OBJECTIVE To investigate the effect and potential mechanism of toosendanin in enhancing the antileukemic activity of cytosine arabinoside against acute myeloid leukemia （AML） based on the mammalian target of rapamycin complex 1 （mTORC1） signaling pathway.METHODS Female NSG immunodeficient mice were used to establish an AML model via a single γ-ray irradiation followed by a single tail-vein injection of a U937 cell suspension. The effects of cytosine arabinoside （2.5 mg/kg）， toosendanin （1.0 mg/kg）， and cytosine arabinoside+toosendanin （2.5 mg/kg+1.0 mg/kg） on body weight， survival time， peripheral blood routine indicators， histopathological morphology， and the expressions of autophagy-related proteins were explored. Using U937 cells as the subject， the effects of cytosine arabinoside （1 μmol/L）， toosendanin （160 nmol/L）， and cytosine arabinoside+toosendanin （1 μmol/L+160 nmol/L） on the expressions of autophagy-related proteins， mTORC1 signaling pathway-related proteins and mRNAs were investigated. The targeting relationship between toosendanin and the selective autophagy ligand 1 （also known as p62） was validated， and the Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses， as well as molecular docking， were performed. A p62 -knockdown U937 stable cell line was constructed， and the underlying mechanism of toosendanin-induced sensitization was verified.RESULTS Animal experiments confirmed that the combination of toosendanin and cytosine arabinoside significantly improved body weight， survival time and peripheral blood routine indicators in AML mice （ P ＜0.05）， alleviated pathological changes such as leukemic cell infiltration and focal necrosis in bone marrow， liver， and spleen tissues， and modulated the expressions of autophagy-related proteins. Cell experiments confirmed that toosendanin could reverse cytosine arabinoside-induced activation of the autophagy cascade （manifested by downregulation of the protein expressions of microtubule-associated protein 1 light chain 3B and Beclin-1， upregulation the protein expression of p62）， and might inhibit the expression of the downstream Unc-51-like autophagy activating kinase 1 （ULK1） complex （including ULK1， ULK2， autophagy-related protein 13， and FAK family interacting protein of 200 kDa） by activating the mTORC1 signaling pathway （ P ＜0.05）. The sensitizing effect of toosendanin was associated with the inhibition of autophagy and the regulation of the mTORC1 signaling pathway； it could stably bind to p62 via hydrophobic interactions. Mechanism verification experiments indicated that upon p62 knockdown， toosendanin was no longer able to activate the mTORC1 signaling pathway or inhibit autophagy.CONCLUSIONS Toosendanin may enhance chemo-sensitivity of AML cells to cytosine arabinoside by directly targeting the p62 protein， which subsequently activates the mTORC1 signaling pathway， and thereby suppresses cytosine arabinoside-induced protective autophagy.

CD20 is a surface marker protein of B-cell lymphoma, and its extracellular region is the target of specific antibodies and drugs. To obtain a cheap and easily modified specific preparation targeting CD20, we optimized the gene of CD20 extracellular region according to codon degeneracy to facilitate its expression in Escherichia coli. The optimized gene was cloned into pGEX-4T-1 vector, and the recombinant vector was transformed into E. coli BL21(DE3) for expression. The purified protein was identified by SDS-PAGE and Western blotting. Systematic evolution of ligands by exponential enrichment (SELEX) was employed to screen the ssDNA aptamer that specifically binds to the fusion protein, and the affinity of the aptamer to CD20 was detected by flow cytometry. Then, the cytotoxicity test was carried out to examine the inhibitory effect of the aptamer on B lymphoma cells. In this study, we established the prokaryotic expression method of CD20 and obtained the aptamer specifically binding to the extracellular region of CD20, which laid a foundation for the development of therapeutic drugs targeting CD20.
Humans ; Escherichia coli/metabolism* ; SELEX Aptamer Technique/methods* ; Aptamers, Nucleotide/genetics* ; Antigens, CD20/metabolism* ; Ligands

