Etiological and epidemiological features of acute meningitis or encephalitis in China: a nationwide active surveillance study.

BACKGROUND: Acute meningitis or encephalitis (AME) results from a neurological infection causing high case fatality and severe sequelae. AME lacked comprehensive surveillance in China. METHODS: Nation-wide surveillance of all-age patients with AME syndromes was conducted in 144 sentinel hospitals of 29 provinces in China. Eleven AME-causative viral and bacterial pathogens were tested with multiple diagnostic methods. FINDINGS: Between 2009 and 2018, 20,454 AME patients were recruited for tests. Based on 9,079 patients with all-four-virus tested, 28.43% (95% CI: 27.50%‒29.36%) of them had at least one virus-positive detection. Enterovirus was the most frequently determined virus in children <18 years, herpes simplex virus and Japanese encephalitis virus were the most frequently determined in 18-59 and ≥60 years age groups, respectively. Based on 6,802 patients with all-seven-bacteria tested, 4.43% (95% CI: 3.94%‒4.91%) had at least one bacteria-positive detection, Streptococcus pneumoniae and Neisseria meningitidis were the leading bacterium in children aged <5 years and 5-17 years, respectively. Staphylococcus aureus was the most frequently detected in adults aged 18-59 and ≥60 years. The pathogen spectrum also differed statistically significantly between northern and southern China. Joinpoint analysis revealed age-specific positive rates, with enterovirus, herpes simplex virus and mumps virus peaking at 3-6 years old, while Japanese encephalitis virus peaked in the ≥60 years old. As age increased, the positive rate for Streptococcus pneumoniae and Escherichia coli statistically significantly decreased, while for Staphylococcus aureus and Streptococcus suis it increased. INTERPRETATION: The current findings allow enhanced identification of the predominant AME-related pathogen candidates for diagnosis in clinical practice and more targeted application of prevention and control measures in China, and a possible reassessment of vaccination strategy. FUNDING: China Mega-Project on Infectious Disease Prevention and the National Natural Science Funds.

Etiological and epidemiological features of acute respiratory infections in China.

Nationwide prospective surveillance of all-age patients with acute respiratory infections was conducted in China between 2009‒2019. Here we report the etiological and epidemiological features of the 231,107 eligible patients enrolled in this analysis. Children <5 years old and school-age children have the highest viral positivity rate (46.9%) and bacterial positivity rate (30.9%). Influenza virus, respiratory syncytial virus and human rhinovirus are the three leading viral pathogens with proportions of 28.5%, 16.8% and 16.7%, and Streptococcus pneumoniae, Mycoplasma pneumoniae and Klebsiella pneumoniae are the three leading bacterial pathogens (29.9%, 18.6% and 15.8%). Negative interactions between viruses and positive interactions between viral and bacterial pathogens are common. A Join-Point analysis reveals the age-specific positivity rate and how this varied for individual pathogens. These data indicate that differential priorities for diagnosis, prevention and control should be highlighted in terms of acute respiratory tract infection patients' demography, geographic locations and season of illness in China.

Etiological, epidemiological, and clinical features of acute diarrhea in China.

National-based prospective surveillance of all-age patients with acute diarrhea was conducted in China between 2009‒2018. Here we report the etiological, epidemiological, and clinical features of the 152,792 eligible patients enrolled in this analysis. Rotavirus A and norovirus are the two leading viral pathogens detected in the patients, followed by adenovirus and astrovirus. Diarrheagenic Escherichia coli and nontyphoidal Salmonella are the two leading bacterial pathogens, followed by Shigella and Vibrio parahaemolyticus. Patients aged <5 years had higher overall positive rate of viral pathogens, while bacterial pathogens were more common in patients aged 18‒45 years. A joinpoint analysis revealed the age-specific positivity rate and how this varied for individual pathogens. Our findings fill crucial gaps of how the distributions of enteropathogens change across China in patients with diarrhea. This allows enhanced identification of the predominant diarrheal pathogen candidates for diagnosis in clinical practice and more targeted application of prevention and control measures.

