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 one of the most common causes of ischemic cerebrovascular disease. Compared with other causes such as extracranial diseases or cardiogenic embolism, symptomatic ICAS (sICAS) has a higher risk of stroke recurrence, often leading to the aggravation of neurological impairment and even death. More and more evidence shows that imaging features play an important role in predicting the risk of stroke recurrence and individualized secondary prevention in patients with sICAS. This article reviews the imaging features of ischemic stroke recurrence in patients with sICAS, which provides a basis for identifying sICAS patients with high risk of recurrent stroke and effective secondary prevention.

Objective : To investigate the awareness of human papillomavirus ( HPV ) vaccine and willingness to vaccinate daughters among parents of primary and middle school students, so as to provide the reference for the promotion of HPV vaccine in primary and middle school girls. Methods : Using multi-stage stratified cluster sampling method, the parents of girls in in Grade Four to Nine from schools in Gongshu District of Hangzhou, Xiuzhou District of Jiaxing and Wuxing District of Huzhou were selected. A questionnaire survey was conducted to collect demographic information, HPV vaccine related knowledge and willingness to vaccinate daughters with HPV vaccines. The multivariate logistic regression model was used to analyze the influencing factors for the willingness to vaccinate daughters with HPV vaccines among parents. Results : Totally 1 500 questionnaires were sent out, and 1 466 were effectively collected, with an effective rate of 97.73%. There were 313 fathers responded, accounting for 21.35%; and 1 153 mothers responded, accounting for 78.65%. The awareness rate of HPV vaccine was 16.81%. The rate of willing to vaccinate daughters with HPV vaccines was 49.86%. The multivariate logistic regression analysis showed that the patients who ever vaccinated daughters with self-paid vaccines ( OR=1.935, 95%CI: 1.473-2.541 ), knew cervical cancer ( OR=1.424, 95%CI: 1.065-1.904 ), knew HPV vaccine dose ( OR=1.672, 95%CI:1.216-2.301 ), knew the best vaccination period ( OR=1.392, 95%CI: 1.032-1.876 ), knew the need of cervical cancer screening even after vaccination ( OR=1.596, 95%CI:1.227-2.075) were more willing to vaccinate daughters with HPV vaccines, while the parents who thought HPV vaccine expensive ( OR=0.154, 95%CI: 0.099-0.240 ) were less willing to vaccinate daughters with HPV vaccines. Conclusions The rates of HPV vaccine awareness and willingness to vaccinate daughters are 16.81% and 49.86% among parents of primary and middle school students. Their knowledge of HPV vaccine and the price of the vaccine may affect their willingness to vaccinate daughters.

Objective: To explore the reliability and validity of the Chinese Pediatric Quality of Life Inventory（PedsQL）in influenza children. Methods: From January 2017 to February 2018,we selected laboratory-diagnosed influenza cases and healthy children according to age and gender ratio by stratified random sampling and systematic sampling method. We employed Chinese version of PedsQL 4.0 to investigate their quality of life,used Cronbach's α to evaluate the reliability,and used Pearson correlation coefficient, t-test,confirmatory factor analysis（CFA）and ROC curve to evaluate the validity. Results: Totally 300 influenza cases and 300 healthy children were surveyed,with 294（98.00%）and 295（98.33%）valid questionnaires recovered. The general Cronbach's α was 0.89,and the Cronbach's α of each dimension ranged from 0.79 to 0.84. The Pearson correlation coefficients between the items and their belonged dimension ranged from 0.537 to 0.755,between the items and other dimension ranged from 0.203 to 0.384. The CFA resulted in RMSEA of 0.06,GFI of 0.88,AGFI of 0.90,CFI of 0.91 and NFI of 0.89. The scores in total and in all the dimensions in influenza cases were significantly different with those in healthy children（P<0.05）. Taking the scores in influenza cases as a golden standard,the area under the ROC curve was 0. 985（P<0.05）,the sensitivity was 0.92,and the specificity was 0.95. When the limit score was 82.18,the Youden index was the largest. Conclusion The Chinese version of PedsQL4.0 has good reliability and validity, which can be applied to quality of life assessment in children.

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.