Objective:To compare the diagnostic efficacy of 68Ga-PSMA-11 PET/ CT and multi-parameter magnetic resonance imaging (mpMRI) for pelvic lymph node metastases in prostate cancer patients who received neoadjuvant endocrinology or not after initial diagnosis. Methods:Data of 52 patients with moderate and high-risk prostate cancer admitted to Xijing Hospital from February to October 2023, aged (65.8±6.6) years, preoperative prostate-specific antigen (PSA) 26.67 (13.09, 84.89) ng/ml, were retrospectively analyzed. Before operation, there were 28 cases of cT 2stage, 16 cases of cT 3 stage and 8 cases of cT 4 stage. There were 22 cases of cN 0 and 30 cases of cN 1. All patients underwent 68Ga-PSMA-11 PET/CT and mpMRI at the same time, and were diagnosed positive lymph nodes in 28 and 21 cases, respectively. Risk stratification were high risk in 45 cases, and medium risk in 7 cases. According to the preoperative endocrine treatment, they were divided into the newly diagnosed group without treatment (24 cases) and the endocrine treated group (28 cases), whose ages were (65.0±7.1) years and (66.8±6.1) years, respectively. Preoperative PSA was 26.17 (16.73, 61.18) ng/ml and 27.32 (11.94, 130.18) ng/ml, respectively. Gleason scores ≤7 were in 10 cases (41.7%) and 6 cases (21.4%), and Gleason scores >7 were in 14 cases (58.3%) and 22 cases (78.6%), respectively. There were 15 (62.5%) and 13 (46.4%) cases of cT 1-2 stage, and 9 (37.5%) and 15 (53.6%) cases of cT 3-4 stage, respectively. There were 16 (66.7%) and 6 (21.4%) cases of stage N 0, 8 (33.3%) and 22 (78.6%) cases of stage N 1, respectively. There were 22 (91.7%) and 20 (71.4%) cases of stage M 0, 2 (8.3%) and 8 (28.6%) cases of stage M 1, respectively. PET/CT diagnosis of lymph node positive was in 9 cases (37.5%) and 19 cases (67.9%), and mpMRI diagnosis of lymph node positive was in 5 cases (20.8%) and 16 cases (57.1%). The number of positive lymph nodes diagnosed by PET/CT was 13 (72.2%) and 47 (90.1%), and the number of positive lymph nodes diagnosed by mpMRI was 8 (44.4%) and 32 (61.5%). There was no significant difference ( P>0.05). All patients underwent radical prostatectomy as well as enlarged pelvic lymph node resection. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the two imaging examinations in the diagnosis of lymph node metastasis were compared according to the results of postoperative pathological examination of lymph nodes. Receiver operating characteristic (ROC) curve was used to compare the accuracy of the two imaging tests in the diagnosis of pelvic lymph node metastasis in the newly diagnosed untreated group and the endocrine treated group. Results:In this study, of 52 cases, 26 (50.0%) had positive lymph nodes by pathological examination. In this study, a total of 681 lymph nodes were dissected, with 70 lymph nodes (10.28%) being pathologically positive, and the positive rate of 26 patients was 17.99% (70/389). The PET/CT and mpMRI detection rates of 26 node-positive patients were 92.3% (24/26) and 57.7% (15/26), respectively. There were 9 (37.5%) and 17 (60.7%) lymph node positive patients in the untreated group and the endocrine therapy group, respectively. There were 320 and 361 lymph nodes were clear, with 18 (5.6%) and 52 (14.4%) positive lymph nodes, respectively. The detection rates of PET/CT and mpMRI were 88.89% (8/9) and 94.12% (16/17)in the untreated group, and 44.44% (4/9) and 64.71% (11/17)in the endocrine treated group, respectively. In the newly treated group, the area under the curve (AUC) of PET/CT and mpMRI for diagnosing positive lymph nodes were 0.911 and 0.689 ( P=0.027), the sensitivity were 88.9% and 44.4%, and the specificity were 93.3% and 93.3%, respectively. PPV were 88.9% and 80.0%, and NPV were 93.3% and 73.7%, respectively. In the endocrine therapy group, the AUC of PET/CT and mpMRI for lymph node positive diagnosis were 0.834 and 0.596 ( P=0.011), the sensitivity were 94.1% and 64.7%, the specificity were 72.7% and 54.5%, and the PPV were 84.2% and 68.8%, respectively. NPV were 88.9% and 50.0%, respectively. Conclusions:For prostate cancer patients, regardless of whether they receive neoadjuvant endocrine therapy, 68Ga-PSMA-11 PET/CT can accurately detect pelvic lymph node metastasis, and the diagnostic efficacy is significantly better than that of mpMRI.

