Inhibition of protein disulfide isomerase (PDI) has been attempted as a promising anti-cancer strategy. However, there is still no currently available PDI inhibitors approved for clinical use. Here, we isolated seven high yield alkaloids from Stephaniae tetrandrae Radix (STR), a medical herb frequently prescribed in anti-tumor condition, and identified two potent natural PDI inhibitors, dicentrine and dicentrinone. Among the seven alkaloids isolated, dicentrinone (1), dicentrine (2), tetrandrine (4), and fangchinoline (5) could significantly reduce cell viability in a dosage dependent manner detected by MTT assay in human hepatoma cells. To examine whether the candidate compounds are potent PDI inhibitors, we performed insulin turbidity assay and found dicentrine and dicentrinone, but not tetrandrine and fangchinoline, could effectively inhibit PDI activity, with IC50 of 56.70 μM and 43.95 μM respectively. Meanwhile, dicentrine and dicentrinone failed to further reduce the cell number index when co-treated with siRNA of PDI, suggesting the compounds behave as PDI inhibitors. Furthermore, dicentrinone and dicentrine have been successfully docked to the active pocket of PDI (PDB #3UEM) by molecular docking, suggesting the existence of physical interaction between compounds and PDI. Our results suggested that dicentrine and dicentrinone may be developed into safe PDI inhibitors.
Purpose The purpose of this study is to compare the open Latarjet procedure versus the all-arthroscopic autologous tricortical iliac crest bone grafting (AICBG) technique for recurrent anterior-inferior glenohumeral instability with glenoid bone loss. Methods All open Latarjet and AICBG procedures for recurrent anterior-inferior shoulder instability with glenoid bone loss performed at two institutions between September 2015 and April 2019 were retrospectively analyzed. Inclusion criteria were a traumatic etiology, a glenoid surface deficiency >13.5%, and a minimum follow-up (FU) of 18 months. Primary outcomes included the subjective shoulder value, the Western Ontario Shoulder Instability (WOSI), Rowe scores including subdomains, and the four subdomains of the Constant score (pain, activities of daily living, internal rotation, external rotation). Secondary outcomes were subjective shoulder instability, EQ-5D-3 L, pain level on the VAS, level of overall satisfaction, operative time, return-to-work rate, and return-to-sports rate. Results Forty-three patients were available for final analysis (Latarjet: n = 21; AICBG: n = 22) at an average FU of 34.9 months (range, 22–66 months). Both techniques provided good outcomes and improved stability. The Rowe score, Rowe-range of motion, and CS-internal rotation ( p = 0.008, p<0.001, p = 0.001) were slightly better in the AICBG group. Furthermore, the WOSI physical symptoms subdomain was significantly better ( p = 0.04) in the AICBG group, while its total score did not reach statistical significance ( p = 0.07). There was no statistically significant difference in the secondary outcomes besides operative time, which was significantly shorter in the Latarjet procedure group ( p = 0.04). Overall complication rate was similar in both groups (Latarjet: 9.5% ( n = 2), AICBG: 9.1% ( n = 2)). Conclusion Open Latarjet and AICBG procedures provide comparable clinical outcomes except for significantly better Rowe score, Rowe-range of motion, WOSI physical symptoms subdomain, and internal rotation capacity in the AICBG group. However, these results should be carefully interpreted in the context of known minimal clinically important differences of these scores.
