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.

Avian influenza virus (AIV) is a kind of zoonotic virus which can cause acute respiratory infectious diseases. Since the report of the world's first human infection case of avian influenza A (H7N9) virus in China in 2013, close attention has been paid to the virus. AIV spreads widely around the world, and human infection with different types of AIV continues to occur, causing huge economic losses. At present, there are no specific treatment and drugs against the disease, and vaccination is considered as the most promising and effective method to control the human infection with AIV. So far, there are many kinds of veterinary and human vaccines for H7N9 AIV, among which four types of human H7N9 AIV vaccines have entered the clinical trial stage, including virus-like particles vaccine, attenuated live vaccine, inactivated vaccine and DNA vaccine, which have shown good safety and immunogenicity. However, the true efficacies of the AIV vaccines remain unknown because no human vaccines are currently available in the market. In addition, although the existing influenza vaccine has good safety and immunogenicity in the human population, there is no cross-antibody response to H7N9 AIV. This paper summarizes the research progress of AIV etiology and epidemiology, the occupational exposure population investigation, the infection prevention and control strategies, and H7N9 AIV vaccine and H7N9 AIV anthropogenic monoclonal antibody, and discuss the remained problems, challenges and future trends in the research of AVI to improve the understanding of the disease and the prevention and control of global spread of AIV.

Objective:To establish a rapid method for detecting the activity of 2019-nCoV2.Methods:The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) detection system was screened after propidium monoazide (PMA) treatment and exposure to heat-inactivated 2019-nCoV samples, and the PMA pretreatment conditions were optimized to establish the 2019-nCoV PMA-RT-qPCR detection method . The established method was used to detect virus inactivated by different temperatures and chlorine-containing disinfectant, to evaluate its effect in detecting virus activity.Results:For the PMA-RT-qPCR assay, 200 μmol/L of PMA, 10 min of incubation time, 15 min of exposure time, and the CDC ORF1ab detection system were selected; there was no significant difference in the result of PMA-RT-qPCR and direct RT-qPCR for the active virus; the Ct values of PMA-RT-qPCR for virus inactivated by 95 ℃ and chlorine-containing disinfectant were higher than that of control groups at different dilutions; only partial dilutions of 70 ℃ and 56 ℃ heat-inactivated virus had higher Ct values than control groups. Conclusions:The established PMA-RT-qPCR for 2019-nCoV activity detection method has a good detection effect on the virus inactivated by 95 ℃ heat and chlorine disinfectant, and provides an auxiliary means for judging the infectivity of the virus in the sample.

Objective:s To evaluate the impacts of prior surgical scores(PSS) on the clinical efficacy and perioperative safety of cytoreductive surgery(CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC) for pseudomyxoma peritonei(PMP).Methods:From the comprehensive PMP database, we collect the cases treated for the first time by CRS+ HIPEC, to form this study cohort. The clinicopathological features, PSS, CRS+ HIPEC details, overall survival(OS), and serious adverse events(SAEs) are systematically analyzed, to study the correlations between PSS and OS or SAEs.Results:335 PMP cases received standardized CRS+ HIPEC in this study. The median OS is 58.2 months for PSS-0 patients, 63.7 months for PSS-1, and 55.4 months for PSS-2/3, with no statistically significant differences in OS among the different PSS groups(χ 2=0.499, P=0.779). Subgroup analysis by pathologic types also found no statistically significant differences among the different PSS groups. Moreover, no significantly statistical differences are observed in overall SAEs(χ 2=0.625, P=0.722), CRS-related SAEs(χ 2=0.267, P=0.901), and non-CRS-related SAEs(χ 2=0.677, P=0.715), among the different PSS groups. Conclusions:PSS does not pose significant impacts on the efficacy and safety of CRS+ HIPEC for PMP patients at experienced treatment center.

