In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC₅₀ values of 3.77 μmol·L^-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.

OBJECTIVETo investigate the expression of Csk-binding protein (CBP) in esophageal carcinoma and its association with the tumorigenesis and progression of esophageal cancer.

METHODSRT-PCR and Western blotting were employed to determine the expressions of CBP at the mRNA and protein levels in 50 pairs of fresh esophageal carcinoma tissue and the adjacent normal tissues.

RESULTSCBP mRNA and protein expressions in normal tissues were 1.43- and 1.28-fold higher than those in the cancer tissues, respectively (P<0.05). The expressions of CBP mRNA and protein were positively correlated (P=0.015). The decreased expressions of CBP were significantly correlated to lymph node metastasis of esophageal cancer (P<0.05).

CONCLUSIONThe expression of CBP gene is decreased in esophageal carcinoma, which might contribute to the tumorigenesis and progression of this malignancy.

Adenocarcinoma ; metabolism ; pathology ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Down-Regulation ; Esophageal Neoplasms ; metabolism ; pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; RNA, Messenger ; genetics ; metabolism ; src-Family Kinases ; genetics ; metabolism

Objective To study the effect of essential oil from Angelica sinensis(EOAS) on neuronal apoptosis induced by ischemia-reperfusion injury.Methods The high differentiated PC12 cells were divided into blank group,model group,control group (10 μmol · L-1 edaravone)and large-,medium-and small-dose expreimental groups(EOAS 25.00,12.50,6.25 μg · mL-1).Except blank group,the remaining groups were treated with sugar-free medium containing 10 mmol · L-1sodium dithionite (Na2S204) for 1 h,reoxygenation for 48 h.The cell proliferation was measured by methyl thiazolyl tetrazolium(MTT) assay.The activity of superoxide dismutase (SOD) and lactate dehydrogenase (LDH),contents of malondialdehyde (MDA) were measured by kit.The apotosis rate and the morphological apoptotic characteristics of cells were observed by flow cytometry and acridine orange/propidium iodide (AO/PI) double staining respectively.The relative activity of caspase-3 were examined with colorimetric assay.The expression of p-ERK1/2 proteins was measured by Western-blot.Results Compared with the blank group,the cell viability in the model group was (67.4 ±0.10)％ with significantly(P ＜0.01).Compared with the model group,the cell viability in the large-dose experimental group and control group were (86.2 ± 0.10)％,(94.5 ± 0.05)％ with significantly (P＜0.05,P ＜ 0.01).Compared with the blank group,the LDH and MDA content in the model group were (912.53±16.71)U · L-1and(9.05 ±0.25)μmol · L-1while SOD level was (12.53 ±0.29)U · mL-1with significantly(all P ＜0.01).Compared with the model group,the LDH and SOD level in the large-dose experimental group were (565.61 ± 11.72) U · L-1 and (12.53 ± 0.29) U · mL-1 with significantly (P ＜ 0.05,P ＜ 0.01) while MDA content in the large-,medium-dose experimental groups were (3.32 ± 0.68),(5.79 ± 0.68) μmol · L-1 with significantly(all P ＜0.01).The absorbance(A) in model group and large-,medium-and small-dose expreimental groups were 0.75 ± 0.06 and 0.10 ± 0.02,0.16 ± 0.03,0.49 ± 0.04.Compared with the model group,the difference had significantly(P ＜0.05,P ＜0.01).Compared with the blank group,the apoptosis rate in the model group was (31.17 ± 2.44)％ with significantly(P ＜ 0.01).Compared with the model group,the apoptosis rate in the large-,medium-dose experimental groups were (4.57 ± 0.32) ％,(5.93 ± 0.81) ％ with significantly (all P ＜ 0.01).Compared with the model group,p-ERK1/2 proteins of large-dose experimental group were up-regulated significantly (P ＜0.01).Conclusion The EOAS could inhibit the apoptosis of neurons after ischemia-reperfusion by activating ERK signaling pathway.

Objective: To establish a survival prediction model based on the independent prognostic factors of long-term prognosis after laparoscopic liver resection(LLR) for intrahepatic cholangiocarcinoma(ICC). Methods: The clinical and pathological data of 351 consecutive patients with ICC who received radical LLR in 13 Chinese medical centers from August 2010 to May 2021 were collected retrospectively. There were 190 males and 161 females,aged(M(IQR)) 61(14)years(range:23 to 93 years). The total cohort was randomly divided into a training dataset(264 cases) and a validation dataset(87 cases). The patients were followed up by outpatient service or telephone,and the deadline for follow-up was October 2021. Based on the training dataset,the multivariate Cox proportional hazards regression model was used to screen the independent influencing factors of long-term prognosis to construct a Nomogram model. The Nomogram model's discrimination,calibration,and clinical benefit were evaluated through internal and external validation,and an assessment of the overall value of two groups was made through the use of a receiver operating characteristic(ROC) curve. Results: There was no significant difference in clinical and pathological characteristics and long-term survival results between the training and validation datasets(all P>0.05). The multivariate Cox analysis showed that CA19-9,CA125,conversion to laparotomy during laparoscopic surgery,and lymph node metastasis were independent prognostic factors for ICC patients after LLR(all P<0.05). The survival Nomogram was established based on the independent prognostic factors obtained from the above screening. The ROC curve showed that the area under the curve of 1, 3 and 5-year overall survival rates of patients in the training dataset were 0.794(95%CI:0.721 to 0.867),0.728(95%CI:0.618 to 0.839) and 0.799(95%CI:0.670 to 0.928),and those in the validation dataset were 0.787(95%CI:0.660 to 0.915),0.831(95%CI:0.678 to 0.983) and 0.810(95%CI:0.639 to 0.982). Internal and external validation proved that the model exhibited a certain discrimination,calibration,and clinical applicability. Conclusion: The survival Nomogram model based on the independent influencing factors of long-term prognosis after LLR for ICC(including CA19-9,CA125,conversion to laparotomy during laparoscopic surgery,and lymph node metastasis) exhibites a certain differentiation,calibration,and clinical practicability.
Bile Duct Neoplasms/surgery* ; Bile Ducts, Intrahepatic/pathology* ; CA-19-9 Antigen ; Cholangiocarcinoma/diagnosis* ; Female ; Humans ; Laparoscopy ; Lymphatic Metastasis ; Male ; Nomograms ; Prognosis ; Retrospective Studies

