[The progress on post-exposure prophylaxis of tetanus immunological preparation in adults].

The tetanus has been eliminated in the pregnancy women and newborns in China. However, there is a gap for adult tetanus immunization, and the risk of tetanus infection cannot be ignored. In order to clearly understand the effect of the tetanus to human beings and the current use of tetanus immunological preparation for adult post-exposure prophylaxis, the incidence of the tetanus, the use status of tetanus immunological preparation and recommendations for post-exposure prophylaxis at home and abroad were reviewed and summarized, which may provide academic evidence for post-exposure prophylaxis procedures and use of tetanus immunological preparation.

[Progress in epidemiological research of norovirus infection].

With characteristics of high infectivity, diverse transmission routes and high variation, norovirus is the main pathogen of sporadic cases and outbreaks of acute gastroenteritis, resulting in a serious disease burden. This paper summarizes the latest progress in epidemiological research of norovirus infection from aspects of disease burden caused by acute gastroenteritis, virus variation and predominant strains, prevention and control measures, and immunization and vaccine development.

[Development and outlook on human challenge trial of vaccine].

Human challenge trial (HCT) is a test in which human volunteers are intentionally infected with pathogens in order to evaluate the efficacy of candidate preventive or therapeutic drugs. During the COVID-19 pandemic, the HCT of vaccines has aroused people's attention due to its significant advantages over clinical trial. This paper introduces the concept, development and application of HCT, the advantages and limitations of HCT for vaccine evaluation, and the consideration of future HCT of COVID-19 vaccine in China.

[Hesitancy of parents towards vaccines in national immunization program in three regions in China: a cross-sectional study].

Objective: To investigate the incidence and determinants of vaccine hesitancy towards national immunization program in China and understand the current status of parents' hesitancy to different vaccines used in national immunization program. Methods: A cross-sectional survey was conducted in Beijing, Sichuan and Gansu. The methods of proportional probability sampling and convenience sampling were used to select the eligible study subjects for questionnaire surveys. Results: A total of 3 592 parents were enrolled in the study, in whom 38.22% fully accepted all the vaccines, 59.35% agreed to let their children to receive all the vaccines but showed slight concern, and 2.42% had hesitancy to the vaccines. The vaccine with the most hesitancy was polio vaccine (0.89%), followed by diphtheria pertussis tetanus vaccine (0.70%) and hepatitis A vaccine (0.64%). The dominant reason for vaccine hesitancy was the risk-benefit perception of vaccination (31.03%), followed by the low awareness of the parents (21.84%) and the inconvenience caused by distance and time (21.84%). Conclusions: The incidence of vaccine hesitancy towards national immunization program was low in parents in China, but over 50% of the parents showed concern to the vaccines. It is essential to improve the service quality of national immunization program and strengthen the health education about the vaccination to reduce the incidence of vaccine hesitancy in parents.

Effect of NT-3 on infection-induced memory impairment of neonatal rats.

OBJECTIVE: To explore the effect of neurotrophin-3 (NT-3) messenger ribonucleic acid (mRNA) in the hippocampus on infection-induced memory impairment of neonatal rats. MATERIALS AND METHODS: 80 female Sprague-Dawley (SD) rats in the neonatal stage were selected to establish memory impairment model by bacterial meningitis infection. Rats were randomly divided into experimental group (n=40) and control group (n=40). Rats in experimental group were injected with ß-amyloid precursor protein 319-335 peptide APP17p into brain tissue to up-regulate the expression of NT-3, and the rats in control group didn't receive treatment. Behavioral changes of rats were observed in Morris water maze and passive avoidance experiment. Apoptosis of nerve cells was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) method and Fluoro-Jade B method. NT-3 mRNA expression level was measured via reverse transcription polymerase chain reaction (RT-PCR). RESULTS: NT-3 expression level in experimental group was higher than that in control group (p<0.05). Apoptosis rate of nerve cells in experimental group was lower than that in control group, but the learning and memory ability of rats in experimental group was better than that in control group (p<0.05). CONCLUSIONS: Reduced NT-3 expression level may be correlated with the occurrence of meningitis because NT-3 can suppress nerve cell apoptosis and ameliorate learning and memory impairment to a certain extent to exert neuroprotective effects.

A study on correlations of procalcitonin and interleukin-6 with viral meningitis.

