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.

Epidemiology characteristics of human coronaviruses in patients with respiratory infection symptoms and phylogenetic analysis of HCoV-OC43 during 2010-2015 in Guangzhou.

Human coronavirus (HCoV) is one of the most common causes of respiratory tract infection throughout the world. To investigate the epidemiological and genetic variation of HCoV in Guangzhou, south China, we collected totally 13048 throat and nasal swab specimens from adults and children with fever and acute upper respiratory infection symptoms in Gunazhou, south China between July 2010 and June 2015, and the epidemiological features of HCoV and its species were studied. Specimens were screened for HCoV by real-time RT-PCR, and 7 other common respiratory viruses were tested simultaneously by PCR or real-time PCR. HCoV was detected in 294 cases (2.25%) of the 13048 samples, with most of them inpatients (251 cases, 85.4% of HCoV positive cases) and young children not in nursery (53.06%, 156 out of 294 HCoV positive cases). Four HCoVs, as OC43, 229E, NL63 and HKU1 were detected prevalent during 2010-2015 in Guangzhou, and among the HCoV positive cases, 60.20% were OC43, 16.67% were 229E, 14.97% were NL63 and 7.82% were HKU1. The month distribution showed that totally HCoV was prevalent in winter, but differences existed in different species. The 5 year distribution of HCoV showed a peak-valley distribution trend, with the detection rate higher in 2011 and 2013 whereas lower in 2010, 2012 and 2014. The age distribution revealed that children (especially those <3 years old) and old people (>50 years) were both high risk groups to be infected by HCoV. Of the 294 HCoV positive patients, 34.69% (101 cases) were co-infected by other common respiratory viruses, and influenza virus was the most common co-infecting virus (30/101, 29.70%). Fifteen HCoV-OC43 positive samples of 2013-2014 were selected for S gene sequencing and phylogenetic analysis, and the results showed that the 15 strains could be divided into 2 clusters in the phylogenetic tree, 12 strains of which formed a separate cluster that was closer to genotype G found in Malaysia. It was revealed for the first time that genotype B and genotype G of HCoV-OC43 co-circulated and the newly defined genotype G was epidemic as a dominant genotype during 2013-2014 in Guanzhou, south China.

Cyclometalated iridium(iii) N-heterocyclic carbene complexes as potential mitochondrial anticancer and photodynamic agents.

Metal N-heterocyclic carbene (NHC) complexes represent a promising class of anticancer therapeutic agents. In this work, four cyclometalated iridium(iii) complexes (Ir1-Ir4) containing N-heterocyclic carbene ligands have been explored as mitochondrial anticancer and photodynamic agents. These complexes are more cytotoxic than cisplatin against the cancer cells screened, can quickly penetrate into A549 cells and are mainly localized in the mitochondria. Mechanism studies show that these complexes exert their anticancer efficacy by increasing the intracellular ROS level, reducing the mitochondrial membrane potential (MMP) and inducing apoptosis. Additionally, Ir1-Ir4 exhibited two orders of magnitude higher cytotoxicity upon irradiation at 450 nm LED light. Our work provides a strategy for the design of highly effective anticancer photodynamic therapeutic agent based phosphorescent iridium complexes.

Neighborhood Frequency Effect in Chinese Word Recognition: Evidence from Naming and Lexical Decision.

Neighborhood frequency is a crucial variable to know the nature of word recognition. Different from alphabetic scripts, neighborhood frequency in Chinese is usually confounded by component character frequency and neighborhood size. Three experiments were designed to explore the role of the neighborhood frequency effect in Chinese and the stimuli were all two-character words. This effect was evaluated on targets with- and without-higher frequency neighbors with neighborhood size matched. Among the experiments, the patterns of the leading character frequency effect and word frequency effect in the naming and lexical decision tasks were compared. The results implied an inhibitory neighborhood frequency effect in Chinese word recognition. Accordingly, a possible cognitive mechanism of the neighborhood frequency effect was thus proposed.

Comparing the Frequency Effect Between the Lexical Decision and Naming Tasks in Chinese.

