Genome-wide identification of replication fork stalling/pausing sites and the interplay between RNA Pol II transcription and DNA replication progression.

BACKGROUND: DNA replication progression can be affected by the presence of physical barriers like the RNA polymerases, leading to replication stress and DNA damage. Nonetheless, we do not know how transcription influences overall DNA replication progression. RESULTS: To characterize sites where DNA replication forks stall and pause, we establish a genome-wide approach to identify them. This approach uses multiple timepoints during S-phase to identify replication fork/stalling hotspots as replication progresses through the genome. These sites are typically associated with increased DNA damage, overlapped with fragile sites and with breakpoints of rearrangements identified in cancers but do not overlap with replication origins. Overlaying these sites with a genome-wide analysis of RNA polymerase II transcription, we find that replication fork stalling/pausing sites inside genes are directly related to transcription progression and activity. Indeed, we find that slowing down transcription elongation slows down directly replication progression through genes. This indicates that transcription and replication can coexist over the same regions. Importantly, rearrangements found in cancers overlapping transcription-replication collision sites are detected in non-transformed cells and increase following treatment with ATM and ATR inhibitors. At the same time, we find instances where transcription activity favors replication progression because it reduces histone density. CONCLUSIONS: Altogether, our findings highlight how transcription and replication overlap during S-phase, with both positive and negative consequences for replication fork progression and genome stability by the coexistence of these two processes.

The role of kinesin family members in hepatobiliary carcinomas: from bench to bedside.

As a major component of the digestive system malignancies, tumors originating from the hepatic and biliary ducts seriously endanger public health. The kinesins (KIFs) are molecular motors that enable the microtubule-dependent intracellular trafficking necessary for mitosis and meiosis. Normally, the stability of KIFs is essential to maintain cell proliferation and genetic homeostasis. However, aberrant KIFs activity may destroy this dynamic stability, leading to uncontrolled cell division and tumor initiation. In this work, we have made an integral summarization of the specific roles of KIFs in hepatocellular and biliary duct carcinogenesis, referring to aberrant signal transduction and the potential for prognostic evaluation. Additionally, current clinical applications of KIFs-targeted inhibitors have also been discussed, including their efficacy advantages, relationship with drug sensitivity or resistance, the feasibility of combination chemotherapy or other targeted agents, as well as the corresponding clinical trials. In conclusion, the abnormally activated KIFs participate in the regulation of tumor progression via a diverse range of mechanisms and are closely associated with tumor prognosis. Meanwhile, KIFs-aimed inhibitors also carry out a promising tumor-targeted therapeutic strategy that deserves to be further investigated in hepatobiliary carcinoma (HBC).

Cerebral endothelial cells mediated enhancement of brain pericyte number and migration in oxygen-glucose deprivation involves the HIF-1α/PDGF-ß signaling.

The present study focused on whether hypoxia-inducible factor-1alpha (HIF-1α) and platelet-derived factor-beta (PDGF-ß) are involved in the crosstalk between brain microvascular endothelial cells (BMECs) and brain vascular pericytes (BVPs) under ischaemic-hypoxic conditions. Mono-cultures or co-cultures of BVPs and BMECs were made for the construction of the blood-brain barrier (BBB) model in vitro and then exposed to control and oxygen-glucose deprivation (OGD) conditions. BBB injury was determined by assessing the ability, apoptosis, and migration of BVPs and the transendothelial electrical resistance and horseradish peroxidase permeation of BMECs. Relative mRNA and protein levels of HIF-1α and PDGF-ß, as well as tight junction proteins ZO-1 and claudin-5 were analyzed by western blotting, reverse transcription quantitative PCR, and/or immunofluorescence staining. Dual-luciferase reporter assays assessed the relationship between PDGF-ß and HIF-1α. Co-culturing with BMECs alleviated OGD-induced reduction in BVP viability, elevation in BVP apoptosis, and repression in BVP migration. Co-culturing with BVPs protected against OGD-induced impairment on BMEC permeability. OGD-induced HIF-1α upregulation enhanced PDGF-ß expression in mono-cultured BMECs and co-cultured BMECs with BVPs. Knockdown of HIF-1α impaired the effect of BMECs on BVPs under OGD conditions, and PDGFR-ß silencing in BVPs blocked the crosstalk between BMECs and BVPs under OGD conditions. The crosstalk between BMECs and BVPs was implicated in OGD-induced BBB injury through the HIF-1α/PDGF-ß signaling.