Objective: To analyze the efficacy of sinonasal adenoid cystic carcinoma (ACC) with perineural invasion (PNI), and explore the prognostic value of PNI on sinonasal adenoid cystic carcinoma. Methods: The clinical data of 105 patients with sinonasal ACC admitted to Cancer Hospital, Chinese Academy of Medical Sciences from January 2000 to December 2016 were retrospectively reviewed. All patients were restaged according to American Joint Committee on Cancer 8th edition. Follow-up visits were conducted to obtain information of treatment failure and survival outcome. The Log rank test was used for univariate analysis of prognostic factors, and Cox regression model was used for multivariate prognostic analysis. Results: The maxillary sinus (n=59) was the most common primary site, followed by the nasal cavity (n=38). There were 93 patients with stage Ⅲ-Ⅳ. The treatment modalities included surgery alone (n=14), radiotherapy alone (n=13), preoperative radiotherapy plus surgery (n=10), and surgery plus postoperative radiotherapy (n=68). The median follow-up time was 91.8 months, the 5-year local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 72.6%, 73.0%, 52.9% and 78.0%, respectively. There were 33 patients (31.4%) with PNI-positive. The 5-year DMFS, PFS, and OS rates of PNI-positive group were 53.7%, 29.4% and 56.5%, respectively, which were significantly inferior to those of PNI-negative group (80.8%, 63.0% and 86.8%, respectively, P<0.05), while there was no significant difference in the 5-year LC rate between both groups (64.5% vs 76.5%, P=0.273). The multivariate Cox regression analysis showed PNI was one of the poor prognostic factors of DMFS (HR=3.514, 95%CI: 1.557-7.932), PFS (HR=2.562, 95%CI: 1.349-4.866) and OS (HR=2.605, 95%CI: 1.169-5.806). Among patients with PNI-positive, the 5-year LC, PFS and OS rates of patients received surgery combined with radiotherapy were 84.9%, 41.3% and 72.7%, respectively, which were significantly higher than 23.3%, 10.0% and 26.7% of patients receiving surgery or radiotherapy alone (P<0.05). Conclusion: The presence of PNI increases the risk of distant metastasis in patients with sinonasal ACC. Compared with patients with PNI-negative, the prognosis of patients with PNI-positive is relatively poor, and surgery combined with radiotherapy for PNI-positive sinonasal ACC results in good clinical outcomes.
Carcinoma, Adenoid Cystic/pathology* ; Humans ; Paranasal Sinus Neoplasms/therapy* ; Prognosis ; Proportional Hazards Models ; Retrospective Studies

Objective: To evaluate the long-term outcomes, failure patterns and prognostic factors of definitive radiotherapy in patients with cervical esophageal carcinoma (CEC). Methods: We retrospectively reviewed the clinical data of 148 CEC patients who treated with definitive radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2001 to December 2017. The median radiation dose was 66 Gy (59.4-70 Gy) and 33.1% of patients received concurrent chemotherapy. The Kaplan-Meier method was used to calculate survival rates. The log rank test was used for survival comparison and univariate prognostic analysis. The Cox model was used for multivariate prognostic analysis. Results: The median follow-up time was 102.6 months. The median survival time, 2- and 5-year overall survival (OS) were 22.7 months, 49.9% and 28.3%. The median, 2- and 5-year progression-free survival were 12.6 months, 35.8% and 25.8%. The 2- and 5-year locoregional recurrence-free survival were 59.1% and 50.8%. The 2- and 5-year distant metastases-free survival were 74.6% and 65.9%. Multivariate analysis showed that EQD(2)>66 Gy was the only independent prognostic indicator for OS (P=0.040). The median survival time and 5-year OS rate significantly improved in patients who received EQD(2)>66 Gy than those who received≤66 Gy (31.2 months vs. 19.2 months, 40.1% vs. 19.1%, P=0.027). A total of 87 patients (58.8%) developed tumor progression. There were 50 (33.8%), 23 (15.5%) and 39 (26.4%) patients developed local, regional recurrence and distant metastases, respectively. Eleven patients (7.4%) underwent salvage surgery, and the laryngeal preservation rate for entire group was 93.9%. Conclusions: Definitive radiotherapy is an effective treatment for cervical esophageal carcinoma with the advantage of larynx preservation. Local recurrence is the major failure pattern. EQD(2)>66 Gy is associated with the improved overall survival.
Humans ; Retrospective Studies ; Esophageal Neoplasms/pathology* ; Carcinoma/drug therapy* ; Prognosis ; Treatment Outcome ; Chemoradiotherapy/methods* ; Radiotherapy Dosage