Amelioration of Obesity in Mice Fed a High-Fat Diet with Uronic Acid-Rich Polysaccharides Derived from Tremella fuciformis.

Obesity is rapidly becoming an emerging disease in developing countries due to the Westernization of societies and lifestyle changes. This study evaluated the ameliorative effect of acidic heteropolysaccharides derived from Tremella fuciformis (TFPS) on high-fat diet (HFD; 34.9% fat)-induced obesity in mice. The TFPS exhibited high uronic acid content and high viscosity in water. The structural characteristics of TFPS showed that average molecular weight was 679 kDa, and the monosaccharide composition was galactose, glucose, fructose, xylose, fucose, and mannose at a ratio of 1.0:6.5:10.0:18.5:30.5:67.5. In an in vivo study, HFD-induced obese C57BL/6 mice were orally given a TFPS treatment at 1 and 2 g/kg of body weight for 8 weeks. The TFPS treatment significantly reduced features of obesity in the mice, namely weight gain, feed efficiency, body fat percentage, and serum cholesterol level and increased fecal lipid content, compared with mice fed an HFD with water. In addition, TFPS exhibited the inhibition of cholesterol micelles in vitro in a concentration-dependent manner. In conclusion, the TFPS treatment ameliorated the diet-induced obesity in the mice, presumably reducing fat absorption in the intestine by interfering with viscous TFPS.

Immunogenicity and Safety of a SARS-CoV-2 Inactivated Vaccine (KCONVAC) in Healthy Adults: Two Randomized, Double-blind, and Placebo-controlled Phase 1/2 Clinical Trials

BackgroundThe 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 a SARS-CoV-2 inactivated vaccine, KCONVAC, in healthy adults. MethodsTwo phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in Chinese healthy adults aged 18 through 59 years. The phase 1 trial was conducted in a manner of dosage escalation. The first 30 participants were randomized in a ratio of 4:1 to receive two doses of either KCONVAC at 5 g per dose or placebo on Day 0 and Day 14, and the second 30 participants were randomized to receive either KCONVAC at 10 g per dose or placebo following the same procedures. The participants in the phase 2 trial were randomized in a ratio of 2:2:1 to receive either KCONVAC at 5 g or 10 g per dose, or placebo on Day 0 and Day 14, or Day 0 and Day 28. In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following each vaccination. Antibody response and cellular response were assayed in the phase 1 trial. In the phase 2 trial, the primary immunogenicity endpoint was the seroconversion and titre of neutralization antibody, and the seroconversion of receptor binding domain (RBD)-IgG 28 days after the second dose. FindingsIn the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-g vaccine (N=24), 10-g vaccine (N=24), or placebo (N=12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-g vaccine (N=100 for 0/14 or 0/28 regimens), 10-g vaccine (N=100 for each regimen), or placebo (N=50 for each regimen). In the phase 1 trial, 13 (54%), 11(46%), and 7 (58%) participants reported at least one adverse event (AE), of whom 10 (42%), 6 (25%), and 6 (50%) participants reported at least one vaccination-related AE after receiving 5-g vaccine, 10-g vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and 9 (18%) participants reported at least one AE, of whom 13 (13%), 17 (17%), and 6 (12%) participants reported at least one vaccination-related AE after receiving 5-g vaccine, 10-g vaccine, or placebo at the regimen of Day 0/14, respectively. Similar results were observed in the three treatment groups of Day 0/28 regimen. All the AEs were grade 1 or 2 in intensity. No AE of grade 3 or more was reported. One SAE (foot fracture) was reported in the phase 1 trial. KCONVAC induced significant antibody response. 87{middle dot}5% (21/24) to 100% (24/24) of participants in the phase 1 trial and 83{middle dot}0% (83/100) to 100% (99/99) of participants in the phase 2 trial seroconverted for neutralising antibody to live virus, neutralising antibody to pseudovirus, and RBD-IgG after receiving two doses. Across the treatment groups in the two trials, the geometric mean titres (GMTs) of neutralising antibody to live virus ranged from 29{middle dot}3 to 49{middle dot}1 at Day 0/14 regimen and from 100{middle dot}2 to 131{middle dot}7 at Day 0/28 regimen, neutralising antibody to pseudovirus ranged from 69{middle dot}4 to 118{middle dot}7 at Day 0/14 regimen and from 153{middle dot}6 to 276{middle dot}6 at Day 0/28 regimen, and RBD-IgG ranged from 605{middle dot}3 to 1169{middle dot}8 at Day 0/14 regimen and from 1496{middle dot}8 to 2485{middle dot}5 at Day 0/28 regimen. RBD-IgG subtyping assay showed that a significant part of RBD-IgG was IgG1. The vaccine induced obvious T-cell response with 56{middle dot}5% (13/23) and 62{middle dot}5% (15/24) of participants in 5-g and 10-g vaccine groups showed positive interferon-{gamma} enzyme-linked immunospot responses 14 days after the second dose in the phase 1 trial, respectively. InterpretationKCONVAC is well tolerated and able to induce robust antibody response and cellular response in adults aged 18 to 59 years, which warrants further evaluation with this vaccine in the upcoming phase 3 efficacy trial. FundingGuandong Emergency Program for Prevention and Control of COVID-19 (2020A1111340002) and Shenzhen Key Research Project for Prevention and Control of COVID-19.

