Using routinely collected data to determine care cascades of hypertension and type-2 diabetes management in China: a cross-sectional study.

Background: China's National Essential Public Health Service Package (NEPHSP) aims to promote health for all at the primary health care level and includes a focus on hypertension and type-2 diabetes mellitus (T2DM). However, there are limited contemporary data to quantify the care cascades of hypertension and T2DM in primary health care. Methods: This cross-sectional study involved individual level linkage of routinely collected data from the NEPHSP, health insurance claims and hospital electronic health records, from four diverse regions in China, including Xiling District (central China), Wenchuan County (western), Acheng District and Jiao District (northern). We first compared numbers of people aged ≥35 with a recorded diagnosis of hypertension and T2DM against expected numbers derived from epidemiological data. We then constructed care cascades to assess the percentages (1) enrolled in the NEPHSP, (2) adherent to the follow-up care of NEPHSP, (3) receiving medication treatment, and (4) having hypertension and/or T2DM controlled. Findings: In the four regions, the total numbers of people aged ≥35 diagnosed of hypertension and T2DM from any data source were 149,176 and 50,828, respectively. This was estimated to be 46.0% (95% confidence interval [CI]: 45.8%-46.2%) and 45.6% (95% CI: 45.3%-45.9%) of the expected totals for hypertension and T2DM, respectively. Among those diagnosed, 65.4% (95% CI: 65.1%-65.6%) with hypertension and 66.1% (95% CI: 65.7%-66.5%) with T2DM were enrolled in the NEPHSP, respectively, in which 54.8% (95% CI: 54.5%-55.2%) with hypertension and 64.7% (95% CI: 64.1%-65.2%) with T2DM were adherent to the required services. Among those enrolled, the overall treatment rates were 70.8% (95% CI: 70.6%-71.1%) for hypertension and 82.2% (95% CI: 81.8%-82.6%) for T2DM. Among those treated, a further 80.9% (95% CI: 80.6%-81.2%) with hypertension and 73.9% (95% CI: 73.3%-74.4%) with T2DM achieved control. These results varied considerably across regions, with the northern sites showing relatively higher enrolment rates while the central site had higher control rates. Interpretation: Detection and control rates for hypertension and T2DM are suboptimal in these four regions of China. Further strategies are needed to improve people's enrolment in and adherence to the NEPHSP and strengthen care delivery processes. Of note, our estimations of the diagnosis rates for each region are based on national level large epidemiological data. The interpretation of these data needs caution due to potential bias caused by regional variations. Funding: This study is funded by National Health and Medical Research Council (NHMRC) Global Alliance for Chronic Diseases funding (APP1169757), and National Natural Science Foundation of China (72074065).

Drug Resistance and Homology of Pathogens of Infective Diarrhea in East Heilongjiang, China.

Objective: To investigate drug resistance and homology of pathogens that can cause infective diarrhea in East Heilongjiang, China, and provide suitable references for the clinical treatment. Methods: The process of isolation and identification of pathogenic bacteria in the faeces and blood of diarrhea patients was conducted. The drug resistance of the isolated pathogenic bacteria was analyzed by VITEK 2 compact drug sensitivity analysis system, and the strain homology was determined by pulsed field gel electrophoresis (PFGE). Results: From 2014 to 2018, 28 different strains of pathogenic bacteria were isolated from 657 samples of faeces and blood, including 23 strains of Salmonella, 3 strains of Vibrio parahaemolyticus and 2 strains of diarrheal Escherichia coli, with detection rates of 3.5%, 0.46% and 0.30% respectively. Among them, 22 strains of Salmonella exhibited significant drug resistance, with a drug resistance rate of 95.65%. A total of 11 different PFGE fingerprints of 23 Salmonella strains were also obtained, with a homology of 56.5-100%. Conclusion: Among the various pathogens causing infective diarrhea in East Heilongjiang, China, Salmonella displayed multiple drug resistance and its distribution was found to be polymorphic.

Multiple biochemical indices and metabolomics of Clonorchis sinensis provide a novel interpretation of biomarkers.

