2023: A year of accomplishments for the 13 Science Citation Index Expanded- and Emerging Sources Citation Index-indexed Baishideng journals.

In 2023, Baishideng Publishing Group (Baishideng) routinely published 47 open-access journals, including 46 English-language journals and 1 Chinese-language journal. Our successes were accomplished through the collective dedicated efforts of Baishideng staffs, Editorial Board Members, and Peer Reviewers. Among these 47 Baishideng journals, 7 are included in the Science Citation Index Expanded (SCIE) and 6 in the Emerging Sources Citation Index (ESCI). With the support of Baishideng authors, company staffs, Editorial Board Members, and Peer Reviewers, the publication work of 2023 is about to be successfully completed. This editorial summarizes the 2023 activities and accomplishments of the 13 SCIE- and ESCI-indexed Baishideng journals, outlines the Baishideng publishing policy changes and additions made this year, and highlights the unique advantages of Baishideng journals.

Comparative study showed that children faced a 78% higher risk of new-onset conditions after they had COVID-19.

AIM: Children have largely been unaffected by severe COVID-19 compared to adults, but data suggest that they may have experienced new conditions after developing the disease. We compared outcomes in children who had experienced COVID-19 and healthy controls. METHODS: A retrospective nested cohort study assessed the incidence rate of new-onset conditions after COVID-19 in children aged 0-14 years. Data were retrieved from an Italian paediatric primary care database linked to Veneto Region registries. Exposed children with a positive nasopharyngeal swab were matched 1:1 with unexposed children who had tested negative. Conditional Cox regression was fitted to estimate the adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for the exposure and outcome associations after adjusting for covariates. RESULTS: We compared 1656 exposed and 1656 unexposed children from 1 February 2020 to 30 November 2021. The overall excess risk for new-onset conditions after COVID-19 was 78% higher in the exposed than unexposed children. We found significantly higher risks for some new conditions in exposed children, including mental health issues (aHR 1.8, 95% CI 1.1-3.0) and neurological problems (aHR 2.4, 95% CI 1.4-4.1). CONCLUSION: Exposed children had a 78% higher risk of developing new conditions of interest after COVID-19 than unexposed children.

Improved prediction of 5-year mortality by updating the chronic related score for risk profiling in the general population: lessons from the italian region of Lombardy.

Objective: The aim of this study was to improve the performance of the Chronic Related Score (CReSc) in predicting mortality and healthcare needs in the general population. Methods: A population-based study was conducted, including all beneficiaries of the Regional Health Service of Lombardy, Italy, aged 18 years or older in January 2015. Each individual was classified as exposed or unexposed to 69 candidate predictors measured before baseline, updated to include four mental health disorders. Conditions independently associated with 5-year mortality were selected using the Cox regression model on a random sample including 5.4 million citizens. The predictive performance of the obtained CReSc-2.0 was assessed on the remaining 2.7 million citizens through discrimination and calibration. Results: A total of 35 conditions significantly contributed to the CReSc-2.0, among which Alzheimer's and Parkinson's diseases, dementia, heart failure, active neoplasm, and kidney dialysis contributed the most to the score. Approximately 36% of citizens suffered from at least one condition. CReSc-2.0 discrimination performance was remarkable, with an area under the receiver operating characteristic curve of 0.83. Trends toward increasing short-term (1-year) and long-term (5-year) rates of mortality, hospital admission, hospital stay, and healthcare costs were observed as CReSc-2.0 increased. Conclusion: CReSC-2.0 represents an improved tool for stratifying populations according to healthcare needs.

Web-based surveillance of respiratory infection outbreaks: retrospective analysis of Italian COVID-19 epidemic waves using Google Trends.

Introduction: Large-scale diagnostic testing has been proven insufficient to promptly monitor the spread of the Coronavirus disease 2019. Electronic resources may provide better insight into the early detection of epidemics. We aimed to retrospectively explore whether the Google search volume has been useful in detecting Severe Acute Respiratory Syndrome Coronavirus outbreaks early compared to the swab-based surveillance system. Methods: The Google Trends website was used by applying the research to three Italian regions (Lombardy, Marche, and Sicily), covering 16 million Italian citizens. An autoregressive-moving-average model was fitted, and residual charts were plotted to detect outliers in weekly searches of five keywords. Signals that occurred during periods labelled as free from epidemics were used to measure Positive Predictive Values and False Negative Rates in anticipating the epidemic wave occurrence. Results: Signals from "fever," "cough," and "sore throat" showed better performance than those from "loss of smell" and "loss of taste." More than 80% of true epidemic waves were detected early by the occurrence of at least an outlier signal in Lombardy, although this implies a 20% false alarm signals. Performance was poorer for Sicily and Marche. Conclusion: Monitoring the volume of Google searches can be a valuable tool for early detection of respiratory infectious disease outbreaks, particularly in areas with high access to home internet. The inclusion of web-based syndromic keywords is promising as it could facilitate the containment of COVID-19 and perhaps other unknown infectious diseases in the future.

