Objective:To evaluate the immunogenicity, safety, and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years.Methods:An open-label, multi-center trial was conducted in October 2021. The eligible healthy individuals, aged 18-84 years who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, were recruited from Shangyu district of Shaoxing and Kaihua county of Quzhou, Zhejiang province. All participants were divided into three groups based on the differences in prime-boost intervals: Group A (3-4 months), Group B (5-6 months) and Group C (7-9 months), with 320 persons per group. All participants received the recombinant COVID-19 vaccine (CHO cell). Blood samples were collected before the vaccination and after receiving the booster at 14 days, 30 days, and 180 days for analysis of GMTs, antibody positivity rates, and seroconversion rates. All adverse events were collected within one month and serious adverse events were collected within six months. The incidences of adverse reactions were analyzed after the booster.Results:The age of 960 participants was (52.3±11.5) years old, and 47.4% were males (455). The GMTs of Groups B and C were 65.26 (54.51-78.12) and 60.97 (50.61-73.45) at 14 days after the booster, both higher than Group A′s 44.79 (36.94-54.30) ( P value<0.05). The GMTs of Groups B and C were 23.95 (20.18-28.42) and 27.98 (23.45-33.39) at 30 days after the booster, both higher than Group A′s 15.71 (13.24-18.63) ( P value <0.05). At 14 days after the booster, the antibody positivity rates in Groups A, B, and C were 91.69% (276/301), 94.38% (302/320), and 93.95% (295/314), respectively. The seroconversion rates in the three groups were 90.37% (272/301), 93.75% (300/320), and 93.31% (293/314), respectively. There was no significant difference among these rates in the three groups (all P values >0.05). At 30 days after the booster, antibody positivity rates in Groups A, B, and C were 79.60% (238/299), 87.74% (279/318), and 90.48% (285/315), respectively. The seroconversion rates in the three groups were 76.92% (230/299), 85.85% (273/318), and 88.25% (278/315), respectively. There was a significant difference among these rates in the three groups (all P values <0.001). During the sequential booster immunization, the incidence of adverse events in 960 participants was 15.31% (147/960), with rates of about 14.38% (46/320), 17.50% (56/320), and 14.06% (45/320) in Groups A, B, and C, respectively. The incidence of adverse reactions was 8.02% (77/960), with rates of about 7.50% (24/320), 6.88% (22/320), and 9.69% (31/320) in Groups A, B, and C, respectively. No serious adverse events related to the booster were reported. Conclusion:Healthy individuals aged 18-84 years, who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, have good immunogenicity and safety profiles following the sequential booster with the recombinant COVID-19 vaccine (CHO cell).

Intracranial atherosclerotic stenosis (ICAS) is closely associated with cognitive impairment and dementia. This article reviews the manifestations, mechanisms, and interventions of cognitive impairment in patients with ICAS, aiming at increasing attention to ICAS, early identification and intervention, and delaying the occurrence and deterioration of cognitive impairment.

Objective : To analyze the expression and immune infiltration levels of the BMP7 gene ( BMP7) in e- sophageal squamous cell carcinoma(ESCC) ． Methods : Initially，in 274 cases of ESCC and 242 cases of normal tissues，the level of BMP7 was verified by immunohistochemistry ，and the relationship between the expression difference and the survival cycle and clinical pathological characteristics of patients with ESCC was explored，and BMP7 overexpression plasmid transfection of ESCC cells was established，and the effect of BMP7 on the biological behavior of ESCC cells was examined by CCK-8，Clone，and Transwell. Results : BMP7 expression in normal e- sophageal tissues was higher than that of ESCC(P＜0. 001) ，the expression level of BMP7 was correlated with the degree of differentiation of patients(P = 0. 006) and TNM staging(P ＜0. 001) ，and the survival of patients with high expression of BMP7 exceeded that of patients with low BMP7 (P = 0. 041) ，and the experiments of CCK-8 and Clone showed that the proliferation effect of cells in the overexpressed BMP7 group was lower than that of the control group．Transwell experiments confirmed that the cell invasion migration capacity of the overexpressed BMP7 group was less than that of the control one．The immune infiltration results showed that BMP7 was positively correlated with macrophages(P = 0. 008) and negatively correlated with γ-δT cells(P = 0. 028) ． Conclusion BMP7 is low in ESCC and associated with poor prognosis and immune infiltration levels in patients.

