Immunogenicity and safety of revaccination of 23-valent pneumococcal polysaccharide vaccine in people aged 60 years and above / 中华流行病学杂志

Objective: To evaluate the immunogenicity and safety of revaccination of 23-valent pneumococcal polysaccharide vaccine (PPV23) in elderly people aged ≥60 years. Methods: The elderly aged ≥60 years with 1 dose of PPV23 vaccination were selected as revaccination group and those without history of pneumococcal vaccine immunization were selected as the first vaccination group. One dose of PPV23 was administered to both groups, and the first blood samples were collected before vaccination while the second blood samples were collected on day 28-40 after vaccination. ELISA was used to detect the concentrations of anti-specific serotype Streptococcus pneumoniae podocyte polysaccharide immunoglobulin G, and the safety of the vaccination was evaluated after 30 days. Results: The geometric mean concentration (GMC) of antibody to 23 serotypes before the vaccination (0.73-13.73 μg/ml) was higher in revaccination group than in the first vaccination group (0.39-7.53 μg/ml), the GMC after the vaccination (1.42-31.65 μg/ml) was higher than that before the vaccination (0.73-13.73 μg/ml) in the revaccination group, and the GMC after the vaccination (1.62-43.76 μg/ml) was higher than that before the vaccination (0.39-7.53 μg/ml) in the first vaccination group; the geometric mean growth multiple in revaccination group (2.16-3.60) was lower than that in the first vaccination group (3.86-16.13); The mean 2-fold antibody growth rate was lower in revaccination group (53.68%, 95%CI: 52.30%-55.06%) than in the first vaccination group (93.16%, 95%CI: 92.18%- 94.15%), all differences were significant (P<0.001). After the vaccination, 13 serotypes of GMC were higher in the first vaccination group than in revaccination group (P<0.001), the differences were not significant for 10 serotypes of GMC (P>0.05). The incidence of local adverse reaction was 19.20% and 13.27% in revaccination group and the first vaccination group, respectively (P=0.174). Conclusions: The antibody level in ≥60 years people who received one dose of PPV23 after a 5-year interval was still higher than that in unvaccinated people. The antibody level decreased after 5 years of the first vaccination, and the antibody level could be rapidly increased by one more dose vaccination, but the overall immune response was lower than that of the first vaccination; revaccination with PPV23 has a good safety.

Research progress of influenza vaccination, pneumococcal vaccination and COVID-19 vaccination among cancer patients / 中华预防医学杂志

This article reviews the relevant studies on the efficacy and safety of influenza, pneumococcal and COVID-19 vaccination among tumor patients worldwide in recent years. By combing and analyzing the retrieved literature, the results show that influenza and pneumococcal vaccination can significantly reduce the morbidity and hospitalization rate of infectious diseases in tumor patients, reduce the risk of cardiovascular events and death, and significantly improve survival prognosis. COVID-19 vaccination can also protect tumor patients, especially those who have completed full dose vaccination. Authoritative guidelines and consensuses worldwide all recommend that tumor patients receive influenza, pneumococcal and COVID-19 vaccines. We should carry out relevant researches, as well as take effective measures to strengthen patient education, so that tumor patients can fully experience the health protection brought by the vaccine to this specific group.

Safety and immunogenicity of a broad-spectrum mosaic vaccine as a booster dose against SARS-CoV-2 Omicron and other circulating variants

BACKGROUNDThe rising breakthrough infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, especially Omicron and its sub-lineages, have raised an urgent need to develop broad-spectrum vaccines against coronavirus disease 2019 (COVID-19). We have developed a mosaic-type recombinant vaccine candidate, named NVSI-06-09, having immune potentials against a broad range of SARS-CoV-2 variants. METHODSAn ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of NVSI-06-09 as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had completed two or three doses of BBIBP-CorV vaccinations at least 6 months prior to the enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against SARS-CoV-2 Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. RESULTSA total of 516 participants received booster vaccination. Interim results showed a similar safety profile between NVSI-06-09 and BBIBP-CorV booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 after the booster vaccination, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline level elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those boosted by BBIBP-CorV. CONCLUSIONSA booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against SARS-CoV-2 prototype strain and immune-evasive variants, including Omicron and its sub-lineages. The immunogenicity of NVSI-06-09 as a booster vaccine was superior to that of BBIBP-CorV. (Funded by LIBP and BIBP of Sinopharm; ClinicalTrials.gov number, NCT05293548).