Risk stratification of hemodynamically significant patent ductus arteriosus by clinical and genetic factors.

BACKGROUND: Hemodynamically significant patent ductus arteriosus (hsPDA) is associated with increased comorbidities in neonates. Early evaluation of hsPDA risk is critical to implement individualized intervention. The aim of the study was to provide a powerful reference for the early identification of high-risk hsPDA population and early treatment decisions. METHODS: We enrolled infants who were diagnosed with PDA and performed exome sequencing. The collapsing analyses were used to find the risk gene set (RGS) of hsPDA for model construction. The credibility of RGS was proven by RNA sequencing. Multivariate logistic regression was performed to establish models combining clinical and genetic features. The models were evaluated by area under the receiver operating curve (AUC) and decision curve analysis (DCA). RESULTS: In this retrospective cohort study of 2199 PDA patients, 549 (25.0%) infants were diagnosed with hsPDA. The model [all clinical characteristics selected by least absolute shrinkage and selection operator regression (all CCs)] based on six clinical variables was acquired within three days of life, including gestational age (GA), respiratory distress syndrome (RDS), the lowest platelet count, invasive mechanical ventilation, and positive inotropic and vasoactive drugs. It has an AUC of 0.790 [95% confidence interval (CI) = 0.749-0.832], while the simplified model (basic clinical characteristic model) including GA and RDS has an AUC of 0.753 (95% CI = 0.706-0.799). There was a certain consistency between RGS and differentially expressed genes of the ductus arteriosus in mice. The AUC of the models was improved by RGS, and the improvement was significant (all CCs vs. all CCs + RGS: 0.790 vs. 0.817, P < 0.001). DCA demonstrated that all models were clinically useful. CONCLUSIONS: Models based on clinical factors were developed to accurately stratify the risk of hsPDA in the first three days of life. Genetic features might further improve the model performance. Video Abstract (MP4 86834 kb).

Outcomes of Escalating Immunosuppressive Treatments for Recalcitrant Noninfectious Posterior Scleritis.

INTRODUCTION: This article aimed to summarize the outcomes of escalating immunosuppressive treatments for patients with recalcitrant noninfectious posterior scleritis (PS). METHODS: Clinical records of 16 patients diagnosed with recalcitrant noninfectious PS in the Ocular Immunity and Uveitis Department of Zhongshan Ophthalmic Center from September 2016 to December 2021 were reviewed. Patients were treated with escalating immunosuppressive regimen including corticosteroid, immunosuppressants (IMTs), and adalimumab (ADA). Demographic characteristics and clinical findings at each visit were recorded. The doses of prednisone were analyzed. Main outcomes were corticosteroid-sparing effects, control of inflammation, visual acuity, and safety profile. RESULTS: Ocular pain was the most common finding (100%), followed by the T sign on the B scan (93.8%) and associated anterior scleritis (75.0%). The average initial dose of prednisone was 25.0 mg/day, and tapered to 11.3 and 5.0 mg/day at month 1 and 3, respectively, with statistical significance (p < 0.05). The median overall periods of prednisone tapering to 10, 5, and 0 mg/day were 1.0, 3.0, and 3.0 months, respectively. There were 93.8% of patients receiving prednisone ≤ 10 mg/day and 68.8% of patients off prednisone at last visit. There were 80% of patients treated with IMT and ADA off prednisone at last visit, reaching the highest percentage compared with others. A best-corrected visual acuity of 1.0 or better at last visit was achieved in 10 eyes (62.5%). The escalating treatments showed good safety profile. CONCLUSION: Patients of recalcitrant noninfectious PS benefited from escalating immunosuppressive treatments with favorable visual outcome, in which methotrexate, ciclosporin, and ADA were preferred with good safety.

Doxycycline vs Placebo at 12 Weeks in Patients With Mild Thyroid-Associated Ophthalmopathy: A Randomized Clinical Trial.

