Abstract Background & Aims Schistosomiasis is a major cause of hepatic fibrosis in endemic regions, yet the host genetic determinants of disease progression remain poorly defined. We aimed to identify genetic drivers and underlying mechanisms of schistosomiasis-induced hepatic fibrosis. Methods We performed a genome-wide association study (GWAS) of 984 Schistosoma japonicum -infected individuals from hyperendemic areas in China followed by multi-omics integration and experimental validation to identify causal genes and fibrogenic pathways. Results Schistosomiasis-associated fibrosis exhibited a genetic architecture distinct from metabolic and viral liver fibrosis, supporting pathogen-specific mechanisms. Eight novel susceptibility loci were identified, including a genome-wide significant signal at 16p13 (rs73575170, P = 3.9 × 10⁻⁸). Integrative mapping linked these loci to 262 genes enriched in liver sinusoidal endothelial cells ( P = 5.84 × 10⁻⁵) and sphingolipid metabolism pathways ( P = 4.19 × 10⁻⁵). Notably, Diacylglycerol kinase gamma ( DGKG , rs6762330, P = 4.37 × 10⁻⁶) emerged as a key candidate, with its expression in peri-granuloma and periportal hepatocytes strongly correlating with fibrosis severity ( r = 0.816). In vivo , Dgkg knockout attenuated hepatic fibrosis and immunopathology while restoring cholesterol homeostasis, whereas Dgkg overexpression exacerbated fibrogenesis and increased TNF-α levels tenfold. Conclusions This study identifies DGKG as a key mediator linking lipid metabolism and immune signaling in schistosomiasis-induced fibrosis, uncovering a pathogen-specific genetic mechanism and providing a potential therapeutic target for infection-associated liver fibrosis. Impact and Implications This study defines a pathogen-specific genetic architecture underlying schistosomiasis-associated hepatic fibrosis, distinguishing it from metabolic and viral fibrotic liver diseases. By integrating GWAS analysis and in vivo functional validation, DGKG is identified as a key regulator linking lipid metabolism and immune-driven fibrogenesis. These findings highlight liver sinusoidal endothelial cells and sphingolipid signaling as critical cellular and molecular contexts for schistosomiasis-associated hepatic fibrosis. Beyond advancing mechanistic understanding of schistosomiasis, this work provides a genetic and functional framework for targeting DGKG -mediated pathways, with potential implications for precision therapies in parasitically mediated liver fibrotic disorders.

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment play an important role in cancer initiation and progression through mediating crosstalk between CAFs and cancer cells. In our study, we unveiled that CAFs-derived extracellular vesicles (EVs) could deliver miR-375 to endothelial cells (EC) and further contribute to tumor angiogenesis by regulating Ras GTPase Activating Protein 1 (RASA1) in hepatocellular carcinoma (HCC). We also found that HCC patients with more advanced disease showed higher levels of miR-375 in plasma EVs, which were preferentially expressed in the EVs of CAFs. These data provided direct evidence supporting the pivotal role of the tumor suppressor miR-375, which is selectively sorted into CAF-derived EVs, in promoting angiogenesis during HCC progression and revealed that genetically modified CAF-derived EVs may provide a potential therapeutic strategy for HCC. Furthermore, our study indicated that miR-375 in plasma EVs could serve as a potential predictive and prognostic biomarker in HCC patients.

