As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC₅₀: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC₅₀: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.

A case of a 69-year-old female patient, with cough, expectoration, chest tightness and shortness of breath for 10 days accompanied by left pleural effusion, was reported. Initially, a large number of suspected malignant lymphoma cells were found in the patient′s pleural effusion through routine cell morphological examination after admission, which was the direction of clinical diagnosis and treatment in the next step. Then the patient was diagnosed as primary pulmonary diffuse large B-cell lymphoma (DLBCL) through imaging, bone marrow and lung biopsy pathology. Finally, the patient was treated effectively with R-CHOP regimen, but she died of respiratory failure 9 weeks later, because she did not receive regular follow-up and treatment after the sixth chemotherapy cycle. Primary pulmonary DLBCL, an extremely rare extranodal lymphoma' lacks specificity clinical manifestations and is easy to be missed and misdiagnosed. DLBCL with a large number of malignant pleural effusion progresses rapidly and has a poor prognosis. The routine cell morphology examination of pleural effusion is simple and intuitive, which can capture key information in the shortest time, preliminarily provide clinical diagnosis and treatment ideas, and provide accurate basis for disease diagnosis.

BACKGROUND: Breast cancer patients with ipsilateral supraclavicular lymph node metastasis (ISLNM) but without distant metastasis are considered to have a poor prognosis. This study aimed to develop a nomogram to predict the overall survival (OS) of breast cancer patients with ISLNM but without distant metastasis. METHODS: Medical records of breast cancer patients who received surgical treatment at the Affiliated Cancer Hospital of Zhengzhou University, Jiyuan People's Hospital and Huaxian People's Hospital between December 21, 2012 and June 30, 2020 were reviewed retrospectively. Overall, 345 patients with pathologically confirmed ISLNM and without evidence of distant metastasis were identified. They were further randomized 2:1 and divided into training (n = 231) and validation (n = 114) cohorts. A nomogram to predict the probability of OS was constructed based on clinicopathologic variables identified by the univariable and multivariable analyses. The predictive accuracy and discriminative ability were measured by calibration plots, concordance index (C-index), and risk group stratification. RESULTS: Univariable analysis showed that estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), human epidermal growth factor receptor 2-positive (HER2+) with Herceptin treatment, and a low axillary lymph node ratio (ALNR) were prognostic factors for better OS. PR+, HER2+ with Herceptin treatment, and a low ALNR remained independent prognostic factors for better OS on multivariable analysis. These variables were incorporated into a nomogram to predict the 1-, 3-, and 5-year OS of breast cancer patients with ISLNM. The C-indexes of the nomogram were 0.737 (95% confidence interval [CI]: 0.660-0.813) and 0.759 (95% CI: 0.636-0.881) for the training and the validation cohorts, respectively. The calibration plots presented excellent agreement between the nomogram prediction and actual observation for 3 and 5 years, but not 1 year, OS in both the cohorts. The nomogram was also able to stratify patients into different risk groups. CONCLUSIONS In this study, we established and validated a novel nomogram for predicting survival of patients with ISLNM. This nomogram may, to some extent, allow clinicians to more accurately estimate prognosis and to make personalized therapeutic decisions for individual patients with ISLNM.
Breast Neoplasms ; Female ; Humans ; Lymph Nodes ; Lymphatic Metastasis ; Nomograms ; Retrospective Studies

【Objective】 To analyze the HIV-, HCV- and HBV- NAT yield rate in different areas of Henan province, so as to provide the basis for disease prevention and control as well as the establishment of a unified quality control standard for nucleic acid testing(NAT) in the Henan province. 【Methods】 The number and prevalence of NAT yielding samples with isolated infectious virus, namely HIV, HCV and HBV, in 18 blood stations in Henan province from 2017~2019, as well as the trends were analyzed. The NAT quality of each laboratory and each testing system was analyzed according to the ratio of reactive individual donation(ID) results to reactive minipools(MP). 【Results】 The HBV, HCV and HIV ID-NAT yield numbers in 3 501 251 blood donations were HBV 2 606(74/100 000), HCV 21 (0.63/100 000), and HIV 34(1.00/100 000). The HBV ID-NAT yield rate showed an upward trend in the whole province from 2017 to 2019, while the prevalence of HIV and HCV ID-NAT yield didn′t differ significantly during three years. 5 kinds of NAT detection systems were applied in 18 blood centers. among which Ⅰ, Ⅱ, Ⅳ and Ⅴ were triplex detection systems. 2661 ID-reactive samples were implicated in 5 595 MP-reactive samples, with a resolution rate of 47.56%. The resolution rate of triplex NAT system Ⅰ, Ⅱ, Ⅳ and Ⅳ was 39.63%~47.95%, 40.43%~54.36%, 51.61% and 70.00%~45.45%, respectively. An upward trend in triplex NAT resolution rate was observed in 8 laboratories, i. e.B, D, E, F, I, K, L and Q, and an descending trend in A and C. The NAT system Ⅲ, a ID-NAT system, was used only by laboratory C, presenting a NAT-yield rate of 0.19% (282/145 474) and resolution rate of 46.45% (131/282). 【Conclusion】 The majority of NAT-yield of one infectious virus in Henan province is HBV, presenting annual increasing trend. The quality management of NAT laboratories should be strengthened as the divergence was seen in the performance of different NAT laboratories.

