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.

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.

Septic shock is a serious stage of sepsis with a hospital mortality rate of more than 40%. The pathophysiology of septic shock is vasodilation and increased permeability. Fluid resuscitation, vasopressor drugs are usually used to maintain the perfusion pressure of the main organs. However, infectious patients usually have the irresponsive vessel to catecholamines and may lead to obvious side effects using high doses of norepinephrine or dopamine. Recent studies have shown that vasopressin (AVP) improves hemodynamics, increases tissue perfusion, and synergizes with norepinephrine in patients with septic shock, showing extent application prospects in the treatment of septic shock. The practice of AVP in septic shock is reviewed in this article in order to provide a reference for clinicians.

Objective To evaluate the clinical effect of endovascular therapy with covered stent in treating aortoiliac occlusive disease. Methods The clinical data of 20 patients with aortoiliac occlusive disease, who received endovascular therapy with covered stent during the period from January 2014 to December 2016, were collected. According to Rutherford standard of clinical symptom classification, gradeⅢ, grade Ⅳ and grade V were seen in 9, 7 and 4 patients respectively. Based on the Trans-Atlantic Society Coalition (TASC) treatment guidelines Ⅱ classification, B type, C type and D type were observed in 4, 7 and 9 patients respectively. The postoperative primary patency and secondary patency of the stent as well as the clinical efficacy were analyzed. Results Endovascular treatment was successfully accomplished in all 20 patients. After the treatment, the clinical symptoms were significantly relieved. Two patients developed complications (10％). One patient developed thrombus at the distal end of stent, which was improved after thrombolytic therapy. Another patient developed hematoma at puncture site, which was absorbed after conservative therapy. No perioperative death occurred. The patients were followed up for 5-37 months, with a mean of (17±10) months. The primary patency rate was 95％ and the secondary patency rate was 100％. Conclusion For the treatment of aortoiliac occlusive disease, endovascular therapy with covered stent has excellent clinical efficacy.

Objective To explore the risk,diagnosis,treatment and prognosis of newborns suffering from congenital latent tuberculosis infection (CLTBI) by vertical transfer of mycobacterium tuberculosis(VTRTB) from mothers with active tuberculosis (TB) mothers during pregnancy.Methods The clinical data of 7 children with CLTBI follow-up of 1-6 years in Children's Hospital of Nanjing Medical University and 2 cases from literatures were reviewed,and they were divided into simple CLTBI group (n =5) and active TB group (n =4).Combined with the maternal history,the epidemiology,clinical features,treatment,prognosis and relative factors of the children were analyzed.Results Eight mothers had active TB during pregnancy,and premature delivery rate and low birth weight rate were 55.56％ (5/9 cases) respectively.The positive conversion rates of purified protein derivative tests (PPD),acid-fast bacilli (AFB) and TB culture were 6/9 cases,0/9 cases and 1/9 cases,respectively.Positive results of T cell enzyme-linked immunospot tuberculous test (T-SPOT.TB) and TB-DNA by fluorescent quantitative polymerase chain reaction (FQ-TB-DNA) were detected in 4 cases respectively,1 of 3 patients with T-SPOT.TB and 1 of 3 patients with FQ-TB-DNA were positive.There were 5 cases with chemoprophylaxis of anti-TB drugs for 1-6 years with isonicid or rifampicin;3 cases with pulmonary hilar or mediastinal lymph nodes enlargement,and 3 cases with pulmonary diffuse punctate,nodular or patchy high density shadow in 3 cases;the rate of VTRTB in 9 cases was 8/9 (88.89％) based on laboratory examination of etiology and immunology,and the risk of active TB in infants and early childhood was close to 50％ in neonates with CLTBI;the incidence of active TB was reduced from 100％ (4/4 cases) of non-intervention down to 0 (0/5 case) of intervention.Conclusions Etiology,immunology,imaging examination of TB and clinical efficacy,can prompt active TB and retrospective diagnosis of CLTBI,and application of T-SPOT.TB and FQ-TB-DNA for early diagnosis of CLTBI has a higher applied value;prophylactic and treatment of anti-tuberculosis drugs can reduce the progression of CLTBI to active TB and improve outcomes.

