Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Attempts have been made to modulate motor sequence learning (MSL) through repetitive transcranial magnetic stimulation, targeting different sites within the sensorimotor network. However, the target with the optimum modulatory effect on neural plasticity associated with MSL remains unclarified. This study was therefore designed to compare the role of the left primary motor cortex and the left supplementary motor area proper (SMAp) in modulating MSL across different complexity levels and for both hands, as well as the associated neuroplasticity by applying intermittent theta burst stimulation together with the electroencephalogram and concurrent transcranial magnetic stimulation. Our data demonstrated the role of SMAp stimulation in modulating neural communication to support MSL, which is achieved by facilitating regional activation and orchestrating neural coupling across distributed brain regions, particularly in interhemispheric connections. These findings may have important clinical implications, particularly for motor rehabilitation in populations such as post-stroke patients.
Humans ; Transcranial Magnetic Stimulation ; Motor Cortex/physiology* ; Male ; Electroencephalography ; Neuronal Plasticity/physiology* ; Female ; Adult ; Evoked Potentials, Motor/physiology* ; Young Adult ; Learning/physiology*

Objective:To study the clinical value of serum microRNA-34a (miR-34a) and aryl hydrocarbon receptor nuclear transcript-like protein 1 (BMAL1) in cervical cancer and their relationship with high-risk human papillomavirus (HR-HPV) infection.Methods:The clinical data of 76 patients with cervical cancer and 50 patients with benign cervical diseases in the Affiliated Hospital of Jining Medical University from January to December 2022 were retrospectively analyzed. The expression levels of serum miR-34a and BMAL1 were detected by real-time fluorescence quantitative polymerase chain reaction, and HR-HPV infection was detected by flow fluorescent hybridization. The patients were followed up until December 2023, and the death and poor prognosis (death, tumor recurrence and progression and severe complications at 1-year of follow-up) were recorded. The receiver operating characteristic (ROC) curve was used to analyze the efficacy of miR-34a, BMAL1 and related indexes in evaluating the poor prognosis in patients with cervical cancer at 1-year. Multivariate Cox regression analysis was used to analyze the independent risk factors for death in patients with cervical cancer. The Kaplan-Meier survival curve was used to analyze the relationship between miR-34a, BMAL1 expression and survival period, and the log-rank test was used for comparison.Results:The expression level of serum miR-34a in patients with cervical cancer was significantly lower than that in patients with benign cervical lesions (0.46 ± 0.08 vs. 0.67 ± 0.11), the expression level of serum BMAL1 was significantly higher than that in patients with benign cervical lesions (0.58 ± 0.07 vs. 0.41 ± 0.07), and there were statistical differences ( t= 12.40 and 13.34, P<0.01). The expression levels of serum miR-34a and BMAL1 in patients with cervical cancer were associated with tumor differentiation, myometrial invasion depth, lymph node metastasis, distant metastasis and International Federation of Gynecology and Obstetrics (FIGO) stage, and there were statistical differences ( P<0.05 or<0.01); they were not associated with age, menopause and pathological type, and there were no statistical differences ( P>0.05). In patients with cervical cancer, the expression level of miR-34a in patients with HR-HPV positive infection (60 cases) was significantly lower than that in patients with HR-HPV negative infection (16 cases): 0.41 ± 0.07 vs. 0.49 ± 0.08, the expression level of BMAL1 was significantly higher than that in patients with HR-HPV negative infection: 0.65 ± 0.09 vs. 0.53 ± 0.06, and there were statistical differences ( t = 3.68 and 4.24, P<0.05 or<0.01). In patients with benign cervical diseases, there were no statistical differences in the expression levels of miR-34a and BMAL1 between patients with HR-HPV positive infection (7 cases) and patients with HR-HPV negative infection (43 cases) ( P>0.05). ROC curve analysis result showed that miR-34a combined with BMAL1 had the highest sensitivity (90.4%), specificity (89.9%) and area under curve (0.911) in assessing the 1-year poor prognosis in patients with cervical cancer ( P<0.01), and the optimal cutoff values of miR-34a and BMAL1 expression level were ≤0.39 and ≥0.64. Multivariate Cox regression analysis result showed that poor differentiation, myometrial invasion depth ≥1/2, lymph node metastasis, distant metastasis, FIGO stage Ⅲ+Ⅳ, miR-34a expression level ≤0.46 and BMAL1 expression level ≥0.58 were independent risk factors for death in patients with cervical cancer ( OR = 1.857, 2.125, 2.337, 2.751, 2.457, 3.885 and 3.666; 95% CI 0.845 to 5.788, 0.726 to 5.924, 0.709 to 5.631, 0.693 to 5.727, 0.801 to 5.936, 1.244 to 6.423 and 1.031 to 5.612; P<0.01). Kaplan-Meier survival curve analysis result showed that the median survival time in cervical cancer patients with miR-34a expression level ≤0.39 and BMAL1 expression level ≥0.64 (21 cases) was significantly lower than that in the other cervical cancer patients (miR-34a expression level>0.39 or BMAL1 expression level<0.64, 55 cases): (26.4 ± 4.2) months vs. (34.2 ± 5.6) months, log-rank χ2 = 17.12, P<0.05. Conclusions:The expression level of serum miR-34a in patients with cervical cancer is significantly reduced and the expression level of BMAL1 is significantly increased, which is related to the condition, prognosis and HR-HPV infection. It can be used as a marker for the assessment of the condition and prognosis of cervical cancer. The combined detection of the two can significantly improve the sensitivity and specificity in predicting poor prognosis of cervical cancer.