【Objective】 To analyze the cause of single-ELISA reactive of four blood screening items in 18 blood stations in Henan, so as to provide the basis for improving the quality of blood screening. 【Methods】 The single-ELISA reactive rate of HBsAg, anti-HCV, HIV Ag/Ab and anti-TP of 18 blood station laboratories in Henan throughout 2019 was calculated, and the causes were analyzed according to different ELISA reagent combinations and gray area settings in each laboratory. 【Results】 The overall single-ELISA reactive rates of HBsAg, anti-HCV, HIV Ag/Ab and anti-TP were 1.740(2 154/1 237 789), 0.564‰(698/1 237 789), 1.421‰(1 759/1 237 789) and 1.561‰(1 932/1 237 789), respectively, showing significant differences by detection items (P <0.05). Person correlation analysis showed that the single-ELISA reactive rate was independent of the gray area settings.but dependent on laboratories and reagent combinations. The single-ELISA reactive rate of HBsAg, anti-HCV, HIV Ag/Ab and anti-TP in D laboratory was the highest and higher than that in other labs using the same reagent.The laboratories with high HBsAg single-ELISA reactive rate were mostly those using a combination of imported reagents and domestic reagents, including the top 6 laboratories. The laboratories with high anti-HCV single-ELISA reactive rate were mostly those using certain domestic reagents. No obvious rules was noticed by single-ELISA reactive for anti-HIV. Laboratories with high anti-TP single-ELISA reactive rate were mostly those using combination 4. 【Conclusion】 The HBsAg single-ELISA reactive rate was the highest in the four blood screening items of blood station laboratories in Henan. The single-ELISA reactive rate is related to the laboratory itself and the reagent manufacturer, suggesting that laboratory quality control should be strengthened and proper reagent combination should be selected to reduce the waste of blood.

Decellularized extracellular matrix (dECM) has been widely used as a scaffold for regenerative medicine due to its high biomimetic and excellent biocompatibility. As a functional polymer material with high water content and controlled fluidity, hydrogel is very promising for some minimally invasive surgery in clinical practice. In recent years, with the rapid development of hydrogel theory and technology, dECM hydrogel has gradually become a research hotspot in the field of regenerative medicine. In this paper, the related researches in recent years are reviewed regarding the preparation of dECM hydrogel and its preclinical application. The future clinical use is also prospected.

Objective To investigate the efficacy of micro?surgery for the treatment of medulla oblongata cavernomas. Methods A retrospective analysis was conducted on the clinical data of 21 patients with cavernous hemangioma who received micro?surgical treatment. Of the 21 patients, 13 were men and 8 women,aged 22 to 63 years. The preoperative Karnofsky performance status(KPS)score was 76.5 ± 10.2. The main clinical manifestations included sensory disorder and difficulty swallowing etc. According to the location of the lesions ,the posterior transchoroidal fissure approach was employed for 16 patients;far?lateral approach,5 patients. Electrophysiological monitoring and nervous system navigation were supple?mentarily adopted in both types of surgery. Further ,KPS scoring was conducted to evaluate the patients 'quality of life. Results The medulla cav?ernous hemangioma was excised in all cases. For 17 patients with primary neurological disorders ,their symptoms were alleviated or resolved;4 pa?tients had severe symptoms and 8 presented with new clinical symptoms. A follow?up visit was conducted 8 to 97 months post?surgery(average 47.6 months). All patients were found capable of caring for themselves in daily life and performing simple or normal learning and working activities without recurrence or bleeding. The mean postoperative KPS score was 83.7 ± 15.5. Conclusion Patients with medulla cavernous hemangioma bleeding or severe symptoms should actively seek surgical treatment. Repeated bleeding is the absolute indication for surgery. Surgical skills ,elec?trophysiological monitoring,and nervous system navigation can reduce nervous system damage and protect the brainstem. The patient's quality of life is expected to significantly improve after surgery.