Pregnancy in patients with Eisenmenger syndrome (ES) is associated with high maternal mortality rates of 30%‒50%, or even up to 65% in the case of a cesarean section (Yuan, 2016). Here, we report a case of term pregnancy complicated with ES and severe pulmonary artery hypertension (PAH), which was managed by a multidisciplinary team (MDT) and resulted in an uncomplicated delivery via elective cesarean section. The goal of this study is to emphasize the importance of multidisciplinary approach in the management of pregnancy with ES, which can profoundly improve maternal and infant outcomes.
Female ; Humans ; Pregnancy ; Cesarean Section ; Eisenmenger Complex/therapy* ; Hypertension, Pulmonary/therapy* ; Maternal Mortality ; Pregnancy Complications, Cardiovascular/therapy* ; Pregnancy Outcome

Objective : To investigate the cross⁃sectional associations of serum interleukin( IL) Ⅳ18 with cartilage volume , cartilage defects , bone marrow lesions ( BML) and biomarkers of cartilage degradation in patients with knee osteoarthritis (OA) , and to provide new ideas and new methods for clinical diagnosis and treatment. Methods: The study included 151 patients with knee OA , a general questionnaire survey was conducted , and the knee strucral was photographed by magnetic resonance imaging (MRI) . The cartilage volume was measured by OsiriX software in 3D⁃FLASH sequence , and cartilage defect and BML were determined in T2⁃weighted sequence. Serum IL-18 and matrix metalloproteinase ( MMP) Ⅳ3 , 13 levels were measured by enzyme⁃linked immunosorbent assay(ELISA) . SPSS software was used for statistical analysis. Results : In multivariable analyses , serum IL⁃18 level was consistent at divided part of joint (femorotibial joint and the patella femoral joint , all P < 0. 05) . Serum IL⁃18 level was positively associated with cartilage defect and BML at media femorotibial area (all P < 0. 01) . Serum IL⁃18 level was positively associated with MMP⁃3 (β = 0. 31 , 95% CI:0. 001 - 0. 010) and MMP⁃13 (β = 0. 86 , 95% CI:0. 08 - 0. 10 , all P < 0. 01) . CI:0. 08 - 0. 10 , all P < 0. 01) . Conclusion Serum IL⁃18 level is negatively associated with cartilage volume and Serum IL⁃18 level is negatively associated with cartilage volume and positively associated with cartilage defect , BML , MMP⁃3 and MMP⁃13 , suggesting IL⁃18 may play a significant role duce the injury of article cartilage in patients with knee OA and delay the progression of disease.

In the past few years, there has seen an increase in the detection rate of early upper gastric cancer. Early upper gastric cancer is of good prognosis. How to further enhance the postoperative quality of life of patients has increasingly become an issue of concern. This has naturally given rise to function-preserving proximal gastrectomy. However, due to its damage to the original structure of cardia and its vicinity, proximal gastrectomy is prone to postoperative reflux. To prevent postoperative reflux, various ways of digestive tract reconstruction have emerged one after another, but the optimal way thereof remains controversial. Therefore, reducing postoperative reflux through an appropriate way of digestive tract reconstruction has been taken as a focus of proximal gastrectomy. Esophagogastric anastomosis with seromuscular flap technique, as a way of digestive tract reconstruction, builds an "artificial cardia" on the basis of guarantee of normal entry of food into the digestive tract, and functions against postoperative reflux. For its good anti-reflux effect, eso-phagogastric anastomosis with seromuscular flap technique has gradually become a research focus. On top of the latest research progress at home and abroad and relevant evidence-based medicine, the authors provide on the principles, key points, improvement, postoperative status, and applica-tion of esophagogastric anastomosis with seromuscular flap technique in laparoscopic proximal gastrectomy.

Resection is one of the most important treatments for esophageal squamous cell carcinoma, and routine postoperative follow-up is an effective method for early detection and treatment of recurrent metastases, which can improve patients' quality of life and prognosis. This consensus aims to provide a reference for colleagues responsible for postoperative follow-up of esophageal squamous cell carcinoma patients in China, and further improve the standardization of the diagnosis and treatment of esophageal squamous cell carcinoma.

Objective: To evaluate the efficacy of Tuina (Chinese therapeutic massage) manipulation plus horse-riding squat exercise in treating knee osteoarthritis (KOA) and optimize the combining protocol. Methods: Based on a 2×2 factorial design, 120 eligible KOA patients were randomized into a manipulation group (group A1B2), a manipulation plus horse-riding squat group (group A1B1), a sitting knee-adjustment group (group A2B2 group), and a sitting knee-adjustment plus horse-riding squat group (group A2B1), with 30 cases in each group. The intervention was conducted three times a week, lasting for four weeks. The Western Ontario and McMaster Universities osteoarthritis index (WOMAC) was taken as the major measure for efficacy evaluation (including three component scores, pain, stiffness, and daily function, and total score). Results: The three component scores (pain, stiffness, and daily function) and the total score of WOMAC showed significant differences after the intervention in the four groups (P<0.05). There were significant inter-group differences in the WOMAC stiffness score amongst the four groups after the intervention (P<0.05). In group A1B1, the step length, stride, walking speed, and knee joint flexion angle changed significantly after treatment (P<0.05). After the intervention, the step length changed significantly in group A1B2 (P<0.05), and the walking speed changed significantly in group A2B1 (P<0.05). There were no significant differences in the step length, stride, walking speed, or knee joint flexion angle among the four groups (P>0.05). The extensor peak torque at 180 °/s changed significantly in group A1B2 after treatment (P<0.05). Neither the intra-group nor the inter-group comparisons of the four groups revealed significant differences in the other isokinetic muscle strength parameters (P>0.05). The main effect of manipulation showed significant in affecting the WOMAC pain and total scores (P<0.05). The main effect of horse-riding squat exercise showed significant in affecting the WOMAC pain and stiffness scores (P<0.05). Conclusion: The four treatment protocols all can improve the symptoms of KOA, for instance, relieving pain and stiffness, and enhancing daily function. Group A2B1 produces the most eminent effect in relieving joint stiffness. The main effects of both manipulation and horse-riding squat exercise are significant in reducing pain. Besides, the main effect of horse-riding squat exercise is significant in relieving joint stiffness.

