Triple-negative breast cancer (TNBC) represents an aggressive breast cancer subtype with poor prognosis and limited targeted treatment options. This investigation examined the anti-cancer potential of Caerulomycin A (Cae A), a natural compound derived from marine actinomycetes, against TNBC. Cae A demonstrated selective inhibition of viability and proliferation in TNBC cell lines, including 4T1, MDA-MB-231, and MDA-MB-468, through apoptosis induction. Mechanistic analyses revealed that the compound induced sustained endoplasmic reticulum (ER) stress and subsequent upregulation of C/EBP homologous protein (CHOP) expression, resulting in mitochondrial damage-mediated apoptosis. Inhibition of ER stress or CHOP expression knockdown reversed mitochondrial damage and apoptosis, highlighting the essential role of ER stress and CHOP in Cae A's anti-tumor mechanism. Both oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) decreased in TNBC cells following Cae A treatment, indicating reduced mitochondrial respiratory and glycolytic capacities. This diminished energy metabolism potentially triggers ER stress and subsequent apoptosis. Furthermore, Cae A exhibited significant anti-tumor effects in the 4T1 tumor model in vivo without apparent toxicity. The compound also effectively inhibited human TNBC organoid growth. These results indicate that Cae A may serve as a potential therapeutic agent for TNBC, with its efficacy likely mediated through the disruption of glucose metabolism and the induction of ER stress-associated apoptosis.
Humans ; Endoplasmic Reticulum Stress/drug effects* ; Triple Negative Breast Neoplasms/genetics* ; Apoptosis/drug effects* ; Cell Line, Tumor ; Female ; Animals ; Glucose/metabolism* ; Mice ; Cell Proliferation/drug effects* ; Transcription Factor CHOP/genetics* ; Antineoplastic Agents/pharmacology* ; Mitochondria/metabolism* ; Mice, Inbred BALB C

Objective:To explore the short-term oncological efficacy of the total prostatic urethra preservation（TPUP）technique in laparoscopic radical prostatectomy and its impact on postoperative urinary continence rate.Methods:The clinical data of 17 prostate cancer patients admitted to Shaoxing People’s Hospital from July 2023 to July 2024 were retrospectively analyzed. The age was（70.5 ± 6.5）years，the body mass index was（23.6 ± 2.5）kg/m 2，and the prostate-specific antigen（PSA）level was（7.845 ± 3.929）ng/ml. The preoperative biopsy pathological Gleason score were 6 in 8 cases，and 7 in 9 cases. All patients underwent laparoscopic radical prostatectomy，and the TPUP technique was used during the operation. The integrity of the preserved urethra was improved by preserving the prostatic surgical capsule closely attached to the corpus spongiosum of the urethra. During the operation，the urethra was completely preserved in 2 cases，nearly completely preserved in 14 cases，and partially preserved in 1 case. The recovery of urinary continence on the day of catheter removal and at 1 and 3 months after the operation was recorded. Recovery of urinary continence was defined as pad within 24 hours. PSA was re - examined at 6 weeks and 3 months after the operation. Results:All 17 operations in this study were successfully completed. The operation time was（143.6 ± 31.6）minutes，and the intraoperative blood loss was 50.0（20.0，50.0）ml. None of the cases was converted to open surgery，and no Clavien - Dindo grade ≥ 2 complications such as blood transfusion or intestinal injury occurred during the peri-operative period. The PSA levels at 6 weeks and 3 months after the operation were 0.054（0.008，0.215）ng/ml and 0.008（0.005，0.037）ng/ml，respectively. The indwelling catheter time after the operation was（13.4 ± 2.1）days. The number of cases with recovered urinary continence on the day of catheter removal and at 1 and 3 months after the operation was 10，15，and 17，respectively.Conclusions:The TPUP technique in laparoscopic radical prostatectomy leads to good recovery of postoperative urinary continence，and there is a slowly PSA decrease in the short term.