OBJECTIVE: To study the change rules of inflammatory factors in cerebrospinal fluid (CSF) and serum of patients with viral meningitis. PATIENTS AND METHODS: 742 patients with suspected viral meningitis admitted to Department of Neurosurgery in our hospital from August 2012 to May 2016 were selected as research objects and retrospectively analyzed. 536 patients were diagnosed with viral meningitis by CSF with the lumbar puncture and brain computed tomography (CT), while the other 206 patients were diagnosed with non-infectious nervous system disease, as the control group. The levels of inflammatory factors interleukin-6 (IL-6) in peripheral blood and procalcitonin (PCT) in cerebrospinal fluid were detected and compared between two groups of patients. RESULTS: Compared with those in control group, the white blood cell (WBC) count, and levels of serum IL-6 and PCT in cerebrospinal fluid of patients with viral meningitis were all increased (p<0.01). PCT and IL-6 were positively correlated with viral meningitis (r=0.8267, 0.9234). The sensitivity of the two items was 77.81% and 81.32%, respectively, and the specificity was 90.53% and 88.64%, respectively. CONCLUSIONS: The levels of inflammatory factors IL-6 and PCT in serum and CSF of patients with viral meningitis are slightly increased. The detection of the expression levels of IL-6 and PCT in patients with viral meningitis is of great significance for the preliminary diagnosis and rehabilitation of viral meningitis.

Lewy pathological study on α-synuclein in gastrointestinal tissues of prodromal Parkinson's disease.

The article "Lewy pathological study on α-synuclein in gastrointestinal tissues of prodromal Parkinson's disease" by Q.-B. Lu, Z.-F. Zhu, H.-P. Zhang, W.-F. Luo, published in Eur Rev Med Pharmacol Sci 2017; 21 (7): 1514-1521 has been withdrawn.

Lewy pathological study on α-synuclein in gastrointestinal tissues of prodromal Parkinson's disease.

OBJECTIVE: In the gastrointestinal neural system, the emergence of Lewy Body (LB) is usually earlier than the clinical diagnosis of Parkinson (PD) motor symptoms. Therefore, this study is aimed to explore whether the LB in the gastrointestinal tract of prodromal PD patients. PATIENTS AND METHODS: 98 paraffin embedded tissue specimens from 57 PD patients were collected in the Second Affiliated Hospital of Soochow University archives, as well as 98 tissue specimens of 90 non-PD patients undergone surgical resection. The pathological sections were stained by the immune-histochemistry method. The positive staining of aggregated a-Synuclein (a-a-syn) and phosphorylated a-Synuclein (p-a-syn) in gastrointestinal tract were counted to analyze the distribution of the expression of a/p-a-syn in the prodromal PD patients before diagnosis (0-5 years, 6-10 years, 11-20 years). RESULTS: According to results from the immunohistochemical staining of a/p-α-syn, 35 (52.23%) and 30 (44.78%) tissue blocks were positively stained respectively in total 67 tissue blocks provided from 39 prodromal PD patients. And there were 46 (46.94%) and 25 (25.51%) positive staining in 98 tissue blocks from the control group. In 31 tissue blocks collected from 18 PD patients, there were 19 (61.29%) and 15 (48.39%) tissue blocks with the a/p-a-syn positive staining. Compared with non-PD patients from the control group, the a-a-syn positive rate was not significantly increased in the pre- and post-diagnosis PD patients (p>0.05). However, p-a-syn of both groups increased significantly (p<0.05). Also, the positive expression rate of a/p-a-syn in the 6-10-year group was lower than that in the 0-5-year and 11-20-year, and the positive rate of the 0-5-year group was the highest (p<0.05). CONCLUSIONS: p-a-syn as the main component of Lewy body of nervous system in the gastrointestinal track may be used as a characteristic predictive marker of PD and the prevention of PD disease.

[Spatial analysis and prediction of severe fever with thrombocytopenia syndrome in Zhejiang province, 2011-2015].

Objective: To understand the distribution of the severe fever with thrombocytopenia syndrome (SFTS) in Zhejiang province, and predict the incidence and the probability of SFTS outbreak. Methods: Based on the cases of SFTS from 2011-2015, software ArcGIS 10.0 was used to analyze the spatial distribution, Moran's I and Getis-Ord Gi were used to analyze the spatial autocorrelation. The incidence trend was explored by trend surface analysis, and the prediction was made by Kriging interpolation. Results: The incidence of SFTS increased and the distribution expanded in Zhejiang from 2011 to 2015, the seasonal and the demographic characteristics of SFTS were similar to the previous research; there were regional clustering of the cases (P<0.001); a downward trend was observed from northeast to southwest in terms of incidence of SFTS; the second-order disjunctive Kriging interpolation based on circular model and the indicator Kriging interpolation based on exponential model had higher prediction accuracy, the probabilities of outbreak in Anji, Daishan and Tiantai were high, the prediction deviation of inland was less than that of edge area. Conclusion: The prediction of SFTS by Kriging interpolation had high accuracy, the incidence of SFTS was higher and the distribution of SFTS was larger than the results of surveillance, the risk areas for epidemic were Anji, Daishan, Ninghai,Tiantai, Sanmen and Linhai.

