Biology subjects

Zhang, L.

Publications and source records attributed to Zhang, L..

At least 1,531 records · Page 85Linked to original sources

bioRxiv2019

Towards a Better Estimation of Functional Brain Network for Mild Cognitive Impairment Identification: A Transfer Learning View

Mild cognitive impairment (MCI) is an intermediate stage of brain cognitive decline, associated with increasing risk of developing Alzheimers disease (AD). It is believed that early treatment of MCI could slow down the progression of AD, and functional brain network (FBN) could provide potential imaging biomarkers for MCI diagnosis and response to treatment. However, there are still some challenges to estimate a \"good\" FBN, particularly due to the poor quality and limited quantity of functional magnetic resonance imaging (fMRI) data from the target domain (i.e., MCI study). Inspired by the idea of transfer learning, we attempt to transfer information in high-quality data from source domain (e.g., human connectome project in this paper) into the target domain towards a better FBN estimation, and propose a novel method, namely NERTL (Network Estimation via Regularized Transfer Learning). Specifically, we first construct a high-quality network \"template\" based on the source data, and then use the template to guide or constrain the target of FBN estimation by a weighted l1-norm regularizer. Finally, we conduct experiments to identify subjects with MCI from normal controls (NCs) based on the estimated FBNs. Despite its simplicity, our proposed method is more effective than the baseline methods in modeling discriminative FBNs, as demonstrated by the superior MCI classification accuracy of 82.4% and the area under curve (AUC) of 0.910.

neuroscience↗

bioRxiv2019

The common neoantigens in colorectal cancer are predicted and validated to be presented or immunogenic

Colorectal cancer (CRC) is a malignant cancer with high incidence and mortality in the world, as the result of the traditional treatments. Immunotherapy targeting neoantigens can induce durable tumor regression in cancer patients, but is almost limited to individual treatment, resulting from the unique neoantigens. Many shared oncogenic mutations are detected, but whether the common neoantigens can be identified in CRC is unknown. Using the somatic mutations data from 321 CRC patients combined with a filter standard and 7 predicted algorithms, we screened and obtained 25 HLA-A*11:01 restricted common neoantigens with high binding affinity (IC50<50 nM) and presentation score (>0.9). Except the positive epitope KRAS_G12V8-16, 11 out of 25 common neoantigens were proved to be naturally processed and presented on constructed K562 cell surface by mass spectroscopy (MS), and 11 out of 25 common neoantigens specifically induced in vitro pre-stimulated cytotoxic lymphocyte (CTL) to secrete IFN-{gamma}. However, only 2 out of 25 common neoantigens were simultaneously presented and immunogenic. Moreover, using cell-sorting technology combined with single-cell RNA sequencing, the immune repertoire profiles of C1orf170_S418G413-421 and KRAS_G12V8-16-specific CTL were clarified. Therefore, common neoantigens with presentation and immunogenicity could be found in CRC, which would be developed as the universal targets for CRC immunotherapy.

immunology↗

bioRxiv2019

A multimodal framework for detecting direct and indirect gene-gene interactions from large expression compendium

The fast accumulation of high-throughput gene expression data provides us an unprecedented opportunity to understand the gene interactions and prioritize disease candidate genes. However, these data are typically noisy and highly heterogeneous, complicating their use in constructing large expression compendium. Recent studies suggest that the collective expression pattern can be better modeled by Gaussian mixtures. This motivates our present work, which applies a Multimodal framework (MMF) to depict the gene expression profiles. MMF introduces two new statistics: Multimodal Mutual Information and Multimodal Direct Information. Through extensive simulations, MMF outperforms other approaches for detecting gene co-expressions or gene regulatory interactions, regardless of the level of noise or strength of interactions. In the principal component analysis for very large collections of expression data, the use of MMI enables more biologically meaningful spaces to be extracted than the use of Pearson correlation. The practical use of MMF is further demonstrated with three biological applications: 1. Prioritizing KIF1A as the candidate causal gene of hereditary spastic paraparesis from familial exome sequencing data; 2. Detecting ANK2 as the hot genes for autism spectrum disorders, derived from exome sequencing family based study; 3. Predicting the microRNA target genes based on both sequence and expression information.

bioinformatics↗

bioRxiv2019

Functional Analysis of FRIGIDA Using Naturally Occurring Variation in Arabidopsis thaliana