In psycholinguistic research, the frequency effect can be one of the indicators for eligible experimental tasks that examine the nature of lexical access. Usually, only one of those tasks is chosen to examine lexical access in a study. Using two exemplar experiments, this paper introduces an approach to include both the lexical decision task and the naming task in a study. In the first experiment, the stimuli were Chinese characters with frequency and regularity manipulated. In the second experiment, the stimuli were switched to Chinese two-character words, in which the word frequency and the regularity of the leading character were manipulated. The logic of these two exemplar experiments was to explore some important issues such as the role of phonology on recognition by comparing the frequency effect between both the tasks. The results revealed different patterns of lexical access from those reported in the alphabetic systems. The results of Experiment 1 manifested a larger frequency effect in the naming task as compared to the LDT, when the stimuli were Chinese characters. And it is noteworthy that, in Experiment 1, when the stimuli were regular Chinese characters, the frequency effect observed in the naming task was roughly equivalent to that in the LDT. However, a smaller frequency effect was shown in the naming task as compared to the LDT, when the stimuli were switched to Chinese two-character words in Experiment 2. Taking advantage of the respective demands and characteristics in both tasks, researchers can obtain a more complete and precise picture of character/word recognition.

The role of orthographic neighborhood size effects in Chinese word recognition.

Previous studies about the orthographic neighborhood size (NS) in Chinese have overlooked the morphological processing, and the co-variation between the character frequency and the the NS. The present study manipulated the word frequency and the NS simultaneously, with the leading character frequency controlled, to explore their influences on word lexical decision (Experiment 1) and naming (Experiment 2). The results showed a robust effect that words with a larger NS produced shorter reaction time than those with a smaller NS, irrespective of the word frequency and the tasks. This facilitative effect may occur due to a semantic network formed by neighbor words, resulting in the semantic activation to accelerate the word recognition. Moreover, the comparison of the effect sizes of word frequency between the two tasks showed that lexical decision responses demonstrated a larger word frequency effect, indicating that the sub-word processing was involved in the multi-character word recognition.

[Up-regulator of cell proliferation predicts poor prognosis in hepatocellular carcinoma].

OBJECTIVE: To explore the potential value of up-regulator of cell proliferation (URGCP) as a biomarker for predicting the prognosis of hepatocellular carcinoma (HCC). METHODS: The expression of URGCP was analyzed in 15 HCC cell lines and in 10 pairs of HCC and adjacent tissues with reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The expression of URGCP in 278 paraffin-embedded, archived clinical HCC samples was analyzed by immunohistochemistry (IHC) and statistic analysis conducted to examine the relationship of prognosis and URGCP expression. RESULTS: IHC analysis revealed a high expression of URGCP in all HCC cell lines and in 122/278 (43.8%) paraffin-embedded archived HCC specimens. The expression level of URGCP was significantly correlated with clinical staging and poor patient survival of HCC in the study cohort and in various clinical subgroups, but not correlated with HCC patient age, tumor size, tumor number or alpha-fetoprotein level. CONCLUSION: URGCP plays an important role in promoting the proliferation and tumorigenesis of HCC and may represent a novel prognostic biomarker and therapeutic target for the disease.

Surveillance and genome analysis of human bocavirus in patients with respiratory infection in Guangzhou, China.

Human bocavirus (HBoV) is a novel parvovirus associated with respiratory tract diseases and gastrointestinal illness in adult and pediatric patients throughout the world. To investigate the epidemiological and genetic variation of HBoV in Guangzhou, South China, we screened 3460 throat swab samples from 1686 children and 1774 adults with acute respiratory infection symptoms for HBoV between March 2010 and February 2011, and analyzed the complete genome sequence of 2 HBoV strains. Specimens were screened for HBoV by real-time PCR and other 6 common respiratory viruses by RT-PCR or PCR. HBoV was detected in 58 (1.68%) out of 3460 samples, mostly from pediatric patients (52/58) and inpatient children (47/58). Six adult patients were detected as HBoV positive and 5 were emergency cases. Of these HBoV positive cases, 19 (32.76%) had co-pathogens including influenza virus (n = 5), RSV (n = 5), parainfluenza (n = 4), adenovirus (n = 1), coronavirus (n = 7). The complete genome sequences of 2 HBoVs strains (Genbank no. JN794565 and JN794566) were analyzed. Phylogenetic analysis showed that the 2 HBoV strains were HBoV1, and were most genetically close to ST2 (GenBank accession number DQ0000496). Recombination analysis confirmed that HBoV strain GZ9081 was an intra-genotype recombinant strain among HBoV1 variants.

A two-year surveillance of 2009 pandemic influenza A (H1N1) in Guangzhou, China: from pandemic to seasonal influenza?