Metallocyclic Ni4Ln2M2 single-molecule magnets.

We herein report the synthesis, crystal structure and magnetic properties of nine new heterotrimetallic complexes. [Ni(Me2valpn)] (H2Me2valpn = N,N'-bis(3-methoxysalicylidene)-2,2-dimethyl-1,3-diaminopropane) was used as the precursor to construct phenoxo-bridged [Ni2Ln]3+ (Ln3+ = Dy, Tb, Gd and Y) species that were respectively connected by two [M(CN)6]3- (M = Cr, Fe or Co) anions to form octanuclear cyclic complexes, i.e. {[Ni(Me2valpn)]2Ln(H2O)M(CN)6}2 in which Ln = Y, Gd, Tb and Dy and M = Cr, Fe or Co (1-9). Each of the complexes contains many lattice-bound molecules of solvation. The Ni(ii) ions are penta-coordinate, while the Ln(iii) ions are nine coordinated with a muffin geometry. The fitting to the χmT vs. T curves of complexes 6-9 gave the parameters of JNiCr = 11.82 cm-1, JNiGd = 0.94 cm-1 and g = 2.04 for complex 6, JNiFe = 10.58 cm-1, JNiGd = 1.24 cm-1 and g = 2.03 for complex 7, JNiCr = 9.4(1) cm-1, zJ' = -0.050(2) cm-1 and g = 2.06(1) for complex 8 and JNiFe = 4.9(7) cm-1, zJ' = -0.35(2) cm-1 and g = 2.24(1) for complex 9, respectively. The dynamic magnetic investigations demonstrate that complexes 1-5 display single-molecule magnet properties with an effective energy barrier (Ueff) of 38.9 K (1, M1 = Dy, M2 = Cr), 37.2 K (2, M1 = Dy, M2 = Cr), 24.4 K (3, M1 = Dy, M2 = Co), 21.9 K (4, M1 = Tb, M2 = Cr) and 29.6 K (5, M1 = Tb, M2 = Fe), respectively. Complex 1 shows the highest energy barrier among the octanuclear [Ni4LnM2] (Ln = Dy or Tb, M = Fe, Cr, Co or W) system. Although the [Ni4Dy2Cr2] complexes have Ueff higher than that of [Ni4Dy2Fe2], complex [Ni4TbCr2] shows lower Ueff than that of [Ni4TbFe2]. The results indicate that besides the M-C[triple bond, length as m-dash]N-Ni magnetic coupling the lanthanide ions can significantly affect the magnetic performances of heterotrimetallic SMMs as well. Moreover, the SMMs are achieved when diamagnetic Co(iii) was substituted by paramagnetic Cr(iii) or Fe(iii) in the [Ni4Tb2 M2] system, suggesting that the trimetallic strategy is effective in the construction of new 3d-4f SMMs.

A trimetallic strategy towards ZnDyCr and ZnDyCo single-ion magnets.

Two cyano- and phenoxo-bridged octanuclear complexes ZnDyCo (complex ) and ZnDyCr (complex ) with diamagnetic Zn(ii) and Co(iii) are reported. Dy(iii) is surrounded by nine oxygen atoms of two [Zn(Me2valpn)] (Me2valpn(2-) = dianion of N,N'-2,2-dimethylpropylenebis(3-methoxysalicylideneimine)) and one water molecule. Magnetic studies reveal that both exhibit single-ion magnet (SIM) behavior with the energy barrier of 85.9 K for complex and 100.9 K for complex .

Slow magnetization relaxation in Ni(II)Dy(III)Fe(III) molecular cycles.

Two cyano- and phenoxo-bridged hexanuclear Ni(II)2Dy(III)2Fe(III)2 (1) and octanuclear Ni(II)4Dy(III)2Fe(III)2 (2) trimetallic cyclic complexes have been obtained. They are the first trimetallic metallocycles. Magnetic studies reveal that 1 and 2 exhibit single-molecule-magnet behavior with an energy barrier of 17.9 K for complex 1 in a 2000 Oe static field and 25.0 K for complex 2 in a zero static field.

