Objective The present study was designed to explore the inhibitory effects of the ADC drug Disitamab Vedotin(RC-48)on breast cancer cells with different HER-2 expression levels by utilizing a tumor organoid culture system.Methods Within the framework of the tumor organoid culture system,the breast cancer cell lines MCF-7(characterized by low HER-2 expression,Luminal A subtype)and BT-474(exhibiting high HER-2 expression,HER-2 positive subtype)were cultured independently and in various mixed ratios.The histological characteristics,as well as the expression levels and distribution of HER-2 in MCF-7 and BT-474 organoids,were analyzed via immunohistochemistry and immunofluorescence techniques.MCF-7 and BT-474 organoids were separately treated with Vedotin(RC-48),Disitamab,and Monomethyl auristatin E(MMAE).Additionally,a drug sensitivity test of Disitamab Vedotin(RC-48)was carried out on mixed MCF-7 and BT-474 cell ratios and on patient-derived breast cancer organoids,with the assessment conducted using the 3D-Glo method.Results In the tumor organoid culture system,immunohistochemistry and immunofluorescence analyses demonstrated that HER-2 was predominantly localized in the cell membrane.Specifically,BT-474 organoids exhibited robust HER-2 expression,while MCF-7 organoids displayed relatively low expression levels.When compared with MCF-7 organoids,RC48-ADC exerted a more pronounced inhibitory effect on BT-474 organoids,with IC50 values of 109.7 μg/mL and 2.792 μg/mL,respectively.The co-culture model further confirmed the bystander effect of RC-48,revealing that the ratio of HER-2-positive to HER-2-negative cells significantly influenced drug efficacy.Additionally,treatment with RC-48 led to a reduction in HER-2 expression in breast cancer organoids with diverse HER-2 expression levels.Conclusions The tumor organoid model can accurately mirror drug sensitivity and bystander effects.Within this model,RC-48 effectively inhibited HER-2 highly-expressing breast cancer cells,augmented the killing effect through the bystander mechanism,and downregulated HER-2 expression,thereby suggesting its potential for targeting HER2-associated breast cancer.

Objective The present study was designed to explore the inhibitory effects of the ADC drug Disitamab Vedotin(RC-48)on breast cancer cells with different HER-2 expression levels by utilizing a tumor organoid culture system.Methods Within the framework of the tumor organoid culture system,the breast cancer cell lines MCF-7(characterized by low HER-2 expression,Luminal A subtype)and BT-474(exhibiting high HER-2 expression,HER-2 positive subtype)were cultured independently and in various mixed ratios.The histological characteristics,as well as the expression levels and distribution of HER-2 in MCF-7 and BT-474 organoids,were analyzed via immunohistochemistry and immunofluorescence techniques.MCF-7 and BT-474 organoids were separately treated with Vedotin(RC-48),Disitamab,and Monomethyl auristatin E(MMAE).Additionally,a drug sensitivity test of Disitamab Vedotin(RC-48)was carried out on mixed MCF-7 and BT-474 cell ratios and on patient-derived breast cancer organoids,with the assessment conducted using the 3D-Glo method.Results In the tumor organoid culture system,immunohistochemistry and immunofluorescence analyses demonstrated that HER-2 was predominantly localized in the cell membrane.Specifically,BT-474 organoids exhibited robust HER-2 expression,while MCF-7 organoids displayed relatively low expression levels.When compared with MCF-7 organoids,RC48-ADC exerted a more pronounced inhibitory effect on BT-474 organoids,with IC50 values of 109.7 μg/mL and 2.792 μg/mL,respectively.The co-culture model further confirmed the bystander effect of RC-48,revealing that the ratio of HER-2-positive to HER-2-negative cells significantly influenced drug efficacy.Additionally,treatment with RC-48 led to a reduction in HER-2 expression in breast cancer organoids with diverse HER-2 expression levels.Conclusions The tumor organoid model can accurately mirror drug sensitivity and bystander effects.Within this model,RC-48 effectively inhibited HER-2 highly-expressing breast cancer cells,augmented the killing effect through the bystander mechanism,and downregulated HER-2 expression,thereby suggesting its potential for targeting HER2-associated breast cancer.