In this two-years surveillance of 2009 pandemic influenza A (H1N1) (pH1N1) in Guangzhou, China, we reported here that the scale and duration of pH1N1 outbreaks, severe disease and fatality rates of pH1N1 patients were significantly lower or shorter in the second epidemic year (May 2010-April 2011) than those in the first epidemic year (May 2009-April 2010) (P<0.05), but similar to those of seasonal influenza (P>0.05). Similar to seasonal influenza, pre-existing chronic pulmonary diseases was a risk factor associated with fatal cases of pH1N1 influenza. Different from seasonal influenza, which occurred in spring/summer seasons annually, pH1N1 influenza mainly occurred in autumn/winter seasons in the first epidemic year, but prolonged to winter/spring season in the second epidemic year. The information suggests a tendency that the epidemics of pH1N1 influenza may probably further shift to spring/summer seasons and become a predominant subtype of seasonal influenza in coming years in Guangzhou, China.

Synthesis and cytotoxic evaluation of eremophilane sesquiterpene 07H239-A derivatives.

Nine new derivatives (6-14) of the eremophilane sesquiterpene 07H239-A (5) were designed and semisynthesized with two types of R-groups by amidation. Most of them were active against five human tumor cell lines, and compounds 6-10 were more potent than the natural product 5. In particular, compounds 6 and 9 exhibited the strongest cytotoxic activity against MDA-MB-435 with IC50 values of 0.91 and 0.96 µM, respectively. Preliminary structure-activity relationships (SARs) analysis indicated that the 14-carboxyl in 5 was an ideal target for chemical modification, and the side chain of 5 might play a necessary role in facilitating their cytotoxic potencies.

Development and validation of a highly rapid and sensitive LC-MS/MS method for determination of SZ-685C, an investigational marine anticancer agent, in rat plasma--application to a pharmacokinetic study in rats.

A sensitive and rapid method was developed and validated for the quantitative analysis of the novel anticancer agent SZ-685C in rat plasma using high-performance liquid chromatography/tandem mass spectrometry (LC/MS/MS) in negative ion mode in order to support the following pre-clinical and clinical studies. SZ-685C and the internal standard (IS, emodin) were extracted from rat plasma by a simple liquid-liquid extraction technique using ethyl acetate as extraction solvent. Chromatographic separation was performed on an Elite Hypersil BDS C18 column (100 mm × 2.1 mm i.d., 3 µm). Elution was carried out using methanol/acetonitrile/2mM ammonium formate (pH 4) (80:15:5 (v/v/v)) at a flow-rate of 0.3 mL/min with a run time of 2.5 min. This assay was linear over a concentration range of 50-10,000 ng/mL with a lower limit of quantification of 50 ng/mL. The intra- and inter-batch precision was less than 15% for all quality control samples at concentrations of 100, 1000 and 7500 ng/mL. These results indicate that the method was efficient with a short run time and acceptable accuracy, precision and sensitivity. This method was successfully applied to explore pharmacokinetics of SZ-685C in rats after oral and intravenous administration of this agent. The absolute bioavailability is about 54.8-66.8% and the t(1/2) is 5.7-9.2h, these results provide basic information for further comprehensive pre-clinical research.

The bioactive metabolites of the mangrove endophytic fungus Talaromyces sp. ZH-154 isolated from Kandelia candel (L.) Druce.

Bioactivity-directed fractionation of the extract of the mangrove endophytic fungus Talaromyces sp. ZH-154, which was isolated from the stem bark of Kandelia candel (L.) Druce, Rhizophoraceae, afforded two new metabolites, 7-epiaustdiol ( 1) and 8-O-methylepiaustdiol ( 2), together with the known compounds, stemphyperylenol ( 3), skyrin ( 4), secalonic acid A ( 5), emodin ( 6), and norlichexanthone ( 7). Their structures were elucidated on the basis of spectroscopic evidences including CD, MS, and 1D, 2D NMR techniques. The absolute configuration of 1 was unequivocally determined by single-crystal X-ray diffraction. All isolated compounds were evaluated for their antimicrobial and in vitro cytotoxic activities.

Structure elucidation of three diphenyl ether derivatives from the mangrove endophytic fungus SBE-14 from the South China Sea.

Two new natural products, tenelate A (1) and B (2), together with the known compound, tenellic acid C (3), were isolated from the mangrove endophytic fungus Talaromyces sp. (SBE-14), from the South China Sea. Their structures were elucidated by spectroscopic methods, mainly 1D and 2D NMR techniques.

