Development and validation of reverse phase-high performance liquid chromatography for determination of residual N-hydroxy succinimide content in semaglutide / 中国生物制品学杂志

@#Abstract： Objective To develop and validate a reverse phase⁃high performance liquid chromatography（RP⁃HPLC） method for determination of residual N⁃hydroxy succinimide（NHS）content in semaglutide. Methods A RP⁃HPLC method was developed based on the screening of chromatographic column and optimization of mobile phase（phosphate concentration and the ratio of acetonitrile），validated for specificity，suitability，accuracy，reproducibility and stability， and determined for linear range，limit of quantitation（LOQ）and limit of detection（LOD）. The NHS contents in three batches of semaglutide were determined by the developed method. Results The optimal condition for RP⁃HPLC was as follows：CAPCELL PAK ADME column（4. 6 mm × 150 mm，3 μm）was adopted，serving 0. 05 mol／L potassium dihy⁃ drogen phosphate solution⁃acetonitrile（98∶2）as mobile phase A，and 70% acetonitrile as mobile phase B with gradient elution（0 min，0% B；10 min，0% B；19 min，90% B；19. 1 min，0% B；25 min，0% B）at a flow rate of 0. 8 mL／min. The detection wave length was set at 260 nm，while the column temperature was 30 ℃. The developed method showed good specificity and systemic suitability，of which the linear range was 0. 2 ~ 3. 0 μg／mL（R2 = 1. 000 0），while the LOD and LOQ were 4. 8 and 9. 6 ng respectively. The RSD of recovery rates of NHS samples at three concentrations was 0. 58%， indicating a high accuracy. The RSD of NHS contents in six test samples was 0. 16%，indicating a high reproducibility. The RSD of peak areas of NHS after storage at room temperature for 0，4，8，12，16，20 and 24 h was 0. 34%，indicating a high stability. No NHS was detected in three batches of semaglutide by the developed method. Conclusion The developed RP⁃HPLC method is simple and sensitive，which may be used for the determination of NHS content in semaglutide.

Possible Risk Factors for Severe Complications Occurring after Primary Total Knee Arthroplasty / 中国医学科学杂志(英文版)

Objective Total knee arthroplasty is one of the most common orthopedic surgeries. Readmission due to severe complications after total knee arthroplasty is a grave concern to surgeons. In this study, we evaluated the risk factors for severe complications after primary total knee arthroplasty. Methods We retrospectively collected clinical data of 2,974 patients who underwent primary total knee arthroplasty from July 2013 to June 2019 in our hospital. Postoperative complication ≥ grade Ⅲ was defined as severe complication according to Clavien-Dindo classification system. Binary logistic regression was used to identify the predictive risk factors for severe complications. Results The complication rate after primary total knee arthroplasty was 6.8% and severe complication rate was 2.5%. Male (OR = 2.178, 95%CI: 1.324-3.585, P= 0.002), individuals above 75 years old (OR = 1.936, 95%CI: 1.155-3.244, P= 0.012), arrhythmia (OR = 2.913, 95%CI: 1.350-6.285, P= 0.006) and cerebrovascular disease (OR = 2.804, 95%CI: 1.432-5.489, P= 0.003) were predictive risk factors for severe complications after primary total knee arthroplasty. Conclusion Advanced age, male, arrhythmia, and cerebrovascular disease might be patients-related risk factors for postoperative severe complications after primary total knee arthroplasty. Special attention should be paid to patients with risk factors.

Therapeutic efficacy of three-dimensional conformal radiation therapy for patients with locally advanced non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To compare the treatment results of three-dimensional conformal radiotherapy (3D-CRT) and conventional radiotherapy (2D) for patients with locally advanced non-small-cell lung cancer (NSCLC).</p><p><b>METHODS</b>Five hundred and twenty seven patients with stage III NSCLC treated between Jan 2000 and Dec 2006 were included in this study. Among them, 253 cases were treated with 3D-CRT, and 274 with conventional radiotherapy. In the 3D group, 159 (62.8%) patients received chemoradiotherapy, 77 with total radiotherapy dose of > 60 Gy, 49 with 50 - 60 Gy. In the 2D group, 127 (46.4%) patients received chemoradiotherapy, 48 with total radiotherapy dose of > 60 Gy, 75 with 50 - 60 Gy.</p><p><b>RESULTS</b>The 1-, 3-, 5-year overall survival rates (OS) and median survival time for patients treated with 3D-CRT were 73.3%, 26.1%, 14.4% and 20.1 months, respectively, and that of patients treated with 2D radiotherapy were 61.0%, 13.8%, 8.0% and 15.6 months, respectively (P = 0.002). The 1-, 3-, 5-year cause-specific survival rates (CSS) were 79.0%, 33.3%, and 20.8% for the 3D group and 65.1%, 16.7%, 11.2%, respectively, for the 2D group (P = 0.000). The 1-, 3-, and 5-year locoregional control rates were 71.6%, 34.3% and 31.0% for patients treated with 3D radiotherapy and 57.3%, 22.1% and 19.2%, respectively, for patients treated with 2D treatment (P = 0.002). The results of multivariate analysis showed that 3D-CRT, KPS, clinical tumor response and pretreatment hemoglobin level were independently associated with increased OS and CSS. No statistically significant differences were found between the radiation complications in the two groups.</p><p><b>CONCLUSIONS</b>The results of our study demonstrate that 3D-conformal radiotherapy improves the survival rate in patients with stage III NSCLC compared with that of 2D radiation therapy.</p>