Objective To compare the clinical value of three-dimensional dynamic contrast enhanced magnetic resonance angiography (3D DCE MRA) and digital subtraction angiography (DSA) in diagnosing inferior vena cava diseases in suspected case of Budd-Chiari syndrome (BCS).Methods Radiological findings of 91 suspected BCS cases obtained from 3D DCE MRA and DSA in the Affiliated Hospital of Xuzhou Medical University were retrospectively analyzed.DSA test was considered as golden standard,which assess the capacity of 3D DCE MRA in diagnosing inferior vena cava diseases,including sensitivity,specificity and accuracy.Kappa test was utilized to compare the coincidence ratio of 3D DCE MRA and DSA in diagnosing inferior vena cava diseases.Results Among 91 suspected BCS cases with 3D DCE MRA,a total of 17 cases without inferior vena cava diseases were misdiagnosed as inferior vena cava stenosis,two patients with inferior vena caval obstruction was misdiagnosed as falsely negative.Seventy-two patients with 3D DCE MRA were confirmed via DSA in diagnosing inferior vena cava diseases,sensitivity was up to 97.7％ (58/60),false positivity 54.8％ (17/31),specificity 45.2％ (14/31),respectively.Fair coincidence ratio of 3D DCE MRA and DSA in diagnosing inferior vena cava diseases (Kappa =0.474,P ＜ 0.05).Conclusions There could be clinical value of 3D DCE MRA for its high sensitivity and low specificity in diagnosing inferior vena cava diseases,and favorable coincidence ratio was discovered between 3D DCE MRA and DSA.Comprehensive consideration is needed for suspected cases of inferior vena cava stenosis detected by 3D DCE MRA,and further analysis may figure out potential causes of misdiagnosis and decline false positive events.

Objective To study the clinical significance of the caudate lobe vein in patients with Budd-Chiari syndrome (BCS) by contrast-enhanced magnetic resonance imaging(MRI).Methods Contrast-enhanced MRI data of 46 patients with BCS, 30 patients with cirrhosis due to hepatitis B virus (HBV) and 49 healthy people in our institution were analyzed retrospectively.The presence and diameter of the caudate lobe vein among the three groups were measured.Among the BCS group, in which the caudate lobe vein could be seen, andpatients were divided into two groups according to disease duration and patency of inferior vena cava (IVC), respectively.And comparative study of diameter between two groups was performed.Results ①The caudate lobe vein was noted in 76.1% of patients with BCS, in 30.0% of patients with cirrhosis due to HBV,and in 36.7% of healthy subjects.The diameter of caudate lobe vein in BCS group was larger than that in both cirrhosis group and healthy group(P<0.01).There was no statistically difference between cirrhosis group and healthy group(P>0.05).②Among BCS group,the caudate vein was shown in 35 patients, with mean diameter of(4.21±1.66)mm.For 35 BCS,the diameter of caudate lobe vein in chronic group was larger than that in acute group(P<0.05).The diameter of caudate lobe vein in IVC obstruction group was larger than that in IVC open group(P<0.05).Conclusion The demonstration of the caudate lobe vein on contrast-enhanced MRI is of great significance in the diagnosis and treatment of BCS.

Objective To explore the application value of CT perfusion imaging for predicting the tiny lymph nodes metastasis and micrometastasis of squamous cell carcinoma in cervix after neoadjuvant chemotherapy.Methods The clinical data and CT perfusion parameters of 46 patients with cervical squamous cell carcinoma who underwent neoadjuvant chemotherapy followed by surgery were enrolled in the study.Based on the surgical pathology findings and short-term follow up,the cases were divided into without tiny lymph nodes metastasis (short axle diameter of lymph nodes＜10 mm) group (n=32) and with tiny lymph nodes metastasis group (n=14).All perfusion data were analyzed retrospectively and the diagnostic value were investigated.Results Blood flow (BF),blood volume (BV) and the maximum diameter of tumor per-chemotherapy in with tiny lymph nodes metastasis group were higher than those in without tiny lymph nodes metastasis group (all P＜0.05).The differences of the maximum diameter of tumor after chemotherapy,permeability,time to peak (TTP) between two groups were not statistically significant (all P＞0.05).Multivariate Logistic regression analysis showed BF and the maximum diameter of tumor per-chemotherapy were independent predictors of the tiny lymph nodes metastasis in cervix after neoadjuvant chemotherapy.ROC showed BF (AUC=0.86,P＜0.001,95％CI [0.75,0.96]) had higher predictive value than maximum diameter of tumor per-chemotherapy (AUC=0.70,P=0.02,95 ％ CI [0.54,0.88]).Conclusion CT perfusion imaging shows the significant predictive value for the tiny lymph nodes metastasis of squamous cell carcinoma in cervix after neoadjuvant chemotherapy.