Safety and immunogenicity of a hybrid-type vaccine booster in BBIBP-CorV recipients: a randomized controlled phase 2 trial

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with immune escape ability raises the urgent need for developing cross-neutralizing vaccines against the virus. NVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluated the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in adults previously vaccinated with the inactivated vaccine BBIBP-CorV in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates (NCT05069129). Three groups of healthy adults over 18 years of age (600 participants per group) who had administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, were vaccinated with either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The primary outcome was immunogenicity and safety of booster vaccinations. The exploratory outcome was cross-reactive immunogenicity against multiple SARS-CoV-2 variants of concerns (VOCs). The incidence of adverse reactions was low in both booster vaccinations, and the overall safety profile of heterologous boost was quite similar to that of homologous boost. Heterologous NVSI-06-08 booster was immunogenically superior to homologous booster of BBIBP-CorV. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster were significantly higher than by the booster of BBIBP-CorV against not only SARS-CoV-2 prototype strain but also multiple VOCs. Especially, the neutralizing activity induced by NVSI-06-08 booster against the immune-evasive Beta variant was no less than that against the prototype strain, and a considerable level of neutralizing antibodies against Omicron (GMT: 367.67; 95%CI, 295.50-457.47) was induced by heterologous booster, which was substantially higher than that boosted by BBIBP-CorV (GMT: 45.03; 95%CI, 36.37-55.74). Our findings showed that NVSI-06-08 was safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which was immunogenically superior to homologous boost with another dose of BBIBP-CorV. Our study also indicated that the design of hybrid antigen may provide an effective strategy for broad-spectrum vaccine developments.

Safety and immunogenicity of a heterologous boost with a recombinant vaccine, NVSI-06-07, in the inactivated vaccine recipients from UAE: a phase 2 randomised, double-blinded, controlled clinical trial

