexamethasone,isazomib,bortezomib,lenalidomide).The efficacy and safety of the treatment were retrospectively analyzed.Results:The median age of 16 patients was 63.5(47-70)years old,including 10 cases of IgG type,2 cases of IgA type,and 4 cases of light chain type.The curative efficacy was judged in all 16 patients,with an overall response rate of 93.75％(15/16),including 4 cases of strict complete remission(sCR),1 case of complete remission(CR),2 case of very good partial remission(VGPR),partial remission(PR)in 5 cases,and minor remission(MR)in 3 cases.The median follow-up time was 11(2-30)months,and the median progression-free survival and median overall survival were not achieved in 16 patients at the median follow-up period.The hematologic adverse effects of the treatment regimen using daratumumab-based were mainly neutropenia,and the non-hematologic adverse effects were mainly infusion-related adverse reactions and infections.Conclusion:Daratumumab-based regimen for the treatment of relapsed refractory MM patients with high risk of mSMART3.0 score has better efficacy and safety.

Objective:To investigate the effects of Schisandrin A on the proliferation and apoptosis of prostate cancer cell and its mechanism.Methods:Human prostate cancer DU145 cell were cultured in vitro and grouped into DU145 group (normal culture), Schisandrin A L group (50 μmol/L Schisandrin A was added), Schisandrin A M group (100 μmol/L Schisandrin A was added), Schisandrin A H group (150 μmol/L Schisandrin A was added) and Simvastatin group (50 μmol/L Simvastatin was added). Cell morphology of each group was observed under microscope, cell proliferation ability was detected by CCK8 method, cell migration ability was detected by cell scratch assay, cell invasion ability was detected by Transwell assay, and cell apoptosis was detected by flow cytometry, the expression of phosphorylation (p) - mammalian STE20-like protein kinase 1 (MST1), MST1, p-large tumor suppressor 1 (LATS1), LATS1, p-Yes associated protein (YAP) and YAP protein were detected by Western blotting. Measurement data were expressed as mean± standard deviation ( ± s), one-way ANOVA for comparisons between multiple groups, and t-test for comparisons between two groups. Results:Compared with DU145 group, the number of cells in Schisandrin A L, M, H groups and Simvastatin group decreased, and the cells gradually shrunk and the spacing became larger, the cell survival rate [(100.00±0.00)%, (88.41±9.36)%, (62.34±7.31)%, (42.57±5.01)%, (45.47±5.65)%], migration [(90.11±13.43)%, (74.16±8.08)%, (57.53±7.34)%, (41.34±6.79)%, (43.44±5.26)%] and invasion [(89.01±10.31)%, (73.11±9.23)%, (55.62±7.67)%, (41.13±6.35)%, (40.36±5.68)%], and the expression of p-YAP/YAP protein (0.98±0.08, 0.83±0.11, 0.69±0.07, 0.55±0.07, 0.53±0.05) were significantly decreased, the apoptosis rate [(2.88±0.34)%, (5.20±0.57)%, (8.37±0.94)%, (12.71±1.58)%, (12.03±2.21)%] and the expression of p-MST1/MST1 (0.41±0.04, 0.53±0.07, 0.75±0.07, 0.89±0.08, 0.88±0.07] and p-LATS1/LATS1 protein (0.40±0.04, 0.52±0.06, 0.64±0.06, 0.77±0.08, 0.79±0.08) were significantly increased, and the differences were statistically significant ( P<0.05). Conclusion:Schisandrin A may inhibit the proliferation of prostate cancer cell and promote cell apoptosis by inhibiting Hippo-YAP signaling pathway.