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).

Objective:To construct a novel dual-specific antibody targeting human CD123 (CD123 DuAb) and study its effects in acute myeloid leukemia (AML) .Methods:Based on the variable region of the CD123 monoclonal antibody independently developed at our institution, the CD123 DuAb expression plasmid was constructed by molecular cloning and transfected into ExpiCHO-S cells to prepare the antibody protein. Through a series of in vitro experiments, its activation and proliferation effect on T cells, as well as the effect of promoting T-cell killing of AML cells, were verified.Results:① A novel CD123 DuAb plasmid targeting CD123 was successfully constructed and expressed in the Expi-CHO eukaryotic system. ②The CD123 DuAb could bind both CD3 on T cells and CD123 on CD123 + tumor cells. ③When T cells were co-cultured with MV4-11 cells with addition of the CD123 DuAb at a concentration of 1 nmol/L, the positive expression rates of CD69 and CD25 on T cells were 68.0% and 44.3%, respectively, which were significantly higher than those of the control group ( P<0.05). ④Co-culture with CD123 DuAb at 1 nmol/L promoted T-cell proliferation, and the absolute T-cell count increased from 5×10 5/ml to 3.2×10 6/ml on day 9, and CFSE fluorescence intensity decreased significantly. ⑤ With the increase in CD123 DuAb concentration in the culture system, T-cell exhaustion and apoptosis increased. When the CD123 DuAb was added at a concentration of 1 nmol/L to the culture system, the proportion of CD8 + PD-1 + LAG-3 + T cells was 10.90%, and the proportion of propidium iodide (PI) - Annexin Ⅴ + T cells and PI + Annexin Ⅴ + T cells was 18.27% and 11.43%, respectively, which were significantly higher than those in the control group ( P<0.05). ⑥ The CD123 DuAb significantly activated T cells, and the activation intensity was positively correlated with its concentration. The expression rate of CD107a on T cells reached 16.05% with 1 nmol/L CD123 DuAb, which was significantly higher than that of the control group ( P<0.05). ⑦The CD123 DuAb promoted cytokine secretion by T cells at a concentration of 1 nmol/L, and the concentration of IFN-γ and TNF-α in the supernatant of the co-culture system reached 193.8 pg/ml and 169.8 pg/ml, respectively, which was significantly higher than that of the control group ( P<0.05). ⑧When CD123 DuAb was added at a concentration of 1 nmol/L to the co-culture system of T cells and CD123 + tumor cells, the killing intensity of T cells significantly increased, and the residual rates of CD123 + MV4-11 cells, CD123 + Molm13 cells, and CD123 + THP-1 cells were 7.4%, 6.7%, and 14.6% on day 3, respectively, which were significantly lower than those in the control group ( P<0.05) . Conclusion:In this study, a novel CD123 DuAb was constructed and expressed. In vitro experiments verified that the DuAb binds to CD123 + tumor cells and T cells simultaneously, promotes T-cell activation and proliferation, and facilitates their anti-leukemia effect, which provides a basis for further clinical research.

Humans ; Pulmonary Disease, Chronic Obstructive ; Smoke/adverse effects* ; Tobacco ; Tobacco Smoke Pollution

Objective:To investigate the characteristics of blood glucose fluctuation and risk factors in type 2 diabetic patients with asymptomatic hypoglycemia.Methods:From September 2018 to July 2021, 342 patients with type 2 diabete mellitus who were hospitalized in the Department of Endocrinology of Hefei Hospital Affilitated to Anhui Medical University were enrolled for a retrospective study. The mean amplitude of glycemic excursions(MAGE), coefficient of variation (CV), 24 hour mean blood glucose level (MG), and time in range (TIR) were obtained by continuous glucose monitoring (CGM). According to the results of CGM and whether the patients have hypoglycemia symptoms, they were divided into three groups: no hypoglycemia group, symptomatic hypoglycemia group, and asymptomatic hypoglycemia group. The differences in blood glucose fluctuations were compared among the three groups. Multivariate logistic regression analysis was used to evaluate the risk factors in type 2 diabete mellitus patients with asymptomatic hypoglycemia. The predictive value of MAGE for asymptomatic hypoglycemia was analyzed by receiver operating characteristic (ROC) curve.Results:Compared with the non-hypoglycemia group, the TIR in asymptomatic hypoglycemia group was higher ( Z=-2.042, P=0.041). The asymptomatic hypoglycemia group had lower MG, higher MAGE and CV compared with the other two groups(all P<0.05). Multivariate logistic regression analysis showed that urinary albumin/creatinine ratio (UACR), MAGE, and CV were the risk factors for asymptomatic hypoglycemia, while MG was the protective factor. After adjustment for other risk factors, MAGE was still associated with asymptomatic hypoglycemia ( OR=1.111, 95% CI 0.999-1.235, P=0.049). The sensitivity and specificity of MAGE in predicting asymptomatic hypoglycemia were 0.769 and 0.776, respectively. Conclusions:Patients with asymptomatic hypoglycemia present with larger TIR and MAGE. MAGE, UACR, and CV were risk factors for asymptomatic hypoglycemia. Moreover, MAGE has some predictive value for the occurrence of asymptomatic hypoglycemia.