BACKGROUND: Clonorchiasis, an infectious disease caused by the liver fluke Clonorchis sinensis, may lead to the development of liver and gallbladder diseases, and even cholangiocarcinoma (CCA). However, the pathogenesis, host-pathogen interaction, and diagnostic markers for clonorchiasis remain unclear. METHODS: Eighteen rabbits were randomly divided into control group (n = 9) and C. sinensis-infected group (n = 9), and their plasma samples were collected at 7, 14, 28, and 63 days post-infection (dpi). Biochemical indices and metabolites in different infection periods were detected. A non-targeted ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach was employed to investigate the metabolic profiles of plasma in rabbits, and related metabolic pathways of differential metabolites and correlation between candidate biochemical indices and differential metabolites were analyzed. Finally, the candidate biomarkers were verified with human samples using a targeted metabolomics method. RESULTS: The result of biochemical indices indicated C. sinensis infection would affect the liver function biochemical indices, especially alanine aminotransferase, aspartate transaminase (AST), glutamyl transpeptidase (GGT), total bile acid, high-density lipoprotein, and cholinesterase. The metabonomic results showed that 58, 212, 23, and 21 differential metabolites were identified in different phases of the infection. Multivariate statistical analysis of differential metabolites revealed distinct metabolic signatures during different phases of infection, with most of these signatures being observed at 14 dpi, which mainly influences the amino acid metabolisms. For metabolites and biochemical indices, AST, GGT, hypoxanthine, L-pipecolic acid, and D-glucuronate represented potential noninvasive biomarkers for the diagnosis of C. sinensis (P < 0.05 and AUC > 0.8). Furthermore, GGT and D-glucuronate levels were positively correlated with the infection (r(28) = 0.98, P < 0.0001) and showed excellent diagnostic performance (AUC = 0.972; 95% confidence interval, 0.921 to 1.000). CONCLUSIONS: The present results provide new insights into plasma metabolic changes in rabbits during C. sinensis infection, and the potential biomarker may be used for developing an effective method to diagnose clonorchiasis in the future.

Continuous monitoring of fine particulate matter in school classrooms and assessment of students exposure level / 中国学校卫生

Objective@#To explore the status of PM 2.5 pollution in school classrooms and the student exposure level, and to provide basic data to safeguard the health of students.@*Methods@#This study continuously monitored the PM 2.5 levels of 16 naturally ventilated classrooms in eight primary and secondary schools in Jiamusi for one academic year using an online environmental monitoring instrument. At the same time, outdoor PM 2.5 data was captured for comparative research, and student exposure to PM 2.5 during school hours was evaluated.@*Results@#The average concentration of PM 2.5 in the classroom in the spring and autumn semesters was (26.93±24.7) and (31.85±30.37)μg/m 3, respectively, and the indoor/outdoor ratio ( I/O ) was 0.92 and 0.95, respectively, which indicated a strong correlation between them. The daily average concentration of all classrooms during both semesters was ( 28.93 ±26.85)μg/m 3, which was slightly higher than the average concentration of (27.53±26.53)μg/m 3 during the daytime when students were in school. In addition, the concentration on workdays was higher than that observed on weekends, and this was termed the "weekend effect". The indoor PM 2.5 concentration was lower on higher floors. The comprehensive exposure concentration of students during school was 28.48 μg/m 3 in spring semester and 31.87 μg/m 3 in autumn semester.@*Conclusion@#PM 2.5 levels in the classrooms varied according to time, the horizontal space, and the vertical space, and the level of indoor PM 2.5 pollution largely depended on outdoor pollution sources. Differences in PM 2.5 exposure were observed between.

Outbreak of KPC-2 Carbapenem-resistant Klebsiella pneumoniae ST76 and Carbapenem-resistant K2 Hypervirulent Klebsiella pneumoniae ST375 strains in Northeast China: molecular and virulent characteristics.

BACKGROUND: Carbapenem-resistant hypervirulent Klebsiella pneumoniae strains have recently come into existence worldwide; however, researchers in northeast China are not aware of their clinical features and molecular characteristics. METHODS: Here, the molecular and virulent characteristics of 44 carbapenem-resistant K. pneumoniae (CRKP) isolates collected from January 2015 to December 2017 were studied. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were carried out to define the clonal relatedness among the isolates. PCR and capsular serotyping of the virulence-associated genes, as well as biofilm formation and serum complement-mediated killing assays, were employed to determine the virulent potential. The genomic features and associated mobile genetic elements of JmsCRE57 were detected by whole genome sequencing. RESULTS: The only positive isolate was JmsCRE57, which belonged to the ST375 serotype K2 that expressed uge, mrkD, fimH, kpn, aerobactin and rmpA virulence-associated genes and showed strong biofilm formation and serum sensitivity. Sequencing results showed that the JmsCRE57 genome mainly consisted of a circular chromosome, three antimicrobial resistant plasmids and a virulent plasmid. The antimicrobial resistant plasmid expressing blaKPC-2, blaCTX-M-15, aph(3″)-Ib, aph(6)-Id, qnrB1, aac(3)-IIa, aac(6')-Ib-cr, blaOXA-1, blaTEM-1B, catB4, sul2, dfrA14 and blaSHV-99. The virulent plasmid belonged to the IncHI1B group, which is mainly composed of mucoid phenotype genes and siderophore-associated genes. The remaining CRKP strains that expressed uge, fimH, mrkD and kpn virulence-associated genes were not successfully typed. CONCLUSION: Our results provide new insights on the epidemiology of carbapenem-resistant K2 hypervirulent K. pneumoniae ST375 and CRKP ST76 strains in northeast China, which may help control their future outbreaks.