Epidemiological and clinical characteristics of severe fever with thrombocytopenia syndrome (SFTS) in China: an integrated data analysis.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was caused by a novel bunyavirus, SFTSV. The study aimed to disclose the epidemiological and clinical characteristics of SFTSV infection in China so far. An integrated clinical database comprising 1920 SFTS patients was constructed by combining first-hand clinical information collected from SFTS sentinel hospitals (n = 1159) and extracted data (n = 761) from published literature. The considered variables comprised clinical manifestations, routine laboratory tests of acute infection, hospitalization duration and disease outcome. SFTSV-IgG data from 19 119 healthy subjects were extracted from the published papers. The key clinical variables, case-fatality rate (CFR) and seroprevalence were estimated by meta-analysis. The most commonly seen clinical manifestations of SFTSV infection were fever, anorexia, myalgia, chill and lymphadenopathy. The major laboratory findings were elevated lactate dehydrogenase, aminotransferase, followed by thrombocytopenia, lymphocytopenia, elevated alanine transaminase and creatine kinase. A CFR of 12·2% was estimated, significantly higher than that obtained from national reporting data, but showing no geographical difference. In our paper, the mortality rate was about 1·9 parts per million. Older age and longer delay to hospitalization were significantly associated with fatal outcome. A pooled seroprevalence of 3·0% was obtained, which increased with age, while comparable for gender. This study represents a clinical characterization on the largest group of SFTS patients up to now. A higher than expected CFR was obtained. A wider spectrum of clinical index was suggested to be used to identify SFTSV infection, while the useful predictor for fatal outcome was found to be restricted.

Discrimination of novel bunyavirus infection using routine laboratory test.

The wide epidemic and high case fatality rate have made severe fever with thrombocytopenia syndrome (SFTS) a significant public health problem. The diagnosis and discrimination of SFTS virus (SFTSV) infection at an early stage of the disease is important for treatment choice. A prospective study was performed in an SFTS reference hospital during 2011-2013. Suspected SFTS patients were recruited and prospectively observed. Comparison between SFTSV-positive and -negative patients was made to identify the parameters that were related to positive detection by discriminant and classification tree analysis. A total of 538 SFTSV-positive and 396 negative patients were recruited and observed. Multiple logistic regression models demonstrated the significant parameters associated with positive detection, including decreased platelet counts and elevated aspartate aminotransferase (AST) level during the first stage (1∼4 days), decreased white blood cell and platelet counts, elevated creatine kinase (CK) and AST levels during the second stage (5∼7 days), and older age, decreased consciousness and elevated CK and AST during the third stage (8-11 days). The classification trees disclosed that the significant predictors for positive SFTSV detection were AST >50.6 U/L and AST/alanine transaminase (ALT) >1.3 at the first stage, CK >257 U/L or 57.7 U/L < CK ≤98.5 U/L with AST/ALT >1.6 at the second stage, as well as CK >630.7 U/L or 114.3 U/L < CK ≤630.7 U/L with decreased consciousness at the third stage. In making the clinically probable diagnosis of SFTS, the supplementation of AST and CK evaluations might remarkably improve the diagnostic capacity of routine laboratory tests, while the leukopenia is of limited use.

Epidemic and molecular evolution of human bocavirus in hospitalized children with acute respiratory tract infection.