Objective To evaluate the clinical safety and efficacy of NOVA stent implantation in the treatment of symptomatic middle cerebral artery(MCA)atherosclerotic stenosis.Methods The clinical data,including surgical results,perioperative complications,imaging manifestations and follow-up findings,of 21 patients with severe MCA atherosclerotic stenosis,who received NOVA stent implantation at the Affiliated Tongji Hospital of Tongji University of China from November 2021 to February 2023,were retrospectively analyzed.Results Successful NOVA stent implantation was accomplished in all the 21 patients.The residual stenosis was less than 30％,with no bleeding complications.After stent implantation,the median stenosis ratio of responsible vessels decreased from preoperative 85.04％to postoperative 5.95％,the difference was statistically significant(P＜0.01).During the follow-up period of 10-14 months,one patient(4.76％)developed in-stent restenosis,one patient developed transient ischemic attack(TIA),and one patient developed posterior circulation cerebral infarction.No cerebral hemorrhage or death occurred.After treatment,the clinical symptoms were stable in 16 patients(76.19％),improved in 4 patients(19.04％),and worsened in one patient(4.76％).Conclusion For the treatment of patients with symptomatic MCA atherosclerotic stenosis,NOVA stent implantation is clinically safe and effective.However,multicenter randomized controlled studies with larger sample size and longer follow-up period need to be conducted before its curative efficacy can be further validated.

Objectives:To investigate the feasibility and ideal trajectory of medialized entry iliac screws(MEIS)placed in the posterior superior iliac in spinopelvic fixation through imaging and anatomic analyses,and to validate in clinical practice.Methods:The imaging data of 90 patients(45 males,45 females;57.5±1.6 years)without spinal or pelvic pathology who underwent pelvic CT scan in the radiology department of our hospital between June 2022 and September 2024 were collected.Three-dimensional pelvic reconstruction was performed using Mimics 21.0 software.The parameters of the bony channels of the iliac were measured and compared between males and females,including short and long axes of teardrop cross-section,the narrowest and widest inter-cortical distances of the iliac corridors,sacroiliac joint angles,and screw-to-sagittal plane angles.The ideal screw trajectory for MEIS was determined based on imaging and anatomical characteristics,and standard surgical procedures were formulated,which were applied in 5 patients.Results:No significant gender differences were observed in the narrowest iliac corridor width(males:15.19±1.81mm vs.females:15.01±2.24mm,P＞0.05),widest corridor width(males:24.16±1.66mm vs.females:24.44±2.92mm,P＞0.05),or sacroiliac joint angle(males:39.63°±4.13° vs.females:40.76°±2.94°,P＞0.05).However,significant gender dif-ferences were found in the screw-to-sagittal angle(males:30.38°±3.15° vs.females:26.72°±5.64°,P＜0.05),as well as in the teardrop short axis(males:22.00±1.25mm vs.females:20.47±1.73mm,P＜0.05)and long axis(males:32.92±2.85mm vs.females:30.80±1.48mm,P＜0.05).Notably,the narrowest and widest inter-cortical distances of the iliac corridors,and short and long axes of teardrop cross-section exceeded the diameter(9mm)of a iliac screw(P＜0.001).Postoperative imaging examinations of the 5 patients who underwent this surgical procedure showed that all implants were stably positioned,with satisfactory improvement in symptoms and functional outcomes.Conclusions:The MEIS placement in the posterior superior iliac is safe and feasible,which can serve as a new option for iliac screw placement trajectory in spinopelvic fixation.