Outbreak of KPC-2-Producing Klebsiella pneumoniae ST76 Isolates in an Intensive Care Unit and Neurosurgery Unit.

Background: The aim of this study was to investigate the characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) ST76 isolates collected during an outbreak in a hospital's intensive care unit and neurosurgery unit. Methods: Seventeen separate clinical isolates of CRKP were collected from patients from March 2016 to February 2017. Bacterial isolates were identified, and antimicrobial susceptibility testing was conducted using the VITEK-2 compact system. Isolates containing antibiotic resistance genes were characterized by polymerase chain reaction and DNA sequencing. Clonal relatedness was assessed by multilocus sequence typing and pulsed-field gel electrophoresis. Conjugation experiments were performed to determine the transferability of plasmids with antibiotic resistance. The genomic features and mobile genetic elements of ST76 CRKP were detected by whole genome sequencing. Results: ST76 KPC-2-producing CRKP prevailed in our hospital, causing an outbreak. The strains also carried blaSHV-1, blaCTX-M-15, blaTEM-1, qnrB, and acc(6')Ib-cr resistance genes. Plasmids from 17.7% of the isolated strains bearing these resistance genes could be transferred into the recipient Escherichia coli J53 through conjugation. Sequencing results showed that the KP4 genome mainly consisted of a circular chromosome and three antibiotic resistance plasmids. The plasmid carrying the blaKPC-2 gene was located on a 437 kb IncFIB (pQil) plasmid with Tn1721-blaKPC-2-ΔT3 gene structure. Genes conferring resistance against aminoglycosides, quinolones, fluoroquinolones, beta-lactamase, phenicols, sulfonamides, and trimethoprims and the presence of virulence-associated genes related to iron acquisition or adhesins were determined. Conclusion: This is the first report of the whole genome sequence of a KPC-2-producing K. pneumoniae ST76 isolate. This work provides a basis for understanding antibiotic resistance and resistant plasmid transmission. Relevant departments should implement infection control and prevention measures to reduce the incidence of nosocomial infections.

Molecular characterization and epidemiology of carbapenem non-susceptible Enterobacteriaceae isolated from the Eastern region of Heilongjiang Province, China.

BACKGROUND: The aim of this study was to elucidate the molecular epidemiology of carbapenem non-susceptible Enterobacteriaceae(CNSE) isolated in the Eastern region of Heilongjiang Province, China, and the mechanism of carbapenem resistance. METHODS: A total of 53 CNSE isolates were collected in a grade-3 hospital in Heilongjiang province. Sensitivity to antibiotics was determined using the VITEK-2 Compact automatic system. The modified Hodge test (MHT) and modified carbapenem inactivation test (mCIM) were performed for phenotypic identification. Beta-lactamases gene were detected by Polymerase chain reaction(PCR) and DNA sequencing. The transfer of blaNDM and blaKPC was investigated through conjugation experiment. The clinical data of patients were retrospectively reviewed. Homology of Carbapenem-resistant Klebsiella pneumoniae(CRKP) was conducted by multilocus sequence typing (MLST). RESULTS: CNSE were highly resistant to the majority of antimicrobial agents. The resistance rate was 100% for first, third, fourth generation cephalosporins and enzyme inhibitor compounds. Gentamicin and tobramycin recorded a resistance rate higher than 80%. Less than 30% resistance was detected for amikacin and levofloxacin. Among CNSE 52(98.1%) and 48(90.6%) of CNSE were positive for mCIM and MHT respectively. There were 42 positive blaKPC genes, three blaNDM-1 genes, three blaNDM-5 genes, one blaNDM-7 gene, and six blaIMP-4 genes. Most isolates harbored multiple drug resistance gene, especially as related to extended-spectrum-ß-lactamases, blaSHV, blaTEM and blaCTX-M-15 genes.The resistant gene was transferred into recipient Escherichia coli J53 through conjugation in 21.3% (10/47) of the strains. MLST revealed that ST76 (n = 36) was the most predominant clone, followed by ST896, ST323 and ST11. A new one ST 2946 was identity by this study. CONCLUSION: The carbapenem resistance phenomenon is alarming and blaKPC-2 is the main resistant gene of CNSE in our hospital. This is the first report of an outbreak caused by blaKPC-2 positive K. pneumoniae ST76 in the Eastern region of Heilongjiang Province, China. Relevant departments should implement infection control and prevention measures to avoid further dissemination of the multi drug-resistant bacteria (MDR).