Human bocavirus (HBoV) is a novel parvovirus, often associated with respiratory tract diseases in children. This study explored the epidemiological characteristics and molecular evolution of HBoV-1 in southeastern China. Nasopharyngeal aspirates were collected from children admitted to hospital with acute respiratory tract infections. HBoV-1 was detected using real-time reverse transcription polymerase chain reaction and further characterized by complete genome sequences analysis. Among the 3,022 recruited children, 386 (12.77%) were HBoV-1-positive and 300 (77.72%) had co-detection with other respiratory viruses. Seasonal prevalence peaked in summer. HBoV-1 presence was significantly associated with asthma attack [odds ratio = 1.74; 95 % confidence interval: 1.30, 2.31; p < 0.001]. Similar results were obtained when either single detection or co-detection of HBoV-1 was considered, demonstrating the minor impact of co-detection on the clinical characteristics or epidemic pattern. Phylogenetic analysis based on the complete genome sequences showed that all the HBoV-1 sequences clustered together and no branch was formed that was supported by bootstrap value ≥ 750. The overall evolutionary rate of the complete genome of HBoV-1 was estimated at 1.08 × 10(-4) nucleotide substitutions per site per year (s/s/y) [95% highest probability density: (0.40-1.86) × 10(-4) s/s/y]. Selective pressure analysis showed that all the ω-values were less than 1, suggesting that HBoV-1 was under negative selective pressure. Site-by-site analysis identified the codon site 40 of the VP1 gene under positive selection. In conclusion, our study disclosed the epidemiological and genetic dynamics of HBoV-1 epidemics in southeastern China in the most recent 3 years, the information of which might help to further improve our understanding of HBoV-1 infection and guide better surveillance and control strategies in the future.

Investigation of ultrasound screening efficiency for neural tube defects during pregnancy in rural areas of China.

OBJECTIVES: To understand the uptake and efficacy of ultrasound screening for neural tube defects (NTDs) during pregnancy, and the outcomes when NTDs were detected in rural areas of China. STUDY DESIGN: Prevalence study. METHODS: Four hundred and twenty-four women who delivered or gestated babies/fetuses with NTDs were selected at random in 20 counties of two provinces of China from March 2008 to January 2009. The uptake of ultrasound screening, NTD detection rate and termination of pregnancy (TOP) rate were calculated and analyzed. Generalized estimating equations were employed to control for potential confounding factors. RESULTS: The uptake of ultrasound screening was 98.8%. Among the study subjects, 361 (85.1%) NTDs were detected and 63 (14.9%) were not detected by prenatal ultrasound screening. The total detection rate was 43.3% (15.6%, 49.6% and 52.2% in the first, second and third trimesters, respectively; P < 0.05). Taking the possibility of NTD detection in the first trimester as 1.0, the possibilities in the second and third trimesters were 10.9 [95% confidence interval (CI) 6.5-18.3] and 25.2 (95% CI 13.3-47.6), respectively. The detection rate at the township health centres (THCs), family planning centres (FPCs), maternal and child care service centres (MCSCs) and hospitals was 24.5%, 29.1%, 53.6% and 78.1%, respectively (P < 0.05). Taking the possibility of NTD detection at THCs as 1.0, the possibilities at FPCs, MCSCs and hospitals were 0.9 (95% CI 0.5-1.6), 3.4 (95% CI 1.9-6.1) and 2.1 (95% CI 1.3-3.4), respectively. Three hundred and fifty-five (98.3%) of the 361 NTDs detected at prenatal ultrasound screening ended in TOP. CONCLUSIONS: The uptake of ultrasound screening was satisfactory, but the NTD detection rate was low. Ultrasound screening did not play its full role in the secondary prevention of NTDs in the study areas. Medical institutions in rural areas in China need to improve their ultrasound screening skills in order to increase the efficacy of NTD control.

Correlation between cosmic rays and ozone depletion.

This Letter reports reliable satellite data in the period of 1980-2007 covering two full 11-yr cosmic ray (CR) cycles, clearly showing the correlation between CRs and ozone depletion, especially the polar ozone loss (hole) over Antarctica. The results provide strong evidence of the physical mechanism that the CR-driven electron-induced reaction of halogenated molecules plays the dominant role in causing the ozone hole. Moreover, this mechanism predicts one of the severest ozone losses in 2008-2009 and probably another large hole around 2019-2020, according to the 11-yr CR cycle.

Resonant dissociative electron transfer of the presolvated electron to CCl4 in liquid: Direct observation and lifetime of the CCl4*- transition state.

We report a pump-probe femtosecond transient absorption spectroscopic study on the electron transfer reaction of CCl(4) in liquid ethanol. By direct observations of the presolvated electron and of the reaction transition state CCl(4) (*-), this study provides direct evidence of the resonant dissociative electron transfer (RDET) of the presolvated electron to CCl(4). Moreover, the lifetime of CCl(4) (*-) in ethanol is directly obtained from the decay kinetics and its measured value is found to be nearly identical to its gas-phase value. Hence, these results also imply that RDET can be an efficient process in an aqueous environment.

Electron transfer reaction mechanism of cisplatin with DNA at the molecular level.