Tumor burden score and carcinoembryonic antigen predict outcomes in patients with intrahepatic cholangiocarcinoma following liver resection: a multi­institutional analysis.

BACKGROUND: The prognostic significance of tumor burden score (TBS) in relation to carcinoembryonic antigen (CEA) has not been investigated among patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC). This study aimed to develop and validate a simplified model, a combination of TBS and CEA (CTC grade), for predicting the long-term outcomes of postoperative ICC patients. METHODS: Patients who underwent curative - intent resection of ICC between 2011 and 2019 were identified from a large multi - institutional database. The impact of TBS, CEA, and the CTC grade on overall survival (OS) and recurrence - free survival (RFS) was evaluated in both the derivation and validation cohorts. The receiver operating characteristic curve was utilized for assessing the predictive accuracy of the model. Subgroup analyses were performed across 8th TNM stage system stratified by CTC grade to assess the discriminatory capacity within the same TNM stage. RESULTS: A total of 812 patients were included in the derivation cohort and 266 patients in the validation cohort. Survival varied based on CEA (low: 36.7% vs. high: 9.0%) and TBS (low: 40.3% vs. high: 17.6%) in relation to 5 - year survival (both p < 0.001). As expected, patients with low CTC grade (i.e., low TBS/low CEA) were associated with the best OS as well as RFS, while high CTC grade (i.e., high TBS/high CEA) correlated to the worst outcomes. The model exhibited well performance in both the derivation cohort (area under the curve of 0.694) and the validation cohort (0.664). The predictive efficacy of the CTC grade system remains consistently stable across TNM stages I and III/IV. CONCLUSION: The CTC grade, a composite parameter derived from the combination of TBS and CEA levels, served as an easy - to - use tool and performed well in stratifying patients with ICC relative to OS and RFS.

A heparin-functionalized bioink with sustained delivery of vascular endothelial growth factor for 3D bioprinting of prevascularized dermal constructs.

Skin tissue engineering faces challenges due to the absence of vascular architecture, impeding the development of permanent skin replacements. To address this, a heparin-functionalized 3D-printed bioink (GH/HepMA) was formulated to enable sustained delivery of vascular endothelial growth factor (VEGF), comprising 0.3 % (w/v) hyaluronic acid (HA), 10 % (w/v) gelatin methacrylate (GelMA), and 0.5 % (w/v) heparin methacrylate (HepMA). The bioink was then used to print dermal constructs with angiogenic functions, including fibroblast networks and human umbilical vein endothelial cell (HUVEC) networks. GH/HepMA, with its covalently cross-linked structure, exhibits enhanced mechanical properties and heparin stability, allowing for a 21-day sustained delivery of VEGF. Cytocompatibility experiments showed that the GH/HepMA bioink supported fibroblast proliferation and promoted collagen I production. With VEGF present, the GH/HepMA bioink promoted HUVEC proliferation, migration, as well as the formation of a richer capillary-like network. Furthermore, HA within the GH/HepMA bioink enhanced rheological properties and printability. Additionally, 3D-bioprinted dermal constructs showed significant deposition of collagen I and III and mature stable capillary-like structures along the axial direction. In summary, this study offers a promising approach for constructing biomimetic multicellular skin substitutes with angiogenesis-induced functions.

Mining channel-regulated peptides from animal venom by integrating sequence semantics and structural information.