The FRIGIDA locus (FRI, AT4G00650) has been extensively studied in Arabidopsis thaliana because of its role creating flowering time diversity. The FRI protein regulates flowering induction by binding partner proteins on its N- and C-terminus domains and creating a supercomplex that promotes transcription of the floral repressor FLC. Despite the knowledge accumulated on FRI, the function of the highly conserved central domain of the protein is still unknown. Functional characterization of naturally occurring DNA polymorphisms can provide useful information about the role of a protein and the localization of its operative domains. In the case of FRI, deleterious mutations are positively selected and widespread in nature, making them a powerful tool to study the function of the different domains of the protein. Here we explore natural sequence variation in the FRI locus in more than 1000 Arabidopsis accessions. We identify new mutations predicted to compromise the function of the protein and confirm our predictions by cloning 22 different alleles of FRI and expressing them in a common null genetic background. Our analysis allows us to pinpoint two single amino acid changes in the central domain that render the protein non-functional. We show that these two mutations determine the stability and cellular localization of the FRI protein. In summary, our work makes use of natural variants at the FRI locus to help understanding the function of the central domain of the FRI protein.

plant biology↗

bioRxiv2019

TCR convergence in individuals treated with immune checkpoint inhibition for cancer

Tumor antigen-driven selection may expand T cells having T cell receptors (TCRs) of shared antigen specificity but different amino acid or nucleotide sequence in a process known as TCR convergence. Substitution sequencing errors introduced by TCR{beta} (TCRB) repertoire sequencing may create artifacts resembling TCR convergence. Given the anticipated differences in substitution error rates across different next-generation sequencing platforms, the choice of platform could be consequential. To test this, we performed TCRB sequencing on the same peripheral blood mononuclear cells (PBMC) from individuals with cancer receiving anti-CTLA-4 or anti-PD-1 using an Illumina-based approach and an Ion Torrent-based approach. While both approaches found similar TCR diversity, clonality, and clonal overlap, we found that Illumina-based sequencing resulted in higher TCR convergence than with the Ion Torrent approach. Using the latter approach, we found that clonality and convergence independently predicted response and could be combined to improve the accuracy of a logistic regression classifier. These results demonstrate the importance of the sequencing platform in assessing TCRB convergence.

cancer biology↗

bioRxiv2019

Shared and Distinct Dysfunction of Dynamic Connectivity Networks across Schizophrenia, Bipolar Disorder and Major Depression Disorder

Dynamic functional connectivity (DFC) analysis can capture time-varying properties of connectivity and may provide further information about transdiagnostic psychopathology across major psychiatric disorders. In this study, we used resting state functional MRI and a sliding-window method to study DFC in 150 schizophrenia (SZ), 100 bipolar disorder(BD), 150 major depressive disorder (MDD), and 210 healthy controls (HC). DFC were clustered into two functional connectivity states. Significant 4-group differences in DFC were found only in state 2. Post hoc analyses showed that transdiagnostic dysconnectivity among there disorders featured decreased connectivity within visual, somatomotor, salience and frontoparietal networks. Our results suggest that decreased connectivity within both lower-order (visual and somatomotor) and higher-order (salience and frontoparietal) networks may serve as transdiagnostic marker of these disorders, and that these dysconnectivity is state-dependent. Targeting these dysconnectivity may improve assessment and treatment for patients that having more than one of these disorders at the same time.

neuroscience↗

bioRxiv2019

Oncoprotein CoAA repeats interact with RNA polymerase II CTD repeats

The heptad repeating sequence of the C-terminal domain (CTD) of the largest subunit of RNA polymerase II is highly conserved in eukaryotes. In yeast, a CTD code consisting of pairs of heptad repeats is essential for viability. However, the strict requirement of diheptad repeats for the CTD function in transcription and splicing is unexplained. Here we show that CoAA (gene symbol RBM14), an oncoprotein and mammalian transcriptional coactivator, possesses diheptad repeats and directly interacts with the CTD. CoAA comprises 27 copies of tyrosine-rich repeats and regulates pre-mRNA synthesis and alternative splicing. Tyrosine substitutions in either the CoAA repeats or the CTD repeats diminish their interactions. Ser2- or Ser5-phosphorylated CTD peptides exhibit higher binding affinity to CoAA than the corresponding non-phosphorylated CTD peptide. CoAA dynamically interacts with both the CTD and hnRNP M, which is an alternative splicing regulator also comprising diheptad repeats. Arginine methylation of CoAA switches its interaction from the hnRNP M repeats to the CTD repeats. This study provides a mechanism for CoAA at the interface of transcription and alternative splicing, and explains the functional requirement of diheptad repeats in the CTD. In the human genome, tyrosine-rich repeats similar to the CoAA repeats were only found in six oncoproteins including EWS and SYT. We suggest that the diheptad sequence is one of the signature features for the CTD interaction among oncoproteins involved in transcription and alternative splicing. We anticipate that direct RNA Pol II interaction is a mechanism in oncogenesis.