The cytotoxicity of cisplatin as a very effective chemotherapeutic anticancer drug is known to arise from its capacity to damage DNA. However, the mechanism of action of cisplatin at the molecular level, in particular, the reaction dynamics of cisplatin with DNA, remains elusive, and the reason why cisplatin binds to the guanine bases rather than to S-donor ligands available in cells remains a mystery. Using time-resolved femtosecond laser spectroscopy, for the first time, we reveal the high reactivity of cisplatin with electrons and its preferential electron-transfer reaction with the DNA guanine base. The results not only provide a molecular mechanistic understanding of cisplatin in cancer therapy but may have far-reaching significance for understanding the role of polar molecules such as NH3 and NH2 in biological reactions.

Molecular reaction mechanisms of combination treatments of low-dose cisplatin with radiotherapy and photodynamic therapy.

Combination of low-dose cisplatin with radiotherapy or photodynamic therapy (PDT) is a novel cancer treatment. Using time-resolved femtosecond laser spectroscopy, we reveal the molecular mechanisms of the combinations of cisplatin with radiotherapy and PDT using indocyanine green (ICG) excited at 800 nm. DNA damage measurements confirm that electron-transfer reactions of cisplatin with electrons generated in ionizing radiation and with the ICG singlet excited state in PDT are responsible for the cytotoxic enhancements.

Spectroscopic characterization of carbon chains in nanostructured tetrahedral carbon films synthesized by femtosecond pulsed laser deposition.

A comparative study of carbon bonding states and Raman spectra is reported for amorphous diamondlike carbon films deposited using 120 fs and 30 ns pulsed laser ablation of graphite. The presence of sp(1) chains in femtosecond carbon films is confirmed by the appearance of a broad excitation band at 2000-2200 cm(-1) in UV-Raman spectra. Analysis of Raman spectra indicates that the concentrations of sp(1)-, sp(2)-, and sp(3)-bonded carbon are approximately 6%, approximately 43%, and approximately 51%, respectively, in carbon films prepared by femtosecond laser ablation. Using surface enhanced Raman spectroscopy, specific vibrational frequencies associated with polycumulene, polyyne, and trans-polyacetylene chains have been identified. The present study provides further insight into the composition and structure of tetrahedral carbon films containing both sp(2) clusters and sp(1) chains.

Direct observation of the transition state of ultrafast electron transfer reaction of a radiosensitizing drug bromodeoxyuridine.

Replacement of thymidine in DNA by bromodeoxyuridine (BrdU) has long been known to enhance DNA damage and cell death induced by ionizing/UV radiation, but the mechanism of action of BrdU at the molecular level is poor understood. Using time-resolved femtosecond laser spectroscopy, we obtain the real-time observation of the transition state of the ultrafast electron transfer (ET) reaction of BrdU with the precursor to the hydrated electron, which is a general product in ionizing/UV radiation. The results show that the ET reaction is completed within 0.2 picosecond (ps) after the electronic excitation, leading to the formation of a transition state BrdU*- with a lifetime of approximately 1.5 ps that then dissociates into Br- and a high reactive radical dU*. The present results can greatly enhance our understanding not only of the mechanism of BrdU as a radio-/photosensitizer but of the role of prehydrated electrons in electron-initiated processes in biological and environmental systems.

Enhancements in dissociative electron attachment to CF4, chlorofluorocarbons and hydrochlorofluorocarbons adsorbed on H2O ice.

We report that the absolute cross sections for dissociative attachment of approximately 0 eV electrons to chlorofluorocarbons (CFCs) and hydrochlorofluorocarbons (HCFCs) are strongly enhanced by the presence of H2O ice. The absolute cross sections for CFCl3, CHF2Cl, and CH3CF2Cl on water ice are measured to be approximately 8.9 x 10(-14), approximately 5.1 x 10(-15), and approximately 4.9 x 10(-15) cm2 at approximately 0 eV, respectively. The former value is about 1 order of magnitude higher than that in the gas phase, while the latter two are 3-4 orders higher. In contrast, the resonances at electron energies > or = 2.0 eV are strongly suppressed either for CFCs and HCFCs or for CF4 adsorbed on H2O ice. The cross-section enhancement is interpreted to be due to electron transfer from precursor states of the solvated electron in ice to an unfilled molecular orbital of CFCs or HCFCs followed by its dissociation. This study indicates that electron-induced dissociation is a significant process leading to CFC and HCFC fragmentation on ice surfaces.