Importance: Mild thyroid-associated ophthalmopathy (TAO) negatively impacts quality of life, yet no clinical guidelines for its treatment are available. Existing evidence supports the use of doxycycline in treating mild TAO. Objective: To evaluate the short-term (12 weeks) efficacy of doxycycline in treating mild TAO. Design, Setting, and Participants: In this placebo-controlled multicenter randomized double-masked trial, 148 patients were assessed for eligibility. After exclusions (patients who were pregnant or lactating, had an allergy to tetracyclines, or had uncontrolled systematic diseases), 100 patients with mild TAO (orbital soft tissue affected mildly) at 5 centers in China were enrolled from July 2013 to December 2019 and monitored for 12 weeks. Interventions: Participants were randomly assigned 1:1 to receive doxycycline (50 mg) or placebo once daily for 12 weeks. Main Outcomes and Measures: The primary outcome was the rate of improvement at 12 weeks compared with baseline assessed by a composite indicator of eyelid aperture (reduction ≥2 mm), proptosis (reduction ≥2 mm), ocular motility (increase ≥8°), and Graves ophthalmopathy-specific quality-of-life (GO-QOL) scale score (increase ≥6 points). Adverse events were recorded. Results: A total of 50 participants were assigned to doxycycline and 50 to placebo. The mean (SD) age was 36.7 (9.1) years; 75 participants (75.0%) were female and 100 (100.0%) were Asian. Medication compliance was checked during participant interviews and by counting excess tablets. At week 12, the improvement rate was 38.0% (19 of 50) in the doxycycline group and 16.0% (8 of 50) in the placebo group (difference, 22.0%; 95% CI, 5.0-39.0; P = .01) in the intention-to-treat population. The per-protocol sensitivity analysis showed similar results (39.6% [19 of 48] vs 16.0% [8 of 50]; difference, 23.6%; 95% CI, 6.4-40.8; P = .009). No adverse events other than 1 case of mild gastric acid regurgitation was recorded in either group. Conclusions and Relevance: The results of this study indicate that oral doxycycline, 50 mg daily, resulted in greater improvement of TAO-related symptoms at 12 weeks compared with placebo in patients with mild TAO. These findings support the consideration of doxycycline for mild TAO but should be tempered by recognizing the relatively short follow-up and the size of the cohort. Trial Registration: ClinicalTrials.gov Identifier: NCT02203682.

Neolignans and Sesquiterpenoid from Piper yunnanense.

Two biphenyl-type neolignans with a rare dibenzofuran skeleton, including a new one piyunneolignan A (1) and a known one piperneolignan D (2), together with a new sesquiterpenoid piyunin A (3), were isolated from the leaves and twigs of Piper yunnanense. Their structures were established on the basis of comprehensive spectroscopic data analysis and electronic circular dichroism (ECD) calculation. Piyunneolignan A (1) featured a rare C-2-C-2'/C-3-O-C-3' linkage. Compounds 1-3 were evaluated for their antimicrobial and cytotoxic activities against a panel of bacteria, fungi, and human cancer cell lines, respectively.

Complete mitogenome of the entomopathogenic fungus Orbiocrella petchii.

In this study, the complete mitogenome of an entomopathogenic fungus Orbiocrella petchii (syn. Torrubiella petchii) was assembled and annotated. This circular mitogenome was 23,794 bp in length and consisted of 2 rRNA genes (rnl and rns), 25 tRNA genes, and 14 standard protein-coding genes of the oxidative phosphorylation system. Two group I introns were identified, and they encoded ribosomal protein S3 (in rnl) or a GIY-YIG endonuclease (in nad1). Phylogenetic analysis based on mitochondrial DNA sequences confirms O. petchii in the family of Clavicipitaceae.

Pillared Graphene Sheets with High-Rate Performance as Anode Material for Lithium-Ion Batteries.

Pillared graphene composite (GP) is prepared by in situ polymerization and subsequent carbonization of graphene oxide (GO) and polyaniline (PANI) precursors. The interlayer spacing of GO layer can reach 1.418 nm with 200% increase compared with the original spacing of 0.706 nm by the intercalation of aniline monomer through π-π conjugate and electrostatic interactions. After carbonization, the graphene composite is reinforced by the intercalated PANI-converted carbon pillars and also has a nitrogen-doped level of ca. 4.49 atom%. Electrochemical characterization studies show that the GP composite exhibits a high reversible capacity of 653 mAh g-1 at a current density of 100 mA g-1 and an excellent rate capability (343 mAh g-1 at a current density of 1 A g-1), which are superior to graphene owing to the unique pillared and the nitrogen-doped structure.

