A Phase I Dose Escalation Study of the Safety,Tolerability, and Pharmacokinetics of Ipilimumab in Chinese Patients with Select Advanced Solid Tumors

Lessons Learned

• The overall safety profiles of ipilimumab 3 mg/kg and 10 mg/kg administered every 3 weeks, were consistent between Chinese patients with solid tumors in the current study and patients from previous U.S. ipilimumab monotherapy studies. No new safety signals were identified.
• The mean systemic exposures to ipilimumab (assessed by first dose area under the curve during the dosing interval and maximum serum concentration) were numerically lower in the Chinese patient population than in U.S. patients for both 3 mg/kg and 10 mg/kg doses; however, the range of serum concentrations in the Chinese and U.S. populations overlapped (3 mg/kg and 10 mg/kg), suggesting that ipilimumab pharmacokinetics was ethnically insensitive in this study.

BackgroundThis phase I, open‐label study assessed ipilimumab safety, tolerability, pharmacokinetics (PK), immunogenicity, and antitumor activity in Chinese patients with unresectable, metastatic, recurrent malignant melanoma (MM) or nasopharyngeal carcinoma (NPC).MethodsOf 39 patients enrolled, 25 received ipilimumab (11 patients received 3 mg/kg, and 14 patients received 10 mg/kg). Reasons for not receiving treatment were withdrawal of consent (3 patients), no longer meeting the criteria (10 patients), and one recorded as “other.” During the induction phase, patients received ipilimumab (3 mg/kg, i.v.), on day 1 of a 3‐week cycle, to a maximum of four doses or progressive disease (PD). During the maintenance phase at week 24, patients received ipilimumab (3 mg/kg, i.v.) on day 1 of a 12‐week cycle, to a maximum of 3 years or PD. Considering the co‐primary safety and PK endpoints, the successive dosing required nine patients with two or fewer dose‐limiting toxicities during the 42‐day observation period to proceed with a new cohort of nine patients at 10 mg/kg.ResultsIpilimumab safety and PK profiles were similar in Chinese and predominantly White populations. Ipilimumab was well tolerated. Most adverse events (AEs) were grades 1–2 and experienced by 11 patients treated with 3 mg/kg and 14 patients treated with 10 mg/kg. There were no new safety concerns. Incidence of anti‐ipilimumab antibodies was low (1 of 10 in the 3 mg/kg patients and 2 of 13 in the 10 mg/kg patients) and without safety implications. In the 3 mg/kg group, 8 of 11 patients had PD. In the 10 mg/kg group (all NPC, 0 MM patients), 11 of 14 patients had PD. Three patients had stable disease (one at 3 mg/kg and two at 10 mg/kg).ConclusionIpilimumab was well tolerated in Chinese patients, showing similar safety and PK to previous studies in predominantly White populations.     

Characterization of two pigeon paramyxovirus type 1 isolates in China

For over three decades, there has been a continuing panzootic caused by a virulent variant avian paramyxovirus type 1 strain, the so-called pigeon paramyxovirus type 1. It is found primarily in racing pigeons, but it has also spread to wild birds and poultry. In this study, two pigeon paramyxovirus type 1 strains, SD12 and BJ13, obtained from diseased pigeons in China, were characterized. Phylogenetic analysis based on complete sequences allowed characterization of both strains as genotype VI, class II. Further phylogenetic analysis of a 374-nucleotide section of the fusion gene showed that SD12 fell into lineage VIbii-d and BJ13 into VIbii-f. The deduced amino acid sequence of the cleavage site of the fusion protein confirmed that both isolates contained the virulent motif ¹¹²K/RRQKR↓F¹¹⁷ at the cleavage site. Nevertheless, the values of intracerebral pathogenicity indices showed the SD12 isolate to be a velogenic strain and BJ13 isolate to be a mesogenic strain. The SD12 isolate was further investigated via clinical observation, RNA detection, histopathology and viral serology in experimentally infected 3-week-old chickens. It showed a mild pathological phenotype in chickens, with viral replication restricted to a few tissues. The molecular mechanism for the SD12 isolate to have a virulent motif but low levels of virulence for chickens requires further study.     