Objective:To analyze the clinical features，diagnosis，treatment and prognosis of children with juvenile dermatomyositis(JDM) complicated with interstitial lung disease(ILD).Methods:The clinical manifestations，laboratory examination，treatment and prognosis of 7 children with JDM-ILD who were hospitalized in the Department of Nephrology and Immunology，Women and Children's Hospital Affiliated to Qingdao University from December 2019 to December 2023 were retrospectively analyzed.Results:Among the 7 cases，4 were male and 3 were female.The age of onset was 1.8-10.0 years（mean age 5.6 years），the occurrence time of pulmonary involvement was 0.6-4.0 months（mean time 2.0 months），and the follow-up time was 1.8-4.0 years.All the 7 cases had typical rash and different degrees of myasthenia.Four cases were accompanied by skin mucosal ulceration and 4 cases had fever during the course of the disease.Of the 7 cases，2 were accompanied by macrophage activation syndrome，and 1 of them had nervous system involvement，including convulsion and coma.All the children had increased creatase of varying degrees，and only 1 case had increased creatine kinase.Five cases had positive anti- melanoma differentiation-associated gene 5（MDA5）antibody and 4 cases had positive anti- Ro-52 antibody.Interleukin-6 was increased in 5 cases，interferon-γ was increased in 3 cases，and tumor necrosis factor-α was increased in 2 cases.Electromyography showed myogenic injury，MRI showed different degrees of myositis.Chest high-resolution CT showed ground glass shadow，rope shadow，consolidation shadow，pleural thickening，mesh shadow，etc.Four cases had limited lung function or mixed ventilation function restriction.All 7 cases received methylprednisolone pulse treatment combined with immunosuppressant treatment，and 5 cases received immunoglobulin treatment.Pulmonary lesions improved in 5 cases and partially improved in 1 case.One case died due to macrophage activation and multiple organ failure.Conclusion:The respiratory symptoms of JDM-ILD are obscure，and the incidence of ILD is high in children with anti-MDA5 antibody positive.High-resolution CT contributes to early diagnosis.Reasonable early application of glucocorticoid and immunosuppressants could improve the survival rate and quality of life.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Objectives:To investigate the feasibility and ideal trajectory of medialized entry iliac screws(MEIS)placed in the posterior superior iliac in spinopelvic fixation through imaging and anatomic analyses,and to validate in clinical practice.Methods:The imaging data of 90 patients(45 males,45 females;57.5±1.6 years)without spinal or pelvic pathology who underwent pelvic CT scan in the radiology department of our hospital between June 2022 and September 2024 were collected.Three-dimensional pelvic reconstruction was performed using Mimics 21.0 software.The parameters of the bony channels of the iliac were measured and compared between males and females,including short and long axes of teardrop cross-section,the narrowest and widest inter-cortical distances of the iliac corridors,sacroiliac joint angles,and screw-to-sagittal plane angles.The ideal screw trajectory for MEIS was determined based on imaging and anatomical characteristics,and standard surgical procedures were formulated,which were applied in 5 patients.Results:No significant gender differences were observed in the narrowest iliac corridor width(males:15.19±1.81mm vs.females:15.01±2.24mm,P＞0.05),widest corridor width(males:24.16±1.66mm vs.females:24.44±2.92mm,P＞0.05),or sacroiliac joint angle(males:39.63°±4.13° vs.females:40.76°±2.94°,P＞0.05).However,significant gender dif-ferences were found in the screw-to-sagittal angle(males:30.38°±3.15° vs.females:26.72°±5.64°,P＜0.05),as well as in the teardrop short axis(males:22.00±1.25mm vs.females:20.47±1.73mm,P＜0.05)and long axis(males:32.92±2.85mm vs.females:30.80±1.48mm,P＜0.05).Notably,the narrowest and widest inter-cortical distances of the iliac corridors,and short and long axes of teardrop cross-section exceeded the diameter(9mm)of a iliac screw(P＜0.001).Postoperative imaging examinations of the 5 patients who underwent this surgical procedure showed that all implants were stably positioned,with satisfactory improvement in symptoms and functional outcomes.Conclusions:The MEIS placement in the posterior superior iliac is safe and feasible,which can serve as a new option for iliac screw placement trajectory in spinopelvic fixation.