[Preparation of 20(S)-Protopanaxadiol-Phospholipid Complex HAP Assemblies].

OBJECTIVE: To study the preparation of 20(S)-protopanaxadiol-phospholipid (20(S)-PPD) complex HAP assemblies. METHODS: 20(S)-PPD phospholipid complex was assembled with the drug carriers of HAP. Effects of technological factors on the assembled amount were investigated, including HAP species, phospholipid complex concentration, ratio of HAP and assembled liquid, and then the preparation technology of 20(S)-PPD phospholipid complex HAP assemblies was determined. RESULTS: The average quality of phospholipid complex assembled was 136. 26 mg/g,the average assembled rate was 5.3% for 20(S)-PPD phospholipid complex HAP assemblies prepared by the determined assembly process. FT-IR showed that 20(S)-PPD phospholipid complex was absorbed in the HAP assemblies, and the hydrogen-bonding effect was the main mechanism of HAP assemblies to assemble and adsorb phospholipid complex. The cumulative release rate in pH 7.4 phosphate buffer of the HAP assemblies indicated that the assemblies had the effect of sustained release. CONCLUSION: The phospholipid complex HAP assembles have the advantages of simple preparation process, and sustaining release effect, which can provide preliminary research foundation for research and development of 20(S)-PPD sustained-release preparations.

[Effects of umbilical cord blood monocytes transplantation on EPO protein and oligodendrocyte progenitors in neonatal rats with hypoxic-ischemic brain damage].

OBJECTIVE: To study the effects of umbilical cord blood monocytes (UCBMC) transplantation on erythropoietin (EPO) protein and oligodendrocyte progenitor cells in hypoxia-ischemia (HI) neonatal rats. METHODS: Forty seven-day-old Sprague-Dawley rats were randomly divided into normal control (N), HI, UCBMC and HI+UCBMC groups (n=10 each). Hypoxic-ischemic brain damage (HIBD) model was prepared according to the Rice method. Twenty-four hours after hypoxia, the N and HI groups were injected with 2 µL phosphate buffered saline (PBS), and the UCBMC and HI+UCBMC groups were injected with 3×10(6) UCBMC via the lateral ventricle. EPO protein and oligodendrocyte progenitor cells in the subventricular zone of the injured brain were observed by EPO/DAPI and NG2/DAPI immunofluorescence double staining, and their correlation was analyzed. RESULTS: Seven days after transplantation, there were more NG2(+)DAPI(+) and EPO(+)DAPI(+) cells in the HI+UCBMC group than in the UCBMC (P<0.05), N and HI groups (P<0.01). More NG2(+)DAPI(+) and EPO(+)DAPI(+) cells were observed in the UCBMC group compared with the N and HI groups (P<0.01). There were more NG2(+)DAPI(+) cells in the N group than in the HI group (P<0.01). The number of NG2(+)DAPI(+) cells was correlated with the number of EPO(+)DAPI(+) cells in the HI+UCBMC group (r=0.898, ß=1.4604, P<0.01). CONCLUSIONS: UCBMC can promote expression of oligodendrocyte progenitor cells, which is correlated with an increase in EPO protein and thus repairs brain white matter damage in neonatal rats with HIBD.

Umbilical cord blood cells regulate endogenous neural stem cell proliferation via hedgehog signaling in hypoxic ischemic neonatal rats.

Umbilical cord blood mononuclear cells (UCBMC) transplantation may improve hypoxia-induced brain injury in neonatal rats, but the mechanism is unclear. This study examines whether UCBMC promote neural stem cell (NSC) proliferation via the Sonic hedgehog (Shh) signaling pathway. The rats underwent left carotid ligation followed by hypoxic stress. UCBMC were transplanted 24h after hypoxia ischemia (HI), and immunohistochemistry, immmunoblotting, and morphology analyses were performed at different time points after transplantation. Increased numbers of NSCs were observed in the subventrical zone (SVZ) of the HI+UCBMC group, but these increases were attenuated by cyclopamine treatment. There were significant increases in Shh and Gli1 protein levels after transplantation in the HI group treated with UCBMC compared to HI rats treated with phosphate-buffered solution (PBS). Significantly more Gli1(+)DAPI(+) cells were observed in the SVZ of the HI+UCBMC group compared to the HI+PBS and N+UCBMC groups, but few Gli1(+)DAPI(+) cells were found in the SVZ of the HI+cyclopamine+UCBMC group. The HI+UCBMC group had significantly less neuronal loss in the cortex and CA1 sector of the hippocampus compared to the HI+PBS group, but more neuron loss was observed in the HI+cyclopamine+UCBMC group compared to HI+UCBMC. These results indicate that UCBMC may promote NSC proliferation and alleviate brain injury in HI neonatal rats via Shh signaling.