BackgroundThe increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccinations. In this study, we reported the safety and immunogenicity of a heterologous boost with a recombinant COVID-19 vaccine (CHO cells), named NVSI-06-07, as a third dose in participants who have previously received two doses of the inactivated vaccine (BBIBP-CorV) at pre-specified time intervals. Using homologous boost with BBIBP-CorV as control, the safety and immunogenicity of the heterologous boost with NVSI-06-07 against various SARS-CoV-2 strains, including Omicron, were characterized. MethodsThis study is a single-center, randomised, double-blinded, controlled phase 2 trial for heterologous boost of NVSI-06-07 in BBIBP-CorV recipients from the United Arab Emirates (UAE). Healthy adults (aged [≥]18 years) were enrolled and grouped by the specified prior vaccination interval of BBIBP-CorV, i.e., 1-3 months, 4-6 months or [≥]6 months, respectively, with 600 individuals per group. For each group, participants were randomly assigned at 1:1 ratio to receive either a heterologous boost of NVSI-06-07 or a homologous booster dose of BBIBP-CorV. The primary outcome was to comparatively assess the immunogenicity between heterologous and homologous boosts at 14 and 28 days post-boosting immunization, by evaluation of the geometric mean titers (GMTs) of IgG and neutralizing antibodies as well as the corresponding seroconversion rate ([≥]4-fold rise in antibody titers). The secondary outcomes were the safety profile of the boosting strategies within 30 days post vaccination. The exploratory outcome was the immune efficacy against Omicron and other variants of concern (VOCs) of SARS-CoV-2. This trial is registered with ClinicalTrials.gov, NCT05033847. FindingsA total of 1800 individuals who have received two doses of BBIBP-CorV were enrolled, of which 899 participants received a heterologous boost of NVSI-06-07 and 901 received a homologous boost for comparison. No vaccine-related serious adverse event (SAE) and no adverse events of special interest (AESI) were reported. 184 (20{middle dot}47%) participants in the heterologous boost groups and 177 (19{middle dot}64%) in the homologous boost groups reported at least one adverse reaction within 30 days. Most of the local and systemic adverse reactions reported were grades 1 (mild) or 2 (moderate), and there was no significant difference in the overall safety between heterologous and homologous boosts. Immunogenicity assays showed that the seroconversion rates in neutralizing antibodies against prototype SARS-CoV-2 elicited by heterologous boost were 89{middle dot}96% - 97{middle dot}52% on day 28 post-boosting vaccination, which was much higher than what was induced by homologous boost (36{middle dot}80% - 81{middle dot}75%). Similarly, in heterologous NVSI-06-07 booster groups, the neutralizing geometric mean titers (GMTs) against the prototype strain increased by 21{middle dot}01 - 63{middle dot}85 folds from baseline to 28 days post-boosting vaccination, whereas only 4{middle dot}20 - 16{middle dot}78 folds of increases were observed in homologous BBIBP-CorV booster group. For Omicron variant, the neutralizing antibody GMT elicited by the homologous boost of BBIBP-CorV was 37{middle dot}91 (95%CI, 30{middle dot}35-47{middle dot}35), however, a significantly higher level of neutralizing antibodies with GMT 292{middle dot}53 (95%CI, 222{middle dot}81-384{middle dot}07) was induced by the heterologous boost of NVSI-06-07, suggesting that it may serve as an effective boosting strategy combating the pandemic of Omicron. The similar results were obtained for other VOCs, including Alpha, Beta and Delta, in which the neutralizing response elicited by the heterologous boost was also significantly greater than that of the homologous boost. In the participants primed with BBIBP-CorV over 6 months, the largest increase in the neutralizing GMTs was obtained both in the heterologous and homologous boost groups, and thus the booster vaccination with over 6 months intervals was optimal. InterpretationOur findings indicated that the heterologous boost with NVSI-06-07 was safe, well-tolerated and immunogenic in adults primed with a full regimen of BBIBP-CorV. Compared to homologous boost with a third dose of BBIBP-CorV, incremental increases in immune responses were achieved by the heterologous boost with NVSI-06-07 against SARS-CoV-2 prototype strain, Omicron variant, and other VOCs. The heterologous BBIBP-CorV/NVSI-06-07 prime-boosting vaccination may be valuable in preventing the pandemic of Omicron. The optimal booster strategy was the heterologous boost with NVSI-06-07 over 6 months after a priming with two doses of BBIBP-CorV. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for clinical trials or prospective/cohort studies involving heterologous booster vaccination in non-immunocompromised population published up to Dec 25, 2021, using the term "(COVID) AND (vaccin*) AND (clinical trial OR cohort OR prospective) AND (heterologous) AND (booster OR prime-boost OR third dose)" with no language restrictions. Nine studies of heterologous prime-boost vaccinations with adenovirus-vector vaccines (ChAdOx1 nCov-19, Oxford-AstraZeneca, Ad26.COV2.S, Janssen) and mRNA vaccines (BNT162b2, Pfizer-BioNtech; mRNA1273, Moderna) were identified. The adenovirus-vector and mRNA heterologous prime-boost vaccination was found to be well tolerated and immunogenic. In individuals primed with adenovirus-vector vaccine, mRNA booster vaccination led to greater immune response than homologous boost. However, varied results were obtained on whether heterologous boost was immunogenically superior to the homologous mRNA prime-boost vaccination. Besides that, A preprint trial in population previously immunized with inactivated vaccines (CoronaVac, Sinovac Biotech) showed that the heterologous boost with adenovirus-vector vaccine (Convidecia, CanSino Biologicals) was safe and induced higher level of live-virus neutralizing antibodies than by the homogeneous boost. A pilot study reported that boosting with BNT162b2 in individuals primed with two doses of inactivated vaccines (BBIBP-CorV) was significantly more immunogenic than homologous vaccination with two-dose of BNT162b2. In addition, a preprint paper demonstrated that heterologous boost of ZF2001, a recombinant protein subunit vaccine, after CoronaVac or BBIBP-CorV vaccination potently improved the immunogenicity. But only a small size of samples was tested in this study and the live-virus neutralization was not detected. Till now, it is still lacking a formal clinical trial to evaluate the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated vaccine followed by a recombinant protein subunit-based vaccine. Added value of this studyTo our knowledge, this is the first reported result of a large-scale randomised, controlled clinical trial of heterologous prime-boost vaccination with an inactivated vaccine followed by a recombinant protein subunit vaccine. This trial demonstrated that the heterologous prime-booster vaccination with BBIBP-CorV/NVSI-06-07 is safe and immunogenic. Its immunoreactivity is similar to that of homologous vaccination with BBIBP-CorV. Compared to homologous boost, heterologous boost with NVSI-06-07 in BBIBP-CorV recipients elicited significantly higher immunogenicity not only against the SARS-CoV-2 prototype strain but also against Omicron and other variants of concern (VOCs). Implications of all the available evidenceBooster vaccination is considered an effective strategy to improve the protection efficacy of COVID-19 vaccines and control the epidemic waves of SARS-CoV-2. Data from our trial suggested that the booster vaccination of NVSI-06-07 in BBIBP-CorV recipients significantly improved the immune responses against various SARS-CoV-2 strains, including Omicron. Due to no Omicron-specific vaccine available currently, the BBIBP-CorV/NVSI-06-07 heterologous prime-boost might serve as an effective strategy combating Omicron variant. Besides that, BBIBP-CorV has been widely inoculated in population, and thus further boosting vaccination with NVSI-06-07 is valuable in preventing the COVID-19 pandemic. But further studies are needed to assess the long-term protection of BBIBP-CorV/NVSI-06-07 prime-booster vaccination.