Objective    To analyze the clinical efficacy of right minithoracotomy approach in the treatment of patients with regurgitation after left-sided valve surgery (LSVS). Methods    The clinical data of 77 patients who suffered tricuspid regurgitation (TR) after LSVS and received surgical treatment in the Heart Center of Henan Provincial People's Hospital from 2012 to 2019 were selected. According to the operation method, the patients were divided into a right minithoracotomy group (n=32), including 13 (40.6%) males, aged 57.3±5.3 years and a median sternotomy group (n=45), including 17 (37.8%) males, aged 55.7±6.6 years. Preoperative and postoperative clinical data of the two groups were compared and analyzed. Results    There was no significant difference in preoperative data between the two groups. There were 24 patients of tricuspid valvuloplasty (TVP) and 8 patients of tricuspid valve replacement (TVR) in the right minithoracotomy group. There were 29 patients of TVP and 16 patients of TVR in the median sternotomy group. The operation time, postoperative hospitalization time, intubation time and ICU stay time of the right minithoracotomy group were shorter than those of the median sternotomy group (P<0.001). The operative bleeding, postoperative drainage in 24 hours, postoperative blood transfusion rate and incision poor healing of the right minithoracotomy group were significantly decreased compared with those of the median sternotomy group (P<0.05). The extracorporeal circulation time between the two groups was not significantly different (P=0.382). The postoperative complications and mortality of the righ minithoracotomy group were significantly lower than those of the median sternotomy group (P<0.05). Conclusion    The procedure of right minithoracotomy access can reduce perioperative morbidity and mortality compared with the median sternotomy, and results in satisfied clinical efficacy.

Abstract Inoculation of COVID-19 vaccines is an important approach to preventing SARS-CoV-2 infections and reducing the severe disease and mortality of COVID-19. The elderly, children and adolescents, pregnant women, lactating women, patients with chronic diseases and immunocompromised individuals are considered to be susceptible to and at a high risk of COVID-19. Early, safe and effective inoculation of COVID-19 vaccines is critical for the successful building of the population immune barrier against COVID-19. This review, based on data from clinical trials, summarizes the safety and efficacy and safety of COVID-19 vaccines among special populations, so as to provide insights into COVID-19 vaccination among special populations.

[Abstract] Objective: To investigate the effect of alantolactone (ALT) on proliferation, migration, invasion and apoptosis of human osteosarcoma 143B cells and the underlying mechanism. Methods: Osteosarcoma 143B cells were treated with different concentrations of ALT (0, 4, 6, 8, 10 µmol/L). Then, the cell proliferation ability was detected by crystal violet staining and MTT assay, cell migration was determined by Wound-healing test, cell invasion was analyzed by Transwell assay and cell apoptosis rate was detected by Hoechst33258 staining. The mRNA and protein expressions of E-cadherin, N-cadherin, caspase-3, cleaved caspase-3 (c-caspase-3), poly ADP-ribose polymerase (PARP) and cleaved PARP (c-PARP) in 143B cells were detected by qPCR and Western blotting (WB), respectively. TCF/LEF (T cell lymphocyte factor/lymphoid enhancer factor) transcriptional activity was examined with Luciferase reporter gene assay. The mRNA and protein expressions of β-catenin as well as MMP-7 and c-Myc were detected by qPCR and WB, respectively. Results: ALT inhibited proliferation, migration and invasion of osteosarcoma143B cells and promoted apoptosis(P<0.05or P<0.01). After the treatment with ALT at 8, 10 µmol/L, the mRNA and protein expressions of E-cadherin and PARP, as well as the protein expressions of c-caspase-3 and c-PARP were up-regulated, while the mRNA and protein expressions of N-cadherin were downregulated (P<0.05 or P<0.01);At the sametime, theTCF/LEF transcriptional activity and the mRNA and protein expressions of β-catenin, MMP-7 and c-Myc were significantly down-regulated (P<0.05 or P<0.01). Conclusion:ALT may inhibit the proliferation, migration and invasion and promote cell apoptosis possibly through suppressing Wnt/β-catenin signaling pathway in osteosarcoma 143B cells.