Objective To explore the selection strategy of diagnostic and therapeutic regimens and assess the efficacy for postoperative infection following internal fixation of patellar fractures. Methods A retrospective analysis was conducted on the clinical data of 12 patients with postoperative infection after internal fixation of patellar fractures. Results A total of 6 patients underwent complete removal of the internal fixation devices during debridement and were subsequently fixed with knee braces, while the other 6 had their original internal fixation devices removed and replaced with Kirschner wire fixation. Three patients developed septic arthritis and underwent knee arthroscopic lavage treatment. All 12 patients underwent bacterial culture and metagenomic next-generation sequencing (mNGS) testing, and the key pathogenic bacteria were successfully identified by mNGS. All wounds achieved primary healing within 2 weeks after closure. At the final follow-up, all patients exhibited good fracture healing, with Böstman patellar fracture function scores ranging from 24 to 29 (mean score of 26.58), and the outcomes were evaluated as excellent in 7 cases and good in 5, resulting in an excellent and good rate of 100.0%. Conclusion For patients with early and delayed postoperative infections following internal fixation of patellar fractures, removal of the internal fixation devices can help reduce the risk of infection recurrence. For patients with concurrent septic arthritis, early diagnosis and timely implementation of arthroscopic joint debridement and irrigation and drainage are crucial.

Microvascular invasion (MVI) is an independent predictor of early recurrence and poor prognosis following hepatocellular carcinoma (HCC) resection and transplantation. As a novel non-invasive diagnostic tool, radiomics can extract the quantitative imaging features of tumors and peritumoral tissues with high throughput, providing more information on tumor heterogeneity than conventional and functional imaging of visual analysis and having a good application prospect in predicting the presence of MVI in HCC patients, thereby improving the accuracy of HCC diagnosis and prognosis. The value of the multimodal radiomics method based on various imaging methods in evaluating the possibility of MVI in HCC patients is elucidated here in combination with the latest research progress.

In the current scientific research training of the academic postgraduate students majoring in clinical laboratory diagnostics, there are many problems including insufficient scientific research level, poor scientific research environment and so on. Based on many years of experience on cultivating postgraduate students and starting from the five factors of 4M1E (man, machine, material, method and environment) method, a scientific strategy is proposed, and then the scientific research ability and level of academic postgraduate students majoring in clinical laboratory diagnostics could be improved by exerting its own self-motivation, strengthening the guidance of tutors, improving training tools, heightening scientific thinking, and enhancing environmental friendliness of scientific research.