Echinococcosis is an important zoonotic parasitic disease caused by Echinococcus spp. Infection. Vaccines represent the most economical and effective means of preventing and controlling echinococcosis. This study aimed to construct a multi-epitope vaccine targeting E. granulosus and evaluate its immunogenicity and protective efficacy against cystic echinococcosis. We identified HLA-bound T-cell epitopes (P1, P2, P3) from the liver of echinococcosis patients using co-immunoprecipitation and incorporated them into the multi-epitope vaccine FL46. In vitro cytotoxicity assessment using BMDCs and U937 cells confirmed that FL46 concentrations below 500 µg/mL did not impair cell proliferation. Forty C57BL/6 mice were randomly divided into vaccine or control groups. The vaccine group received three subcutaneous immunizations (100 µg FL46/mouse, emulsified 1:1 with Freund’s adjuvant) at two-week intervals. Two weeks post-final immunization, all mice were challenged intraperitoneally with 2000 protoscoleces and sacrificed eight months post-infection. Vaccinated mice exhibited significantly elevated serum levels of IL-2, TNF-α, IL-5, IL-6, and Keratinocyte-derived cytokine (KC) after immunization three times. Splenic B1 and B2 lymphocyte proportions increased dramatically eight months after the third immunization. Significantly higher levels of IgM, IgG, and IgG2a were detected in the vaccine group eight weeks post-infection, persisting for at least eight months. The vaccine group demonstrated a significantly reduced cyst burden (number and weight) compared to the controls, corresponding to a 59.16% cyst suppression rate. The indicators of liver fibrosis were also significantly lower in vaccinated mice. These results demonstrate that the multi-epitope vaccine FL46 elicits a robust mixed Th1/Th2 immune response and confers significant protection against cystic echinococcosis, highlighting its potential as a candidate vaccine.

Schistosoma japonicum eggs in the host liver form granuloma and liver fibrosis and then lead to portal hypertension and cirrhosis, seriously threatening human health. Natural killer (NK) cells can kill activated hepatic stellate cells (HSCs) against hepatic fibrosis. We used single-cell sequencing to screen hepatic NK cell subsets against schistosomiasis liver fibrosis. Hepatic NK cells were isolated from uninfected mice and mice infected for four and six weeks. The NK cells underwent single-cell sequencing. The markers’ expression in the NK subsets was detected through Reverse Transcription–Quantitative PCR (RT-qPCR). The proportion and granzyme B (Gzmb) expression of the total NK and Thy1+NK were detected. NK cells overexpressing Thy1 (Thy1-OE) were constructed, and functions were detected. The results revealed that the hepatic NK cells could be divided into mature, immature, regulatory-like, and memory-like NK cells and re-clustered into ten subsets. C3 (Cx3cr1+NK) and C4 (Thy1+NK) increased at week four post-infection, and other subsets decreased continuously. The successfully constructed Thy1-OE NK cells had significantly higher effector molecules and induced greater HSC apoptosis than the control NK cells. It revealed a pattern of hepatic NK cells in a mouse model of schistosomiasis. The Thy1+NK cells could be used as target cells against hepatic fibrosis.

The central challenge to internationalizing China's health care lies in the absence of an end-to-end, one-stop service pathway for international patients, spanning professional licensure, drug and device market access, insurance and payment, and research compliance. As an institutional intermediation zone, the Hengqin Guangdong-Macao Deep Cooperation Zone promotes coordinated governance between mainland China and Macao, advancing reforms focused on rule alignment, mechanism linkage, data governance, and scenario-based policy testing. Early measures include expedited green-channel access for drugs and medical devices approved in Hong Kong and Macao, accelerated registration for traditional Chinese medicines, promotion of international hospital accreditation and multilingual outpatient services, and pilots of cross-border professional practice and direct billing with international insurers. Interim results indicate that this model has improved access to drugs and devices, streamlined cross-border service workflows, and established research platforms. In parallel, cross-border patient volumes are rising, the number of foreign patients is steadily increasing, and outward-facing service capacity is taking shape. These developments underscore Hengqin's growing appeal as a window of openness and offer evidence supporting China's position in the international patient market. Nonetheless, challenges persist in legal harmonization, regulatory convergence, payment integration, and mutual recognition of credentials and technologies. The authors propose a low-risk, use-cases-first and list-based, issue-by-issue approach to gradually close these gaps. This article emphasizes a patient-journey-oriented design, the use of a minimum viable dataset as the foundation for data governance, and iterative improvement guided by both process and outcome metrics to develop a replicable pathway for the internationalization of digital health.