biochemistry↗

bioRxiv2019

Single-cell whole-genome sequencing reveals mutational landscapes of DNA mismatch repair deficiency in mouse primary fibroblasts

DNA Mismatch repair (MMR) deficiency is a major cause of hereditary non-polyposis colorectal cancer, and is also associated with increased risk of several other cancers. This is generally ascribed to the role of MMR in avoiding mutations by correcting DNA replication errors. In MMR knockout mice very high frequencies of somatic mutations, up until 100-fold of background, have been reported. However, these results have been obtained using bacterial reporter transgenes, which are not representative for the genome overall, and mutational patterns of MMR deficiency remain largely unknown. To fill this knowledge gap, we performed single-cell whole-genome sequencing of lung fibroblasts of Msh2-/- and wild-type mice. We observed a 4-fold increase of somatic single nucleotide variants (SNVs) in the fibroblasts of Msh2-/- mice compared to those of wild-type mice. The SNV signature of Msh2 deficiency was found to be driven by C>T and T>C transitions. By comparing it to human cancer signatures, we not only confirmed the inferred MMR-deficiency-related etiology of several cancer signatures but also suggested that MMR deficiency is likely the cause of a cancer signature with its etiology previously unknown. We also observed a 7-fold increase of somatic small insertions and deletions (INDELs) in the Msh2-/- mice. An elevated INDEL frequency has also been found in human MMR-related cancers. INDELs and SNVs distributed differently across genomic features in the Msh2-/- and control cells, with evidence of selection pressure and repair preference. These results provide insights into the landscape of somatic mutations in normal somatic cells caused by MMR deficiency.\n\nSignificanceOur results show that MMR deficiency in the mouse is associated with a much lower elevation of somatic mutation rates than previously reported and provides the first MMR whole-genome mutational landscapes in normal somatic cells in vivo.

genomics↗

bioRxiv2019

Genome analysis and Hi-C assisted assembly of Elaeagnus angustifolia L., a deciduous tree belonging to Elaeagnaceae

Elaeagnus angustifolia L. is a deciduous tree of the Elaeagnaceae family. It is widely used in the study of abiotic stress tolerance in plants and for the improvement of desertification-affected land due to its characteristics of drought resistance, salt tolerance, cold resistance, wind resistance, and other environmental adaptation. Here, we report the complete genome sequencing using the Pacific Biosciences (PacBio) platform and Hi-C assisted assembly of E. angustifolia. A total of 44.27 Gb raw PacBio sequel reads were obtained after filtering out low-quality data, with an average length of 8.64 Kb. And 39.56 Gb clean reads was obtained, with a sequencing coverage of 75x, and Q30 ratio > 95.46%. The 510.71 Mb genomic sequence was mapped to the chromosome, accounting for 96.94% of the total length of the sequence, and the corresponding number of sequences was 269, accounting for 45.83% of the total number of sequences. The genome sequence study of E. angustifolia can be a valuable source for the comparative genome analysis of the Elaeagnaceae family members, and can help to understand the evolutionary response mechanisms of the Elaeagnaceae to drought, salt, cold and wind resistance, and thereby provide effective theoretical support for the improvement of desertification-affected land.

genetics↗

bioRxiv2019

The small noncoding RNA sr8384 determines solvent synthesis and cell growth in industrial solventogenic clostridia