Objective:To evaluate and share the novel method for recruiting participants in clinical trials of vaccines in emergency situations.Methods:To publish recruitment notice in local areas of Wuhan through websites and medium, and guide interested persons to log in to the“Clinical Trials of SARS-CoV-2 Vaccine Reservation and Health Declaration System”to appoint and register their health information. The "Health Declaration System" provides each volunteer evaluation and risk levels to preliminarily exclude those who do not meet the inclusion criteria. Researchers review the qualified volunteers by telephone, organize them to go to the vaccination site, and finally conduct a strict medical screening to determine the final subjects.Results:A total of 4 819 people and 5 132 people registered in the Phase Ⅰ and Phase Ⅱ recruitment system respectively, with men 2 912 (60.43%) and 2 887 (56.25%) more than women 1 907 (39.57%) and 2 245 (43.75%), mostly in the 20-39 age group, with 3 211 (66.63%) and 3 966 (77.28%). All 13 districts in Wuhan have interested residents to participate clinical research.The initial qualified rate of the Phase Ⅱ recruitment system was higher than that of Phase Ⅰ, with men 2 047 (70.28%) and 2 135(73.95%), higher than women 1 083 (56.80%) and 1 472 (65.57%); 440 and 689 people were reviewed by telephone in Phase Ⅰ and Phase Ⅱ respectively, and the number of verified volunteers was about 440 (35.00%) and 689 (67.20%); Of the 201 603 people who arrived at the vaccination site, 12 and 26 of them were positive for the SARS-CoV-2 antibody with an antibody positive rate of 6.00% and 4.31% respectively.Conclusion:The novel method for recruiting subjects in this clinical study is efficient and reliable, and the recruitment situation of Phase Ⅰ had set a good example for Phase Ⅱ but the medium-and long-term compliance of subjects and the separation of willingness and behaviors still need to be further studied.

Objective:To evaluate and share the novel method for recruiting participants in clinical trials of vaccines in emergency situations.Methods:To publish recruitment notice in local areas of Wuhan through websites and medium, and guide interested persons to log in to the“Clinical Trials of SARS-CoV-2 Vaccine Reservation and Health Declaration System”to appoint and register their health information. The "Health Declaration System" provides each volunteer evaluation and risk levels to preliminarily exclude those who do not meet the inclusion criteria. Researchers review the qualified volunteers by telephone, organize them to go to the vaccination site, and finally conduct a strict medical screening to determine the final subjects.Results:A total of 4 819 people and 5 132 people registered in the Phase Ⅰ and Phase Ⅱ recruitment system respectively, with men 2 912 (60.43%) and 2 887 (56.25%) more than women 1 907 (39.57%) and 2 245 (43.75%), mostly in the 20-39 age group, with 3 211 (66.63%) and 3 966 (77.28%). All 13 districts in Wuhan have interested residents to participate clinical research.The initial qualified rate of the Phase Ⅱ recruitment system was higher than that of Phase Ⅰ, with men 2 047 (70.28%) and 2 135(73.95%), higher than women 1 083 (56.80%) and 1 472 (65.57%); 440 and 689 people were reviewed by telephone in Phase Ⅰ and Phase Ⅱ respectively, and the number of verified volunteers was about 440 (35.00%) and 689 (67.20%); Of the 201 603 people who arrived at the vaccination site, 12 and 26 of them were positive for the SARS-CoV-2 antibody with an antibody positive rate of 6.00% and 4.31% respectively.Conclusion:The novel method for recruiting subjects in this clinical study is efficient and reliable, and the recruitment situation of Phase Ⅰ had set a good example for Phase Ⅱ but the medium-and long-term compliance of subjects and the separation of willingness and behaviors still need to be further studied.