Purpose:The ratio of gamma-glutamyl transferase (GGT) to high-density lipoprotein cholesterol (HDL-C) (GHR) represents a novel non-insulin-based biomarker for evaluating the risk of NAFLD and T2DM. However, its correlation with diabetic kidney disease (DKD) remains unexplored. This study aims to explore the association between GHR and DKD in patients with T2DM. Patients and Methods:In this cross-sectional study, 2798 patients diagnosed as T2DM admitted to the hospital from 2018 to 2023 were assessed. The analysis was conducted through restricted cubic spline (RCS) and logistic regression methodologies, complemented by additional stratified and interaction analyses. Results:As the quartiles of GHR increase, there is a notable increase in the prevalence of DKD, with the rates of 43.2%, 47.2%, 52.1%, and 57.4%, respectively. Logistic regression analysis showed a positive association between GHR and DKD (OR=1.17, 95% CI: 1.05-1.30), which was consistently observed across all subgroups through stratified analysis. RCS analysis identified an inverted L-shaped association, with an inflection point at 84.5. Additionally, AUC for GHR (AUC = 0.637, 95% CI: 0.616-0.657) was significantly higher compared to those of GGT and HDL alone. Conclusion:GHR exhibits a positive association with the risk of DKD, underscoring its potential utility as a cost-effective biomarker for stratifying the risk of DKD.

Purpose: Ischemic stroke is a high-incidence disease that threatens human well-being.The potent neuroprotective effects render reactive oxygen species (ROS) scavengers potential agents for acute ischemic stroke therapy.Challenges such as inadequate permeability across the blood-brain barrier (BBB), limited half-life, and adverse effects hinder the widespread utilization of small molecule and inorganic ROS scavengers.Thus, there is an urgent demand for efficacious neuroprotective agents targeting ischemic stroke.Our study discovered the superoxide dismutase (SOD)-mimetic activity of recombinant human heavy chain ferritin (rHF) nanoparticles expressed from Escherichia coli (E.coli).Subsequent investigations delved into the ROS-scavenging proficiency of rHF within neural cells, its therapeutic efficacy against ischemic stroke, and the elucidation of its neuroprotective mechanisms.Methods: rHF protein nanoparticles were expressed in E. coli and purified via size-exclusion chromatography.The superoxide anion (•O 2 -) scavenging SOD-mimetic activity of rHF nanoparticles was measured using a SOD detection kit.The ROS scavenging ability and protection effects against oxidative damage of rHF nanoparticles were studied in H 2 O 2 -induced PC12 cells.Therapeutic effects and neuroprotective mechanisms of rHF against ischemic stroke were investigated with transient middle cerebral artery occlusion (MCAO) reperfusion mice model.Results: rHF nanoparticles can eliminate excessive ROS in nerve cells and alleviate oxidative damage.The results of animal experiments demonstrated that rHF nanoparticles passed across BBB, reduced infarct areas in brain tissue, and lowered the neurological deficit score of ischemia-reperfusion model mice.Additionally, rHF nanoparticles mitigated neuronal apoptosis and ferroptosis, suppressed microglial activation, maintained oxygen homeostasis, and exhibited negligible organ toxicity.Conclusion: rHF nanoparticle could be developed as a new ROS scavenger for nerve cells and has therapeutic potential as a drug for cerebral ischemia-reperfusion injury.

Infectious disease is the most ancient and common human diseases. In China and BRI countries, there are a variety of infectious diseases. People and animals on the ancient Silk Road have been threatened and tortured by infectious diseases. With the development of the RBI, we are faced with the risk of the spread of various infectious diseases. According on the WHO report, the top 5 of the most serious infectious diseases were tuberculosis，pertussis，tetanus，leprosy and AIDS. Except the central and eastern Europe countries, the standardized disability adjusted life years(DALYs)of BRI counties is higher than China. In addition, mosquito is a vector of many infectious diseases.It is one of important public health problem for controlling mosquito. After the BRI, the risk of imported infectious diseases is increasing, some mosquito-borne diseases are more risky(eg. Malaria). It’s necessary to strengthen control of infectious diseases while improving international exchanges and co-operation with B&R countries. Of course, China’s formula for success in parasitic and neglected tropical disease control might translate to BRI countries.

To clarify the expression of N6‐methyladenosine (m6A) modulators involved in the pathogenesis of type 2 diabetes mellitus (T2DM). We further explored the association of serum insulin‐like growth factor 2 mRNA‐binding proteins 3 (IGF2BP3) levels and odds of T2DM in a high‐risk population.