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).

Immunogenicity and Safety of a SARS-CoV-2 Inactivated Vaccine in Healthy Adults Aged 18-59 years: Report of the Randomized, Double-blind, and Placebo-controlled Phase 2 Clinical Trial

BACKGROUNDThe top priority for the control of COVID-19 pandemic currently is the development of a vaccine. A phase 2 trial conducted to further evaluate the immunogenicity and safety of a SARS-CoV-2 inactivated vaccine (CoronaVac). METHODSWe conducted a randomized, double-blind, placebo-controlled trial to evaluate the optimal dose, immunogenicity and safety of the CoronaVac. A total of 600 healthy adults aged 18-59 years were randomly assigned to receive 2 injections of the trial vaccine at a dose of 3 g/0.5 mL or 6 g /0.5mL, or placebo on Day 0,14 schedule or Day 0,28 schedule. For safety evaluation, solicited and unsolicited adverse events were collected after each vaccination within 7 days and 28 days, respectively. Blood samples were taken for antibody assay. RESULTSCoronaVac was well tolerated, and no dose-related safety concerns were observed. Most of the adverse reactions fell in the solicited category and were mild in severity. Pain at injection site was the most frequently reported symptoms. No Grade 3 adverse reaction or vaccine related SAEs were reported. CoronaVac showed good immunogenicity with the lower 3 g dose eliciting 92.4% seroconversion under Day 0,14 schedule and 97.4% under Day 0,28 schedule. 28 days after two-dose vaccination, the Nab levels of individual schedules range from 23.8 to 65.4 among different dosage and vaccination schedules. CONCLUSIONSFavorable safety and immunogenicity of CoronaVac was demonstrated on both schedules and both dosages, which support the conduction of phase 3 trial with optimum schedule/dosage per different scenarios.

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.

Intrarater reliability of measuring the patella position by ultrasonography in weight-bearing condition.

[Purpose] The aim of this study was to determine the intrarater reliability of using ultrasonography as a measurement tool to assess the patella position in a weight-bearing condition. [Subjects and Methods] Ten healthy adults participated in this study. Ultrasonography was used to assess the patella position during step down with the loading knee in flexion (0° and 20°). The distance between the patella and lateral condyle was measured to represent the patella position on the condylar groove. Two measurements were obtained on the first day and the day after 1 week by the same investigator. [Results] Excellent intrarater reliability, ranging from 0.83 to 0.93, was shown in both conditions. Standard errors of the measurements were 0.5 mm in the straight knee and 0.7 mm in the knee flexion at 20°. Minimal differences in knee flexion at 0° and knee flexion at 20° were 1.5 mm and 1.9 mm, respectively. [Conclusion] Ultrasonography is a reliable assessment tool for evaluating the positional changes of the patella in weight-bearing activities, and it can be easily used by practitioners in the clinical setting.

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.

[Effect of nylestriol and levonorgestrel on the expression of Opg/OPGL in human osteosarcoma MG-63 cell lines].

OBJECTIVE: To determine the effect of nylestriol and levonorgestrel on mRNA expression of OPG/OPGL in MG-63 cell lines, and to explore whether the paracrine effect is involved in the regulation course. Methods Semi-quantitive RT-PCR was conducted to analyze mRNA expression of OPG/OPGL in MG-63 cell lines treated with nylestriol and levonorgestrel. Results Both medicines could stimulate MG-63 cell lines to express OPG, and the best action levels of the two medicines were 10(-6) mol/L. Both medicines could decrease mRNA expression levels of OPGL dramatically. In NYL 10(-10) mol/L treatment group, medium renewal has negative effect on mRNA expression of OPG. Conclusion Both the two medicines can promote mRNA expression of OPG in MG-63 cell lines, while decrease mRNA expression of OPGL. The paracrine effect of MG-63 cell lines may be involved in the regulation of mRNA expression of OPG by NYL.