Long-term trend of viral hepatitis mortality and potential years of life lost in Jing’an District of Shanghai， 1976-2015 / 上海预防医学

Objective:To analyze the long-term trend of viral hepatitis mortality in Jing’an District of Shanghai， and to provide a reference for viral hepatitis prevention and control. Methods:Mortality rate， standard mortality rate， PYLL and potential years of life lost rate （PYLL‰） of viral hepatitis in Jing’an district of Shanghai from 1976 to 2015 were calculated. The annual percent change （APC） of the mortality and PYLL‰ were analyzed by Joinpoint regression analysis. Results:From 1976 to 2015， there were 1 342 viral hepatitis death cases， including 832 males and 510 females. The average crude mortality rate was 8.31/100 000， and the average age-standardized mortality rate was 5.45/100 000. Among the deaths of viral hepatitis， men had a higher mortality rate， age-standardized mortality rate and PYLL% than women （χ2Pearson=107.34， 112.93， 39.15， all P<0.01）， men were mainly in the age group of 35-64 years （accounted for 62.62%）， while women were mainly in the age group of 65 years and above （accounted for 55.49 %）， and the average death age of men was earlier than that of women （by rank-sum test： Z=-8.879，P<0.01）. After 1990 （except in 2002）， hepatitis B was the main cause of deaths from viral hepatitis， accounting for 75.00%-100%， and the proportion of other and unclassified cases gradually decreased. Overall， the mortality rate of viral hepatitis declined significantly during 1976-2015 （APC=-2.0%，P<0.05）， with the turning point in 2002. The mortality rate of viral hepatitis declined significantly from 2002 to 2015 （APC=-8.1%，P<0.05）. The overall PYLL‰ of viral hepatitis declined significantly during 1976-2015 （APC=-3.7%，P<0.05）， with the turning point in 1992. After 1992， the PYLL‰ of viral hepatitis declined significantly during 1992-2015 （APC=-6.5%，P<0.05）. Conclusion:There has been a significant decline trend of viral hepatitis in the mortality rate in Jing’an District of Shanghai from 2002 to 2015， with hepatitis B as the main cause of death.

Trends in the incidence and mortality of colorectal cancer in Jing'an District of Shanghai from 1993 to 2017 / 上海预防医学

Objective:To characterize the trends in the incidence and mortality of colorectal cancer in Jing'an District of Shanghai， thus optimizing the prophylactic options for this malignancy. Methods:Data from Shanghai Cancer Registration and Reporting System were used to analyze the colorectal cancer prevalence in Jing'an District from 1993 to 2017. Joinpoint software was used to analyze the trends in the standardized incidence rate and mortality rate by calculating the annual percentage of change （APC） and the average annual percentage of change （AAPC）. Results:A total of 13 580 new cases of colorectal cancer were reported in Jing'an District during 1993 and 2017， with an average crude incidence rate of 52.94/105 and a standardized incidence rate of 24.77/105. The total number of deaths was 7 572， with an average crude mortality rate of 29.52/105 and a standardized mortality rate of 12.20/105. The standardized incidence rate of colorectal cancer in Jing'an District from 1993 to 2017 showed an increasing trend （AAPC=1.64%，P<0.001）， and the standardized incidence rate of colorectal cancer in both sexes increased （AAPC： 2.10% in men， 1.04% in women）. The age-standardized mortality rate （ASMR） did not change significantly. The incidence rate of colorectal cancer increased in men in both age groups of 50 to 74 years and 75 years and older， with an AAPC of 2.07% and 3.32%， respectively. However， this was not evident in women of all age groups. The mortality rate of colorectal cancer in men aged 0-49 years， as well as in men and women at 50-74 age groups， decreased significantly， with an AAPC of -7.46%，-1.13%， and -2.72%， respectively. The mortality rate of colorectal cancer in men of 75 years or older showed no significant trend， while that in women of 75 years or older increased （AAPC=2.30%）. Conclusion:The overall standardized incidence rate of colorectal cancer in Jing'an District from 1993 to 2017 was increased， and ASMR did not change significantly. Public health prophylactic options are suggested， including improvement of lifestyle/physical activity and eradication of precancerous lesion polypus in males aged ≥50 years to reduce the incidence of colorectal cancer， and enforcement of second-grade prophylaxis in females aged ≥75 years to decrease the mortality of colorectal cancer.

