Amoenucles A-F (1-6), six previously undescribed nucleoside derivatives, and two known analogs (7 and 8) were isolated from the culture of Aspergillus amoenus TJ507. Their structures were elucidated through spectroscopic analysis, single-crystal X-ray crystallography, and chemical reactions. Notably, 3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety. Of particular significance, the absolute configuration of the sugar moiety of 1-4 was determined using nuclear magnetic resonance (NMR), electric circular dichroism (ECD) calculations, and a hydrolysis reaction, presenting a potentially valuable method for confirming nucleoside structures. Furthermore, 1, 2, and 5-8 exhibited potential tumor necrosis factor α (TNF-α) inhibitory activities, which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.
Aspergillus/chemistry* ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Molecular Structure ; Nucleosides/isolation & purification* ; Crystallography, X-Ray ; Animals ; Humans ; Mice ; Magnetic Resonance Spectroscopy

This study aims to investigate the function of lmo2363 gene in stress resistance of Liste-ria monocytogenes strain LM83-1.In this study,the lmo2363 gene deletion strain and complement-ation strain of Listeria monocytogenes were constructed using overlapping extended PCR and ho-mologous recombination techniques,and the growth ability,stress survival rate and biofilm forma-tion ability of wild,deletion strain and complementation strain were compared under different stress environments.lmo2363 gene deletion strain and complementation strain of Listeria monocy-togenes were successfully constructed in this experiment.The growth curves showed that the growth capacity of the deletion strain was weaker than the wild strain LM83-1 under 4 ℃,7％NaCl,10％NaCl,3.5％ethanol,4.0％ethanol and pH5 stress(P＜0.001).The results of stress survival test showed that the survival rate of the deletion strain was significantly lower than the wild strain after 1 h treatment with pH3 and 10 mmol/L H2 O2 stress(P＜0.010).The biofilm forming ability of the deletion strain was decreased compared with that of the wild strain(P＜0.050).This study confirmed that lmo2363 gene mediated the adaptation of LM to low temperature,high osmotic pressure,ethanol and acid stress environment and affected the formation of LM bio-film.This study laid a foundation for further exploring the function of lmo2363 gene in the stress resistance process of Listeria monocytogenes.

Objective:To explore which configuration schemes of proximal humerus internal locking system (PHILOS) fixation with endosteal augmentation can provide the optimal biomechanical stability for treatment of osteoporotic proximal humeral fractures by means of finite element analysis.Methods:Based on the CT data of the humerus of an old female volunteer (78 years old, with a bone density T-value of -3.0), a three-dimensional finite element model of the humerus was established by digital medical software such as Mimics 19.0, Geomagic Studio 12, and Creo 2.0 ANSYS Workbench2019. Next, a model of unstable proximal humerus fracture was established and subjected respectively to 5 different fixations: simple PHILOS fixation (PHILOS group), PHILOS plus 6-cm fibula fixation with calcar screws (PHILOS-F-C-6 group), PHILOS plus 6-cm fibula fixation without calcar screws (PHILOS-F-6 group), PHILOS plus 9-cm fibula fixation with calcar screws (PHILOS-F-C-9), and PHILOS plus 9-cm fibula fixation without calcar screws (PHILOS-F-9 group). After a stress mode of shoulder joint abduction at 25° was simulated, a compressive load of 200N was applied to the 5 fixation models. The stress distribution and displacement of fracture ends in different fixation models were tested, and the biomechanical stability was compared among the 5 different internal fixations.Results:Under a shoulder joint abduction at 25° and a load of 200 N, the maximum stress and the displacement of the fracture ends in PHILOS-F-C-9 group (38.678 Mpa and 0.012 mm) decreased by 30.08% and 45.45%, respectively, compared with PHILOS-F-C-6 group (55.321 Mpa and 0.022 mm), and decreased by 12.48% and 15.38%, respectively, in PHILOS-F-9 group (77.012 Mpa and 0.033 mm) compared with PHILOS-F-6 group (88.106 Mpa and 0.039 mm). The maximum stress and the displacement of the fracture ends in PHILOS-F-C-6 group decreased by 37.21% and 43.59%, respectively, compared with PHILOS-F-6 group while decreased by 49.83% and 63.63% in PHILOS-F-C-9 group compared with PHILOS-F-9 group, respectively.Conclusion:For treatment of osteoporotic proximal humeral fractures with medial instability, PHILOS fixation with longer fibula endosteal augmentation plus insertion of calcar screws is a more appropriate choice which can reduce the stress of internal fixation and reduce the displacement of the fracture ends.