Bronchopulmonary dysplasia is one of the most common complications of preterm infants.The main pathological feature is dysplasia of the alveoli and pulmonary microvessels.Vitamin D is a steroid hormone.By binding to vitamin D receptors, it can protect the barrier function of alveolar epithelium, promote pulmonary vascularization, inhibit pulmonary fibrosis, regulate immune function, and repair damaged lung epithelial cells.It is beneficial to lung development and the improvement of lung function in preterm infants.Therefore, monitoring the level of vitamin D in the perinatal period and supplementing with appropriate doses is expected to be one of the ways to reduce the occurrence of moderate and severe bronchopulmonary dysplasia and improve the lung development of preterm infants.

Objective:To explore the clinical value of introducing 68Ga PSMA PET / CT into the prostate cancer(PCa)screening clinic, and to analyze the incidence rate and biopsy of PCa in the screening clinic of our hospital. Methods:The data of the people who participated in PCa screening in the urology screening clinic of our hospital from March 2021 to November 2021 were retrospectively analyzed. Serum PSA was used as the screening index. The subjects with PSA≥4ng/ml were first examined by mpMRI to find suspicious nodules, and the positive ones were further examined by 68Ga-PSMA PET/CT to determine the lesions.The puncture target was outlined, and systematic+ targeted puncture was conducted under ultrasound guidance. The age, PSA distribution, puncture detection rate, Gleason score and clinical stage of patients with PCa were recorded. Results:A total of 1 079 subjects were included in the screening, with an average age of (63.9±9.9)(ranging 40-92) years old, and 249 patients (23.1%, 249/1 079) with PSA≥4ng/ml. Among them, 87 cases (87/249, 34.9%) received mpMRI, and 34 cases (34/249, 13.7%) had PI-RADS score ≥3 points. These 34 patients with suspected nodules on MRI were further scanned with 68Ga-PSMA PET/CT, and 11 cases (11/249, 4.4%) had abnormal uptake of PSMA nuclide. A total of 32 patients (12 patients with PSA abnormalities and 20 patients with positive imaging) finally received prostate biopsy, and 11 patients were diagnosed with PCa, with a positive detection rate of 34.4% (11/32), accounting for 1.0% (11/1 079) of the screening population. Among them, 20 patients with positive imaging (9 patients with only mpMRI positive and 11 patients with both mpMRI and 68Ga-PSMA PET/CT positive) underwent system + targeted fusion biopsy, and the positive rate was 45% (9/20). 12 patients (only PSA abnormal) underwent routine systematic puncture biopsy, and the positive detection rate was 16.7% (2/12). The difference between the two groups was statistically significant ( P<0.05). Among the patients with confirmed PCa, 27.3% (3/11) had Gleason score less than 7, and 72.7% (8/11) had Gleason score≥7. Localized PCa (≤T 2) accounted for 45.4% (5/11), local progression (T 3-T 4) accounted for 18.2% (2/11), and metastatic PCa suggested by 68Ga-PSMA PET/CT accounted for 36.4% (4/11), including 3 systemic multiple bone metastases and one bone metastasis with distant lymph node metastasis. Clinically significant PCa accounted for 90.9% (10/11) of the confirmed patients, and the proportion of high-risk patients in localized or locally advanced PCa was 71.4% (5/7). Conclusions:In PCa screening, if 68Ga-PSMA PET/CT is introduced on the basis of conventional mpMRI, the detection rate of clinically meaningful PCa can be improved. Combined with targeted puncture, tumor lesions can be found early and the screening efficiency of PCa can be improved. In this study, the detection rate of PCa in outpatient screening reached 1.0%. In confirmed cases, the proportion of high-risk patients and metastatic patients was higher.