Accurate communication between fibroblasts and keratinocytes is crucial for diabetic wound healing. Extracellular vesicles are being explored as essential mediators of intercellular communication in the skin. However, the mechanisms underlying wound healing mediated by fibroblast-derived extracellular vesicles (Fib-EVs) remain unclear. The present study evaluated the role of long noncoding RNA upregulated in diabetic skin (lnc-URIDS) packed in Fib-EVs in the wound healing of streptozotocin-induced diabetes and the potential mechanisms of the effects. We demonstrated that high glucose induced the enrichment of lnc-URIDS in Fib-EVs, facilitated the transfer of lnc-URIDS to primary rat epidermal keratinocytes, and increased the expression of matrix metalloproteinase-9. Mechanistically, the binding of lnc-URIDS to YTH domain family protein-2 enhanced the degradation of YTH domain family protein-2 in the lysosomes, which increased the translational activity of the messenger RNA of matrix metalloproteinase-9 and ultimately induced the degradation of collagen for wound healing. The results provided an insight into the crosstalk and cooperation between fibroblasts and keratinocytes in collagen homeostasis in diabetic wounds and clarified the mechanism by which lnc-URIDS degrades collagen for diabetic wound healing.

PurposeIn order to meet restrictions and difficulties in the development of hospital medical informatization and clinical databases in China, in this study, a disease-specific clinical database system (DSCDS) was designed and built. It provides support for the full utilization of real world medical big data in clinical research and medical services for specific diseases.MethodsThe development of DSCDS involved (1) requirements analysis on precision medicine, medical big data, and clinical research; (2) design schematics and basic architecture; (3) standard datasets of specific diseases consisting of common data elements (CDEs); (4) collection and aggregation of specific disease data scattered in various medical business systems of the hospital; (5) governance and quality improvement of specific disease data; (6) data storage and computing; and (7) design of data application modules.ResultsA DSCDS for liver cirrhosis was created in the gastrointestinal department of a 3A grade hospital in China and had more than nine data application modules. Based on this DSCDS, a series of clinical studies are being carried out, such as retrospective or prospective cohorts, prognostic studies using multimodal data, and follow-up studies.ConclusionThe development of the DSCDS for liver cirrhosis in this paper provides experience and reference for the design and development of DSCDSs for other specific diseases in China; it can even expand to the development of DSCDSs in other countries if they have the demand for DSCDS and the same or better medical informatization foundation. DSCDS has more accurate, standard, comprehensive, multimodal and usable data of specific diseases than the general clinical database system and clinical data repository (CDR) and provides a credible data foundation for medical research, clinical decision-making and improving the medical service quality of specific diseases.

Abstract Objective To clarify the expression of N6‐methyladenosine (m6A) modulators involved in the pathogenesis of type 2 diabetes mellitus (T2DM). We further explored the association of serum insulin‐like growth factor 2 mRNA‐binding proteins 3 (IGF2BP3) levels and odds of T2DM in a high‐risk population. Methods The gene expression data set GSE25724 was obtained from the Gene Expression Omnibus, and a cluster heatmap was generated by using the R package ComplexHeatmap. Differential expression analysis for 13 m6A RNA methylation regulators between nondiabetic controls and T2DM subjects was performed using an unpaired t test. A cross‐sectional design, including 393 subjects (131 patients with newly diagnosed T2DM, 131 age‐ and sex‐matched subjects with prediabetes, and 131 healthy controls), was carried out. The associations between serum IGF2BP3 concentrations and T2DM were modeled by restricted cubic spline and logistic regression models. Results Two upregulated (IGF2BP2 and IGF2BP3) and 5 downregulated (methyltransferase‐like 3 [METTL3], alkylation repair homolog protein 1 [ALKBH1], YTH domain family 2 [YTHDF2], YTHDF3, and heterogeneous nuclear ribonucleoprotein [HNRNPC]) m6A‐related genes were found in islet samples of T2DM patients. A U‐shaped association existed between serum IGF2BP3 levels and odds of T2DM according to cubic natural spline analysis models, after adjustment for body mass index, waist circumference, diastolic blood pressure, total cholesterol, and triglyeride. Multivariate logistic regression showed that progressively higher odds of T2DM were observed when serum IGF2BP3 levels were below 0.62 ng/mL (odds ratio 3.03 [95% confidence interval 1.23–7.47]) in model 4. Conclusion Seven significantly altered m6A RNA methylation genes were identified in T2DM. There was a U‐shaped association between serum IGF2BP3 levels and odds of T2DM in the general Chinese adult population. This study provides important evidence for further examination of the role of m6A RNA methylation, especially serum IGF2BP3 in T2DM risk assessment.