Objective To investigate the anesthetic efficacy of topical dyclonine hydrochloride mucilage for preputial encircling in children. Methods Sixty children under preputial encircling, 13 patients with redundant prepuce, 47 patients with phimosis, aged 4-12 years, weighing 14-38 kg, falling into ASA physical status Ⅰ or Ⅱ, were randomly divided into two groups with 30 cases each: dyclonine group (group D) and control group (group C). Children with redundant prepuce in group D were smeared evenly 1％ dyclonine hydrochloride mucilage on the anterior 2/3 foreskins, glans and coronary sulcus by anesthesiologists who were assisted by the their parents 30 min before entering the operating room. Children with phimosis in group D were smeared evenly 1％ dyclonine hydrochloride mucilage on the anterior 2/3 foreskins, and then the tube was inserted near the coronary sulcus with the 18# straight indwelling needle. The syringe was injected into the 1％ dyclonine hydrochloride mucilage, and the glans and the coronary sulcus were squeezed repeatedly several times by anesthesiologists who were assisted by the their parents 30 min before entering the operating room. The dosage of dyclonine hydrochloride mucilage for each child was 0.2-0.3 ml/kg. Children in group C were smeared evenly isodose normal saline at the same time. All the children were treated with ketamine and propofol anesthesia after entering. The occurrence of intraoperative body reaction were observed and recorded, HR and MAP were recorded before anaesthesia induction (T0), at the beginning of surgery (T1), at the time of the coronary sulcus was exposed (T2), at the time of ligating (T3), at the time of the excess foreskin was cut (T4), the dosage of ketamine and propofol were recorded, and the occurrence of postoperative recovery time and emergence agitation during recovery period were observed. Results Body dynamic reaction rate in group D was significantly lower than that in group C (P ＜ 0.05), HR and MAP was significantly lower than that in group C at T3-T4 (P ＜ 0.05), the dosage of ketamine and propofol was significantly smaller than that in group C (P ＜ 0.05), the recovery time was significantly shorter than that in group C (P ＜ 0.05), the incidence of emergence agitation was significantly decreased compared with group C (P ＜ 0.05). Conclusion Topical dyclonine hydrochloride mucilage can effectively decrease body movement, lessen cyclic fluctuation, economize general anesthetics, shorten recovery time, reduce emergence agitation in children undergoing preputial encircling.

Objective To analyze the clinical and biochemical,as well as genetic characteristics of a patient with Wiedemann-Steiner syndrome (WDSTS).Methods The clinical data of a patient with WDSTS were collected.The patient was treated with recombinant human growth hormone (rhGH) combined with gonadotrophine-releasing hormone agonist (GnRHa).Blood samples of the patient and her parents were taken for whole-Exome Sequencing (WES).Relevant literatures about KMT2A mutations were reviewed.Results The 5-year old girl presented with growth retardation,with height 100 cm (-2.4 SD),torpid reaction,and facial anomalies including low hairline,thick eyebrow and hair,hypertelorism,a wide nasal bridge.She had small and puffy hands and feet,excessive hair around back of neck,bilateral forearm and lower limbs.Her GH peak level was 26.6 ng/ml during GH stimulation test.She was re-examined at the age of 10.4 years,with severe short stature (120 cm/-3.58 SD) and a Tanner stage 2 of breast development.Her bone age was found to be approximately 11.4 years.Height increased from 120 cm at the age of 10.4 years to 147.3 cm after rhGH treatment combined with GnRHa for 2.5 years.rhGH therapy alone continued for 1.1 years and a height of 150 cm was reached at the age of 14.9 years,with bone age 14 years.Gene sequencing revealed a de novo frameshift mutation (c.10051 delA,p.Thr3351 Leufs * 17) of exon 27 in KMT2A gene of the patient,but without any mutation in her parents.Through a literature review,seventy-one patients with WDSTS (including present case) presented with intellectual disability (70/71),facial anomalies (70/71),short stature (50/71),and hypertrichosis (39/71).Conclusion Patients presented with short stature,typical facial dysmorphism,intellectual disability,and hypertrichosis should be considered for WDSTS.The mutation p.Thr3351Leufs * 17 in the KMT2A gene detected in our patient is a novel mutation.This is so far the first report of WDSTS patient who was successfully treated with a combination of GH and GnRHa at the onset of puberty to improve her adult height.