Objective:To investigate the patients with hepatocellular carcinoma suitable for transcatheter arterial chemoembolization (TACE) after radical resection who were screened based on microvascular invasion (MVI) and Ki-67 expression.Methods:Of 400 patients with hepatocellular carcinoma who underwent radical resection in the Affiliated Hospital of Qingdao University from January 2013 to December 2019 were included and analyzed retrospectively, including 324 males and 76 females, aged (59.7±9.8) years, ranging from 32 to 87 years. According to whether they received adjuvant TACE treatment after operation, they were divided into simple operation group ( n=210) and TACE + operation group ( n=190). The recurrence in the first year after operation was followed up by outpatient reexamination. Univariate and multivariate Cox regression analysis were used to analyze the influencing factors of recurrence free survival after surgical resection. Subgroup analysis was performed according to Ki-67 and MVI to compare the recurrence free survival. Results:Multivariate Cox regression analysis showed that patients with proportion of Ki-67 positive cells ≥27.5% ( HR=2.073, 95% CI: 1.433-3.000, P<0.001) and MVI positive ( HR=2.339, 95% CI: 1.584-3.456, P<0.001) had increased risk of recurrence after radical resection. The 1-year cumulative recurrence free survival rate in the simple operation group was 70.0%, and there was no significant difference compared with 67.9% in the operation + TACE group( χ 2=0.08, P=0.774). Subgroup analysis: in the low expression of Ki-67 combined with negative MVI group ( n=128), the cumulative recurrence free survival rate of one year after operation in the simple operation group ( n=84) was 91.7%, which was significantly higher than 72.7% in the operation + TACE group ( n=44)( χ 2=8.22, P=0.004). There was no significant difference in the 1-year cumulative recurrence free survival rate between the simple operation group and the operation + TACE group (both P>0.05) in patients of Ki-67 high expression combined with MVI negative or Ki-67 low expression combined with MVI positive. In the Ki-67 high expression combined with MVI positive group ( n=107), the cumulative one-year recurrence free survival rate in the simple operation group ( n=62) was 40.3%, which was significantly lower than 60.0% in the operation + TACE group ( n=45)(χ 2=4.22, P=0.040). Conclusion:High expression of Ki-67 (≥27.5%) combined with positive MVI are the prediction factors for postoperative TACE treatment. Low expression Ki-67 (<27.5%) combined with negative MVI was contraindicated for postoperative TACE treatment.