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 investigate the manifestations of liver injury in hospitalized patients with coronavirus disease 2019 (COVID-19), to investigate the prognosis indicators of the disease, and to provide the reference for clinical diagnosis and treatment.Methods:From January 10 to February 14, 2020, at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, the data of 333 hospitalized patients with COVID-19 were collected. The changes of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), direct bilirubin (DBil), indirect bilirubin (IBil) and albumin of the first liver function test after admission and the reexaminations of liver function test during hospitalization period in patients with liver injury were retrospectively analyzed. Student t test and Chi-square test were used for statistical analysis. Results:Liver injury occurred in 39.6% (132/333) of COVID-19 patients. There was no statistically significant difference in the rate of liver injury between patients in intensive care unit (ICU) and in general ward (45.6%, 26/57 vs. 38.4%, 106/276; χ2=1.026, P>0.05). 67.4% (89/132) of COVID-19 patients with liver injury presented with increased ALT or AST level on admission. During hospitalization, the level of ALT was higher than that of the first examination after admission ((60.28±50.44) U/L vs. (42.25±32.21) U/L), and the difference was statistically significant ( t=-3.230, P<0.05). The levels of ALT and AST of 71.2% (94/132) patients were both <80 U/L, which indicated that most of the patients showed mild liver injury. The patients with elevated level of TBil, DBil and IBil accounted for 3.9% (13/333), 5.4% (18/333) and 2.4% (8/333) of the COVID-19 patients, respectively. The albumin level of COVID-19 patients with liver injury during hospitalization was lower than that of the first examination after admission ((31.8±5.1) g/L vs. (33.7±5.4) g/L), and the difference was statistically significant ( t=2.712, P<0.05). The albumin levels at first examination on admission and reexamination during hospitalization of patients in ICU were both significantly lower than those of patients in general ward ((29.3±3.7) g/L vs. (34.8±5.1) g/L and (27.6±2.8) g/L vs. (32.9±5.1) g/L), and the differences were statistically significant ( t=4.928 and 4.783, both P<0.05). Conclusions:The incidence of liver injury in COVID-19 patients is high. A slight increase in aminotransferase levels is particularly common. Bilirubin abnormality is relatively rare and mild. The level of albumin may be one of the indicators for the severity and prognosis of COVID-19.

Objective To investigate the clinical efficacy of Dahuang Xiaozhi Suppository combined with tetracycline in treating type Ⅲ prostatitis infected with nano-bacteria. Methods Totally 120 patients of type Ⅲprostatitis infected with nano-bacteria were randomly divided into treatment group and control group, with 60 cases in each group. Both groups were disabled anti-infective drugs and other preparations for diet and life intervention. Both groups received tetracycline, once a tablet, twice a day, orally. The treatment group received Dahuang Xiaozhi Suppository, once a capsule, once a day, placing in the anus 3-4 cm. 10 d was a treatment course, for 3 courses. The clinical efficacy, major symptoms improving time, NIH-CPSI, leukocyte count and ecithin corpuscles in expressed prostatic secretion (EPS), urinary flow rate, and cytokine content of TNF-α, IL-6, IL-8, were evaluated. Results The total effective rate was 100.0% (60/60) in treatment group and 83.3% (50/60) in the control group, and treatment group was higher than the control group (P<0.05). Pelvic pain, urinary symptom, and scrotum wet improvement time of treatment group were lower than the control group (P<0.05). Compared with before the treatment, the NIH-CPSI pain scores, urinary symptom scores, life quality score, leukocyte count and TNF-α, IL-6, IL-8 content of EPS in both groups were significantly lower after treatment (P<0.05), and the cases with lecithin corpuscles +++ - ++++ in both groups significantly increased after treatment (P<0.05). The urinary peak flow rate and mean flow rate in both groups were higher after treatment (P<0.05). There was statistical significance in the scores of NIH-CPSI pain, urinary symptom and life quality, leukocyte count and TNF-α, IL-6, IL-8 content of EPS, and the cases with lecithin corpuscles ++++ between the two groups (P<0.05). Conclusion Dahuang Xiaozhi Suppository can improve the efficacy of treating type Ⅲ prostatitis infected with nano-bacteria. Combining Dahuang Xiaozhi Suppository with tetracycline can reduce prostate inflammation, with obvious efficacy.