Objective:To investigate the clinical value of open abdomen therapy in non-traumatic critically patients.Methods:The retrospective cohort study was conducted. The clinical data of 23 non-traumatic critically patients who underwent open abdomen therapy in 5 hospitals in China from July 2015 to July 2024 were collected. There were 17 males and 6 females, aged 70(range, 24-84)years. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Repeated measurement data were analyzed using the repeated ANOVA, and pairwise comparison within groups was conducted using the least significant difference method. The Boruta algorithm was applied for analyzing variables related to survival outcomes. Results:(1) Treatment of patients undergoing open abdomen therapy. ① The intra-abdominal pressure, lactate, heart rate, central venous pressure, mean arterial pressure, sequential organ failure assessment score of 23 patients from preoperation to postoperative day 3 were changed from (19.7±5.4)mmHg (1 mmHg=0.133 kPa), (6.1±1.9)mmol/L, (120±14)beats/minutes, (13.1±4.3)cmH 2O (1 cmH 2O=0.098 kPa), (58.8±6.8)mmHg, 13.2±1.8 to (10.6±1.3)mmHg, (2.3±0.6)mmol/L, (95±10)beats/minutes, (8.8±2.0)cmH 2O, (75.2±8.5)mmHg, 10.1±1.6, respectively, showing significant differences in the time effect of changes in the above indicators ( Ftime=46.40, 29.19, 24.91, 11.84, 27.81, 11.71, P<0.05). ② The oxygenation index, total intake, total output of 23 patients from preoperation to postoperative day 3 were changed from (255.0±54.2)mmHg, (5388±1562)mL, (2 520±630)mL to (291.7±25.0)mmHg, (2 886±866)mL, (3 221±923)mL, respectively, showing significant differences in the time effect of changes in the above indicators ( Ftime=7.61, 13.83, 2.97, P<0.05). ③The daily caloric intake, daily protein supplementation of 23 patients from preoperation to postoperative day 3 were changed from (465±116)kcal, (18±5)g to (1 628±472)kcal, (60±18)g, respectively, showing significant differences in the time effect of changes in the above indicators ( Ftime=40.31, 41.23, P<0.05). (2) Patients outcomes after open abdomen therapy. Of 23 patients, 18 cases survived and 5 cases died. The duration of intensive care unit stay and duration of hospital stay of 23 patients were 26(range, 5-82)days and 40(range, 5-98)days. Twelve of 23 patients received renal replacement therapy for 12 (range, 5-32)days. Time of pain and sedation management, mechanical ventilation, antimicrobial therapy, vasopressor therapy of 23 patients were 13(range, 5-74)days, 12(range, 5-74)days,20(range, 5-50)days, 6(range, 2-35)days. (3) Analysis of variables related to survival outcomes for patients after open abdomen therapy. Results of Boruta analysis showed that postoperative high-output enteric fistula, postoperative bile fistula, postoperative intra-abdominal hemorrhage, postoperative enteric air fistula, and preoperative mean arterial pressure were significantly associated with survival outcomes. Conclusions:Open abdomen therapy is effective in the treatment of non-traumatic critically patients. Postoperative high-output enteric fistula, postoperative bile fistula, postoperative intra-abdominal hemorrhage, postoperative enteric air fistula, and preoperative mean arterial pressure reduction are significantly associated with survival outcomes.

Objective To compare the clinical efficacy of emergency and elective laparoscopic common bile duct exploration(LCBDE)in the treatment of choledocholithiasis with acute cholangitis based on propensity score matching(PSM).Methods Retro-spective cohort study was used.The clinical data of 162 patients with choledocholithiasis complicated with acute cholangitis who underwent LCBDE in Wuhu Hospital,East China Normal University from January 2021 to October 2023 were retrospectively analyzed.Among them,59 patients underwent emergency LCBDE(emergency group),and 103 patients underwent elective LCBDE after conservative treatment(elective group).The PSM method was used to match the two groups of patients by 1∶1,and the relevant clinical data of the two groups were compared.Results The two groups successfully matched 44 pairs of patients.The intraoperative blood loss in the emergency group was more than that in the elective group(65.00±19.88ml vs 54.89±17.90ml,P=0.014).The use time of antibiotics was lower than that in the elective group(3.68±1.46days vs 5.95±1.46days,P＜0.001).The total hospitalization time was lower than that in the e-lective group[7.0(6.0,8.0)days vs 8.0(7.0,9.0)days,P＜0.001].The hospitalization cost was lower than that in the elective group[1.19(1.10,1.45)ten thousand yuan vs 1.43(1.22,1.67)ten thousand yuan,P=0.001].There was no significant difference in operation time,conversion rate,operation method,peritoneal drainage tube removal time,postoperative hospital stay,and postoperative complication rate between the two groups(P＞0.05).Conclusion Both emergency and elective LCBDE are safe and effective in the treatment of choledocholithiasis with mild to moderate acute cholangitis,but emergency LCBDE has significant advantages in the use of an-tibiotics,total hospitalization time and hospitalization costs.