Small noncoding RNAs (sncRNAs) are crucial regulatory molecules in organisms and are well known not only for their roles in the control of diverse essential biological processes but also for their value in genetic modification. However, to date, in gram-positive anaerobic solventogenic clostridia (which are a group of important industrial bacteria with exceptional substrate and product diversity), sncRNAs remain minimally explored, leading to a lack of detailed understanding regarding these important molecules and their use as targets for genetic improvement. Here, we performed large-scale phenotypic screens of a transposon-mediated mutant library of Clostridium acetobutylicum, a typical solventogenic clostridial species, and discovered a novel sncRNA (sr8384) that functions as a determinant positive regulator of growth and solvent synthesis. Comparative transcriptomic data combined with genetic and biochemical analyses revealed that sr8384 acts as a pleiotropic regulator and controls multiple targets that are associated with crucial biological processes, through direct or indirect interactions. Notably, modulation of the expression level of either sr8384 or its core target genes significantly increased the growth rate, solvent titer and productivity of the cells, indicating the importance of sr8384-mediated regulatory network in C. acetobutylicum. Furthermore, a homolog of sr8384 was discovered and proven to be functional in another important Clostridium species, C. beijerinckii, suggesting the potential broad role of this sncRNA in clostridia. Our work showcases a previously unknown potent and complex role of sncRNAs in clostridia, providing new opportunities for understanding and engineering these anaerobes, including pathogenic Clostridium species.\n\nIMPORTANCEThe discovery of sncRNAs as new resources for functional studies and strain modifications are promising strategies in microorganisms. However, these crucial regulatory molecules have hardly been explored in industrially important solventogenic clostridia. Here, we identified sr8384 as a novel determinant sncRNA controlling cellular performance of solventogenic Clostridium acetobutylicum and performed detailed functional analysis, which is the most in-depth study of sncRNAs in clostridia to date. We reveal the pleiotropic function of sr8384 and its multiple direct and indirect crucial targets, which represents a valuable source for understanding and optimizing this anaerobe. Of note, manipulation of these targets leads to improved cell growth and solvent synthesis. Our findings provide a new perspective for future studies on regulatory sncRNAs in clostridia.

microbiology↗

bioRxiv2019

Aquila: diploid personal genome assembly and comprehensive variant detection based on linked reads

Variant discovery in personal, whole genome sequence data is critical for uncovering the genetic contributions to health and disease. We introduce a new approach, Aquila, that uses linked-read data for generating a high quality diploid genome assembly, from which it then comprehensively detects and phases personal genetic variation. Assemblies cover >95% of the human reference genome, with over 98% in a diploid state. Thus, the assemblies support detection and accurate genotyping of the most prevalent types of human genetic variation, including single nucleotide polymorphisms (SNPs), small insertions and deletions (small indels), and structural variants (SVs), in all but the most difficult regions. All heterozygous variants are phased in blocks that can approach arm-level length. The final output of Aquila is a diploid and phased personal genome sequence, and a phased VCF file that also contains homozygous and a few unphased heterozygous variants. Aquila represents a cost-effective evolution of whole-genome reconstruction that can be applied to cohorts for variation discovery or association studies, or to single individuals with rare phenotypes that could be caused by SVs or compound heterozygosity.

genomics↗

bioRxiv2019

Development of a potent and protective germline-like antibody lineage against Zika virus in a convalescent human

Zika virus (ZIKV) specific neutralizing antibodies hold a great promise for antibody-based interventions and vaccine design against ZIKV infection. However, their development in infected patients remain unknown. Here, we report on the dynamic development of a potent and protective ZIKV-specific human antibody ZK2B10 initially isolated from a ZIKV convalescent individual using next-generation sequencing (NGS). The unbiased repertoire analysis showed dramatic changes in many families of heavy and light chain variable regions. However, lineage tracing of ZK2B10 revealed limited somatic hypermutation throughout the 12 months since the onset of symptom. In particular, NGS-derived germline-like somatic variants neutralized and protected mice from lethal challenge of ZIKV without detectable cross-reactivity with Dengue virus (DENV). Site-directed mutagenesis identified two residues within {lambda} chain, N31 and S91 that are essential to the functional maturation. The dynamic features unveiled here will assist us to better understand the pathogenesis of ZIKV infection and inform rational design of vaccines.\n\nAuthor summaryRecently emerged ZIKV is associated with severe neurological complications such as Guillain-Barre syndrome in adults and congenital microcephaly in newborns. No ZIKV-specific therapeutics or vaccines are currently available. We and others have identified a number of neutralizing antibodies capable of protecting experimental animals from ZIKV infection. However, the development of these potent antibodies during ZIKV natural infection remains unknown. Here, we report on the longitudinal analysis of one such antibody ZK2B10 using next-generation sequencing (NGS), bioinformatics and functional analysis. We found that the ZK2B10 germline-like antibodies possess strong neutralizing activity in vitro and impressive protectivity against lethal ZIKV infection in vivo. These findings suggest that the potent and protective antibody response against ZIKV can be generated within relative short term with high germline identity which provide great hope and promise for successful vaccine development against ZIKV.