Clinical analysis of 126 patients with primary small cell carcinoma of the esophagus / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the prognostic factors and the principles of treatment of primary esophageal small cell carcinoma (SCEC) retrospectively.</p><p><b>METHODS</b>The data of 126 patients with histologically confirmed SCEC treated in our department between May 1985 and June 2005 were retrospectively analyzed. 85 patients were in limited disease stage (LD) and 41 patients as extensive disease stage (ED) according to the Veterans Administration Lung Study Group staging system. Among the 84 patients treated with esophagectomy, 8 cases were in stage I, 16 in stage IIa, 10 in stage IIb, 40 in stage III, 4 in stage IVa and 6 in stage IVb, according to the TNM system (6(th) edition, AJCC). Cox's hazard regression model was used to identify the prognostic factors, and Chi-square test to detect the difference of frequencies among different groups. Kaplan-Meier and log-rank methods were used to estimate and compare the survival rates.</p><p><b>RESULTS</b>The median follow-up duration of this series was 13 months. One hundred and eight patients died of the disease during the follow-up, 10 were still alive and 8 were lost to follow-up. The 1-, 3-, and 5-year overall survival rates (OS) were 52.2%, 15.9%, and 12.2%, respectively, with a median survival time (MST) of 12.5 months. The 1-, 2-, and 3-year OS were 62.1%, 30.8%, and 22.4% with a MST of 14.0 months for LD, and 29.3%, 13.6% and 2.7% with a MST of 7.0 months for ED, respectively. There was a statistically significant difference in OS between LD and ED (P = 0.0001). The MST of the patients treated with chemotherapy was 14.5 months, significantly longer than the 5.2 months of the patients without (P = 0.0001). Multivariate analysis showed that stage (HR 1.91, 95% CI 1.26 approximately 2.91, P = 0.002), length of the primary lesion (HR 1.75, 95% CI 1.17 approximately 2.63, P = 0.007), and chemotherapy (HR 0.42, 95% CI 0.28 approximately 0.65, P = 0.000) were independent prognostic factors.</p><p><b>CONCLUSION</b>Esophageal small cell carcinoma is a systemic disease. The tumor stage (LD or ED), length of the primary lesion and chemotherapy are independent prognostic factors. Therefore, a systemic therapy based on chemotherapy should be recommended.</p>

Effect of different chemotherapy regimens for concurrent chemoradiotherapy on locally advanced non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To retrospectively analyze the effects of different chemotherapy regimens for concurrent chemoradiation on locally advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>The data from 106 patients diagnosed as locally advanced NSCLC (IIIa: 29, IIIb: 77), who received various chemotherapy regimens for concurrent chemoradiotherapy, were retrospectively analyzed. Paclitaxel-based chemotherapy regimen was administered in 55 patients, topotecan regimen in 21 patients, PE (cisplatin and etopside) regimen in 26 patients, and other regimens in the remaining 4 patients. The effect of different chemotherapy regimens on overall survival and toxicity was analyzed.</p><p><b>RESULTS</b>The median survival time was 18.6 months, and the overall 1- and 3-year survival rates were 72.2% and 27.5%, respectively. The median survival time of 102 patients treated with paclitaxel-containing, topotecan-containing or PE regimens was 16.3, 27.3 and 29.1 months, respectively. The overall survival times of topotecan and PE groups were superior to that of paclitaxol-based group, but not significantly different (P = 0.32). Both univariate and multivariate analysis showed that paclitaxol-based chemotherapy regimen was significantly associated with a poorer survival (P < 0.05). N stage was another significant prognostic factor determined by COX multivariate regression model. Compared with the other regimens (10.6%), paclitaxel-based regimen (27.3%) had more acute radiation pneumonitis (grade >or= 2, P = 0.03), but no significant differences were observed in blood toxicity and esophagitis.</p><p><b>CONCLUSION</b>There is a correlation between different chemotherapy regimens for concurrent chemoradiotherapy and the overall survival and acute radiation pneumonitis in patients with locally advanced NSCLC.</p>

Determination of gaseous organic compounds in Hyogo Prefecture, Japan.

