Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Pharmacological inhibitors targeting CDK4/6 have demonstrated promising efficacy across various cancer types. However, their clinical benefits in ovarian cancer patients fall short of expectations, with only a subset of patients experiencing these advantageous effects. This study aims to provide further clinical and biological evidence for antineoplastic effects of a CDK4/6 inhibitor (TQB4616) in ovarian cancer and explore underlying mechanisms involved. Patient-derived ovarian cancer organoid models were established to evaluate the effectiveness of TQB3616. Potential key genes related to TQB3616 sensitivity were identified through RNA-seq analysis, and TRIM4 was selected as a candidate gene for further investigation. Subsequently, co-immunoprecipitation and GST pull-down assays confirmed that TRIM4 binds to hnRNPDL and promotes its ubiquitination through RING and B-box domains. RIP assay demonstrated that hnRNPDL binded to CDKN2C isoform 2 and suppressed its expression by alternative splicing. Finally, in vivo studies confirmed that the addition of siTRIM4 significantly improved the effectiveness of TQB3616. Overall, our findings suggest that TRIM4 modulates ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitors in ovarian cancer treatment. TRIM4 may serve as a valuable biomarker for predicting sensitivity to CDK4/6 inhibitors in ovarian cancer.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Animals ; Tripartite Motif Proteins/genetics* ; Mice ; Cyclin-Dependent Kinase 4/antagonists & inhibitors* ; Cell Line, Tumor ; Cyclin-Dependent Kinase 6/antagonists & inhibitors* ; Protein Kinase Inhibitors/pharmacology* ; Ubiquitin/metabolism* ; Xenograft Model Antitumor Assays ; Ubiquitination ; Antineoplastic Agents/pharmacology*

Objective To explore the difference in terahertz signal characteristics between rat skin scar and normal skin using terahertz time-domain spectroscopy technology,thereby providing a novel non-invasive detection technique for the pathological examination of skin scars.Methods A rat model of whole-layer skin defect was prepared,and a reflectance terahertz time-domain spectroscopy system was used to obtain the terahertz signal maps of normal skin and scarred area.Results The terahertz signals of normal skin showed two obvious reflection time-domain signal peaks,and the characteristics of the reflection peaks at different reflection points were relatively regular.The terahertz signals of skin scar also had two obvious reflection time-domain signal peaks,but the highest peak was lower than that of normal skin.In addition,principal component analysis revealed that skin scar signals and normal skin signals were clustered together separately.The terahertz signal at different sites differed significantly(P<0.05).Conclusion Terahertz time-domain spectroscopy technology can be applied to the non-invasive detection of skin scarring,exhibiting a good application prospect in biomedicine.

Objective To explore the differences in terahertz(THz)signal characteristics between normal and ischemic liver tissues of New Zealand rabbits using THz time-domain spectroscopy(THz-TDS),thereby providing a novel detection technique for the pathological detection of liver tissues.Methods Liver ischemia models were established in New Zealand rabbits.The THz scanning signal maps of normal and ischemic liver tissues were obtained using a reflective THz-TDS system,and the acquired signals were subjected to principal component analysis.Results Both normal and ischemic liver tissues displayed two distinct peaks in their THz signals.However,the amplitude of the THz signal in ischemic liver tissue was higher than that in normal liver tissue,with significant differences also observed in their signal morphologies.Principal component analysis results revealed a clear clustered distribution between the signals of normal and ischemic liver tissues,indicating that THz-TDS could effectively distinguish between the two tissue types.Conclusion THz-TDS can be applied to the detection of ischemic liver tissue,providing experimental evidence to support further research on the early diagnosis of liver ischemia and exhibiting broad prospects for clinical application.

Objective To explore the differences in terahertz(THz)signal characteristics between normal and ischemic liver tissues of New Zealand rabbits using THz time-domain spectroscopy(THz-TDS),thereby providing a novel detection technique for the pathological detection of liver tissues.Methods Liver ischemia models were established in New Zealand rabbits.The THz scanning signal maps of normal and ischemic liver tissues were obtained using a reflective THz-TDS system,and the acquired signals were subjected to principal component analysis.Results Both normal and ischemic liver tissues displayed two distinct peaks in their THz signals.However,the amplitude of the THz signal in ischemic liver tissue was higher than that in normal liver tissue,with significant differences also observed in their signal morphologies.Principal component analysis results revealed a clear clustered distribution between the signals of normal and ischemic liver tissues,indicating that THz-TDS could effectively distinguish between the two tissue types.Conclusion THz-TDS can be applied to the detection of ischemic liver tissue,providing experimental evidence to support further research on the early diagnosis of liver ischemia and exhibiting broad prospects for clinical application.