Objective To compare the clinical efficacy of emergency and elective laparoscopic common bile duct exploration(LCBDE)in the treatment of choledocholithiasis with acute cholangitis based on propensity score matching(PSM).Methods Retro-spective cohort study was used.The clinical data of 162 patients with choledocholithiasis complicated with acute cholangitis who underwent LCBDE in Wuhu Hospital,East China Normal University from January 2021 to October 2023 were retrospectively analyzed.Among them,59 patients underwent emergency LCBDE(emergency group),and 103 patients underwent elective LCBDE after conservative treatment(elective group).The PSM method was used to match the two groups of patients by 1∶1,and the relevant clinical data of the two groups were compared.Results The two groups successfully matched 44 pairs of patients.The intraoperative blood loss in the emergency group was more than that in the elective group(65.00±19.88ml vs 54.89±17.90ml,P=0.014).The use time of antibiotics was lower than that in the elective group(3.68±1.46days vs 5.95±1.46days,P＜0.001).The total hospitalization time was lower than that in the e-lective group[7.0(6.0,8.0)days vs 8.0(7.0,9.0)days,P＜0.001].The hospitalization cost was lower than that in the elective group[1.19(1.10,1.45)ten thousand yuan vs 1.43(1.22,1.67)ten thousand yuan,P=0.001].There was no significant difference in operation time,conversion rate,operation method,peritoneal drainage tube removal time,postoperative hospital stay,and postoperative complication rate between the two groups(P＞0.05).Conclusion Both emergency and elective LCBDE are safe and effective in the treatment of choledocholithiasis with mild to moderate acute cholangitis,but emergency LCBDE has significant advantages in the use of an-tibiotics,total hospitalization time and hospitalization costs.

Objective:To investigate the clinical value of open abdomen therapy in non-traumatic critically patients.Methods:The retrospective cohort study was conducted. The clinical data of 23 non-traumatic critically patients who underwent open abdomen therapy in 5 hospitals in China from July 2015 to July 2024 were collected. There were 17 males and 6 females, aged 70(range, 24-84)years. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Repeated measurement data were analyzed using the repeated ANOVA, and pairwise comparison within groups was conducted using the least significant difference method. The Boruta algorithm was applied for analyzing variables related to survival outcomes. Results:(1) Treatment of patients undergoing open abdomen therapy. ① The intra-abdominal pressure, lactate, heart rate, central venous pressure, mean arterial pressure, sequential organ failure assessment score of 23 patients from preoperation to postoperative day 3 were changed from (19.7±5.4)mmHg (1 mmHg=0.133 kPa), (6.1±1.9)mmol/L, (120±14)beats/minutes, (13.1±4.3)cmH 2O (1 cmH 2O=0.098 kPa), (58.8±6.8)mmHg, 13.2±1.8 to (10.6±1.3)mmHg, (2.3±0.6)mmol/L, (95±10)beats/minutes, (8.8±2.0)cmH 2O, (75.2±8.5)mmHg, 10.1±1.6, respectively, showing significant differences in the time effect of changes in the above indicators ( Ftime=46.40, 29.19, 24.91, 11.84, 27.81, 11.71, P<0.05). ② The oxygenation index, total intake, total output of 23 patients from preoperation to postoperative day 3 were changed from (255.0±54.2)mmHg, (5388±1562)mL, (2 520±630)mL to (291.7±25.0)mmHg, (2 886±866)mL, (3 221±923)mL, respectively, showing significant differences in the time effect of changes in the above indicators ( Ftime=7.61, 13.83, 2.97, P<0.05). ③The daily caloric intake, daily protein supplementation of 23 patients from preoperation to postoperative day 3 were changed from (465±116)kcal, (18±5)g to (1 628±472)kcal, (60±18)g, respectively, showing significant differences in the time effect of changes in the above indicators ( Ftime=40.31, 41.23, P<0.05). (2) Patients outcomes after open abdomen therapy. Of 23 patients, 18 cases survived and 5 cases died. The duration of intensive care unit stay and duration of hospital stay of 23 patients were 26(range, 5-82)days and 40(range, 5-98)days. Twelve of 23 patients received renal replacement therapy for 12 (range, 5-32)days. Time of pain and sedation management, mechanical ventilation, antimicrobial therapy, vasopressor therapy of 23 patients were 13(range, 5-74)days, 12(range, 5-74)days,20(range, 5-50)days, 6(range, 2-35)days. (3) Analysis of variables related to survival outcomes for patients after open abdomen therapy. Results of Boruta analysis showed that postoperative high-output enteric fistula, postoperative bile fistula, postoperative intra-abdominal hemorrhage, postoperative enteric air fistula, and preoperative mean arterial pressure were significantly associated with survival outcomes. Conclusions:Open abdomen therapy is effective in the treatment of non-traumatic critically patients. Postoperative high-output enteric fistula, postoperative bile fistula, postoperative intra-abdominal hemorrhage, postoperative enteric air fistula, and preoperative mean arterial pressure reduction are significantly associated with survival outcomes.