Objective:To investigate the diagnosis, treatment and prognosis of squamous cell carcinoma of renal pelvis.Methods:The clinic data of 28 cases with squamous cell carcinoma of renal pelvis confirmed by pathologic examination treated during June 2007 and September 2019 was retrospectively analyzed. There were 19 male and 9 female patients, with a median age of 56 years. Hematuria was present in 18 cases, flank pain was present in 11 cases, and abdominal mass was present in 1 case. All 28 cases accepted CT or MRI examination. Renal pelvis or renal tumors were found in 26 cases, and severe hydronephrosis was observed in 2 cases. 2 cases underwent PET/CT, and bone metastasis was found in 1 case. Preoperative diagnoses were renal pelvic tumor in 13 cases, renal tumor in 13 cases and renal abscess in 2 cases. Coexisting renal calculi or renal pelvic calculus was detected in 19 cases. All 28 cases underwent surgical excision, including radical nephroureterectomy in 13 cases, radical nephrectomy in 12 cases, palliative resection in 1 case, and pyonephrenectomy in 2 cases. Enlarged lymph nodes were found in 9 cases during the surgery, and local lymph node dissection was performed in these cases.Results:The mean diameter of the tumors was 8.5 cm. Histopathological examination revealed that 9 cases were well differentiated, 11 cases were moderately differentiated, and 8 case was poorly differentiated. 1 case had pT 2 stage, 15 cases had pT 3 stage and 12 cases had pT 4 stage. 9 cases had lymph node metastasis. 5 cases had renal vein thrombosis. Immunohistochemistry staining exhibited consistent characteristics including CK5(+ ), 34βE12(+ ), p63(+ ), CK20(-) and GATA3(-). Postoperatively, 12 cases received adjuvant therapy including chemotherapy, radiotherapy and/or immunotherapy. Within a median follow-up of 6.0 months (ranging 1-80 months), median overall survival was 10.0 months. 15 cases died of tumor progression. Conclusion:Squamous cell carcinoma is a rare and highly aggressive neoplasm, typically associated with long-lasting renal calculi, hydronephrosis and chronic inflammation. The diagnosis should be established on pathologic examination.CK5, 34βE12 and p63 positivity contribute to the diagnosis of squamous cell carcinoma. Surgery is the foremost choice of treatment, but the risk of recurrence and metastasis is high. The prognosis is extremely poor as the majority of patients are diagnosed with advanced stages.

Objective:To study the pathological characteristics, diagnosis and treatment of primary adenocarcinoma of renal pelvis and ureter.Methods:The clinical pathological characteristics, treatment and prognosis of 5 patients with adenocarcinoma of upper urinary tract treated between January 2007 and May 2019 was retrospectively reviewed. There were 4 male and 1 female patients, with a median age of 60 years. The major symptoms were hematuria in 5 cases and low back pain in 4 cases. All cases underwent B-ultrasound and CT examination, and 4 cases accepted cystoscopy. Preoperative diagnoses were ureter tumor in 2 cases, renal pelvis tumor in 1 case, renal tumor in 1 case and renal calculus in 1 case.Results:5 cases were treated with surgery. Radical nephroureterectomy was performed in 3 cases, and nephrectomy in one case. 1 case underwent first-stage percutaneous nephrolithotomy and second-stage radical nephroureterectomy due to the discovery of tumor. 1 case was treated with radiotherapy and immune checkpoint inhibitor postoperatively. The mean diameter of the tumors was 4.4 cm. There were 3 renal pelvis adenocarcinomas and 2 ureter adenocarcinomas confirmed by pathologic examination, including 3 cases of pT 3 stage and 1 case of pT 4 stage. Lymph node metastasis was found in 2 cases. Immunohistochemistry revealed that CDX2(+ ), p63(-), GATA3(-), β-catenin(-)were the common features of five cases. The median survival was 12 months with a median follow-up of 6 months. 2 cases died of tumor progression within 1 year. Conclusions:Adenocarcinoma is an extremely rare malignancy, typically associated with long-standing calculi and chronic inflammation. Given the fact that clinical and imaging findings are nonspecific, the diagnosis is based on pathologic examination, supported by glandular structure of histology. Immunohistochemical staining exhibited CDX2 and CK20 positivity and β-catenin negativity, moreover, GATA3, p63 and CK7 was usually negative or partially positive. Surgery is the foremost choice of treatment. The prognosis is correlated with subtypes, whereas the overall prognosis is poor due to high rates of recurrence and metastasis.

