Immunogenicity and safety of a severe acute respiratory syndrome coronavirus 2 inactivated vaccine in healthy adults: randomized, double-blind, and placebo-controlled phase 1 and phase 2 clinical trials / 中华医学杂志(英文版)

BACKGROUND@#The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults.@*METHODS@#Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.@*RESULTS@#In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.@*CONCLUSIONS@#Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.@*TRIAL REGISTRATION@#http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).

Risk of micro-fracture in femoral head after removal of cannulated screws for femoral neck fracture / 中国修复重建外科杂志

Objective: To explore the changes of bone and risk of micro-fracture in femoral head after removal of cannulated screws following femoral neck fracture healing under the impact force of daily stress. Methods: A total of 42 specimens of normal hip joint were collected from 21 adult fresh cadaveric pelvic specimens. Wiberg central-edge (CE) angle, bone mineral density, diameter of femoral head, neck-shaft angle, and anteversion angle of femoral neck were measured. Then, the 3 cannulated screws were implanted according to the AO recommended method and removed to simulate the complete anatomical union of femoral neck fracture. The morphology of screw canal in the femoral head was observed by CT. Finally, the specimens were immobilized vertically within the impact device in an upside-down manner, and the femoral heads were impacted vertically. Every specimen was impacted at 200, 600, and 1 980 N for 20 times with the impacting device. After impact, every specimen was scanned by CT to observe the morphology changes of screw canal in the femoral head. Micro-fractures in the femoral head could be confirmed when there was change in the morphology of screw canal, and statistical software was used to analyze the risk factors associated with micro-fractures. Results: After impact at 200 and 600 N, CT showed that the morphology of screw canal of all specimens did not change significantly compared with the original. After impact at 1 980 N, there were protrusion and narrowing in the screw canal of the 22 femoral head specimens (11 pelvic specimens), showing obvious changes compared with the original screw canal, indicating that there were micro-fractures in the femoral head. The incidence of micro-fracture was 52.38% (11/21). logistic regression results showed that there was correlation between micro-fracture and bone mineral density ( P= 0.039), but no correlation was found with CE angle, diameter of femoral head, neck-shaft angle, and anteversion angle ( P>0.05). Conclusion: The micro-fractures in the femoral head may occur when the femoral head is impacted by daily activities after removal of cannulated screws for femoral neck fractures, and such micro-fractures are associated with decreased bone density of the femoral head.

Deviation of guide needle in orthopedics robotic surgery / 中华创伤骨科杂志

Objective To investigate the causes and preventive measures for deviation of guide needle in orthopedics robot surgery.Methods A robotic surgery was simulated on a wooden stick.The guide needle was inserted under the guidance of the robot.A lateral deviation force was applied respectively onto the tail and tip of the needle.The actual offset distance at the guide needle tip was measured and compared with the 1mm offset allowed by robot monitoring.Results The offset distance of the guide needle tip was 0,5+0.07 mm when the deviation force was applied onto the tail,significantly smaller than the 1 mm offset allowed by the robot monitoring(l=22.588,P<0.001).The offset distance of the guide needle tip was 4.92+0.16 mm when the deviation force was applied onto the tip,significantly larger than the 1 mm offset allowed by the robot monitoring(t=17.416,P<0.001).Conclusions The deviation of guide needle may be caused chiefly by the deviation force onto the tip.As the actual offset distance of the guide needle tip may be larger than that shown on the robot monitor in orthopedics robotic surgery,the intraoperative monitoring should serve only as a reference to the deviation of the guide needle.The operative details may be the key to prevention of such deviations.

Detection of neutralizing antibodies and DNA of human papillomavirus 16, 18 in women aged 18-45 years in Funing, Jiangsu province / 中华流行病学杂志

<p><b>OBJECTIVE</b>To understand the distributions of DNA and neutralizing antibodies of human papillomavirus (HPV)16, 18 in 18-45 year-old women.</p><p><b>METHODS</b>Totally, 1494 women were enrolled through multistage random sampling in Funing, Jiangsu province. Cervical exfoliated cells were collected from them for HPV DNA testing, and serum samples were taken from them for the detection of HPV16, 18 neutralizing antibodies by using pseudovirion-based neutralization assay(PBNA).</p><p><b>RESULTS</b>Among the 1494 women, 28(1.9%) and 188(12.6%) were positive for DNA and neutralizing antibody of HPV16 respectively, and 15(1.0%) and 60(4.0%) were positive for DNA and neutralizing antibody of HPV18, respectively. There were no significant differences in the detection rates of DNA and neutralizing antibody of HPV16, 18 among different age groups. About 16.7% of the women were infected with HPV16, 18, or both.</p><p><b>CONCLUSION</b>In Funing county of Jiangsu province, most women aged 18-45 years has no immunity to HPV16 and 18, indicating that they are appropriate targets for HPV 16/18 vaccination.</p>

Epidemiological investigation on an outbreak of autumn tsutsugamushi disease in Taizhou region of Jiangsu Province / 中华传染病杂志

Objective To analyze the epidemiological and clinical characteristics of an outbreak of tsutsugamushi disease in Taizhou region of Jiangsu Province,and to clarify new changes of endemic focus of tsutsugamushi disease in Jiangsu Province.Methods The definition of tsutsugamushi infected cases was determined,field epidemiological investigation with analysis of clinical features and polymerase chain reaction (PCR) results to diagnose tsutsugamushi disease were combined.Some of the positive samples were conducted genotyping by amplification and sequencing.Results The outbreak occurred from October to November,2011.The endemic focus located on the plain with humid climate and abundant rainfall.Fifteen cases of tsutsugamushi disease were found,including 6 PCR confirmed cases,5 clinically diagnosed cases,and 4 suspected cases.The main clinical symptoms were fever in 15 cases,skin rash in 14 cases,lymphadenectasis in 3 cases,skin eschar or ulcer in 12 cases,and liver dysfunction in 3 cases.None of the patients developed severe complications,and all recovered rapidly after the treatment.Comparing the sequencing results of positive samples with standard strains,the homology of base sequences was 99.00％ with that of Kawasaki.Conclusions The outbreak of tsutsugamushi disease in Jiangsu Province in 2011 is of autumn type in transitional endemic focus,and the pathogen is Kawasaki Orientia tsutsugamushi.