Heterodinuclear M(II)-Ln(III) single molecule magnets constructed from exchange-coupled single ion magnets.

The synthesis and characterization of four dinuclear 3d-4f complexes [M(II)Ln(III)(L)(DBM)3] (ZnDy = 1, CoY = 2, CoDy = 3·3.5CH3CN, CoGd = 4·3.5CH3CN) are reported (H2L = N,N'-dimethyl-N,N'-(2-hydroxy-3-methoxy-5-methyl-benzyl)ethylenediamine, DBM(-) = anion of 1,3-diphenyl-propane-1,3-dione). In each of the four complexes, the M(II) ion occupies the internal N2O2 site whereas the Ln(III) ion occupies the external O4 site. There are diphenoxo bridges between the M(II) and Ln(III) ions in these complexes. The remaining coordination sites are occupied by three DBM(-) anions. Direct current (dc) magnetic susceptibility measurements indicate the presence of intramolecular ferromagnetic interactions in complexes 3 and 4. The magnetic coupling constant, JCoGd, of complex 4 is estimated to be 0.26 cm(-1) (H = -2JCoGdSCoSGd). Alternating current (ac) magnetic susceptibility studies reveal that complexes 1 and 2 show field-induced single molecule magnet behavior, with ΔE values of 36.5 K and 8.56 K, respectively. Complex 3 shows frequency dependent out-of-phase signals, indicating the presence of a slow relaxation of the magnetization, whereas complex 4 does not display slow magnetization relaxation.

Toward higher nuclearity: tetranuclear cobalt(II) metallogrid exhibiting spin crossover.

Supramolecular strategy was employed to achieve the highest nuclearity Co(II) cluster exhibiting spin-crossover (SCO) behavior. Magnetic susceptibility characterization of the Co4(II) complex shows that two different spin-transition processes occur. The SCO behavior is directed by the partially deprotonated polydentate ligand, which favors the structural distortion required by the spin transition.

A cyano-bridged single-chain magnet featuring alternate high- and low-spin manganese(III) porphyrins.

The chains in complex [Mn(TPP)][Mn(TPP)(CN)2] (H2TPP = meso-tetra(4-phenyl)-porphyrin) demonstrate perfect linearity, and are well isolated with the nearest interchain Mn-Mn separation of 12.95 Å. Ferromagnetic coupling is present among adjacent Mn(III) ions, and single-chain magnet (SCM) behaviour is verified.

In Situ Formation of Semichelating Ligands: A Strategy for Tuning the Magnetic Coupling in Azide-Bridged Copper(II) Complexes.

Five CuII complexes of trinuclear [Cu3 (L1 )2 (N3 )6 ] (1), one-dimensional chain [Cu5 (L2 )2 (N3 )10 ]n  (2), trinuclear [Cu3 (L3 )2 (N3 )6 ] (3) and dinuclear [Cu2 (L4 )2 (N3 )2 Cl2 ] (4) and [Cu2 (L5 )2 (N3 )2 Cl2 ] (5) (L1-5 =RCH2 OR', R=substituted pyrazole or imidazole, R'=Me, Et or nPr) were synthesized by the reaction of CuCl2 ⋅2 H2 O, sodium azide with RCH2 Cl in CH3 OH, C2 H5 OH or n-C3 H7 OH. The ether ligands L1 and L2 can be alternatively prepared by the alcoholysis of RCH2 Cl in the presence of sodium azide, whereas the ligands L3-5 form in corresponding alcohols without azide. For complexes 1-5, the oxygen atom of the ether ligands is located at the Jahn-Teller axis of CuII with the long CuO separations of 2.377(3)-2.830(3) Å. The nitrogen atoms of bridging azides are located in the equatorial or basal planes of CuII ions, favoring strong magnetic coupling. The Cu-Nazido -Cu bridging angles in complexes 1-3 are 98.8(2)°-101.6(1)°, leading to ferromagnetic coupling, whereas the Cu-Nazido -Cu angles in complexes 4 and 5 are close to 103°, leading to antiferromagnetic coupling.