Catalytic Direct Construction of Cyano-tetrazoles.

Cyano-tetrazole is the first reported compound that bears four nitrogen atoms in a single five-membered ring. This unique molecular scaffold has long been ignored after its discovery in 1885, mainly attributed to the scarcity of available synthetic methods. Indeed, the most popular approach to tetrazoles (that is the cycloaddition reaction between nitriles and azides) has inevitably excluded the possibility of introducing valuable cyano groups to decorate the final heterocyclic cores. Here, we describe a completely different disconnection strategy to the long time-pursued cyano-tetrazoles via a simple, direct, and practical cycloaddition transformation between readily accessible aryl diazonium salts and diazoacetonitrile. This method provides both regioisomers of disubstituted tetrazoles from the same set of starting materials in a metal cation controlled fashion.

One-stage transpedicular debridement, posterior internal fixation and fusion for the treatment of senile thoracolumbar tuberculosis / 中国骨伤

OBJECTIVE@#To evaluate the clinical outcomes of one-stage transpedicular debridement, posterior internal fixation, RBK mixed streptomycin filled bone grafting for the treatment of elderly patients with thoracolumbar tuberculosis.@*METHODS@#The clinical data of 20 elderly patients with thoracolumbar tuberculosis underwent one stage transpedicular debridement, posterior internal fixation, OSTEOSET RBK mixed streptomycin-filled bone grafting from September 2006 to July 2017 were retrospectively analyzed. There were 12 males and 8 females, aged from 62 to 83 years with an average of (72.4±6.9) years old. Visual analogue scale (VAS), Oswestry Disability Index (ODI)were used to evaluate the pain and spinal function. The kyphosis angle (Cobb angle) of the lesion segment and the bone growth of the lesion area were observed by the X-ray films.@*RESULTS@#All the operations were successful, the operation time was (160.9±23.8) min, and the intraoperative blood loss was (317.9± 112.7) ml. The incisions were healed by first intention, and no sinus and incision were delayed. Spinal tuberculosis was completely cured, Frankel grade has one or more improvements. The VAS score decreased from (7.50±1.15) points before surgery to (1.70±1.39) points at 12 months after surgery (<0.05). The ODI score decreased from preoperative (92.50±1.17)% to (12.80±0.89)% at the final follow up (<0.05). The sagittal Cobb angle of the lesion segment decreased from preoperative (24.2±1.6)° to (8.3±0.7)°at 12 months after surgery(<0.05), the kyphosis deformity was significantly corrected. In all cases, bone fusion was achieved in bone graft area, without bone nonunion and device fracture complications.@*CONCLUSION@#One-stage transpedicular debridement, posterior internal fixation, RBK mixed streptomycin filled bone grafting is suitable for thoracolumbar tuberculosis patients with good general condition and less vertebral destruction.

Relationship between alterations of spine-pelvic sagittal parameters and clinical outcomes after oblique lumbar interbody fusion / 中国骨伤