Mimotopes selected by biopanning with high-titer HIV-neutralizing antibodies in plasma from Chinese slow progressors.

OBJECTIVE: One approach to identifying HIV-1 vaccine candidates is to dissect the natural antiviral immune response in treatment-naïve individuals infected for over ten years, considered slow progressor patients (SPs). It is suspected that SP plasma has strongly neutralizing antibodies (NAb) targeting specific HIV viral epitopes. METHODS: NAbs levels of 11 HIV-1-infected SPs were detected by PBMC-based neutralization assays. To investigate SP NAb epitope, this study used a biopanning approach to obtain mimotopes of HIV-1 that were recognized by SP plasma NAbs. IgG was purified from high-titer NAb SP plasma, and used as the ligand for three rounds of biopanning to select HIV-specific mimotopes from a phage-displayed random peptide library. Double-antibody sandwich ELISA, competitive inhibition assays, and peptide sequence analysis were used to evaluate the characteristics of phage-borne mimotopes. RESULTS: SPs had significantly more plasma neutralizing activity than typical progressors (TPs) (p=0.04). P2 and P9 plasma, which have highest-titer HIV-NAb, were selected as ligands for biopanning. After three rounds of biopanning, 48 phage clones were obtained, of which 22 clones were consistent with requirement, binding with HIV-1 positive plasma and unbinding with HIV-1 negative plasma. Compared with linear HIV-1 protein sequence and HIV-1 protein structure files, only 12 clones were possible linear mimotopes of NAbs. In addition, the C40 clone located in gp41 CHR was found to be a neutralizing epitope, which could inhibit pooled HIV-1 positive plasma reaction. CONCLUSION: Biopanning of serum IgG can yield mimotopes of HIV-1-related antigen epitopes. This methodology provides a basis for exploration into HIV-1-related antigen-antibody interactions and furthers NAb immunotherapy and vaccine design.

Identification and characterization of broadly cross-reactive neutralizing antibodies in patients infected with HIV-1 B'/C recombinant (CRF07_BC).

The identification of broadly cross-reactive neutralizing (BCN) antibodies is essential for the development of a more universally effective vaccine for human immunodeficiency virus (HIV). In this study, CRF07_BC serum was analyzed for cross-clade antibody reactivity and neutralization. A total of 117 HIV-1 sera (CRF07_BC) were screened for their capacity to neutralize three primary HIV-1 isolates. A total of 18 out of 117 sera cross-neutralized all three viruses, and were tested along with eight randomly selected non-BCN sera against seven primary HIV-1 isolates and two laboratory strains that represented different clades and tropisms. BCN sera neutralized eight or all nine of these primary isolates. Non-BCN sera did not display any broadly cross-reactive neutralizing responses. BCN sera neutralized with higher frequency and geometric mean titers compared to non-BCN sera. Sera from asymptomatic individuals on average neutralized a significantly greater number of the three key isolates than sera from symptomatic individuals. Our data indicate that the three HIV-1 isolated strains are sufficient to screen broad cross-neutralizing sera, and that BCN responses may contribute to protection from infection and disease progression. The neutralizing antibody response demonstrated extensive cross-neutralization, suggesting that neutralizing antibodies induced by vaccines will have a relatively low epitope diversity to overcome in patients infected with HIV-1 B'/C recombinant (CRF07_BC).

R-848 triggers the expression of TLR7/8 and suppresses HIV replication in monocytes.