[Correlation of Epstein-Barr virus-encoded latent membrane protein 1 (LMP1) to fascin and phosphorylated Stat3 in nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Latent membrane protein 1 (LMP1) of Epstein-Barr (EB) virus is an important oncogene. Fascin is an actin cross-linking protein involved in cell migration and adhesion. Phosphorylated signal transducer and activator of transcription 3 (pStat3) is a member of STATs family, which is closely related to tumorigenesis. This study was to investigate expressions of LMP1, Fascin and pStat3 in nasopharyngeal carcinoma (NPC) tissues and lymph node metastases of NPC, thus to explore their correlations to the initiation and progression of NPC. METHODS: Expressions of EBV-encoded small RNA (EBER), LMP1, Fascin, pStat3, p53, Ki-67 and Bcl-2 were detected in 43 NPC tissues (21 with and 22 without lymph node metastases) and 21 corresponding lymph node metastases using in situ hybridization or immunohistochemistry (IHC). Data were statistically analyzed. Expressions of pStat3 and Fascin were measured in the NPC cell line CNE1 transfected with LMP1-expressing plasmid using Western blot. RESULTS: Positive EBER expression was detected in all 43 NPC tissues and 21 lymph node metastases in NPC. The expression rates of LMP1, Fascin, pStat3, p53, Ki-67, and Bcl-2 were 69.8% (30/43), 93.0% (40/43), 72.1% (31/43), 90.7% (39/43), 88.4% (38/43) and 88.4% (38/43)in 43 NPC tissues, respectively. LMP1 expression was positively correlated with the expression level of Fascin, pStat3, p53, Ki-67 and Bcl-2 in 43 NPC cases(P < 0.05). LMP1 was found in 10 out of 21 (46.7%) lymph node metastases in NPC. In addition, LMP1 expression dramatically increased pStat3 and Fascin in CNE1 cells. CONCLUSIONS: LMP1 is expressed in lymph node metastatases in NPC. The expression of LMP1 is positively correlated with Fascin, pStat3 and the proliferation index of tumor cells. Moreover, LMP1 up-regulates pStat3 and Fascin in NPC cells.

[Analysis of Epstein-Barr virus BamH I "f" variant in nodal metastasis of nasopharyngeal carcinoma].

OBJECTIVE: To investigate the Epstein-Barr virus (EBV) BamH I "f" variant in primary nasopharyngeal carcinoma (NPC) and its metastases in lymph nodes (LN). METHODS: In situ hybridization was used to detect EBV-encoded small RNA (EBER) expression in 21 paired paraffin-embedded tissue from primary NPC and their lymph node metastases and 22 primary NPC without lymph node metastasis. PCR and restriction fragment length polymorphism (RFLP) assay were used to detect EBV BamH I "f" variant in all cases of NPCs, lymph node metastases and 50 cases of chronic inflammation of nasopharynx from Canton. RESULTS: All cases of NPCs and their lymph node metastases showed EBER expression, indicating a high EBV-positive rate in Cantonese NPC patients. EBV BamH I "f" variant was found in 11 cases (52.4%, 11/21) of primary NPCs with LN metastasis, 12 cases (57.1%, 12/21) of the LN metastases, and 18 cases (81.8%, 18/22) of primary NPCs without LN metastasis. However, of the 50 cases of chronic inflammation of nasopharynx, only one case (2.1%, 1/47) demonstrated BamH I "f" variant. The frequency of BamH I "f" variant in NPC was therefore dramatically higher than that in chronic inflammation of nasopharynx. It is of note that atypical hyperplasia was observed in a few epithelial cells from the case of chronic inflammation of nasopharynx expressing BamH I "f" variant. CONCLUSIONS: The frequency of EBV BamH I "f" variant in NPC is significantly higher than that in chronic inflammation of nasopharynx. It is the first demonstration that the BamH I "f" variant is also present in the LN metastases of NPC. The frequency of BamH I "f" variant in metastatic NPC of the lymph node is almost equal to that of primary NPCs.

1H and 13C NMR assignments for 6-demethylvermistatin and two penicillide derivatives from the mangrove fungus Guignardia sp. (No. 4382) from the South China Sea.

One new compound 6-demethylvermistatin (1), together with two known compounds, the penicillide derivatives (2) and (3) were isolated from the mangrove fungus Guignardia sp. No. 4382 obtained from the South China Sea. Their structures were assigned using high-resolution electron ionization mass spectrometry(HREIMS), (1)H and (13)C NMR spectra, DEPT, and by 2D COSY, HMQC, and HMBC experiments. The absolute configuration of 1 was established by comparison of its CD with that of vermistatin.