Telemedicine technology was rapidly and widely adopted during the early phase of the coronavirus disease 2019 (COVID-19) response, and its efficacy in orthopedic surgery is still undetermined. The objective of this study was to determine the efficacy of new patient orthopedic surgery ambulatory encounters performed using telemedicine during the early phase of the COVID-19 crisis. Failure of the telemedicine encounter was assessed in this study by 2 separate criteria: (1) an unplanned visit to the emergency department (ED) within 6 weeks of the telemedicine encounter and (2) a planned subsequent in-person encounter for inability to formulate a complete diagnosis virtually. The authors retrospectively identified all new patient orthopedic surgery ambulatory encounters performed using telemedicine in the orthopedic surgery department of an academic tertiary care center during the first 6 weeks of the COVID-19 response, from March 16, 2020, to April 26, 2020. The study cohort included 298 new patients treated by 41 providers. The mean age of the 298 patients was 48 years, and 59% were women. Two hundred encounters were performed with video, and 98 were performed with telephone only. Three (1%) patients presented to the ED within 6 weeks of their new patient telemedicine encounter, and 8 (3%) patients presented for a planned in-person encounter. The authors concluded that new patient orthopedic surgery ambulatory encounters performed using telemedicine were able to effectively direct patients to a variety of treatments and dispositions, with a low rate of unplanned presentation to the ED or need for supplementary in-person assessment. [ Orthopedics . 2021;44(2):e211–e214.]
The SARS-CoV-2 (COVID-19) pandemic has had a global influence on health care. The authors examined the early effect of hospital- and state-mandated restrictions on an orthopedic surgery department and hypothesized that the volume of ambulatory clinic encounters, office and surgical procedures, and cases would dramatically decrease. A retrospective review was performed of all encounters in an orthopedic surgery department at a level I academic trauma center during a 4-week period, from March 16, 2020, to April 12, 2020. The results were compared with two control 4-week periods, February 17, 2020, to March 15, 2020, and March 16, 2019, to April 12, 2019. Weekly volume and work relative value units (RVUs) of clinic encounters, office and surgical procedures, and cases were assessed. The type of ambulatory visit also was recorded. Comparisons of mean weekly volume and RVUs between the study and control periods were performed with Student's t test. Surgical cases were categorized into fracture or dislocation, acute soft tissue or nerve injury, infection, oncology, and elective or nonurgent. After implementation of hospital- and state-mandated restrictions on elective health care, the volume of ambulatory orthopedic surgery clinic encounters decreased by 74% to 77%, the volume of clinic procedures decreased by 95%, and the volume of surgical cases decreased by 88%. The percentage of clinic visits performed via telemedicine increased from 0.3% to 81.2%. Elective surgical cases ceased, and the volume of nonelective surgical cases decreased by 51%. During the first 4 weeks after COVID-19–related restrictions were imposed, an immediate and dramatic effect was observed. Compared with the control periods, significant reductions were seen in the volume of ambulatory encounters, office-based procedures, and surgical cases. In addition, the volume of nonelective surgical cases decreased by 51%. [ Orthopedics . 2020;43(4):228–232.]
Objective
To investigate the significance of tumor markers CEA and CA19-9 in predicting the clinicopathologic characteristics and prognosis of primary duodenal carcinoma.
Methods
A retrospective analysis of 110 cases with primary duodenal carcinoma treated in our hospital from January 1999 to December 2016 was conducted. ROC analysis, univariate and multivariate analysis were performed to investigate the relationship between CEA, CA19-9 and the clinicopathologic characteristics of primary duodenal carcinoma. Kaplain-Meier method was used to analyze the relationship between CEA and CA19-9 and the prognosis of primary duodenal carcinoma.
Results
CEA level was of value for predicting the depth of infiltration, lymphatic involvement, metastasis and TNM stage. The receiver operating characteristic was 0.629, 0.672, 0.749, 0.692 respectively. Univariate analysis showed serum CA19-9 lever was related to the depth of infiltration and serum CEA lever were related to tumor differentiation, lymphatic invasion, metastasis and TNM stage. Logistic analysis showed that CEA value was only associated with metastasis (OR: 9.853, P<0.01). Patients with elevated serum CEA level had a significant worse prognosis than patients with normal serum CEA level(P<0.05).
Conclusion
Serum CEA level was closely associated with the clinicopathologic characteristics and prognosis of primary duodenal carcinoma.
Key words:
Duodenal neoplasms; Carcino embryonic antigen; Pathology, clinical; Prognosis