[Characterization of human rhinovirus in children with acute respiratory infections in Gansu Province during 2011].

To study the epidemic characteristics of human rhinovirus (HRV) in children with acute respiratory infections in Gansu Province. 286 throat swabs were collected from children with acute respiratory in fections in Gansu Province during 2011. Multiplex reverse transcription-PCR (multiplex RT-PCR) assay was used to screen those specimens for detection of common respiratory tract pathogens. For HRV-positive samples, nested reverse transcription polymerase chain reaction (nested RT-PCR) was performed to amplify VP1 and VP4/VP2 gene fragments of HRV. The VP4/VP2 and VP1 regions of HRV-positive samples were sequenced and performed genotype analysis. Of 286 specimens fested, 27 were positive for HRV by multiplex RT-PCR and nested RT-PCR, of which 16 children were made (16/185), 8.64%) and 11 female (11/101,10.89%). The positive rate was 9.44% (27/286). The mean age of HRV-positive children was 3 years in this study, children less than one year old had the highest proportion 44.4% (12/ 27, 44.4%). The highest HRV positive rate fell on May, 2011 (6/27, 22.2%). Common cold accounted for the highest proportion, 12.24% (12/98) followed by pneumonia, 8.50% (13/153). The remaining 2 cases were bronchitis. Sequence analysis showed HRV A was the predominant genotype in Gansu Province in 2011, accounting for 84.62% (22/26) of positive cases, followed by HRV C (11.54%, 3/26) and only one HRV B was detected (3.85%, 1/26). HRV could be detected throughout the year in Gansu Province and primarily infected children under one year old. The group A was the epidemic genotype of HRV and move than one genotype existed in Gansu Province during 2011.

[Analysis on genetic characteristics of mumps virus strains circulating in Hunan province in 2011].

OBJECTIVE: To be acquainted with genetic characteristics and variation of mumps virus strains circulating in Hunan province. METHODS: Mumps virus (MV) strains were isolated using Vero/ SLAM cells. The small hydrophobic protein (SH) genes of MV isolates were sequenced, and the sequences were analysed phylogenetically between the isolated strains and other reference mumps strains. RESULTS: 4 mumps virus strains were isolated from 16 specimens collected in 2011 from different regions of Hunan province. The genotype of isolated strains were supposed to be F type. CONCLUSION: Genotype F is the main genotype of circulating strains in Hunan province in 2011 and there is no variation between genotype.

[Analysis the viral etiology of fever and respiratory tract infection syndrome in Shaanxi province].

OBJECTIVE: Analysis the viral pathogenic spectrum for patients with fever and respiratory tract infection syndrome in Shaanxi province during 2010 and investigate the molecular epidemiology characteristics of respiratory syncytial virus. METHODS: A total of 208 patients' pharyngeal swabs were collected based on surveillance definition from January 2010 to January 2011 and screened for sixteen human respiratory virus types/subtypes by Qiaxcel-based multiplex reverse transcription-PCR assay, including HRV,HCoV, Flu, HPIV, ADV, HRSV, HMPV and HBoV and investigate molecular epidemiology of HRSV by sequencing and phylogenetic analysis of the C-terminal second hypervariable region of the G gene. RESULTS: 109 out of 208 specimens (53%) were positive for one or more viruses. HRSV(42. 2%) was the dominant pathogen detected, followed by Flu(24. 5%), PIV(20%), HRV(13.6%) and ADV( 10.9%),there were also 8 strains of HCoV, 5 strains of HMPV and 3 strains of HBoV detected. The results showed that 22 specimens were positive for two or more viruses, PIV (14/22) was the most frequently detected viral agent among co-infection specimens, and the highest incidence of mixed infection is aged 15-39 years group (P < 0.05). The overall viral detection rate was no related to age. In addition to Flu, HMPV and PIV, other viruses (HRV, HBoV, HCoV, ADV, RSV) mainly infected 0 to 4 years old children. Among 46 HRSV positive specimens, 42 HRSV-A strains clustered into NA1 genotype and two HRSV-B strains clustered into two genotypes, BA9 and GB2. CONCLUSION: HRSV is the dominate pathogen collected from patients with fever and respiratory tract infection syndrome in Shaanxi and HRSV A is the predominant subtype. For most viruses, infection was most prevalent among children aged <4 years. PIV was the most common pathogen in co-infection.