Role of a novel functional variant in the PPP2R1A promoter on the regulation of PP2A-Aalpha and the risk of hepatocellular carcinoma.

Previously, we identified the genetic variant -241 (-/G) (rs11453459) in the PP2A-Aα gene (PPP2R1A) promoter and demonstrated that this variant influences the DNA-binding affinity of nuclear factor-kappa B (NF-κB). In this study, we further confirmed that the transcriptional activity of PPP2R1A may be regulated by NF-κB through the functional genetic variant -241 (-/G). Moreover, we also demonstrated that the methylation status of CpG islands in the promoter of PPP2R1A influences the activity of this gene promoter. Few studies have examined the role of this -241 (-/G) variant in genetic or epigenetic regulation in hepatocellular carcinoma (HCC). To investigate whether this functional variant in the PPP2R1A promoter is associated with the risk of HCC and confirm the function of the -241 (-/G) variant in the HCC population, we conducted a case-control study involving 251 HCC cases and 252 cancer-free controls from a Han population in southern China. Compared with the -241 (--) homozygote, the heterozygous -241 (-G) genotype (adjusted OR  = 0.32, 95% confidence interval (CI)  = 0.17-0.58, P<0.001) and the -241 (-G)/(GG) genotypes (adjusted OR  = 0.38, 95% CI  = 0.22-0.67, P  = 0.001) were both significantly associated with a reduced risk of HCC. Stratification analysis indicated that the protective role of -241 (-G) was more pronounced in individuals who were ≤ 40 years of age, female and HBV-negative. Our data suggest that the transcriptional activity of PPP2R1A is regulated by NF-κB through the -241 (-/G) variant and by the methylation of the promoter region. Moreover, the functional -241 (-/G) variant in the PPP2R1A promoter contributes to the decreased risk of HCC. These findings contribute novel information regarding the gene transcription of PPP2R1A regulated by the polymorphism and methylation in the promoter region through genetic and epigenetic mechanisms in hepatocarcinogenesis.

[Effects of bone marrow mesenchymal stem cell transplantation on retinal cell apoptosis in premature rats with retinopathy].

OBJECTIVE: To explore the effects of marrow mesenchymal stem cell (BMSC) transplantation on retinal cells apoptosis and changes to neurotrophin-3 (NT-3 and ciliary neurotrophic factor (CNTF) in rats with retinopathy of prematurity (ROP). METHODS: Seven-day-old Sprague-Dawley rats were randomly divided into normal control (CON), ROP, BMSC transplantation (BMSCs were transplanted 5 days after oxygen conditioning) and phosphate buffered saline (PBS) groups. The ROP model was prepared according to the classic hyperoxygen method. Seven days after transplantation, TUNEL/DAPI, NT-3/API and CNTF/DAPI double-labeled immunofluorescence were used to examine the effects of BMSC transplantation on both the apoptosis of retinal cells and the expression of NT-3 and CNTF protein in the retinal cells of the ROP rats. RESULTS: Seven days after BMSC transplantation, there were few TUNEL+ DAPI+ cells observed in the CON group. There were fewer TUNEL+DAPI+ cells observed in the BMSC group than in the ROP group (P<0.01), but there was no significant difference between the ROP and PBS groups (P>0.05). There were few NT-3+DAPI+ cells and CNTF+DAPI+ cells in the CON group. There were more NT-3+DAPI+ and CNTF+DAPI+ cells in the ROP group than in the CON group, but there was no significant difference between the ROP and CON groups (P>0.05). More NT-3+DAPI+ and CNTF+DAPI+ cells were observed in the BMSC group compared with the ROP group (P<0.01), and there was no significant difference in either NT-3+DAPI+ or CNTF+DAPI+ cells between the ROP and PBS groups (P>0.05). CONCLUSIONS: BMSC transplantation therapy could alleviate the apoptosis of retinal cells in ROP rats, and its mechanisms might be associated with promoting the expression of NT-3 and CNTF protein in retinal cells.

The intracellular controlled release from bioresponsive mesoporous silica with folate as both targeting and capping agent.