Channel-regulated peptides (CRPs) derived from animal venom hold great promise as potential drug candidates for numerous diseases associated with channel proteins. However, discovering and identifying CRPs using traditional bio-experimental methods is a time-consuming and laborious process. While there were a few computational studies on CRPs, they were limited to specific channel proteins, relied heavily on complex feature engineering, and lacked the incorporation of multi-source information. To address these problems, we proposed a novel deep learning model, called DeepCRPs, based on graph neural networks for systematically mining CRPs from animal venom. By combining the sequence semantic and structural information, the classification performance of four CRPs was significantly enhanced, reaching an accuracy of 0.92. This performance surpassed baseline models with accuracies ranging from 0.77 to 0.89. Furthermore, we employed advanced interpretable techniques to explore sequence and structural determinants relevant to the classification of CRPs, yielding potentially valuable bio-function interpretations. Comprehensive experimental results demonstrated the precision and interpretive capability of DeepCRPs, making it an accurate and bio-explainable suit for the identification and categorization of CRPs. Our research will contribute to the discovery and development of toxin peptides targeting channel proteins. The source data and code are freely available at https://github.com/liyigerry/DeepCRPs.

Leukemia inhibitory factor suppresses hepatic de novo lipogenesis and induces cachexia in mice.

Cancer cachexia is a systemic metabolic syndrome characterized by involuntary weight loss, and muscle and adipose tissue wasting. Mechanisms underlying cachexia remain poorly understood. Leukemia inhibitory factor (LIF), a multi-functional cytokine, has been suggested as a cachexia-inducing factor. In a transgenic mouse model with conditional LIF expression, systemic elevation of LIF induces cachexia. LIF overexpression decreases de novo lipogenesis and disrupts lipid homeostasis in the liver. Liver-specific LIF receptor knockout attenuates LIF-induced cachexia, suggesting that LIF-induced functional changes in the liver contribute to cachexia. Mechanistically, LIF overexpression activates STAT3 to downregulate PPARα, a master regulator of lipid metabolism, leading to the downregulation of a group of PPARα target genes involved in lipogenesis and decreased lipogenesis in the liver. Activating PPARα by fenofibrate, a PPARα agonist, restores lipid homeostasis in the liver and inhibits LIF-induced cachexia. These results provide valuable insights into cachexia, which may help develop strategies to treat cancer cachexia.

Bilibili, TikTok, and YouTube as sources of information on gastric cancer: assessment and analysis of the content and quality.

BACKGROUND: Gastric cancer has attracted widespread attention on social media due to its high incidence and severity. The Bilibili, TikTok, and YouTube video-sharing platforms have received considerable interest among general health consumers. Nevertheless, it remains unclear whether the information in videos on these platforms is of satisfactory content and quality. METHODS: A total of 300 eligible videos related to gastric cancer were screened from three video-sharing platforms, Bilibili, TikTok, and YouTube, for assessment and analysis. First, the basic information presented in the videos was recorded. Next, we identified the source and content type of each video. Then, the Global Quality Scale (GQS), Journal of the American Medical Association (JAMA), and Modified DISCERN were used to assess the educational content and quality of each video. A comparative analysis was undertaken of the videos procured from these three sources. RESULTS: We identified six categories of uploaders of the 300 videos: 159 videos (53%) were uploaded by health professionals, 21 videos (7%) by users in science communications, 29 videos (9.67%) by general users, 27 videos (9%) from news agencies, 63 videos (12%) by nonprofit organizations, and one video (0.33%) by a for-profit organization. In terms of the content types of the 300 videos, we identified five distinct categories. There were 48 videos (16%) on early signals, 12 videos (4%) on late symptoms, 40 videos (13.33%) on etiologies and causations, 160 videos (53.33%) on scientific introductions, and 40 videos (13.33%) on treatment methods. The overall quality of the videos was evaluated by the GQS, JAMA, and Modified DISCERN and was found to be medium, with scores of 2.6/5, 2.41/4, and 2.71/5 points, respectively. CONCLUSIONS: This innovative study demonstrates that videos on social media platforms can help the public learn about early signals, late symptoms, treatment methods, etiologies and causations, and scientific introductions of gastric cancer. However, both the content and quality of uploaded recordings are inadequate currently. More efforts should be made to enhance the content and quality of videos on gastric cancer and to increase public awareness.

p53 suppresses MHC class II presentation by intestinal epithelium to protect against radiation-induced gastrointestinal syndrome.