microbiology↗

bioRxiv2019

Nonlinear Dispersive Cell Model for Microdosimetry of Nanosecond Pulsed Electric Fields

For nanosecond pulsed electric fields (nsPEFs) based application, the underlying transmembrane potential (TMP) distribution of the plasma membrane is influenced by electroporation (EP) of the plasma membrane and dispersion (DP) of all cell compartments and is important for predicting the bioelectric effects. In this study, we analysed temporal and spatial distribution of TMP induced by nsPEFs of various durations (3 ns, 5 ns unipolar, 5 ns bipolar, and 10 ns) with the consideration of both DP and EP. Based on the double-shelled dielectric spherical cell model, we used second-order Debye equation to characterize the dielectric relaxation of plasma membrane and nuclear membrane in the frequency domain and transformed the Debye equation into the time domain with the introduction of polarization vector, then we obtained the time course of TMP by solving the combination of Laplace equation and time-domain Debye equation. Next, we used the asymptotic version of the smoluchowski equation to characterize electroporation of plasma membrane and added it to our model to achieve the temporal and spatial distribution of TMP and pore density. Much faster and more pronounced increased in TMP can be found with the consideration of dielectric relaxation of plasma membrane and nuclear membrane, and much larger electroporated area of at least half of the plasma membrane was obtained with the consideration of both DP and EP. Through the simulation it is clearer to understand the relationship.

bioengineering↗

bioRxiv2019

PI3K/AKT inhibition in tumor propagating cells of DLBCL reverses R-CHOP resistance by destabilizing SOX2

Drug resistance is a major obstacle for the success of conventional anticancer therapy, and the development of drug resistance is at least partly attributed to tumor propagating cells (TPCs). Up to one-third of diffuse large B cell lymphoma (DLBCL) patients eventually develop resistance to R-CHOP regimen. We found that the TPC proportion was remarkably increased in resistant germinal center B cell-like (GCB) and activated B cell-like (ABC) DLBCL subtypes. Elevated SOX2 was the determinant for resistance development, and SOX2 was phosphorylated by activated PI3K/AKT1 signaling, thus preventing ubiquitin-mediated SOX2 degradation. Furthermore, multiple factors, including BCR, integrins, chemokines and FGFR1/2 signaling, regulated PI3K/AKT1 activation. CDK6 in the GCB subtype and FGFR1/2 in the ABC subtype were SOX2 targets in the PI3K/AKT1 pathway. Chemical inhibition of PI3K/AKT1 in both subtypes, CDK6 in the GCB subtype, and FGFR1/2 in the ABC subtype significantly enhanced the susceptibility of resistant cells to CHO treatment. More importantly, PI3K and FGFR1/2 inhibitors but not a CDK6 inhibitor effectively suppressed the tumor growth of R-CHO-resistant DLBCL cells, most likely by converting TPCs to chemo-sensitive differentiated cells. Therefore, this pro-differentiation therapy against TPCs warrants further study in clinical trials for the treatment of resistant DLBCL.

cancer biology↗

bioRxiv2019

Transferrin plays a central role to maintain coagulation balance by interacting with clotting factors

Coagulation balance is maintained through fine-tuning interactions among clotting factors. Physiological concentrations of clotting factors are huge difference. Especially, coagulation proteases concentration (pM to nM) is much lower than their natural inactivator antithrombin III (AT-III, [~]3 M). Here we show that transferrin (normal plasma concentration [~]40 M) interacts with fibrinogen, thrombin, FXIIa and AT-III with different affinity to maintain coagulation balance. Normally, transferrin is sequestered by binding with fibrinogen (normal plasma concentration [~]10 M) with a molar ratio of 4:1. In atherosclerosis, abnormally up-regulated transferrin interacts with and potentiates thrombin/FXIIa and blocks AT-IIIs inactivation on coagulation proteases by binding to AT-III, and thus induces hypercoagulability. In mouse models, transferrin-overexpression aggravated atherosclerosis while transferrin-knockdown, anti-transferrin antibody or designed peptides interfering transferrin-thrombin/FXIIa interactions alleviated it. Collectively, these findings identify transferrin as a clotting factor and an adjuster for maintaining coagulation balance and modify the coagulation cascade.

molecular biology↗

bioRxiv2019

Microbial composition of the human nasopharynx varies according to influenza virus type and vaccination status.

