To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.

To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.

To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.

Fe/Mn/Gd polymetallic nanooxide(FMGN)were prepared by one-step solvent thermal reaction by using Fe(acac)3,Mn(acac)2 and Gd(acac)3 as reaction precursors.Next,hyaluronic acid(HA)was used to modify FMGN to fabricate tumor-targeting T 1-T 2 dual-mode magnetic resonance imaging(MRI)contrast agent(HA-FMGN)for accurate diagnosis of prostate cancer.The structure and morphology of FMGN were observed by transmission electron microscope(TEM).It was found that FMGN exhibited a uniform nanocluster spherical structure when the feeding ratio of iron acetylacetonate,manganese acetylacetonate,and gadolinium acetylacetonate was 3:2:1.X-ray diffraction(XRD)analysis showed that FMGN had a typical inverse spinel structure of Mn doped Fe 3O 4,with Gd existing in the form of amorphous gadolinium oxide.The longitudinal relaxivity(r 1)and transverse relaxivity(r 2)of FMGN were 13.395 and 428.535 L/(mmol·s),respectively,measured by 0.5 T MRI analyzer,which proved that FMGN had excellent T 1-T 2 dual-mode MRI contrast capability.The cytotoxicity and hemolysis test found that HA-FMGN didn't damage red cells and induce toxicity for normal cells,indicating that HA-FMGN had excellent cell biocompatibility.The internalization efficacy of HA-FMGN was observed by CLSM,and the results showed that HA-FMGN possessed excellent prostate tumor-targeting ability.In vivo MRI experiment showed that HA-FMGN significantly enhanced T 1 and T 2 weighted MRI signal to noise ratio(SNR)of prostate tumor,which promoted the accurate diagnosis of orthotopic prostate cancer.

Objective To investigate the ultrasonographic characteristics of acute Stanford type A aortic dissection (ATAAD) involving the renal arteries and their relationship with renal function. Methods Patients with ATAAD admitted to Deyang People's Hospital from February 2013 to May 2023 were selected for the study. Based on whether the renal arteries were involved in the dissection, the patients were divided into two groups: a renal artery involvement group and a renal artery non-involvement group. General data and ultrasound characteristics of the two groups were compared. Logistic regression analysis and model correction were performed to analyze the relationship between ultrasound characteristics and renal function involvement in ATAAD patients. Receiver operating characteristic (ROC) curves were used to evaluate the predictive value of ultrasound characteristics for renal artery involvement in ATAAD patients. Additionally, patients in the renal artery involvement group were divided into normal renal function and abnormal renal function subgroups based on serum blood urea nitrogen (BUN) and serum creatinine (Scr) levels. Clinical data of the two subgroups were compared, and a log-binomial model was used to analyze the risk effects of ultrasound characteristics for abnormal renal function. Pearson correlation analysis was performed to assess the correlation between ultrasound characteristics of renal artery involvement and renal function indicators. Results A total of 163 patients were included, consisting of 106 males and 57 females, with a mean age of (50.06±10.46) years (ranging from 20 to 85 years). Significant differences in gender, Scr, and BUN were observed between the renal artery involvement group and the renal artery non-involvement group (P<0.001). Compared to the renal artery non-involvement group, the renal artery involvement group had an increased ascending aorta diameter, a greater proportion of ascending aortic dilation and poor renal perfusion (P<0.05). Logistic regression analysis indicated that ascending aorta diameter, ascending aortic dilation, and poor renal perfusion were independent factors for renal artery involvement (P<0.05). Ultrasonographic characteristics showed good predictive ability for renal artery involvement in ATAAD patients. Furthermore, the combination of the three characteristics yielded a higher predictive value for renal artery involvement. Compared to the normal renal function group, the abnormal renal function group had higher BUN and Scr levels, increased ascending aortic diameter, a greater proportion of ascending aortic dilation and poor renal perfusion (P<0.05). The log-binomial model analysis revealed that the risk ratios for ascending aortic diameter, ascending aortic dilation, and poor renal perfusion were statistically significant both before and after adjustment (P<0.05). Pearson correlation analysis revealed that ascending aortic diameter, ascending aortic dilation, and poor renal perfusion were strongly correlated with renal function parameters (P<0.05). Conclusion Ultrasound characteristics of ATAAD involving the renal arteries are associated with renal function. Ascending aorta diameter, ascending aortic dilation, and poor renal perfusion are independent risk factors for abnormal renal function.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.

Objective:To develop and design a during-treatment records auto-review program to comply the quality assurance(QA)requirement of radiotherapy chart auditing,and thereby improve the review efficiency and accuracy.Methods:Based on the items the guideline required,the Aria Oncology Information System database backup files was analyzed by Java,Vue,and etc.languages and the corresponding review logic was formulated.A total of 530 treatment records generated at Shanghai Concord Cancer Center from January to March 2024(10 weeks)were auto-reviewed and compared with the manual results for evaluating the accuracy and efficiency of the program.Results:The auto-review program was running smoothly.Overall with the above data,the sensitivity,specificity,accuracy and the error-miss rate were 73.4%,14.3%,87.7%and 12.3%respectively.For sub-set items,the source-skin distance(SSD)error detecting rate was 100%,the wrong session reporting was 100%correlated with the plans switching and the wrong fraction reporting was 100%related to plan revision.For the other items,auto and manual reviews gave out the same accuracy.Conclusion:The none-error results from the program are all true,so the manual rechecking could limit to those auto-review error records,which can reduce the workload by 73.4%,therefore improve the effectiveness and accuracy of the radiotherapy data review.

Objective:To compare the efficacy and safety of LY01011,a recombinant anti-RANKL fully human monoclonal antibody injection,versus denosumab in the treatment of bone metastases from solid tumors.Methods:A randomized,double-blind,positive drug parallel-controlled,multicenter clinical trial was conducted.A total of 850 subjects were randomly assigned(1:1)to either the experimental group(424 subjects)or the control group(426 subjects).The experimental group received 13 doses of LY01011,while the control group received 3 doses of denosumab followed by 10 doses of LY01011.Results:The primary efficacy endpoint was the natural logarithmic change from baseline in urinary N-terminal telopeptide of type I collagen corrected by urinary creatinine(uNTX/uCr)at week 13.The change was-1.740(0.042 0)in the experimental group and-1.745(0.042 1)in the control group.The least-squares mean difference between groups was 0.005(90%CI:-0.088 to 0.097),indicating no statistically significant difference(P>0.05).Safety profiles,including treatment-emergent adverse events,laboratory tests,vital signs,physical examinations,and electrocardiograms,were comparable between groups(P>0.05).Conclusions:LY01011 demonstrated biosimilarity to denosumab,with favorable safety profile,tolerability,and potential for clinical application.

To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.