Objective To explore the difference in terahertz signal characteristics between rat skin scar and normal skin using terahertz time-domain spectroscopy technology,thereby providing a novel non-invasive detection technique for the pathological examination of skin scars.Methods A rat model of whole-layer skin defect was prepared,and a reflectance terahertz time-domain spectroscopy system was used to obtain the terahertz signal maps of normal skin and scarred area.Results The terahertz signals of normal skin showed two obvious reflection time-domain signal peaks,and the characteristics of the reflection peaks at different reflection points were relatively regular.The terahertz signals of skin scar also had two obvious reflection time-domain signal peaks,but the highest peak was lower than that of normal skin.In addition,principal component analysis revealed that skin scar signals and normal skin signals were clustered together separately.The terahertz signal at different sites differed significantly(P<0.05).Conclusion Terahertz time-domain spectroscopy technology can be applied to the non-invasive detection of skin scarring,exhibiting a good application prospect in biomedicine.

OBJECTIVE: To investigate the effects of melatonin (MT) on bone mass and serum inflammatory factors in rats received ovariectomy (OVX) and to investigate the effects of MT on the levels of inflammatory factors in culture medium and osteogenic ability of bone marrow mesenchymal stem cells (BMSCs) stimulated by lipopolysaccharide. METHODS: Fifteen 12-week-old Sprague Dawley (SD) rats were randomly divided into 3 groups. The rats in Sham group only received bilateral lateral abdominal incision and suture, the rats in OVX group received bilateral OVX, and the rats in OVX+MT group received 100 mg/(kg·d) MT oral intervention after bilateral OVX. After 8 weeks, the levels of serum inflammatory factors [interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α)] were detected using ELISA assay. Besides, the distal femurs were detected by Micro-CT to observe changes in bone mass and microstructure, and quantitatively measured bone volume fraction, trabecular thickness, and trabecular number. The BMSCs were extracted from the femurs of three 3-week-old SD rats using whole bone marrow culture method and passaged. The 3rd-5th passage BMSCs were cultured with different concentrations of MT (0, 1, 10, 100, 1 000 µmol/L), and the cell viability was then detected using cell counting kit 8 (CCK-8) to select the optimal concentration of MT for subsequent experiments. Cells were devided into osteogenic induction group (group A) and osteogenic induction+1/5/10 μg/mL lipopolysaccharide group (group B-D). The levels of inflammatory factors (IL-1β, IL-6 and TNF-α) in cell culture medium were detected using ELISA assay after corresponding intervention. According to the results of CCK-8 method and ELISA detection, the cells were intervened with the most significant concentration of lipopolysaccharide for stimulating inflammation and the optimal concentration of MT with osteogenic induction, defining as group E, and the cell culture medium was collected to detect the levels of inflammatory factors by ELISA assay. After that, alkaline phosphatase (ALP) staining and alizarin red staining were performed respectively in groups A, D, and E, and the expression levels of osteogenic related genes [collagen type Ⅰ alpha 1 chain (Col1a1) and RUNX family transcription factor 2 (Runx2)] were also detected by real time fluorescence quantitative PCR (RT-qPCR). RESULTS: ELISA and Micro-CT assays showed that compared with Sham group, the bone mass of the rats in the OVX group significantly decreased, and the expression levels of serum inflammatory factors (IL-1β, IL-6, and TNF-α) in OVX group significantly increased (P<0.05). Significantly, the above indicators in OVX+MT group were all improved (P<0.05). Rat BMSCs were successfully extracted, and CCK-8 assay showed that 100 µmol/L was the maximum concentration of MT that did not cause a decrease in cell viability, and it was used in subsequent experiments. ELISA assays showed that compared with group A, the expression levels of inflammatory factors (IL-1β, IL-6, and TNF-α) in the cell culture medium of groups B-D were significantly increased after lipopolysaccharide stimulation (P<0.05), and in a concentration-dependent manner. Moreover, the expression levels of inflammatory factors in group D were significantly higher than those in groups B and C (P<0.05). After MT intervention, the expression levels of inflammatory factors in group E were significantly lower than those in group D (P<0.05). ALP staining, alizarin red staining, and RT-qPCR assays showed that compared with group A, the percentage of positive area of ALP and alizarin red and the relative mRNA expressions of Col1a1 and Runx2 in group D significantly decreased, while the above indicators in group E significantly improved after MT intervention (P<0.05). CONCLUSION MT may affect the bone mass of postmenopausal osteoporosis by reducing inflammation in rats; MT can reduce the inflammation of BMSCs stimulated by lipopolysaccharide and weaken its inhibition of osteogenic differentiation of BMSCs.
Female ; Rats ; Animals ; Tumor Necrosis Factor-alpha ; Osteogenesis ; Rats, Sprague-Dawley ; Core Binding Factor Alpha 1 Subunit ; Melatonin/pharmacology* ; Interleukin-6/genetics* ; Lipopolysaccharides/pharmacology* ; Coloring Agents ; Inflammation