Schistosomiasis japonica is a zoonotic parasitic disease causing liver fibrosis. Liver sinusoidal endothelial cells (LSECs) exhibit fenestrations, which promote hepatocyte regeneration and reverses the process of liver fibrosis. To investigate the pathological changes of LSECs in schistosomiasis, we established a Schistosomiasis model. The population, phenotype, and secretory function of LSECs were detected by flow cytometry at 20, 28, and 42 days post infection. The changes in LSEC fenestration and basement membrane were observed through scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Quantitative real-time PCR and Western blotting were used to detect the expression of molecules associated with epithelial–mesenchymal transition (EMT) and fibrosis of LSECs and the liver. The flow cytometry results showed that the total LSEC proportions, differentiated LSEC proportions, and nitric oxide (NO) secretion of LSECs were decreased, and the proportion of dedifferentiated LSECs increased significantly post infection. The electron microscopy results showed that the number of fenestrate was decreased and there was complete basement membrane formation in LSECs following infection. The qPCR and Western blot results showed that EMT, and fibrosis-related indicators of LSECs and the liver changed significantly during the early stages of infection and were aggravated in the middle and late stages. The pathological changes in LSECs may promote EMT and liver fibrosis induced by Schistosoma japonicum infection.

Schistosoma parasites, causing schistosomiasis, exhibit typical host specificity in host preference. Many mammals, including humans, are susceptible to infection, while the widely distributed rodent, Microtus fortis , exhibits natural anti-schistosome characteristics. The mechanisms of host susceptibility remain poorly understood. Comparison of schistosome infection in M. fortis with the infection in laboratory mice (highly sensitive to infection) offers a good model system to investigate these mechanisms and to gain an insight into host specificity. In this study, we showed that large numbers of leukocytes attach to the surface of human schistosomes in M. fortis but not in mice. Single-cell RNA-sequencing analyses revealed that macrophages might be involved in the cell adhesion, and we further demonstrated that M. fortis macrophages could be mediated to attach and kill schistosomula with dependence on Complement component 3 (C3) and Complement receptor 3 (CR3). Importantly, we provided direct evidence that M. fortis macrophages could destroy schistosomula by trogocytosis, a previously undescribed mode for killing helminths. This process was regulated by Ca 2+ /NFAT signaling. These findings not only elucidate a novel anti-schistosome mechanism in M. fortis but also provide a better understanding of host parasite interactions, host specificity and the potential generation of novel strategies for schistosomiasis control.

BACKGROUND:Liver cirrhosis (LC) is a prevalent and severe disease in China. The burden of LC is changing with widespread vaccination of hepatitis B virus (HBV) and antiviral therapy. However, the recent transition in etiologies and clinical features of LC cases requiring hospitalization is unclear.AIM:To identify the transition in etiologies and clinical characteristics of hospitalized LC patients in Southern China.METHODS:In this retrospective, cross-sectional study we included LC inpatients admitted between January 2001 and December 2020. Medical data indicating etiological diagnosis and LC complications, and demographic, laboratory, and imaging data were collected from our hospital-based dataset. The etiologies of LC were mainly determined according to the discharge diagnosis, and upper gastrointestinal bleeding, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatocellular carcinoma (HCC), portal vein thrombosis, hepatorenal syndrome, and acute-on-chronic liver failure (ACLF) were considered LC-related complications in our study. Changing trends in the etiologies and clinical characteristics were investigated using logistic regression, and temporal trends in proportions of separated years were investigated using the Cochran-Armitage test. In-hospital prognosis and risk factors associated with in-hospital mortality were also investigated.RESULTS:A total of 33143 patients were included in the study [mean (SD) age, 51.7 (11.9) years], and 82.2% were males. The mean age of the study population increased from 51.0 years in 2001-2010 to 52.0 years in 2011-2020 (P < 0.001), and the proportion of female patients increased from 16.7% in 2001-2010 to 18.2% in 2011-2020 (P = 0.003). LC patients in the decompensated stage at diagnosis decreased from 68.1% in 2001-2010 to 64.6% in 2011-2020 (P < 0.001), and the median score of model for end-stage liver disease also decreased from 14.0 to 11.0 (P < 0.001). HBV remained the major etiology of LC (75.0%) and the dominant cause of viral hepatitis-LC (94.5%) during the study period. However, the proportion of HBV-LC decreased from 82.4% in 2001-2005 to 74.2% in 2016-2020, and the proportion of viral hepatitis-LC decreased from 85.2% in 2001-2005 to 78.1% in 2016-2020 (both P for trend < 0.001). Meanwhile, the proportions of LC caused by alcoholic liver disease, autoimmune hepatitis and mixed etiology increased by 2.5%, 0.8% and 4.5%, respectively (all P for trend < 0.001). In-hospital mortality was stable at 1.0% in 2011-2020, whereas HCC and ACLF manifested the highest increases in prevalence among all LC complications (35.8% to 41.0% and 5.7% to 12.4%, respectively) and were associated with 6-fold and 4-fold increased risks of mortality (odds ratios: 6.03 and 4.22, respectively).CONCLUSION:LC inpatients have experienced changes in age distribution and etiologies of cirrhosis over the last 20 years in Southern China. HCC and ACLF are associated with the highest risk of in-hospital mortality among LC complications.