Purpose To study the clinical features,pathological manifestation and immunohistochemical phenotype and improve the diagnosis and treatment of myoepithelial carcinoma in salivary glands.Methods Histomorphology and immunohistochemical phenotype were analyzed after the sections were stained with routine HE and immunohistochemical methods,and the relevant literatures were reviewed.Results The tumours were predominantly composed of pale-stained clear cells.In some cases,plasma-like cells,epithelioid cells and spindle cells were also seen.The cells were arranged in nest,solid or cords.Mitosis was easily seen,cytological atypia was obvious and necrosis existed in 4 cases.The results of immunohistochemical staining showed that CK was expressed in all cases.EMA was expressed in 8 cases.p63 and CK5/6 were expressed in 11 cases.S-100 was expressed in 10 cases.vimentin was expressed in 4 cases.Calponin was expressed in 2 cases.SMA was expressed in one case.The proliferation index of Ki-67 was 5％ to 40％.Conclusion The histological changes of myoepithelial carcinoma cells are diverse,and pathological and immunohistochemical methods are helpful for improving the rate of right diagnosis.Sugery is the main treatment for myoepithelial carcinoma.

Background and objective Progesterone and adiponectin receptor family member 3 (PAQR3) is a recently discovered tumor suppressor gene,which affects the development of a tumor by inhibiting cell proliferation,cell malignant transformation,angiogenesis,and tumor metastasis.This study investigates the expression of PAQR3 in lung cancer and its clinical significance.Methods A total of 106 patients with lung cancer received surgical treatment in hospital,and adjacent normal tissues of these patients were utilized as control group.The diagnosis of all patients was confirmed through clinical pathology.The expression of PAQR3 protein was detected by immunohistochemistry in lung cancer and adjacent normal tissues.The clinical significance of its expression was also investigated.Results The positive expression rate of PAQR3 protein in lung cancer was lower than that in adjacent normal tissues (P＜0.01).The positive expression rate of PAQR3 protein was unrelated to age,tumor size,and gender,but it exhibited a significant relationship with the pathological type and differentiation,TNM staging,and lymph node metastasis (P＜0.05).Kaplan-Meier survival analysis showed that the five-year survival rate of patients with PAQR3 protein positive expression was higher than that in patients with negative expression (P=0.026).Conclusion The expression of PAQR3 protein significantly decreased in lung cancer,indicating that PAQR3 protein plays an important role in the pathogenesis of PAQR3 in lung cancer.

Shuangdan oral liquid (SDO) containing radix Salviae miltiorrhizae (Chinese name Danshen) and cortex moutan (Chinese name Mudanpi) is a traditional Chinese medicine using for treating vascular diseases. Danshensu (DSS) is a main effective monomer composition derived from radix Salviae miltiorrhizae and paeonol (Pae) from cortex moutan. Although the two herbs are widely used in traditional Chinese medicine, the pharmacological functions of their active compositions were not reported. Therefore, the research of DSS and Pae in mechanisms and pharmacodynamics interaction can provide scientific evidence to support clinical application. The diabetic nephropathy (DN) rats which were induced by streptozotocin (STZ) were treated with SDO, DSS, Pae, and DSS+Pae for eight weeks. The positive effects on DN animal models were investigated by detection of physiological and biochemical indexes and oxidative stress markers, within five treatments: SDO, DSS, Pae, DSS+Pae and insulin group. Compared with the model group, the DSS+Pae group improved the renal function, blood lipid metabolism and blood viscosity, increased the vitality of T-SOD or T-AOC and decreased the level of MDA or NO after the treatment. The study was successfully showed that the DSS+Pae group could delay the process of DN, especially in the renal injury part of histopathology changes. Our results suggest that the co-administration of DSS and Pae significantly may play a protective role in DN rats through decreasing the oxidative stress and improving the blood lipid metabolism mechanisms.
Animals ; Blood Viscosity ; Diabetic Nephropathies* ; Insulin ; Lipid Metabolism ; Medicine, Chinese Traditional ; Models, Animal ; Oxidative Stress ; Rats* ; Salvia ; Streptozocin ; Vascular Diseases