[Epidemiology and etiology of hand-foot-and-mouth disease in Hainan, 2010].

To reveal the epidemiological and pathogenic characteristics of Hand-foot-and-mouth disease (HFMD) in Hainan province in 2010, epidemiology data of HFMD reporting cases were analyzed, clinical specimens from 1346 HFMD cases were collected for enterovirus (EV) detection. Viral isolation was performed for EV nucleic acid positive samples. Complete VP1 encoding region of EV71 were sequenced and analyzed with Sequencher (version 5.0) and MEGA software (version 5.0). The epidemiology data showed that all 18 prefectures in Hainan had reporting cases during 2010, with higher incidence in the northeast; and the children less than 4 years old accounted for the majority of the suffered; the epidemic reached peak during September to October, which was different from other Provinces in China. The laboratory results indicated that EV71 and CA16 were identified as the major causative pathogens in Hainan in 2010, however, EV71 infection was absolutely dominant among severe and fatal cases. In addition, some HFMD cases were identified associated with other serotypes of EV infections. Molecular epidemiological analysis showed that all the EV71 strains belonged to C4a evolutionary branch, which is the dominant evolutionary branch in China in recent years, and at least three transmission chains existed. This study has an important information in clarifying the characteristics of epidemics and transmission of HFMD in Hainan, and to provide the guidance for HFMD prevention and control in the future.

Synthesis, crystal structure and magnetic properties of dinuclear NiIILnIII complexes based on a flexible polydentate ligand.

The synthesis and characterization of three isomorphous complexes [NiII(L)LnIII(DBM)3] (Ln = Gd (1·2.5CH3CN·0.5H2O), Tb (2·2CH3CN·0.5MeOH), and Dy (3·2CH3CN·0.5MeOH·0.5H2O)) are reported (H2L = N,N'-dimethyl-N,N'-(2-hydroxy-3-methoxy-5-methylbenzyl)ethylenediamine, DBM⁻ = anion of 1,3-diphenylpropane-1,3-dione). The flexible ligand L²â» contains an N2O2-inner and an O4-outer coordination site. There are diphenoxo bridges between NiII and LnIII ions in these complexes. The remaining coordination sites are occupied by DBM⁻ anions. Direct current (dc) magnetic susceptibility measurements indicate the presence of intramolecular ferromagnetic interactions in desolvated complexes 1-3. The magnetic coupling constant JNiGd in complex 1 is estimated to be 1.11 cm⁻¹ (H = -2JNiGdSNiSGd). Alternating current (ac) magnetic susceptibility studies reveal that complexes 2 and 3 show frequency-dependent out-of-phase signals, which indicate that they exhibit SMM behavior. The energy barriers for complexes 2 and 3 under a 2 kOe applied direct current (dc) magnetic field are estimated from Arrhenius plots to be 14.4 and 11.3 K, respectively.

Spin transitions in Fe(II) metallogrids modulated by substituents, counteranions, and solvents.

Two bis(tridentate) Schiff base ligands H2L(x) were used to construct three 2×2 grid-type tetranuclear Fe(II) complexes 1-3 to obtain polynuclear spin-crossover materials. Magnetic susceptibility measurements show that the spin states of the complexes are related to the substituents of H2L(x), and that spin transition occurs only in complexes 1 and 2, which are derived from a bulky ligand, whereas complex 3 is diamagnetic. The transition temperatures of complexes 1 and 2 are close to room temperature and are dependent on counteranions. The spin transition of complex 1 can be reversibly tuned by the dehydration and hydration process.

Supramolecular lanthanide metallogrids exhibiting field-induced single-ion magnetic behavior.