Objective:To investigate the current trend of breast cancer neoadjuvant therapy and provide reference for the improvement of breast cancer clinical guideline in the future.Methods:Questionnaires of cross-sectional survey were sent to 110 hospitals (breast cancer surgery quantity surpassing 200) between July 2018 and September 2018. The stages and subtypes, therapeutic regimen, treatment assession, operation choice and preforming of patients underwent neoadjuvant therapy were recorded.Results:Neoadjuvant treatment has been performed in all of the 110 hospitals. The total number of breast patients underwent neoadjuvant therapy was about 14 550 (17.0% in surgical patients) in 2017. For all of the neoadjuvant patients, the proportion of stageⅡ patients was less than 30% in 81 hospitals, and the proportion of stage Ⅲ was more than 50% in 84 hospitals. The numbers of estrogen receptor (ER) (+ )/human epidermal growth factor receptor-2 (HER-2) (-), ER (-)/HER-2 (+ ) and triple negative subtype breast cancer patients were 3 550 (24.4%), 6 024 (41.4%) and 4 991 (34.3%), respectively. Patient′s scruples of relatively delayed operation and weak will of breast conservation after neoadjuvant therapy were the majority reasons for neoadjuvant therapy restriction. Anthracycline followed by taxane was the most usual neoadjuvant therapeutic regimens in 53.6% hospitals, and anthracycline plus taxane was the first choice in 42.7% hospitals. Chemotherapy with targeting therapy was recommended to HER-2 positive neoadjuvant patients in 80.9% hospitals. To assess treatment outcome of neoadjuvant treatment, 42.7% hospitals used MRI in more than 50% patients while the usage rate of MRI was less than 20% in 37.3% hospitals. The proportions of hospital using repeat-marking, tattoo and metal clip as the first method to identify the primary tumor region and lymph nodes were 60.0%, 29.1% and 10.9%, respectively. Breast-conservation rate after neoadjuvant therapy was less than 20% in 87.3% hospitals.Conclusions:Neoadjuvant therapy for breast cancer is widely performed in most hospitals in China, while the proportion of neoadjuvant treatment in patients with operable breast cancer is still low. Meanwhile, the idea of achieving de-escalation operation through neoadjuvant treatment is not promoted and the therapeutic evaluation method of neoadjuvant treatment needs further studies to improve.

Objective:To investigate the current trend of breast cancer neoadjuvant therapy and provide reference for the improvement of breast cancer clinical guideline in the future.Methods:Questionnaires of cross-sectional survey were sent to 110 hospitals (breast cancer surgery quantity surpassing 200) between July 2018 and September 2018. The stages and subtypes, therapeutic regimen, treatment assession, operation choice and preforming of patients underwent neoadjuvant therapy were recorded.Results:Neoadjuvant treatment has been performed in all of the 110 hospitals. The total number of breast patients underwent neoadjuvant therapy was about 14 550 (17.0% in surgical patients) in 2017. For all of the neoadjuvant patients, the proportion of stageⅡ patients was less than 30% in 81 hospitals, and the proportion of stage Ⅲ was more than 50% in 84 hospitals. The numbers of estrogen receptor (ER) (+ )/human epidermal growth factor receptor-2 (HER-2) (-), ER (-)/HER-2 (+ ) and triple negative subtype breast cancer patients were 3 550 (24.4%), 6 024 (41.4%) and 4 991 (34.3%), respectively. Patient′s scruples of relatively delayed operation and weak will of breast conservation after neoadjuvant therapy were the majority reasons for neoadjuvant therapy restriction. Anthracycline followed by taxane was the most usual neoadjuvant therapeutic regimens in 53.6% hospitals, and anthracycline plus taxane was the first choice in 42.7% hospitals. Chemotherapy with targeting therapy was recommended to HER-2 positive neoadjuvant patients in 80.9% hospitals. To assess treatment outcome of neoadjuvant treatment, 42.7% hospitals used MRI in more than 50% patients while the usage rate of MRI was less than 20% in 37.3% hospitals. The proportions of hospital using repeat-marking, tattoo and metal clip as the first method to identify the primary tumor region and lymph nodes were 60.0%, 29.1% and 10.9%, respectively. Breast-conservation rate after neoadjuvant therapy was less than 20% in 87.3% hospitals.Conclusions:Neoadjuvant therapy for breast cancer is widely performed in most hospitals in China, while the proportion of neoadjuvant treatment in patients with operable breast cancer is still low. Meanwhile, the idea of achieving de-escalation operation through neoadjuvant treatment is not promoted and the therapeutic evaluation method of neoadjuvant treatment needs further studies to improve.