Objective:To evaluate the long-term outcome of Viabahn stent graft in the treatment of complex femoropopliteal occlusive lesions.Methods:From Sep 2013 to Mar 2020, clinical data of TASC C and D femoropopliteal lesions treated with Viabahn were retrospectively analyzed. Patency rates, the freedom rate from clinically-driven target lesion revascularization (F-TLR), limb salvage and survival after five years were calculated.Results:A total of 65 patients (67 lower limbs) were included. 20 limbs were TASC C lesions, 47 limbs were TASC D lesions. The mean lesion length was (29.1±9.4) cm, including 48 chronic total occlusion (CTO) lesions (71.6%) with mean lesion length of (26.1±10.4) cm. Technique success rate was 98.6%. Mean length of stent graft was (31.3±10.1) cm.Major amputation was performed in 4.2% cases within 5 years. All-cause mortality in 5 years was 23.1%. Primary patency rates at 1,3,and 5 years were 76.8%,59.4%,50.9%, Assisted primary patency rates were 88.4%, 83.4%, 83.4% and secondary patency rates were 88.4%, 85.8%, and 85.8% . F-TLR at 1, 3 and 5 year was 88.2%,76.9%,73.1% .Conclusion:Viabahn for complex and long femoropopliteal artery occlusions is an acceptable treatment with fair long-term outcome.

Objective:To evaluate the mid-term outcome of drug coated balloon (DCB) in the treatment of femoropopliteal artery occlusive disease(FPOD). Methods Clinical date of FPOD patients receiving DCB treatment at Renji Hospital from Dec 2016 to Dec 2020 were retrospectively analyzed . The primary patency, primary assisted patency, secondary patency, free from clinically-driven target lesion revascularization (F-TLR) and the safety outcomes such as perioperative adverse events, major amputation rate and all-cause mortality were calculated. Results:One hurdred and seventy two patients (191 lower limbs) received DCB treatment. Among them, 13 lesions were TASC A (6.8%), 38 lesions were TASC B (19.9%), 98 lesions were TASC C (51.3%), and 42 lesions were TASC D (22.0%). One hundred and twenty six lesions were de novo lesions (66.0%), 33 lesions were in-stent restenosis (17.3%, ISR), and 32 lesions were both de novo lesions and ISR (16.8%). The average length of lesions was (27.8±10.4) mm. Fourty-eight lesions were mildly calcified (25.1%), 20 lesions were moderately calcified (10.5%), and 25 lesions were severely calcified (13.1%). Among de novo lesions, 97 lesions were chronic total occlusion (CTO) lesions (61.4%), and the average length of CTO lesions was (17.2±12.4) cm. The technical success rate was 97.4%.The provisonal stent rate was 22.0%. 12 month and 24 month after operation, the primary patency rate was 68.4% and 55.9%, the primary assisted patency rate was 78.8% and 69.8%, the secondary patency rate was 95.8% and 91.5%, and the F-TLR rate was 85.3% and 81.9%. The de novo lesion subgroup had a 24-month postoperative primary patency rate of 62.7%, while the in-stent restenosis subgroup had a rate of 44.9%.All cause mortality was 13.4% and major amputation rate was 4.7%. Chronic limb-threatening ischemia ( P=0.046) and CTO lesions length ≥15 cm ( P=0.006) were independent risk factors affecting the primary patency rate. Conclusion:DCB is a safe and effective endovascular intervention therapy for the treatment of femoropopliteal artery disease.

Objective:To evaluate the efficacy and safety of drug-coated balloon (DCB) with paclitaxel in the treatment of femoropopliteal artery in-stent restenosis.Methods:From Dec 2016 to Jul 2020, clinical and follow-up data of femoropopliteal artery in-stent restenosis (ISR) treated with paclitaxel DCB were retrospectively analyzed.Results:Firty-two patients (56 lower limbs) with femoropopliteal artery ISR underwent DCB therapy. According to Rutherford classification, 1 case was R2 (1.7%), 9 cases were R3 (23.2%), 23 cases were R4 (41.1%), 15 cases were R5 (26.8%) and 4 cases were R6 (7.1%). According to Tosaka classification of ISR, 46 (81.2%)limbs were Tosaka Ⅱ, 10(17.9%)limbs were Tosaka Ⅲ Mean lesion length of ISR was (240±122)mm. Bail-out stent implantation was performed in 25% cases. The median follow-up time was 18 months. The all-cause mortality rate was 11.8%, the major amputation rate was 5.9%, the primary patency rate was 53.4%, the primary assisted patency rate was 67.1%, the secondary patency rate was 93.2%, and the F-TLR was 77.2%.Conclusion:DCB is a safe and effective endovascular therapy for femoropopliteal artery ISR.