Objective:To investigate the safety of intraoperative prophylactic addition of tirofiban on the basis of preoperative oral administration of aspirin and clopidogrel in patients with unruptured intracranial aneurysms accepted stent-assisted coil embolization, and explore the effect of tirofiban on perioperative thrombotic events.Methods:The clinical data of 275 patients with unruptured intracranial aneurysms who underwent stent assisted coil embolization in our hospital from January 2016 to December 2019 were retrospectively collected. Among them, 110 patients admitted to our hospital from January 2016 to December 2017 only received preoperative oral administration of aspirin and clopidogrel combined with antiplatelet treatment (classic group), and 165 patients admitted to out hospital from January 2018 to December 2019 received intraoperative prophylactic addition of tirofiban on the basis of preoperative oral administration of aspirin and clopidogrel (improved group). The differences of perioperative safety and thrombotic events between the two groups were compared and analyzed.Results:The incidence of intraoperative visual thrombotic events in the classic group and the improved group were 6.4% (7/110) and 1.2% (2/165), respectively, with significant difference ( P<0.05); the incidence of postoperative thrombotic events was 4.5% (5/110) and 2.4% (4/165), respectively, without significant difference ( P>0.05); the incidence of urethrorrhagia was 9.1% (10/110) and 21.2% (35/165), respectively, with significant difference ( P<0.05); and the incidence of gingival hemorrhage was 13.6% (15/110) and 19.4% (32/165), respectively, without significant difference ( P>0.05). No acute gastrointestinal hemorrhage or cerebral hemorrhage occurred in both groups; urethrorrhagia and gingival hemorrhage were transient and relieved spontaneously. Conclusion:Intraoperative prophylactic addition of tirofiban on the basis of preoperative oral administration of aspirin and clopidogrel can reduce the incidence of intraoperative visual thrombotic events without increasing the risk of hemorrhage in stent-assisted coil embolization of unruptured intracranial aneurysms.

Objective:To investigate the predominant serotypes and diversification of Echovirus (ECHOV) from viral encephalitis children in Quzhou area of Zhejiang province and the molecular characteristics of the ECHOV VP1 genes.Methods:Cerebrospinal fluid samples from 53 children with viral encephalitis were collected for viral isolation/culture. Fluorescent RT-PCR or PCR was used to detect human enteroviruses (HEV) including ECHOV, coxsackievirus(CoV) and new enterovirus (EV), and japanese encephalitis virus(JEV), mumps virus(MuV), west Nile virus(WNV) and chikungunya virus(CHLKV) or herpes simplex virus(HSV) and cytomegalovirus(CMV) in the cerebrospinal fluid samples. The complete VP1 gene sequence of HEV-B group in the HEV-positive cerebrospinal fluid samples was amplified by RT-PCR and sequenced, and then the typing of Echovirus isolates was performed. The VP1 genotypes of Echovirus isolates, gene recombination, inheritance and evolution characteristics were analyzed using multiple bioinformatic software.Results:Six viral strains were isolated by cell culture using rhabdomyosarcoma (RD) cells but not human epithelial-2 (Hep-2) cells. Eleven cerebrospinal fluid samples were positive for HEV by RT-PCR but the detection result of all the other viruses were negative. In the 11 HEV-positive samples, 6 samples were positive for ECHOV (4 for ECHO6, 1 for ECHO7 and 1 for ECHO30 serotype), which was coincident with the isolation result , but CoV and EV were undetectable. The 4 ECHO6 isolates belonged to ECHO6-C2 subgenotype but can be divided into two epidemic clones (ECHO6-41/46 and ECHO6-45/48). The ECHO7 and ECHO30 isolates belonged to ECHO7-C and ECHO30-C genotypes. The VP1 gene recombination between the ECHO6 and ECHO30 isolates were found during their evolutionary process.Conclusions:ECHOV is the major pathogen of viral encephalitis children in the area, and there is a possibility of local outbreak or epidemic. Because of the possibility of recombination of the VP1 gene of ECHO6 and ECHO30 virus, ECHO6 may become the dominant ECHOV serotype.