农村青少年不同时期家庭逆境与精神病理症状的关联

目的探讨家庭逆境致精神病理症状结局的累积性与关键期效应,为预防与干预逆境伤害提供依据。方法2017年12月,采用方便抽样的方法选取安徽省阜阳地区2所农村学校的710名青少年。采用《童年期不良经历问卷》评估家庭逆境,《MacArthur健康与行为问卷》评价内化症状和外化症状。采用多元线性回归分析家庭逆境发生时间与数量和精神病理症状的关联。结果持续家庭逆境组与内化症状、外化症状增加均有相关性[β值(95%CI)分别为0.35(0.15~0.54),0.16(0.01~0.32)]。家庭逆境数量为2和≥3与内化症状[β值(95%CI)分别为0.20(0.04~0.36),0.42(0.24~0.60)]、外化症状[β值(95%CI)分别为0.14(0.01~0.26),0.23(0.09~0.37)]增加有关。在仅童年期家庭逆境中,家庭逆境数量为2和≥3的内化症状[β值(95%CI)分别为0.23(0.06~0.41),0.34(0.11~0.58)]、外化症状[β值(95%CI)分别为0.17(0.02~0.31),0.21(0.02~0.39)]的风险增高。在持续家庭逆境组中,逆境数量≥3与内化症状、外化症状相关[(β值(95%CI)分别为0.56(0.31~0.82),0.24(0.02~0.45)]。仅青春期家庭逆境与精神病理症状无关。结论家庭逆境的多次发生可增加精神病理症状风险,童年期可能是家庭逆境致精神病理症状的关键期。     

Modified superficial parotidectomy: preserving both the great auricular nerve and the parotid gland fascia.

OBJECTIVE: To reduce the incidence of sensory deficits and Frey's syndrome by modifying the traditional superficial parotidectomy. STUDY DESIGN: After raising the skin flap, the parotid gland fascia (PGF) was elevated to form a posterior pedicle fascial flap and then was replaced after the gland removal. The great auricular nerve (GAN) that runs within the PGF was not separated, so both the GAN and the PGF were preserved. Before this modification, the GAN and PGF were examined anatomically. The complication rates in the modified and control groups were compared. RESULTS: 1) The GAN, which runs within the thick and pycnotic PGF, trifurcates into postauricular, preauricular and lobule branches. The modification could be carried out practically based on the anatomy study. 2) Long-term sensory deficit was encountered in 13.3% of the control group, but 0% in the modified one. Frey's syndrome was suffered by 66.7% and 16.7% cases in the control and modified group respectively. The incidence of other complications was not significantly different. CONCLUSION: Our modification is practical. It decreases the complications significantly. EBM rating: B-3b.     

Structural shielding design for a gamma ray stereotactic body radiotherapy system.

An OUR-QGD gamma ray stereotactic body radiotherapy system (body knife), made in China, is described. According to its structure and the principle of gamma radiation revolved on a focus, the energy distribution of scattered radiation in its treatment room is calculated. The structural shielding of the wall, roof, and door for a certain treatment room is calculated according to the local radiation protection law.     

Anatomic bases of tongue flaps

Summary The morphological structure of the lingual a. was studied in 50 dissected and 14 vascular cast specimens. The course of this artery is divided into 4 segments: the original segment, the segment within hyoglossus, the ascending and the horizontal segments of the deep lingual a. The root of the tongue is supplied by 2 to 3 root branches of the lingual a., the ascending palatine a. and the tonsillar a. The body of the tongue is nourished on average by 25 arterial branches from the deep lingual a. The ventral surface of the tongue, as well as the sublingual gland and the floor of the mouth, is supplied by the sublingual a. The termination of the lingual a. anastomoses with the submental branch of the facial a. to form the lingual frenal a. Except for a submucous arterial network on the dorsum of the tongue, all blood vessels are separated completely by the lingual septum, through which arterial anastomoses (2.0 mm in diameter) can be found occasionally.This work was supported by the National Natural Science Fund     

Comparative study of long-term effects of surgical excision and excision combined with radiotherapy or chemotherapy in breast cancer: an analysis of 192 cases

Clinical data of 192 patients with breast cancer with a primary lesion of 2-5 cm (stage II according to the criteria recommended by the UICC) and with histopathologically confirmed positive axillary lymph nodes were analyzed. The patients were divided into three groups: 1) surgical excision alone; 2) surgery plus irradiation; and 3) surgery plus chemotherapy. It was shown that the 5-year survival rates for these groups were 40.5%, 61.0%, and 62.0%, respectively (P less than .05).