Radiation-induced gastrointestinal syndrome is a major complication and limiting factor for radiotherapy. Tumor suppressor p53 has a protective role in radiation-induced gastrointestinal toxicity. However, its underlying mechanism remains unclear. Here we report that regulating the IL12-p40/MHC class II signaling pathway is a critical mechanism by which p53 protects against radiation-induced gastrointestinal syndrome. p53 inhibits the expression of inflammatory cytokine IL12-p40, which in turn suppresses the expression of MHC class II on intestinal epithelial cells to suppress T cell activation and inflammation post-irradiation that causes intestinal stem cell damage. Anti-IL12-p40 neutralizing antibody inhibits inflammation and rescues the defects in intestinal epithelial regeneration post-irradiation in p53-deficient mice and prolongs mouse survival. These results uncover that the IL12-p40/MHC class II signaling mediates the essential role of p53 in ensuring intestinal stem cell function and proper immune reaction in response to radiation to protect mucosal epithelium, and suggest a potential therapeutic strategy to protect against radiation-induced gastrointestinal syndrome.

Fetuin-B Overexpression Promotes Inflammation in Diabetic Retinopathy Through Activating Microglia and the NF-κB Signaling Pathway.

PURPOSE: To investigate the expression, source, role, and mechanism of Fetuin-B (FETUB) in diabetic retinopathy (DR). METHODS: ELISA and immunofluorescence were used to analyze the concentration of FETUB in plasma, aqueous fluid, and tissue specimens of patients with DR and healthy controls. Immunofluorescence, q-PCR, and western blotting were used to examine the expression of FETUB in DR mice and cells cultured with different concentrations of glucose. BV2 microglia cell line and DR mice were treated using FETUB recombination protein and FETUB shRNA to explore the function of FETUB in DR by q-PCR, western blotting, and immunofluorescence. RESULTS: FETUB concentrations in plasma, aqueous fluid, and tissue specimens were significantly increased in DR patients. The mice in DR group had a higher concentration of FETUB in the retina and liver tissues than those in the control group, and the expression of FETUB was increased in both ARPE19 and BV2 cells under a high-glucose environment. The ratio of p-P65 (Phospho-P65)/P65 and the expression levels of TNF-α, VEGF, and ionized calcium binding adaptor molecule (IBA)-1 were increased in BV2 cells cultured with FETUB recombinant protein, while they were decreased in BV2 cells transfected with FETUB shRNA. Immunofluorescence staining showed that there were more IBA-1+ activated microglia in the retinas of the FETUB recombination protein group than in the retinas of the DR group, and there were fewer IBA-1+ activated microglia in the retinas of the FETUB shRNA group than in the retinas of the DR group. CONCLUSIONS: FETUB sourced from endocrine, autocrine, and paracrine pathways could promote inflammation in DR by activating the NF-κB pathway and microglia.

Streptomyces tamarix sp. nov.: antagonism against Alternaria gaisen producing streptochlorin, isolated from Tamarix root soil.

By the end of 2021, the pear yield in Xinjiang reached 1,795,900 tons, accounting for 1/9 of the country. Pear black spot, caused by Alternaria gaisen disease, has had a significant impact on the pear industry. A. gaisen can infect nearly all pear plants, resulting in black spots on the fruit that negatively affect both yield and quality. This study focused on the TRM76323 strain of Streptomyces, which was isolated from the soil of Tamarix chinensis in Xinjiang Province. Through a multiphase classification and identification method, the genetic classification status of the antagonistic strains was determined. The study also identified the antibacterial active components of streptochlorin using modern isolation and purification techniques. The antagonistic activity of Streptomyces against Alternaria was analyzed through in vitro and in vivo experiments. This research not only expanded the resource bank of antagonistic microorganisms in extreme environments in Xinjiang, but also identified active components that could contribute to the development of new drug lead compounds. Additionally, this study presents a novel approach for the prevention and control of pear black spot disease.

Air pollutants in bronchoalveolar lavage fluid and pulmonary tuberculosis: A mediation analysis of gene-specific methylation.