OBJECTIVE@#To investigate the relationship between spine-pelvic sagittal parameters and clinical efficacy before and after oblique lumbar interbody fusion(OLIF).@*METHODS@#A retrospective analysis of clinical data of 65 patients with lumbar degenerative diseases treated with OLIF were performed from July 2017 to July 2018. There were 26 males and 39 females aged from 33 to 79 years old with an average of (62.72±10.23) years old. Oswestry Disability Index (ODI) and visual analogue scale (VAS) before and at the latest follow up were evaluated. Disc height (DH) and spine- pelvic sagittal parameters of the surgical segment were measured before and at the latest follow- up, including pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS) and lumbar lordosis (LL). According to the difference of PI-LL, it was judged whether PI and LL match and the patients were grouped, PI-LL ranged from -9° to 9° was set as matching group, and PI-LL less than -9° or larger than 9° was set as mismatching group. The spine-pelvic sagittal parameters were analyzed before and at the latest follow-up of OLIF in patients with lumbar degenerative diseases, and the correlation between changes and clinical efficacy was compared.@*RESULTS@#All patients were followed up from 8 to 20 months with an average of (14.20±3.68) months. Operation time was (91.54±25.97) min, intraoperative blood loss was (48.15±10.14) ml, and the hospitalization time ranged from 6 to 19 days with an average of (9.28± 2.50) days. Totally 84 surgical levels, 46 patients were single segment and 19 patients were double segments. VAS and ODI score were improved from (4.88±0.99) point, (67.60±13.73) % preoperatively to (2.85±1.30) points, (30.57±6.48) % at the latest follow-up. There were significant differences in VAS and ODI scores between before and at the latest follow-up. The sagittal parameters of LL, PT, SS, PI, PI -LL and the surgical level DH were (42.80 ±16.35)° , (23.22 ±10.91)° , (26.95 ± 13.30)°, (50.22±14.51)°, (7.53±16.13) °, (0.91±0.29) cm preoperatively and improved to the latest follow-up (49.95± 12.82) °, (17.94±9.24) °, (33.71±12.66) °, (51.65±10.26) °, (1.68±17.00) °, (1.20±0.40) cm;there were statistical differences in LL, PT, SS, PI-LL, DH before operation and at the latest follow up, while no difference in PI. LL of preoperative PI-LL in matched group was (48.76±11.09)° , and (38.00±18.37)° in PI-LL mismatch group, there was difference between two groups. There were no differences in VAS, ODI, PT, SS, PI and DH between two groups. At the latest follow-up, ODI between PI-LL matched group and PI-LL mismatched group were (29.40±5.93)% and (32.86±7.02)% respectively, and had difference in ODI between two groups;while there were no significant differences in VAS, LL, PT, SS, PI, and DH. Pearson correlation analysis showed preoperative PT-LL was positively correlated with VAS;PT was positively correlated with ODI at the latest follow-up.@*CONCLUSION@#OLIF has a good surgical effect on lumbar degenerative diseases, and could change spine-pelvic sagittal parameters of patient to a certain extent, and further restoring the balance of the sagittal plane of lumbar spine.

Analysis on the prevalence of thyroid cancer in Jing′an District, Shanghai / 上海预防医学

Objective To explore and analyse the prevalence of thyroid cancer among population of Jing′an District, Shanghai, providing a scientific basis for prevention and intervention. Methods Analysis was made on the prevalence of thyroid cancer in Jing′an District in 2014 and its incidence and death trend from 2009 to 2014 based on the data of Shanghai Cancer Registration and Reporting System. Results From 2005 to 2014, the total number of thyroid cancer cases in Jing′an District were 2 430, ranking fourth of all malignant tumors.The crude incidence rate of thyroid cancer was 24.33/100 000, the standardized incidence rate was 16.67/100 000.The ratio of male to female was 0.34 : 1;the difference in incidence between male and female was significant(χ2=579.77, P < 0.01).In different age groups the difference in incidence was also statistically significant(χ2=419.90, P < 0.01).The highest incidence was in 45-64 years old group, followed by 15-44 years old group. Only 155 deaths occurred; the ratio of death to morbidity was 1 : 15.68.Standardized incidence of thyroid cancer was increasing in Jing′an District from 2005 to 2014(trend Chi-square tests, χ2=7.33, P < 0.01).APC was 20.69%(male 23.81%, female 19.44%).The standardized mortality rate from 2005 to 2014 was at a relatively low level, and the trend of change was not statistically significant. Conclusion The government and society should pay high attention to the status of high detection rate and low mortality rate of thyroid cancer.The focus of prevention and control is rational diagnosis and treatment for a large number of thyroid cancer patients.

A review of combined immunization: current research situation and its promising future / 中华流行病学杂志

Combined immunization consists of combined vaccines (including polyvalent vaccines) and simultaneous administration of vaccines, aiming to reduce unnecessary inoculating times for children, and to broaden immunization coverage and a significant larger group of population would be benefit from the Expanded Program on Immunization. In this review, we have summarized a list of research papers focused on combined immunization. By scrutinizing the safety and effectiveness outcomes of combined immunization, we provide some suggestions about upgrading the current immunization program as well as research and development of new combined vaccines.