Objective: To investigate the current status of breast reconstruction surgery in China and analyze the specific views of Chinese doctors on the relationship between radiotherapy and breast reconstruction surgery. Methods: A total of 110 medical institutions nationwide with more than 200 cases of breast cancer surgery yearly were selected into this questionnaire survey. The questionnaire survey included basic information of the surgeons and their hospitals, information of breast cancer surgeries in 2017, types of reconstruction surgery and specific views on the relationship between radiotherapy and reconstruction surgery. Results: In total, 110 hospitals participated in the survey, 96(87.3%) had undergone breast reconstruction surgery. Reconstruction with implants accounted for 65.7% of the total reconstruction surgery and the proportion of autologous reconstruction was 20.1%. For patients who probably required postoperative radiotherapy, the preferred surgical procedure in the surveyed hospitals was implant based reconstruction surgery. For those who were confirmed to receive postoperative radiotherapy or had undergone radiotherapy after total mastectomy, autologous tissue reconstruction was recommended. Postoperative radiotherapy was a negative factor for immediate breast reconstruction, and most hospitals believed that radiotherapy exerted slight effect on surgery. The proportion of delay-immediate breast reconstruction reached 66% and 86% of hospitals preferred to replace with the prosthesis at 6 months after radiotherapy. Patients with local recurrence after breast-conserving surgery could also receive immediate reconstruction and implant reconstruction was the preferred surgical procedure. Conclusions The proportion of breast reconstruction in China is relatively low and Chinese doctors still lack of technical mastery. In the face of conflict with radiotherapy, the regime selected by Chinese doctors is not in accordance with those recommended by the guideline and consensus, prompting that more professional training should be delivered for Chinese doctors to further promote the development of breast reconstruction in China.

Objective: To investigate the risk factors affecting the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), and establish a new scoring model to predict the short-term prognosis of patients. Methods: This study enrolled 222 patients with HBV-ACLF. According to their clinical outcomes during hospitalization and 90 days after discharge, they were divided into survival and death group. Clinical data were collected to calculate the Child-Turcotte-Pugh (CTP), model for end-stage liver disease (MELD), albumin-bilirubin (ALBI), and age-bilirubin-international normalized ratio-creatinine (ABIC) scores for prognosis. Multivariate logistic regression analysis was used to analyze the independent risk factors affecting 90-day mortality in HBV-ACLF patients. Cox regression model was used to establish a new prediction model. Area under the receiver operating characteristic curve was used to calculate short-term prognostic value of the models. K-M survival curve was used to predict the prognosis of patients. Results: CTP and ABIC scores were independent risk factors for 90-day mortality in HBV-ACLF patients, and the risk of death from liver failure had increased with increase of score. Cox regression model established a new predictive model CTP-ABIC = 0.551 × CTP + 0.297 × ABIC. Area under the receiver operating characteristic curve of all three scoring models (CTP, ABIC and CTP-ABIC) were 0.878, 0.829, 0.927, respectively. CTP-ABIC score was superior to the CTP and ABIC score (P value < 0.001). Patients with CTP-ABIC score ≥9.08 had higher mortality rate than patients with CTP-ABIC score < 9.08, and the difference was statistically significant (P < 0.001). Conclusion All three scoring systems can predict short-term prognosis in patients with HBV-ACLF, but the accuracy of CTP-ABIC is superior.