OBJECTIVE: Segmented cardiac cine magnetic resonance imaging (MRI) is the gold standard for cardiac ventricular volumetric assessment. In patients with difficulty in breath-holding or arrhythmia, this technique may generate images with inadequate quality for diagnosis. Real-time cardiac cine MRI has been developed to address this limitation. We aimed to assess the performance of retrospective electrocardiography-gated real-time cine MRI at 3T for left ventricular (LV) volume and mass measurement. MATERIALS AND METHODS: Fifty-one patients were consecutively enrolled. A series of short-axis cine images covering the entire left ventricle using both segmented and real-time balanced steady-state free precession cardiac cine MRI were obtained. End-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), and LV mass were measured. The agreement and correlation of the parameters were assessed. Additionally, image quality was evaluated using European CMR Registry (Euro-CMR) score and structure visibility rating. RESULTS: In patients without difficulty in breath-holding or arrhythmia, no significant difference was found in Euro-CMR score between the two techniques (0.3 ± 0.7 vs. 0.3 ± 0.5, p > 0.05). Good agreements and correlations were found between the techniques for measuring EDV, ESV, EF, SV, and LV mass. In patients with difficulty in breath-holding or arrhythmia, segmented cine MRI had a significant higher Euro-CMR score (2.3 ± 1.2 vs. 0.4 ± 0.5, p < 0.001). CONCLUSION: Real-time cine MRI at 3T allowed the assessment of LV volume with high accuracy and showed a significantly better image quality compared to that of segmented cine MRI in patients with difficulty in breath-holding and arrhythmia.
Arrhythmias, Cardiac ; Diagnosis ; Heart Ventricles ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Imaging, Cine* ; Retrospective Studies* ; Stroke Volume

OBJECTIVE： To explore potential mechanism of “Astragalus membranaceus-Draba nemorosa” couplet medicine for heart failure. METHODS： By network pharmacology， based on drug-like and oral bioavailability， the active components of “A. membranaceus-D. nemorosa” for chronic heart failure were screened and the targets of treating chronic heart failure were predicted by using TCMSP，GeneCards database， OMIM database and DRAR-CPI. The active component-chronic heart failure target network was established by Cytoscape 3.6.0 software. The protein-protein interaction network was constructed by utilizing STRING database. Then top 5 targets in the list of connectivity were screened and performed a molecular docking in molecular docking server. Finally， GO bioprocess analysis and KEGG pathway enrichment analysis were performed in DAVID database. RESULTS： The study predicted 28 active components in total， including 20 A. membranaceus and 12 D. nemorosa， such as kaempferol and quercetin， there were four components in common. Totally 92 target gene of active components were obtained， including heat shock protein 90α （HSP90AA1）， tyrosine protein kinase SRC gene， etc. Results of GO bioprocess analysis showed an association with mitochondrial electron transport， mitochondrial intima， cytoplasmic sol， extracellular body， mitochondrial matrix and drug response. KEGG pathway enrichment analysis showed a link with MAPK signal pathway， TGF signal pathway， PI3K signal pathway， cAMP signal pathway， protein kinase B signal pathway， EPK1 signal pathway and NF-κB signal pathway. CONCLUSIONS： “A. membranaceus-D. nemorosa” couplet medicine exerts therapeutic effects on heart failure from multiple targets as HSP90AA1， SRC and mitochondrial electron transport and MAPK signaling pathway. The study can provide reference for further researches on its material basis and mechanism.