Construction of Difluoromethylated Tetrazoles via Silver-Catalyzed Regioselective [3 + 2] Cycloadditions of Aryl Diazonium Salts.

A silver-catalyzed regioselective [3 + 2] cycloaddition reaction of PhSO2CF2CHN2 with aryl diazonium salts is described. This protocol enables the straightforward construction of a novel class of difluoromethylated tetrazoles under mild conditions, tolerates a broad spectrum of functionalities, and is applicable to one-pot operation from commercially available aniline derivatives. The synthetic merit of this method is further demonstrated by the facile preparation of versatile difluoromethylated azoles, including a valuable HCF2-analogue of P2X3 receptor antagonist.

Current situation and reflection of preserving reproductive function in cervical cancer patients / 中国实用妇科与产科杂志

With the standardization and popularization of cervical cancer screening techniques,more and more young patients with cervical cancer are being detected at an early stage,and most patients with cervical cancer at reproductive age have a strong intention to preserve fertility.This article will summarize the operation indication,operation methods,safety,oncologic outcomes and related controversies of fertility preservation surgery in patients with cervical cancer.

Prevention of chemotherapy-induced ovarian damage in patients with gynecological malignant tumors / 中国实用妇科与产科杂志

Improvement in diagnosis has made it possible to have the early detection of gynecologic malignancies.Among premenopausal women,the loss of future fertility or ovarian function is considered among the most dreadful long-term side effects of treatments.Therefore,the preservation of fertility and ovarian function during chemotherapy treatment is of great important.This article will summarize the effect of chemotherapy on ovarian function and protective measures for chemotherapy-induced ovarian damage.

Dynamics of Proliferation and Differentiation after Transplantation of Hematopoietic Cells in Mouse / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of Listeria monocytogenes infection on hematopoietic stem and progenitor cell (HSPC) composition, cell cycle and cell colony-forming ability in mouse bone marrow.@*METHODS@#The C57BL/6J mice were divided into infected group and control group. The mice in injected group were infected intraperitoneally with 6.7×10 CFU Listeria monocytogenes,while the mice in control group were injecfed with PBS of same volume.The serum levels of IFNγ were detected at different time points. After 24 hours, the HS/PC composition, cell cycle and cell colony-forming ability in bone marrow of mice were measured, and the difference between the control group and the infected group was statistically analyzed.@*RESULTS@#Serum IFNγ levels peaked at 24 hours after infection with Listeria monocytogenes. After 24 h, the proportion of LSK, LSK in S phase, and short-term hematopoietic stem cells (ST-HSC) in the infected group were significantly higher than those in the control group (P＜0.001), long-term hematopoietic stem cells (LT-HSC) and the proportion of LT-HSC in S phase were significantly increased (P＜0.01), and the cell colony-forming ability of bone marrow significantly decreased (P＜0.01). [WTHZ]Conclusion: [WTB1]After infection with Listeria monocytogenes, bone marrow hematopoietic stem cells enter the proliferative state from rest, the cell colony-forming ability decreases, suggesting that Listeria monocytogenes infection can cause hematopoietic stem cell depletion.

Preparation,Characterization and in Vitro and in Vivo Absorption Characteristics of Daidzein Nanosuspension Capsules / 中国实验方剂学杂志

Objective:To prepare daidzein nanosuspension capsules,and to investigate intestinal absorption and oral bioavailability by comparing with commercial daidzein capsules. Method:Daidzein nanosuspensions were prepared by precipitation method combined with high pressure homogenization,orthogonal design method was utilized to optimize its formulation.Daidzein nanosuspensions was characterized by X-ray powder diffraction(XRPD),Fourier transform infrared spectroscopy(FT-IR),transmission electron microscope(TEM),and indexes including mean particle size,polydispersity index(PDI),and Zeta potential.Intestinal absorption study was carried out to compare the accumulative permeated amount of daidzein from daidzein nanosuspensions and commercial daidzein capsules.Biodistribution of daidzein in gastrointestinal tract was investigated,and oral bioavailability was examined through pharmacokinetic study by HPLC. Result:The in vitro small intestinal absorption enhancement ratio of daidzein nanosuspension capsules was approximately 2.49-fold higher than that of commercial capsules(PConclusion:Daidzein nanosuspensions prepared by combined method can be applied to the production of capsules,which is beneficial to increase the absorption of drug in small intestine and improve its bioavailability after oral administration.