Hepato-pancreato-biliary (HPB) cancer is a serious category of cancer including tumors originating in the liver, pancreas, gallbladder and biliary ducts. It is limited by two-dimensional (2D) cell culture models for studying its complicated tumor microenvironment including diverse contents and dynamic nature. Recently developed three-dimensional (3D) bioprinting is a state-of-the-art technology for fabrication of biological constructs through layer-by-layer deposition of bioinks in a spatially defined manner, which is computer-aided and designed to generate viable 3D constructs. 3D bioprinting has the potential to more closely recapitulate the tumor microenvironment, dynamic and complex cell-cell and cell-matrix interactions compared to the current methods, which benefits from its precise definition of positioning of various cell types and perfusing network in a high-throughput manner. In this review, we introduce and compare multiple types of 3D bioprinting methodologies for HPB cancer and other digestive tumors. We discuss the progress and application of 3D bioprinting in HPB and gastrointestinal cancers, focusing on tumor model manufacturing. We also highlight the current challenges regarding clinical translation of 3D bioprinting and bioinks in the field of digestive tumor research. Finally, we suggest valuable perspectives for this advanced technology, including combination of 3D bioprinting with microfluidics and application of 3D bioprinting in the field of tumor immunology.

Objective To investigate the critical values of four coagulation indexes in neonates of different gestational ages at the beginning of life. Methods A total of 1 110 eligible newborns hospitalized in 3 level-A tertiary hospitals in Shenzhen from January 1, 2012 to December 31, 2021 were selected. Based on the gestational age, they were divided into early preterm infants, middle preterm infants, late preterm infants and term infants, and four indicators of coagulation function were detected within 24 hours after admission. To establish the reference ranges of four critical values of neonatal coagulation function in the early stage of life, and to determine the condition of 1 588 neonates admitted to the Eighth Affiliated Hospital of Sun Yat-sen University during the same period. Results The critical values of coagulation function in early preterm infants were APTT ≥96.6 s or ≤46.7 s, PT ≥21.4 s or ≤12.5 s, TT ≥23.9 s or ≤15.7 s, FIB ≥3.1 g/L or ≤0.9 g/L; In medium preterm infants were APTT ≥92.4 s or ≤49.1 s, PT ≥18.9 s or ≤12.3 s, TT ≥23.5 s or ≤15.4 s, FIB ≥3.0 g/L or ≤1.1 g/L; In Late premature infants were APTT ≥93.4 s or ≤54.8 s, PT ≥17.1 s or ≤12.5 s, TT ≥19.3 s or ≤15.3 s, FIB ≥2.2 g/L or ≤1.1 g/L; In full-term infants were APTT ≥77.6 s or ≤42.0 s, PT ≥17.4 s or ≤12.2 s, TT ≥19 s or ≤14.5 s, FIB ≥2.4 g/L or ≤1.3 g/L. Among the 1 588 neonates, the detection rate of critical values in early preterm infants was 12.61%（14/111）, mainly respiratory distress syndrome; the detection rate of critical values in mid-term preterm infants was 10.99%（21/191）, mainly respiratory distress syndrome and neonatal hemorrhagic diseases. The detection rate of critical values in late preterm infants was 5.33%（25/469）, mainly neonatal hyperbilirubinemia, neonatal hemorrhagic diseases and neonatal asphyxia. The detection rate of critical values in full-term infants was 4.28%（35/817）, mainly neonatal hemorrhagic diseases and neonatal asphyxia. Conclusion The reference ranges of four critical values of coagulation function in neonates with different gestational ages at the early stage of life have been established, which has an important reference value for predicting the condition of severe neonates.