Objective To evaluate the efficacy and safety of Qingpeng ointment for the treatment of localized eczema in children.Methods A multicenter,randomized,open-labeled,tacrolimus 0.03％ ointment-controlled clinical trial was conducted.A total of 442 children with localized eczema were enrolled into this study,and divided into 2 groups to topically apply Qingpeng ointment (Qingpeng group) and tacrolimus 0.03％ ointment (tacrolimus group) respectively twice a day for 2 weeks.The children were followed up before the treatment and 1,2 weeks after the treatment,and the efficacy and safety were evaluated at the same time.Results Clinical data from 426 children were included in the efficacy analysis.At 1,2 weeks after the treatment,there were no significant differences in the response rate between the Qingpeng group and tacrolimus group (1 week after the treatment:78.92％ vs.81.77％,x2 =0.545,P =0.460;2 weeks after the treatment:98.65％ vs.97.54％,x2 =0.721,P =0.396).However,the pruritus scores at 1,2 weeks after the treatment were both significantly lower in the Qingpeng group than in the tacrolimus group (1 week:F =14.001,P =0.000;2 weeks:F =11.252,P =0.001).At 1 week after the treatment,the incidence rate of adverse reactions was significantly lower in the Qingpeng group than in the tacrolimus group (P ＜ 0.05).Mild itching,burning sensation and other local irritant sensations were the most common adverse reactions.Conclusion Qingpeng ointment is safe and effective for the treatment of localized eczema in children with good tolerability.

Objective To compare the value of central venous pressure (CVP) measured by peripherally inserted central catheters (PICC) and centrally inserted central catheters (CICC) in elderly patients with severe diseases.Methods Paired design and self-controlled was applied in the research. CVP was measured by 2 different measurement approaches in patients with PICC and CICC simultaneously. The sample size was calculated by the enumeration method through the accuracy estimation of consistency evaluation of quantitative measurement, and the required number was 70.Results Among the 70 collected samples, the mean values of the measured CVP by PICC and CICC were (7.995±3.435) cmH2O and (7.743±3.277) cmH2O; no statistically significant difference was observed (t=1.622,P=0.109). The pearson's linear correlation coefficient of the CVP measured by 2 different measurement approaches was 0.926 (P<0.0001). A linear regression model through the origin of the CVP measured by 2 different measurement approaches was fitted with the linear regression equation of CVPPICC=1.023 CVPCICC (R2=0.978); and the 95%CI of the prediction line contained the reference line. The Bland-Altman plot showed that 64 samples fell within limits of agreement (LoA), LoA was -2.300-2.804, with a consistent rate of 91.43%. All the plots out of the LoA did not exceeded the 95%CI.Conclusions The CVP measured by CICC and PICC exhibit high consistency. Therefore, PICC can be used to replace the CICC in the CVP monitoring.

OBJECTIVETo clarify the related factors of marginal bone loss (MBL) around tissue level implants in the posterior part of the mandible.

METHODSA total of 116 tissue level implants were implanted in the mandibular posterior region of 76 patients. Patients' information, including general characteristics, implant characteristics, implant site characteristics, and prosthesis characteristics, was recorded. Their cone beam computed tomography data were measured immediately after implant placement, 3 months later, and 3 and 12 months after prosthesis loading. The measurement of MBL was conducted by One Volume Viewer software. SPSS 20.0 was used for statistic analysis.

RESULTSSmoking, cortical bone thickness (CBT), collum angle (CA), and implant local sanitation showed significant differences with body mass loss (P<0.05). No significant differences were found among sex, age, length of implant, diameter of implants, implant systems, bone height, prosthesis type, and MBL (P>0.05).

CONCLUSIONThe risk factors that caused MBL were smoking, thicker CBT, larger CA, and poor implant local sanitation. Among them, poor implant local sanitation had the highest correlation with MBL.

Alveolar Bone Loss ; epidemiology ; etiology ; Cone-Beam Computed Tomography ; Dental Implants ; adverse effects ; Dental Prosthesis Design ; Dental Prosthesis, Implant-Supported ; Follow-Up Studies ; Humans ; Mandible ; Mandibular Prosthesis ; statistics & numerical data ; Oral Hygiene ; Postoperative Complications ; Smoking ; adverse effects ; Treatment Outcome