A supramolecular strategy has been applied to construct two tetranuclear lanthanide complexes for investigating the magnetic properties of individual lanthanide ions. The Ln(III) complexes (Ln = Dy, Tb) display field-induced slow magnetization relaxation, typical of single-molecule magnet behavior. The four lanthanide ions in the molecules are well separated by distances of ca. 9 Å, and thus the slow magnetization relaxation should be assigned to single-ion magnet (SIM) behavior. Therefore, the present complexes are novel supramolecular aggregates of four isolated SIMs.

[Genetic characterization of human parainfluenza virus 3 circulating in Gansu and Shaanxi Provinces from 2009 to 2011].

To investigate the genetic characterization of Human parainfluenza virus-3 (HPIV-3) circulating in Gansu and Shaanxi Provinces of China, 719 throat swabs were collected from pediatric patients with acute respiratory infections from 2009-2011. Multiplex RT-PCR was used to screen common respiratory viral pathogens. For HPIV-3-positive specimens, nested RT-PCR was used to amplify the HN gene of HPIV-3. The nucleotides of Hemagglutinin-neuraminidase(HN)gene of 13 HPIV-3 positive strains identified in Gansu and Shaanxi Provinces were successfully sequenced and compared with those downloaded from GenBank. The phylogenetic analysis based on the nucleotides sequence of HN gene showed that 13 HPIV-3 strains belonged to sub-cluster C3 with little sequence variation (overall nucleotide divergence of 0.2%-2.3% and amino acid divergence at 0-1.1%). Compared with the complete gene of HPIV-3 strains from U.S.A., Canada, and Australia, the biggest divergence of the nucleotide and amino acid lovels was 6.0% and 3.4%, respectively. The nucleotide divergence between shaanxi09-2 and shaanxi10-H0091 was 0.9%, while the nucleotide divergence between shaanxi10-H005 and gansull-62110372 was 0.5%, between shaanxi09-2 and BJ/291/09 was 0.6%. However, there was no amino acid divergence among them. It is likely that HPIV-3 virus had been transmitting in Gansu and Shaanxi Provinces for several years. Human parainfluenza virus-3 (HPIV-3) circulated in Gansu and Shaanxi Provinces from 2009 to 2011 belonged to sub-cluster C3.

[Development of A synthetic positive control for the nucleic acid detection of mumps virus].

To rapidly identify the cross-contamination problems caused by the positive control in the process of mumps virus nucleic acid detection, a new mumps virus RNA positive control was developed in this study. Using the same primers and reaction conditions, the cross-contamination problems caused by the positive control could be readily identified by comparing the fragments lengths of the PCR products between the positive control and the samples. This new RNA positive control of mumps virus can be widely used in the diagnosis and genotyping of mumps virus as a better laboratory quality control.

[Genetic analysis of a genotype F mumps virus based on its complete genome sequence].

Mumps virus strains of genotype F have been circulating in China for decades. To identify genetic variation of mumps virus based on the complete genome sequence of a mumps isolate of genotype F, the complete genome of the genotype F reference strain, MuVi/Shandong. CHN/4.05 [F] was sequenced. Genetic characteristics of this virus were analyzed and compared with the complete genome sequences of others genotypes available in GenBank. The genetic differences in antigenic sites were also compared between the genotype F strain and the vaccine strains. The nucleotide differences between MuVi/Shandong. CHN/4.05 [F] and other genotypes of mumps virus based on the whole genome ranged between 3.8% and 6.5%. The maximum and minimum difference was found between MuVi/Shandong. CHN/4.05 [F] and genotype A (the vaccine strains), and genotype B-N strains, respectively. There were 26 N-glycosylation sites in the strain MuVi/Shandong. CHN/4.05 [F] and all other genotypes of mumps virus, however, one N-glycosylation site was absent from the vaccine strains, which was at the aa position 464-466 of the HN gene. Variation was detected at some of the known antigenic sites of mumps virus strain MuVi/Shandong. CHN/4.05 [F] and the vaccine strains. Genetic variations were detected in the epidemic mumps virus strain in China as well as in other genotypes of mumps virus strains and the vaccine strains across the complete genome. These results indicate the need to further strengthen the surveillance of genetic variation of wild type mumps virus.