Low light (LL) resulting in shading are among the detrimental abiotic stresses limiting plant growth and suppressing crop productivity. Shading is a key cultivation technique in cigar wrapper tobacco production but little is known about its impact on transcriptional and translational regulatory networks. Here, we integrate transcriptomic and proteomic profiling with physio-biochemical and anatomical analyses under different light intensities [T200 (200 μmol m−2 s−1), T100 (100 μmol m−2 s−1), and T50 (50 μmol m−2 s−1)] to uncover the underlying molecular response mechanisms of tobacco plants. We found that the leaf anatomical structure impacts photosynthetic capacity and that LL intensities (particularly T50) decrease leaf and palisade thickness (42%) and spongy tissues (16%), which leads to a lower photosynthetic rate (84%) compared with T200. Furthermore, we identified 3045 and 590 significantly differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) in the transcriptome and proteome of cigar tobacco, respectively. A total of 110 pairs were correlated which were upregulated in photosynthesis-antenna proteins, photosynthesis, and defense/detoxification-related pathways, according to integrated omics analyses, and downregulated in tyrosine metabolism, starch and sucrose metabolism, mitochondrial electron transport chain, and glycolysis pathways; and associated with decreased activities of glyceraldehyde-3-phosphate dehydrogenase (31%), starch phosphorylase (25%), and pyruvate kinase (24%) enzymes related to glycolysis. Our results show that cigar tobacco efficiently utilizes low light to reconfigure its energy metabolism, and offer profound insights into the response mechanisms at the physio-biochemical, anatomical, and molecular levels. This study thus represents a valuable resource of genes and proteins for future functional studies underlying LL response.

Background The previous study investigated whether the functions of small, medium, and large high density lipoprotein (S/M/L-HDL) are correlated with protein changes in mice. Herein, the proteomic and functional analyses of high density lipoprotein (HDL) subclasses were performed in humans and rats. Methods After purifying S/M/L-HDL subclasses from healthy humans ( n = 6) and rats ( n = 3) using fast protein liquid chromatography (FPLC) with calcium silica hydrate (CSH) resin, the proteomic analysis by mass spectrometry was conducted, as well as the capacities of cholesterol efflux and antioxidation was measured. Results Of the 120 and 106 HDL proteins identified, 85 and 68 proteins were significantly changed in concentration among the S/M/L-HDL subclasses in humans and rats, respectively. Interestingly, it was found that the relatively abundant proteins in the small HDL (S-HDL) and large HDL (L-HDL) subclasses did not overlap, both in humans and in rats. Next, by searching for the biological functions of the relatively abundant proteins in the HDL subclasses via Gene Ontology, it was displayed that the relatively abundant proteins involved in lipid metabolism and antioxidation were enriched more in the medium HDL (M-HDL) subclass than in the S/L-HDL subclasses in humans, whereas in rats, the relatively abundant proteins associated with lipid metabolism and anti-oxidation were enriched in M/L-HDL and S/M-HDL, respectively. Finally, it was confirmed that M-HDL and L-HDL had the highest cholesterol efflux capacity among the three HDL subclasses in humans and rats, respectively; moreover, M-HDL exhibited higher antioxidative capacity than S-HDL in both humans and rats. Conclusions The S-HDL and L-HDL subclasses are likely to have different proteomic components during HDL maturation, and results from the proteomics-based comparison of the HDL subclasses may explain the associated differences in function.