Objective:To evaluate the safety and immune effect of recombinant hepatitis B vaccine （CpG ODN adjuvant).Methods:On Oct. 26, 2016, we launched volunteer recruitment in Kaihua county, Quzhou city, Zhejiang Province. In the randomized, double-blind, controlled trial, a total of 48 subjects with negative HBV screening tests and normal hepatorenal function among 18 and 60 years old were selected and divided into two groups randomly, 24 cases each. The experimental group was given 250 μg of CpG ODN recombinant （Hansenula polymorpha) Hepatitis B vaccine and the control group was given 10 μg of commercial Hepatitis B vaccine with timed at 0, 1and 6 months. The inoculation reactions were compared the difference between the two groups after observed and recorded in time periods. We also collected serum before and after immunization to compare the two groups of anti-HBs positive rate, geometric mean concentration（GMC).Results:During the study period, the incidence of adverse events was 66.67%（16/24) in the experimental group and 54.17%（13/24) in the control group, with no significant difference（ P=0.556). The severities of adverse events were level 1 or level 2, and no level 3 or above adverse reactions occurred. After full-course immunization, in the FAS data set, the anti-HBs GMC in the experimental group [2 598.56（1 127.90-5 986.90) mIU/ml] was higher than that in the control group[371.97（164.54-840.91) mIU/ml] In the PPS set, the GMC of test group was 7 808.21（3 377.00-18 052.00) mIU/ml, which was higher than that of the control group [843.22（213.80-3 325.90) mIU/ml]. The anti-HBs positive rate of FAS（PPS) was 95.83%（100.00%) in the experimental group and the control group; The anti-HBs strongly positive rate of FAS（PPS) was 79.17%（90.00%) in the experimental group and 33.33%（50.00%) in the control group, with statistically significant differences among the FAS set（ P=0.003) and no statistically significance differences among the PPS set（ P=0.074). Conclusion:CpG Hepatitis B Vaccine is safe and shows better immunogenicity than the control vaccine.

Objective:To evaluate the safety and immune effect of recombinant hepatitis B vaccine （CpG ODN adjuvant).Methods:On Oct. 26, 2016, we launched volunteer recruitment in Kaihua county, Quzhou city, Zhejiang Province. In the randomized, double-blind, controlled trial, a total of 48 subjects with negative HBV screening tests and normal hepatorenal function among 18 and 60 years old were selected and divided into two groups randomly, 24 cases each. The experimental group was given 250 μg of CpG ODN recombinant （Hansenula polymorpha) Hepatitis B vaccine and the control group was given 10 μg of commercial Hepatitis B vaccine with timed at 0, 1and 6 months. The inoculation reactions were compared the difference between the two groups after observed and recorded in time periods. We also collected serum before and after immunization to compare the two groups of anti-HBs positive rate, geometric mean concentration（GMC).Results:During the study period, the incidence of adverse events was 66.67%（16/24) in the experimental group and 54.17%（13/24) in the control group, with no significant difference（ P=0.556). The severities of adverse events were level 1 or level 2, and no level 3 or above adverse reactions occurred. After full-course immunization, in the FAS data set, the anti-HBs GMC in the experimental group [2 598.56（1 127.90-5 986.90) mIU/ml] was higher than that in the control group[371.97（164.54-840.91) mIU/ml] In the PPS set, the GMC of test group was 7 808.21（3 377.00-18 052.00) mIU/ml, which was higher than that of the control group [843.22（213.80-3 325.90) mIU/ml]. The anti-HBs positive rate of FAS（PPS) was 95.83%（100.00%) in the experimental group and the control group; The anti-HBs strongly positive rate of FAS（PPS) was 79.17%（90.00%) in the experimental group and 33.33%（50.00%) in the control group, with statistically significant differences among the FAS set（ P=0.003) and no statistically significance differences among the PPS set（ P=0.074). Conclusion:CpG Hepatitis B Vaccine is safe and shows better immunogenicity than the control vaccine.