Factors that contribute to enhanced susceptibility to severe bacterial disease after influenza infection are not well defined, but likely include the microbiome of the respiratory tract. Vaccination against influenza, while having variable effectiveness, could also play a role in microbial community stability. We collected nasopharyngeal samples from 215 individuals infected with influenza A/H3N2 or influenza B and profiled the microbiota by target sequencing of the 16S rRNA gene. We identified signature taxonomic groups by performing linear discriminant analysis and effective size comparisons (LEfSe) and defined bacterial community types using Dirichlet Multinomial Mixture (DMM) models. Influenza infection was shown to be significantly associated with microbial composition of the nasopharynx according to the virus type and the vaccination status of the patient. We identified 4 microbial community types across the combined cohort of influenza patients and healthy individuals with one community type most representative of the influenza-infected group. We also identified microbial taxa for which relative abundance was significantly higher in the unvaccinated elderly group; these taxa include species known to be associated with pneumonia.\n\nImportanceOur results suggest that there is a significant association between the composition of the microbiota in the nasopharynx and the influenza virus type causing the infection. We observe that vaccination status, especially in more senior individuals, also has an association with the microbial community profile. This indicates that vaccination against influenza, even when ineffective to prevent disease, could play a role in controlling secondary bacterial complications.

microbiology↗

bioRxiv2019

Genome-wide association study of appendicular lean mass in UK Biobank cohort

Lean body mass (LBM), an important physiological measure, has a strong genetic determination. To clarify its genetic basis, a large-scale genome-wide association study (GWAS) of appendicular lean mass (ALM) was conducted in 450,580 UK Biobank subjects. A total of 717 variants (p<5x10-9) from 561 loci were identified, which were replicated across genders (achieving p<5x10-5 in both genders). The identified variants explained ~11% phenotypic variance, accounting for one quarter of the total ~40% GWAS-attributable heritability. The identified variants were enriched in gene sets related to musculoskeletal and connective tissue development. Of interest are several genes, including ADAMTS3, PAM, SMAD3 and MEF2C, that either contain multiple significant variants or serve as the hub genes of the associated gene sets. Polygenic score prediction based on the associated variants was able to distinguish subjects of high from low ALM. Overall, our results offered significant findings on the genetic basis of lean mass through an extraordinarily large sample GWAS. The findings are important to not only lean mass per se but also other complex diseases, such as type 2 diabetes and fracture, as our Mendelian randomization analysis showed that ALM is a protective factor for these two diseases.

genetics↗

bioRxiv2019

The Role of the Public Health Service Equalization Program in the Control of Hypertension in China: Results from a Cross-sectional Health Interview Survey

ObjectivesNon-communicable diseases (NCDs) have become the main cause of mortality in China. In 2009, the Chinese government introduced the Public Health Service Equalization (PHSE) program to restore the primary healthcare system in both essential medical care and public health service provision. This study evaluates the impact of management on hypertension control and evaluate how the program works.\n\nMethodsThe China National Health Development Research Centre (CNHDRC) undertook the Cross-sectional Health Service Interview Survey (CHSIS) of 62,097 people from primary healthcare reform pilot areas, across 17 provinces from eastern, central and western parts of China in 2014. This study is based on CHSIS survey responses from 9,607 participants, who had been diagnosed with hypertension. Regression analysis was used to estimate the impact of management provided under PHSE on hypertension control adjusting for the effects of other known determinants of hypertension control.\n\nFindingsUncontrolled hypertension was markedly lower among respondents, whose hypertension had been managed (22.4% in managed patients versus 31.1% in unmanaged patients, p<0.001). The interaction between PHSE management and the geographical region was highly significant in the model (p<0.001), suggesting that the PHSE program was not equally effective in all regions. Further analysis suggested that approximately 10% of regional variability was attributed to differences in administrative systems, as there was a significant association (P=0.014) between the presence of established regional Information Management Systems (IMS) and increased PHSE effectiveness. Insurance ({chi}2(5)=4.4, p=0.496) and Hukou ({chi}2(1)=2.4, p=0.121), which denote social security and urban rural differences, respectively, were not significant predictor of hypertension control.\n\nConclusionActive management of hypertension through the PHSE program was effective with 7.31 million more patients receiving hypertension control and equalization of service delivery was reflected to some extent. The link between established IMS and regional variability in the impact of PHSE highlights the importance of effective management of patient referrals and follow-up. Further investigation is needed to explore the factors that influence the effectiveness of PHSE.

scientific communication and education↗