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Objective:To analyze the clinical features，diagnosis，treatment and prognosis of children with juvenile dermatomyositis(JDM) complicated with interstitial lung disease(ILD).Methods:The clinical manifestations，laboratory examination，treatment and prognosis of 7 children with JDM-ILD who were hospitalized in the Department of Nephrology and Immunology，Women and Children's Hospital Affiliated to Qingdao University from December 2019 to December 2023 were retrospectively analyzed.Results:Among the 7 cases，4 were male and 3 were female.The age of onset was 1.8-10.0 years（mean age 5.6 years），the occurrence time of pulmonary involvement was 0.6-4.0 months（mean time 2.0 months），and the follow-up time was 1.8-4.0 years.All the 7 cases had typical rash and different degrees of myasthenia.Four cases were accompanied by skin mucosal ulceration and 4 cases had fever during the course of the disease.Of the 7 cases，2 were accompanied by macrophage activation syndrome，and 1 of them had nervous system involvement，including convulsion and coma.All the children had increased creatase of varying degrees，and only 1 case had increased creatine kinase.Five cases had positive anti- melanoma differentiation-associated gene 5（MDA5）antibody and 4 cases had positive anti- Ro-52 antibody.Interleukin-6 was increased in 5 cases，interferon-γ was increased in 3 cases，and tumor necrosis factor-α was increased in 2 cases.Electromyography showed myogenic injury，MRI showed different degrees of myositis.Chest high-resolution CT showed ground glass shadow，rope shadow，consolidation shadow，pleural thickening，mesh shadow，etc.Four cases had limited lung function or mixed ventilation function restriction.All 7 cases received methylprednisolone pulse treatment combined with immunosuppressant treatment，and 5 cases received immunoglobulin treatment.Pulmonary lesions improved in 5 cases and partially improved in 1 case.One case died due to macrophage activation and multiple organ failure.Conclusion:The respiratory symptoms of JDM-ILD are obscure，and the incidence of ILD is high in children with anti-MDA5 antibody positive.High-resolution CT contributes to early diagnosis.Reasonable early application of glucocorticoid and immunosuppressants could improve the survival rate and quality of life.

Objective:To explore the short-term oncological efficacy of the total prostatic urethra preservation（TPUP）technique in laparoscopic radical prostatectomy and its impact on postoperative urinary continence rate.Methods:The clinical data of 17 prostate cancer patients admitted to Shaoxing People’s Hospital from July 2023 to July 2024 were retrospectively analyzed. The age was（70.5 ± 6.5）years，the body mass index was（23.6 ± 2.5）kg/m 2，and the prostate-specific antigen（PSA）level was（7.845 ± 3.929）ng/ml. The preoperative biopsy pathological Gleason score were 6 in 8 cases，and 7 in 9 cases. All patients underwent laparoscopic radical prostatectomy，and the TPUP technique was used during the operation. The integrity of the preserved urethra was improved by preserving the prostatic surgical capsule closely attached to the corpus spongiosum of the urethra. During the operation，the urethra was completely preserved in 2 cases，nearly completely preserved in 14 cases，and partially preserved in 1 case. The recovery of urinary continence on the day of catheter removal and at 1 and 3 months after the operation was recorded. Recovery of urinary continence was defined as pad within 24 hours. PSA was re - examined at 6 weeks and 3 months after the operation. Results:All 17 operations in this study were successfully completed. The operation time was（143.6 ± 31.6）minutes，and the intraoperative blood loss was 50.0（20.0，50.0）ml. None of the cases was converted to open surgery，and no Clavien - Dindo grade ≥ 2 complications such as blood transfusion or intestinal injury occurred during the peri-operative period. The PSA levels at 6 weeks and 3 months after the operation were 0.054（0.008，0.215）ng/ml and 0.008（0.005，0.037）ng/ml，respectively. The indwelling catheter time after the operation was（13.4 ± 2.1）days. The number of cases with recovered urinary continence on the day of catheter removal and at 1 and 3 months after the operation was 10，15，and 17，respectively.Conclusions:The TPUP technique in laparoscopic radical prostatectomy leads to good recovery of postoperative urinary continence，and there is a slowly PSA decrease in the short term.