Effect of prmt3 knockout on A549 cell line using CRISPR/Cas9 / 军事医学

Objective To construct plasmids for knock-out of protein arginine methyltransferase 3 (prmt3) gene using CRISPR/Cas9 gene editing method and examine the effect of prmt3 knockout on the proliferation of human non-small cell lung cancer(NSCLC)A549 cells.Methods Synthesized sgRNA oligos targeting prmt3 gene were cloned into LentiCRISPR vector and positive constructs confirmed by sequencing later .After infection with the packaged virus , A549 cells were screened with puromycin , and then the single clones were isolated .The protein level of PRMT3 in individual cell clones was analyzed with Western blot . Biological assay of clone formation , wound healing , flow cytometry assay and mass spectrometry ( MS) analysis were used to compare cellular proliferation behavior changes between control cells and cells with prmt3 gene knockout .Results The LentiCRISPR plasmids targeting prmt3 gene were confirmed by sequencing , and the PRMT3 protein level was significantly decreased in PRMT 3 KO cells compared with control cells .Depletion of PRMT3 promoted cell proliferation and led to cell cycle arrest at G 2/M phase, but had no influence on cell migration .Besides, some PRMT3 substrate candidates were identified with mass spectrum assays .Conclusion A549 cells with prmt3 gene knockout based on CRISPR/Cas9 are successfully established .PRMT3 can regulate cell cycle and proliferation .

Construction of BRCC3 gene knockout mice and preliminary analysis of the pheno-type / 军事医学

Objective To construct BRCC3(BRCA1/BRCA2-containing complex subunit 3)gene knockout mice and preliminarily study the phenotypes.Methods Using the Cas9/sgRNA-Mediated genome Editing, the BRCC3 knockout mouse models were constructed.Genomic DNAs of mouse tail tissues were extracted and identified, the genotypes of mice were determined at the DNA level,and RNAs and proteins of tissues, such as the heart, liver, spleen, lung, kidney of mice were extracted and the expression of BRCC3 gene was detected by real-time-PCR and Western blotting(WB).The trend of relative body mass change and indexes that might affect the growth development and metabolism were observed. Major organs were hematoxylin-eosin(HE)stained and observed.The routine blood test of peripheral blood of mice was conducted.Results The mouse model of BRCC3 knockout was successfully constructed.BRCC3 knockout mouse survived and were fertile, indexes of blood lipid and liver function were normal, organs were not degenerative and indexes of peripheral blood in routine blood test were all in the normal range.The relative body mass of BRCC3 knockout mice was higher than that of wild type mice,and the level of serum cholesterol was increased.Conclusion BRCC3 may be involved in relative body mass regulation and cholesterol metabolism in mice.

Expression and significance of Wnt-5a gene in a model of intervertebral disc degeneration / 中国组织工程研究

BACKGROUND: Important extracellular matrixes are reduced with the prolongation of duration of cyclic pressure in the endplate of the intervertebral disc. Meanwhile, the expression of Wnt-5a gene is significantly decreased. There is an important relationship between Wnt-5a gene and intervertebral disc degeneration (IDD). OBJECTIVE: To investigate the expression of Wnt-5a gene under cyclic pressure in a rabbit model of IDD and to explore its role in IDD progress. METHODS: Lumbar intervertebral discs were removed from the 6-month-old New Zealand white rabbits to prepare IDD models and were then randomly divided into experimental (cyclic pressure ) and control (no intervention) groups. The morphological changes of intervertebral discs were observed by hematoxylin-eosin staining and safranin O-fast green staining. The mRNA expression levels of proteoglycan, collagen type Ⅱ, and Wnt-5a were detected by real-time PCR. The protein expression level of Wnt-5a was detected by western blot assay. RESULTS AND CONCLUSION: The morphology of intervertebral discs cultured for 7 days in the experimental and control groups showed a certain change, but was still intact; expression levels of aggrecan, type Ⅱ collagen, Wnt-5a showed differences from the intervertebral discs cultured for 0 day. On day 14, the damage to the histomorphology was severer in the experimental group than the 0-day control group. The mRNA expression levels of proteoglycan, collagen type Ⅱ, and Wnt-5a were decreased in both groups, especially the experimental group, at 7 and14 days. The mRNA and protein expression levels of Wnt-5a revealed the same change trend with time. To conclude, regulation of Wnt-5a expression may alter the process of endplate cartilage degeneration, and thus providing new ideas for the prevention and treatment of IDD.