Objective To investigate the expressions of CD28 and CD117 in patients with newly diagnosed multiple myeloma (MM) and their clinical significances. Methods The clinical data of 115 newly diagnosed MM patients in the First Affiliated Hospital of Zhengzhou University from May 2015 to December 2017 were retrospectively analyzed. The expressions of CD28 and CD117 were detected by using multiparameter flow cytometry. The relationship between the expressions of CD28 and CD117 and MM staging and clinical parameters was analyzed. The staging was performed according to the International Staging System (ISS). Results Among these 115 patients, there were 15 patients with CD117 positive and 30 patients with CD28 positive. Erythrocyte sedimentation rate (r ＝ -0.481, P ＝ 0.039), Cˉreactive protein level (r ＝ -0.314, P＝0.015), the proportion of plasma cells detected by bone marrow cytology (r＝-0.027, P＝0.001) were negatively correlated with CD117 positive expressions. CD28 positive expression was positively correlated with lactate dehydrogenase level (r ＝ 0.249, P ＝ 0.033) and ISS stage (r ＝ 0.319, P ＝ 0.017), while it was negatively correlated with hemoglobin level (r ＝ -0.372, P ＝ 0.026). CD28 positive was associated with light chain type, and nonˉsecretory type mostly occurred (P ＝ 0.016). The incidence of osteolytic lesions in CD28 positive group and CD117 positive group was high, but there was no statistical difference between CD28 positive group, CD117 positive group and CD28 negative group, CD117 negative group (P ＝ 0.052, P＝0.479). Conclusions The positive expression of CD117 in the early stage of MM patients is higher than that in the advanced stage, and the expression of CD28 positive in the advanced stage of MM patients is higher than that in the early stage. CD28 and CD117 can be used as indicators of prognosis stratification in the patients with newly diagnosed MM.

Objective: To explore the relationship between liver controlled attenuation parameters (CAP) and body fat mass and its distribution. Methods: From May to December 2018, 978 adult patients visited at the fatty liver center of the Third People's Hospital of Changzhou were treated. The patient's liver controlled attenuation parameters were measured by transient elastography and the body fat mass and its distribution were measured by bioelectrical impedance technology. Pearson’s correlation coefficient was adopted to describe the correlation between liver CAP value and body mass index (BMI), body fat mass index (BFMI), trunk fat mass index (TFMI), limbs fat mass index (LFMI) and visceral fat area (VFA). Receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to evaluate BMI, BFMI, TFMI, LFMI and VFA to differentiate the cut-off points and efficacy of CAP for diagnosing grading of fatty liver changes in S0-1 and S2-3. Results: In 653 cases of male, S0 ~ S3 accounted for 4.90%, 3.37%, 22.36% and 69.37%, respectively, and in 325 cases of females, S0 ~ S3 accounted for 7.38%, 6.46%, 13.23% and 72.92%, respectively. Female patients had more visceral, trunk and limbs fat than male (P < 0.01). Body mass, body fat mass, body fat percentage, BMI, BFMI, TFMI, LFMI, and VFA were increased in male and female patients with increasing liver fat grade (P < 0.01). CAP values ​​of male and female patients were positively correlated with BMI, BFMI, TFMI, LFMI and VFA. Percentage of body fat mass increased with increasing liver fat grade (male: F = 13.42, P < 0.001; female: F = 3.22, P = 0.023); while limb fat mass percentage did not increase with liver fat grade (Male: F = 1.13, P = 0.34; female: F = 1.05, P = 0.37). Hepatic steatosis grading (S0 ~ 1 or S2 ~ 3) diagnosed with CAP were distinguished through BMI, BFMI, TFMI, LFMI and VFA. AUC was 0.80 ~ 0.82 in males (P < 0.01), and 0.75 ~ 0.78 in females (P < 0.01). Conclusion The liver CAP value is positively correlated with the body's limbs, trunk and visceral fat, and has a strong correlation with trunk and visceral fat. BMI, BFMI, TFMI, LFMI and VFA up to some extent can identify the CAP diagnosis of grading of fatty liver changes in S0-1 and S2-3.

Objective To investigate the correlation between phlegm and humid type and blood lipid and blood glucose, and the countermeasures.Methods From August 2014 to September 2016, 162 patients with physical identification were selected as the subjects.According to the screening criteria, the patients were divided into phlegm constitution group and flat body constitution group.Fasting blood glucose(FPG), total cholesterol(TC), triglyceride(TG), high density lipoprotein cholesterol(HDL-C) and low density lipoprotein(HDL-C) were measured for all patients after fasting for 10-12 hours Cholesterol(LDL-C), and for analysis and comparison.Results The score of spleen deficiency was lower than that of phlegm constitution group, the difference was statistically significant(P<0.05).The level of blood glucose and blood lipid in the group was significantly better than that in phlegm constitution group(P<0.05).Conclusion The blood lipid, blood glucose level and spleen and stomach function of phlegm constitution are relatively poor, and the phlegm constitution can be improved by developing good living habits and combining spleen and dampness medicine.