OBJECTIVE： To systematically evaluate the efficacy of Compound xuanju capsules combined with chemical medicine versus chemical medicine alone in the treatment of polycystic ovarian syndrome （PCOS）， in order to provide evidence-based medicine guidelines for clinical medication. METHODS： Retrieved from PubMed， Embase， Cochrane library， CBM， VIP， CJFD and Wanfang database from database establishment to Apr. 5， 2019， randomized controlled trials （RCTs） about therapeutic efficacy （total response rate， ovulation rate， pregnancy rate， FSH level， LH level， testosterone level， degree of endometrial thickening） of Compound xuanju capsules combined with chemical medicine （trial group） versus chemical medicine alone （control group） in the treatment of PCOS were collected. After data extraction and quality evaluation of included studies with modified Jadad scale， Meta-analysis was conducted by using STATA 14.0 software. Trial sequential analysis （TSA） was conducted by using TSA 0.9 software. RESULTS： A total of 15 RCTs were included， involving 1 259 patients. The results of Meta-analysis showed that the total response rate [RR＝1.27，95％CI（1.13，1.44），P＜0.001]， ovulation rate [RR＝1.18，95％CI（1.03，1.37），P＜0.001]， pregnancy rate [RR＝1.34，95％CI（1.11，1.61），P＜0.001]， serum hormone level {FSH [SMD＝－0.66，95％CI （－0.51，  －0.82），P＜0.001]， 95％CI（－1.76，－1.41），P＜0.001]， LH [SMD＝－1.24，95％CI（－1.39， －1.08），P＜0.001]， testosterone [SMD＝－1.59，95％CI（－1.76，－1.41），P＜0.001]} and endometrial thickness [SMD＝1.20，95％CI（1.04，1.37），P＜0.001] of the trial group were better than those of the control group， with statistical significance. The results of TSA were reliable. CONCLUSIONS： In the treatment of PCOS， Compound xuanju capsules combined with chemical medicine is better than chemical medicine alone in improving total response rate， pregnancy rate， ovulation rate and endometrial thickness， and reducing serum hormone levels.

OBJECTIVE： To screen the active component， target and pathway of couplet medicine of “Bupleuri Radix- Atractylodis macrocephalea Rhizoma”， and to comprehensively explore its potential mechanism. METHODS： Based on the method of network pharmacology， main active componets and potential targets of  couplet medicine of “Bupleuri Radix-A. macrocephalea Rhizoma” were retrieved from TCMSP， DRAR-CPI， Genecards and OMIM database. The active component-potential target network and interaction network of potential targets were established by Cytoscape 3.6.0 software. Five potential core targets were screened， and its affinity with active components were validated with molecule docking method. GO classified enrichment analysis and KEGG pathway enrichment analysis of potential targets were carried out to obtain key pathway so as to construct active component-potential target-key pathway network. RESULTS： Totally 17 active components and 47 active component-potential targets were obtained from couplet medicine of “Bupleuri Radix-A. macrocephalea Rhizoma”. Five core targets were obtained， including AKT1， PRKCA， PRKCE， HRas， and PIK3CA. Five signaling pathways were involved， including MAPK pathway， PI3K/AKT pathway， RAS pathway， Estrogen pathway， BMP pathway. CONCLUSIONS： The couplet medicine of “Bupleuri Radix-A. macrocephalea Rhizoma” not only act on multiple targets through multiple components for mammary hyperplasia， but also play a complex network regulation role through the interaction between potential targets.