The aim of this study was to analyze gaseous organic chemicals (GOCs) of high traffic (Nishinomiya City: 979,987 vehicles/day) and low traffic areas (Miki City: 29,338 vehicles/day) by gas chromatography-mass spectrometry (GC-MS) and to evaluate general environment exposure by PAHs in GOCs. After air sampling using an OMNIPORE membrane filter (< 0.45 microm) and Porapak-QS, sorbents were extracted with solvent (dichloromethane: acetone (4:1 v/v), and analysis was carried out by GC-MS. Oxidative derivatives of diethylbenzene, such as diacethylbenzene and ethylacetophenone, were detected in GOCs. PAHs and phthalates in GOCs were measured. Pyrene, benz[a]anthracene, benzo[a]pyrene and benzo[ghi]perylene level were significantly higher in high traffic areas. The geometric mean of pyrene was 0.76 ng/m3 for low traffic areas and 1.96 ng/m3 for high traffic areas; benz[a]anthracene was found at 0.72 ng/m3 and 1.80 ng/m3 in low and high traffic areas, respectively; benzo[a]pyrene was found at 0.87 ng/m3 and 3.60 ng/m3 in low and high traffic areas, respectively and benzo[ghi]perylene was found at 0.57 ng/m3 and 3.04 ng/m3 in low and high traffic areas, respectively. The bis(2-ethylhexyl) phthalate (DEHP) level was the highest in the detected GOCs. The geometric mean of the DEHP levels in high traffic and low traffic areas were 484.85 and 387.26 ng/m3, respectively. Adult and child DEHP exposure levels were 145.32 and 300.33 ng/kg/day, respectively, in high traffic areas. In low traffic areas, adult and child DEHP exposure levels were 116.18 and 240.10 ng/kg/day, respectively.

Postoperative three-dimensional conformal radiotherapy for resected non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the association between survival and postoperative three-dimensional conformal radiotherapy (3DCRT) in patients with resected non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Eighty-four patients were treated with surgery and postoperative 3DCRT for NSCLC. Sixty-five (77.4%) patients received lobectomy, and 19 (22.6%) received pneumonectomy. Fifty-four (64.3%) patients achieved R0 resection and 30 cases (35.8%) received R1/R2 resection. Fifty-two patients were of stage IIIA and 24 patients were of stage IIIB. Photon energy of 6 MV was used for all the patients. The median 3DCRT dose was 60 Gy (40 - 70 Gy) with a fraction size of 2 Gy. Thirty-seven patients received median 3 cycles of adjuvant chemotherapy. The median follow-up was 35.5 months for survivors.</p><p><b>RESULTS</b>The overall 3-year survival rate was 58.6%, and the 4-year overall survival rate was 43.9%. Of the 43 patients who had treatment failure, only 8 (9.9%) patients showed intrathoracic recurrence, but 38 (46.9%) patients had distant metastasis. The univariate analysis for all patients showed that sex, age, weight loss, tumor size, pathology and stage were not correlated with prognosis. R1/R2 resection was associated with a significantly worse survival. Toxicities were acceptable, with 9 (11.1%) patients appeared higher than NCI CTC grade 2 radiation pneumonitis.</p><p><b>CONCLUSION</b>In a population-based cohort, postoperative 3DCRT for NSCLC provides a good prognosis, and the radiation-related pneumonitis is acceptable.</p>

Three-dimensional conformal radiotherapy for locoregionally recurrent non-small cell lung cancer after initial radiotherapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the feasibility, therapeutic effects and normal tissue complications of three-dimensional conformal radiotherapy (3DCRT) for locoregionally recurrent non-small cell lung cancer after initial radiotherapy.</p><p><b>METHODS</b>Between August 1999 and August 2003, 27 such patients were treated with 3DCRT after initial radiotherapy. This series consisted of 25 men and 2 women with a median age of 64 years. Radiotherapy was delivered at 2 Gy per fraction, 5 fractions per week, to a median dose of 50 Gy. Treatment results and normal tissue complications were assessed with WHO and RTOG/EORTC criteria.</p><p><b>RESULTS</b>Based upon a median follow-up time of 20.6 months, 25 patients (92.6%) completed the planned 3DCRT treatment. Their clinical symptom relief rate was 79.1%, and the response rate was 59.3% with a complete remission rate of 14.8% (4/27), partial remission rate of 44.4% (12/27). The overall 1- and 2-year survival (OS) rates were 73.8% and 25.4% with a median survival time (MST) of 20 months. The 1- and 2-year local progression free survival (LPFS) rates were both 88.8%. Grade 2 and grade 3 acute radiation pneumonitis developed in 7.4% (2/27) and 11.1% (3/27). Grade 2 late radiation pneumonitis developed in 11.1% (3/27).</p><p><b>CONCLUSION</b>3DCRT is feasible and advisable for locoregionally recurrent non-small-cell lung cancer, giving a good immediate tumor response and acceptable normal tissue complications.</p>