At present, the situation of COVID-19 epidemic prevention and control in China is gradually improving, but the situation of overseas import prevention and control remains difficult. The COVID-19 epidemic may exist for long due to the undetermined source of infection, the difficulty in completely cutting off the transmission route, and a large number of susceptible people. Therefore, prevention and control will be a long-term and arduous task, making it necessary to adhere to the principle of combining emergency response with regular prevention and control, coordinating the epidemic prevention and social-economic development in a balanced way. In retrospect, the epidemic has exposed the ambiguous positioning and unsatisfying hardware construction of hospital laboratory departments, and delayed intervention of laboratory experts in the public health treatment system of China. This paper reflects on the hospital laboratory departments′ problems during the anti-epidemic activities, and put forward suggestions to improve the future development of clinical laboratories in the national public health system.

Objective To investigate the prevalence of depression among the patients with diabetic foot and analyze the influence factors. Methods One hundred and ten patients with diabetic foot were inquired and assessed with patient health questionnaire for self-administered measurement (PHQ-9), meanwhile, the demo-graphic data, metabolic data and diabetes behaviors were also investigated. Results Prevalence of depression was 47.3%. Logistic regression analysis showed that alternation of diarrhea and astriction (OR = 6.901, P =0.017) and formication (OR = 23.401, P = 0.009) were risk factors, and medical insurance (OR = 0.217, P =0.007) was a protective factor. Conclusions Depression is a frequent mental disorder in patients with diabet-ic foot and its influence factors include alternation of diarrhea and astriction , formication and medical insur-ance .

Objective To evaluate the safety and effectiveness of endourological techniques in the treatment of benign prostate hyperplasia (BPH) in elderly high-risk patients.Methods A total of 202 BHP patients over 70 years old were treated with endourological techniques and followed up for 3-24 months.Patients were divided into transurethral resection of the prostate(TURP) group (n=90)and transurethral plasmakinetic resection of the prostate(PKRP) group (n =112).Results Compared with pre-treatment,the scores of IPSS and quality of life (QOL),residual urine volume and Qmax were improved in the TURP group after treatment [(6.3±1.2) vs.(27.8±2.5),(1.0±0.4)vs.(5.5±1.1),(18.0±2.8) ml vs.(95.0±18.0) ml,(17.5±1.4) ml/s vs.(5.4±2.0) ml/s,respectively,all P＜0.05].Compared with before treatment,the scores of IPSS and QOL,residual urine volume and Qmax were also improved in the PKRP group after treatment [(8.4 ± 2.5) vs.(27.9±2.3),(1.0±0.4) vs.(1.5±0.5),(25±4) mlvs.(150±26) ml,(19±2.3) ml/svs.(7.0±2.3) ml/s,respectively,all P＜0.05].There were no significant differences in IPSS,QOL,Qmax and RUV between the two groups after treatment (P＞0.05),but the complication incidence was less in PKRP group than in TURP group (6.25％ vs.22.2％,x2 =10.99,P＜0.05).Conclusions PKRP is a safe and effective therapy for elderly high risk patients with BPH.The individual treatment,intensive monitoring and adjustment before operation,and skilled manipulation are the key points to the successful operation.