A smart mesoporous silica nanocarrier with intracellular controlled release is fabricated, with folic acid as dual-functional targeting and capping agent. The folate not only improves the efficiency of the nanocarrier internalized by the cancer cells, but also blocks the pores of the mesoporous silica to eliminate premature leakage of the drug. With disulfide bonds as linkers to attach the dual-functional folate within the surface of mesoporous silica, the controlled release can be triggered in the presence of reductant dithiothreitol (DTT) or glutathione (GSH). The cellular internalization via folate-receptor-mediated endocytosis and the intracellular controlled release of highly toxic anticancer drug DOX were demonstrated with an in vitro HeLa cell culture, indicating an efficient cancer-targeted drug delivery.

Identification and functional analysis of variant haplotypes in the 5'-flanking region of protein phosphatase 2A-Bδ gene.

Serine-threonine protein phosphatase 2A (PP2A) is a trimeric holoenzyme that plays an integral role in the regulation of cell growth, differentiation, and apoptosis. The substrate specificity and (sub)cellular localization of the PP2A holoenzymes are highly regulated by interaction with a family of regulatory B subunits (PP2A-Bs). The regulatory subunit PP2A-B/PR55δ (PP2A-Bδ) is involving in the dephosphorylation of PP2A substrates and is crucial for controlling entry into and exit from mitosis. The molecular mechanisms involved in the regulation of expression of PP2A-Bδ gene (PPP2R2D) remain largely unknown. To explore genetic variations in the 5'-flanking region of PPP2R2D gene as well as their frequent haplotypes in the Han Chinese population and determine whether such variations have an impact on transcriptional activity, DNA samples were collected from 70 healthy Chinese donors and sequenced for identifying genetic variants in the 5'-flanking region of PPP2R2D. Four genetic variants were identified in the 1836 bp 5'-flanking region of PPP2R2D. Linkage disequilibrium (LD) patterns and haplotype profiles were constructed for the genetic variants. Using serially truncated human PPP2R2D promoter luciferase constructs, we found that a 601 bp (-540 nt to +61 nt) fragment constitutes the core promoter region. The subcloning of individual 5'-flanking fragment revealed the existence of three haplotypes in the distal promoter of PPP2R2D. The luciferase reporter assay showed that different haplotypes exhibited distinct promoter activities. The EMSA revealed that the -462 G>A variant influences DNA-protein interactions involving the nuclear factor 1 (NF1). In vitro reporter gene assay indicated that cotransfection of NF1/B expression plasmid could positively regulate the activity of PPP2R2D proximal promoter. Introduction of exogenous NF1/B expression plasmid further confirmed that the NF1 involves in the regulation of PPP2R2D gene expression. Our findings suggest that functional genetic variants and their haplotypes in the 5'-flanking region of PPP2R2D are critical for transcriptional regulation of PP2A-Bδ.

Identification and functional analyses of polymorphism haplotypes of protein phosphatase 2A-Aα gene promoter.

The serine-threonine protein phosphatase 2A (PP2A) is a heterotrimeric enzyme family that plays an essential regulatory role in cell growth, differentiation, and apoptosis. Mutations in the genes encoding PP2A-Aα/ß subunits are associated with tumorigenesis and other human diseases. To explore whether genetic variations in the promoter region of the PP2A-Aα gene (PPP2R1A) and their frequent haplotypes in the Han Chinese population have an impact on transcriptional activity, we collected DNA samples from 63 healthy Chinese donors and searched for genetic variations in the 5'-flanking promoter region of PPP2R1A (PPP2R1Ap). Haplotypes were characterized by Haploview analysis and individual subcloning. A set of molecular and functional experiments was performed using reporter genes and electrophoretic mobility shifting assay (EMSA). Seven genetic variations were identified within the promoter locus (2038bp) of PPP2R1A. Linkage disequilibrium (LD) patterns and haplotype profiles were analyzed using the identified genetic variants. Using serially truncated human PPP2R1A promoter luciferase constructs, we found that a 685bp (-448nt to +237nt) fragment around the transcription start site (TSS) was the core promoter region. Individual subcloning revealed the existence of six haplotypes in this proximal promoter region of PPP2R1Ap. Using luciferase reporter assays, we found that different haplotypes bearing different variant alleles exhibit distinct promoter activities. The EMSA revealed that the -241 -/G variant influences DNA-protein interactions involving the transcription factor NF-κB, which may regulate the activity of the PPP2R1A proximal promoter. Our findings suggest that functional genetic variants in the proximal promoter of the PP2A-Aα gene and their haplotypes are critical in the regulation of transcriptional activation.