[Application of seamless phase â ¡/â ¢ design in vaccine clinical trials].

The seamless phase Ⅱ/Ⅲ design integrates independent phase Ⅱ and phase Ⅲ clinical trials into a continuous, phased adaptive clinical trial design. Compared with traditional independent phase Ⅱ and phase Ⅲ clinical trials, the seamless design offers significant advantages in accelerating drug or vaccine development and improving clinical trial efficiency. Currently, the application of this design in anti-tumor drug research is becoming increasingly mature, and it is gradually expanding to clinical trials of vaccines, including the 9-valent human papillomavirus vaccine, sabin strain inactivated polio vaccine, and others. This paper aims to clarify the seamless phase Ⅱ/Ⅲ design concept and offer valuable insights into its implementation. It accomplishes this by presenting a clinical trial example featuring a phase Ⅱ/Ⅲ seamless design for a 9-valent human papillomavirus vaccine. The article delves into the specific considerations and potential challenges related to implementing the seamless design, aiming to provide valuable insights for optimizing vaccine clinical trials within our country.

[Kinetics of SARS-CoV-2-specific antibodies among inactivated COVID-19 vaccine recipients, SARS-CoV-2 natural infection cases, and breakthrough cases].

Between August and September, 2021, this study included 605 SARS-CoV-2 natural infection cases and 589 SARS-CoV-2 breakthrough cases from Nanjing and Yangzhou, as well as 690 inactivated COVID-19 vaccine recipients from Changzhou, China. In SARS-CoV-2 natural infection cases, the age range was 19-91 years (median age: 66 year), and the medians(Q1,Q3) of IgG titers were 0.19 (0.06-1.31), 3.70 (0.76-69.48), 15.31 (2.59-82.16), 4.41 (0.99-31.74), 2.31 (0.75-13.83), 2.28 (0.68-9.94) and 2.80 (1.00-9.53) at one to seven weeks after SARS-CoV-2 infection, respectively. In SARS-CoV-2 breakthrough cases, the age range was 18-76 years (median age: 45 year), and the medians(Q1,Q3)of IgG titers were 1.93 (0.34-26.67), 38.87 (7.90-121.0), 75.09 (11.85-123.70), 21.97 (5.20-95.58), 13.97 (3.47-46.82), 9.56 (2.48-33.38) and 4.38 (1.87-11.00) at one to seven weeks after SARS-CoV-2 infection, respectively. In inactivated COVID-19 vaccine recipients, the age range was 18-87 years (median age: 47 years), and the medians(Q1,Q3)of IgG titers were 16.22 (15.84-33.42), 5.35 (2.96-13.23), 3.30 (2.18-6.18), 3.14 (1.16-5.70), 2.77 (1.50-4.52), 2.72 (1.76-4.36), 2.01 (1.27-3.51) and 1.94 (1.35-3.09) at one to eight months after SARS-CoV-2 infection, respectively. The results suggested that IgG antibodies increased gradually within two weeks after SARS-CoV-2 infection, then declined gradually at three to seven weeks in SARS-CoV-2 natural infection cases. In SARS-CoV-2 breakthrough cases, IgG antibodies increased rapidly within two weeks, then declined gradually at three to seven weeks after SARS-CoV-2 infection. Additionally, IgG antibodies decreased rapidly within three months, then decreased gradually and remained at a low level within three months after immunization.

Pulmonary infarction presenting as aseptic cavitation.

A case of pulmonary infarction presenting as aseptic cavitation was reported. Basically, the patient suffered from rheumatic heart disease, mitral stenosis and insufficiency, and atrial fibrillation with predominant right heart enlargement. Hemoptysis, chest pain and dyspnea were present. Chest film simulated a thin wall lung abscess. The clinical picture suggested aseptic cavitation, which was confirmed by 99mTc-MAA lung scan.

Omental autotransplantation in treatment of thromboangiitis obliterans.

From 1981 to 1985, omental autotransplantation was performed for 28 patients with thromboangiitis obliterans on the left lower extremities in 16 patients, the right ones 11, and the right upper limb 1. The early results in all patients were satisfactory. In 19 patients followed up from 1 to 4 years, the results were encouraging, with the improvement of symptoms after operation. In 18 patients, digital ulcers healed within 2-4 weeks. Doppler and electrical impedance plethysmography examinations showed the blood circulation of affected extremities was markedly improved in the 18 patients except one who had the recurrence of digital ulcer 2 years later. In one of the 19 patients the disease recurred one month after the operation, and a lumbar sympathectomy was performed. The indications, the operative technique, and the mechanism of this operation are discussed.

[Sites of seizure discharges after intracerebroventricular injection of anisodamine and the antagonism by diazepam in rabbits].

Anisodamine is a tropine alkaloid isolated from Scopolia tangutica Maxim. To determine the original sites of anisodamine seizure discharge, permanent electrodes were implanted into different parts of the brain in rabbits and the electrical activities were continuously recorded by monopolar leads. Injection of anisodamine 1.5 mg/kg into the lateral ventricle of conscious rabbits always produced abnormal discharges. The spike discharges appeared first in the amygdala and consisted of rhythmic large surface-positive spikes. Multiple spikes then appeared in the hippocampus, caudate nucleus, midbrain reticular formation and frontal cortex. Diazepam 1.5-2.5 mg/kg did not inhibit the spike discharges from the amygdala, but did inhibit the discharges from other sites as well as clonic convulsions. When the dosage of diazepam was increased to 4.5 mg/kg, the spike discharges from the amygdala were also inhibited. The above findings indicate that the site of origin of anisodamine seizure discharges in rabbits is the amygdala. The seizure discharges then spread to the mesencephalic reticular formation, the hippocampus, the caudate nucleus and the cortex. Diazepam was shown to be an effective antagonist against central stimulation induced by anisodamine.