BACKGROUND: Toll-like receptors (TLR) 7 and 8 are important in single-stranded viral RNA recognition and may play a role in HIV infection and disease progression. We analyzed TLR7/8 expression and signaling in monocytes from HIV-infected and uninfected subjects to investigate a pathway with new potential for the suppression of HIV replication. METHODS: Eighty-one HIV-infected and uninfected subjects from Liaoning and Henan provinces in China participated in this study. Monocytes were isolated from subjects' peripheral blood mononuclear cells by magnetic bead selection. TLR7 and TLR8 mRNA was measured using quantitative real-time reverse transcriptase PCR. R-848 (resiquimod) was used as a ligand for TLR7 and TLR8 in order to 1) assess TLR7/8-mediated monocyte responsiveness as indicated by IL-12 p40 and TNF-α secretion and 2) to examine HIV replication in cultured monocytes in the presence of R-848. RESULTS: We found that expression of TLR7/8 mRNA in peripheral blood monocytes decreased with disease progression. TLR7 expression was decreased with stimulation with the TLR7/8 agonist, R-848, in vitro, whereas TLR8 expression was unaffected. Following R-848 stimulation, monocytes from HIV-infected subjects produced significantly less TNF-α than those from uninfected subjects, but trended towards greater production of IL-12 than stimulated monocytes from uninfected subjects. R-848 stimulation also suppressed HIV replication in cultured monocytes. CONCLUSIONS: Our study provides evidence that the TLR7 and TLR8 triggering can suppress HIV replication in monocytes and lead to postpone HIV disease progression, thereby offering novel targets for immunomodulatory therapy.

The associations of hA3G and hA3B mRNA levels with HIV disease progression among HIV-infected individuals of China.

OBJECTIVE: To explore correlations between mRNA (hA3G, hA3F, and hA3B) levels and CD4 T-cell counts and HIV-1 viral loads to evaluate their respective roles in disease progression. METHODS: Real-time polymerase chain reaction was used to quantify the mRNA levels of hA3G, hA3B, and hA3F in peripheral blood mononuclear cells from slow progress patients (SP), asymptomatic HIV-infected patients (AS), AIDS patients, and HIV-negative controls. RESULTS: The levels of hA3G and hA3B mRNA correlated positively with CD4 T-cell counts (r = 0.436, P = 0.002, r = 0.334, P = 0.025), and negatively with HIV-1 viral loads (r = -0.306, P = 0.038, r = -0.301 P = 0.044). The levels of hA3G and hA3B mRNA in HIV-infected subjects were lower than in HIV-negative controls (P < 0.05), and hA3G and hA3B mRNA levels were significantly higher in SP than in AIDS patients (P < 0.05). There was no correlation between the hA3F mRNA level and CD4 T-cell counts or between the hA3F mRNA level and HIV-1 viral loads. CONCLUSIONS: Higher expression levels of hA3G and hA3B mRNA in the peripheral blood mononuclear cells of Chinese HIV-infected individuals were found to be associated with slower HIV disease progression, suggesting their potential roles in antiviral innate immunity.

Association of variations of NAb 2F5 and 4E10 epitopes and disease progression in Chinese antiretroviral treatment-naïve patients infected with HIV-1 clade B'.

BACKGROUND: Studies on human immunodeficiency virus type 1 (HIV-1) vaccines have recently focused on targeting the conserved neutralizing epitopes 2F5 and 4E10, and hence it is important to understand the extent of mutations in these two viral epitopes. Here, we investigated the amino acid mutations in epitopes of 2F5 (ELDKWA, HIV-1 HXB2 env 662 - 667 aa) and 4E10 (NWFDIT, HIV-1 HXB2 env 671 - 676 aa) in the membrane proximal-external region of gp41 from clade B' HIV-1-infected individuals living in Henan province, China. We also examined the frequency of a mutation and its relation to disease progression. METHODS: A cohort of 54 treatment-naïve HIV-1-infected individuals was recruited in this study, and 16 individuals were selected for a short-term longitudinal study on sequence evolution. The HIV-1 env gp41 gene was amplified, cloned, and sequenced, and predicted amino acid sequences were aligned for analysis. RESULTS: The mutations E662A and K665E on the 2F5 epitope and N671S and T676S on the 4E10 epitope were seen. Simultaneous RNA sequencing showed some discrepancies with proviral DNA sequences. In our longitudinal study, mutation levels of these two neutralizing epitopes were low but diverse and persistent. The frequencies of mutations within the 4E10 peptide NWFDIT in slow progressors were noticeably lower than those in AIDS patients (P < 0.05). CONCLUSIONS: Antigenic variation of the neutralizing epitopes 2F5 and 4E10 is limited in subtype B' infection, and that 4E10 peptide mutation is correlated with disease progression. Monitoring epitope mutations will offer useful data for development of the candidate 2F5-like and 4E10-like antibodies to prevent and treat AIDS.