Objectives: To evaluate the safety of inactivated enterovirus A71(EV-A71) vaccines after large-scale immunization in the community. Methods: We selected EV-A71 susceptible people (healthy children) aged 6-59 months in vaccination clinics from 89 counties in Zhejiang Province between April 2016 and March 2018. All local and systematic adverse actions were collected by 30 min on-site inspection, within 3 days and 4-30 days follow-up. Chi-square test and Fisher′s exact test were used to compare the difference of AEs incidence in various characteristics among two groups. Results: A total of 71 663 doses of vaccines were included for active safety analysis, which included 37 331 doses in boys and 34 332 doses in girls. Among all the doses, children aged 6 to 11 months, 12 to 23 months and 24 to 59 months were received 13 707, 32 639 and 25 317 doses respectively. The incidence of adverse reactions within 30 min, 3 days and 4-30 days were 0.33% (239 doses), 1.58% (1 133 doses) and 0.34% (244 doses) respectively. Adverse reactions within 3 days were 1 372 doses, with a incidence of 1.91%; among all the cases, 539 doses (0.75%) were grade 1, 677 doses (0.94%) were grade 2 and 156 doses (0.22%) were grade 3, no grade-4 adverse reaction was reported. The common local adverse reactions were redness, swelling and pruritus, with the incidence rates were 0.05% (39 doses), 0.02% (16 doses) and 0.02% (12 doses), respectively, while the most common systemic adverse reaction was pyrexia with an incidence of 1.19% (856 doses), followed by diarrhea and anorexia with the incidence rates were 0.15% (104 doses) and 0.13% (90 doses) respectively. Conclusion Most adverse actions of EV-A71 vaccines were mild and moderate and majority of them were common adverse actions. No new adverse reactions were found in the study.

Objective To study the anesthetic effect of oral dyclonine hydrochloride mucilage combined with laryngopharyngeal spray of lidocaine in infant esophagus dilatation.Methods Eighty infants with anastomotic stenosis after surgical correction of esophageal atresia under esophagus dila-tation assisted with gastroscope,51 males and 29 females,age 6 months to 3 years,weighing 5-12 kg,ASA physical status Ⅰ or Ⅱ,were randomly divided into four groups with 20 cases each:general anesthesia group (group A),general anesthesia combined with dyclonine surface anesthesia group (group B),general anesthesia combined with lidocaine surface anesthesia (group C),general anesthesia combined with dyclonine and lidocaine surface anesthesia group (group D).Infants in group B and group D were given 1 % dyclonine hydrochloride mucilage 0.2-0.3 ml/kg by their parents who were guided by the anesthesiologist at 10-15 min before entering the operating room,followed by slow intravenous injection of penehyclidine hydrochloride 0.01-0.02 mg/kg, propofol 2-2.5 mg/kg, remifentanil 1 μg/kg.After the induction,the children of group C and group D were exposed to 2% lidocaine 0.1 5-0.2 ml/kg through laryngoscope under laryngoscope to spray the laryngeal mucosa surface.All the children were converted to oxygen supply (6 L/min)asing double nasal high flow af-ter the mask was added to the stable breathing.Anesthesia was maintained by propofol 6 mg·kg-1·h-1,remifentanil 0.1 μg·kg-1·h-1infusion.In the case of somatic or choking during the operation,propofol and (or)remifentanil were inj ected into the pump to deepen the anesthesia. The occurrence of intraoperative oxygen saturation (SpO2<94%),cough and body reaction were ob-served and recorded,and the occurrence of postoperative recovery time and emergence agitation during recovery period were observed.Results The patients with oxygen saturation in group D de-creased,the incidence of cough was significantly lower than that of groups A and B (P<0.05 ), without significant difference in group C, body dynamic reaction rate was significantly lower compared with the other three groups (P<0.05),the recovery time was significantly shorter com-pared with the other three groups (P<0.05),the incidence of emergence agitation significantly de-creased (P<0.05).Conclusion Oral dyclonine hydrochloride mucilage combined with laryngopha-ryngeal spray of lidocaine can effectively decrease hypoxemia,cough,body movement,shorten recov-ery time,reduce emergence agitation in infants undergoing the esophageal dilatation.