Particulate matter (PM) exposure could alter the risk of tuberculosis, but the underlying mechanism is still unclear. We enrolled 132 pulmonary tuberculosis (PTB) patients and 30 controls. Bronchoalveolar lavage fluid samples were collected from all participants to detect organochlorine pesticides, polycyclic aromatic hydrocarbons, metal elements, and DNA methylation of immunity-related genes. We observed that γ-HCH, Bap, Sr, Ag, and Sn were related to an increased risk of PTB, while Cu and Ba had a negative effect. IFN-γ, IL-17A, IL-2, and IL-23 had a higher level in the PTB group, while IL-4 was lower. The methylation of 18 CpG sites was statistically associated with PTB risk. The methylation at the IL-4_06_121 site showed a significant mediating role on γ-HCH, Sr, and Sn. Our study suggests that PM exposure can increase the risk of tuberculosis by affecting DNA methylation and cytokine expression.

Protective Efficacy of Novel Engineered Human ACE2-Fc Fusion Protein Against Pan-SARS-CoV-2 Infection In Vitro and in Vivo.

Enduring occurrence of severe COVID-19 for unvaccinated, aged, or immunocompromised individuals remains an urgent need. Soluble human angiotensin-converting enzyme 2 (ACE2) has been used as a decoy receptor to inhibit SARS-CoV-2 infection, which is limited by moderate affinity. We describe an engineered, high-affinity ACE2 that is consistently effective in tissue cultures in neutralizing all strains tested, including Delta and Omicron. We also found that treatment of AC70 hACE2 transgenic mice with hACE2-Fc receptor decoys effectively reduced viral infection, attenuated tissue histopathology, and delayed the onset of morbidity and mortality caused by SARS-CoV-2 infection. We believe that using this ACE2-Fc protein would be less likely to promote the escape mutants of SARS-CoV-2 as frequently as did those neutralizing antibody therapies. Together, our results emphasize the suitability of our newly engineered hACE2-Fc fusion protein for further development as a potent antiviral agent against Pan-SARS-CoV-2 infection.

Super-resolution imaging based on cascaded microsphere compound lenses.

In this paper, a cascaded microsphere compound lens (CMCL) is introduced, in which a 20-µm-diameter barium titanate glass (BTG) primary microsphere and a 250-nm-diameter or 200-nm-diameter polystyrene (PS) secondary microsphere array constitute CMCL1 and CMCL2, respectively. The field of view (FOV) depends on the size of the BTG microsphere, while the waist of the photon nanojet (PNJ) can be adjusted by the size of the PS microsphere. The narrower the waist of the PNJ, the higher the imaging resolution. In the experiment, a 200-nm-diameter hexagonally close-packed PS nanoparticle array is successfully observed by the CMCL with a high magnification of  ∼11.6× and a FOV of  ∼14µm, while the single BTG microsphere is incapable of observing the array. The point spread function is used to quantify the resolution of the CMCL. A well-designed CMCL can improve the imaging performances of a microsphere-assisted microscope.

Interkingdom ecological networks between plants and fungi drive soil multifunctionality across arid inland river basin.

Despite the known collective contribution of above- (plants) and below-ground (soil fungi) biodiversity on multiple soil functions, how the associations among plant and fungal communities regulate soil multifunctionality (SMF) differentially remains unknown. Here, plant communities were investigated at 81 plots across a typical arid inland river basin, within which associated soil fungal communities and seven soil functions (nutrients storage and biological activity) were measured in surface (0-15 cm) and subsurface soil (15-30 cm). We evaluated the relative importance of species richness and biotic associations (reflected by network complexity) on SMF. Our results demonstrated that plant species richness and plant-fungus network complexity promoted SMF in surface and subsurface soil. SMF in two soil layers was mainly determined by plant-fungus network complexity, mean groundwater depth and soil variables, among which plant-fungus network complexity played a crucial role. Plant-fungus network complexity had stronger effects on SMF in surface soil than in subsurface soil. We present evidence that plant-fungus network complexity surpassed plant-fungal species richness in determining SMF in surface and subsurface soil. Moreover, plant-fungal species richness could not directly affect SMF. Greater plant-fungal species richness indirectly promoted SMF since they ensured greater plant-fungal associations. Collectively, we concluded that interkingdom networks between plants and fungi drive SMF even in different soil layers. Our findings enhanced our knowledge of the underlying mechanisms that above- and below-ground associations promote SMF in arid inland river basins. Future study should place more emphasis on the associations among plant and microbial communities in protecting soil functions under global changes.

Identification of biomarkers associated with immune scores in diabetic retinopathy.

Background: Diabetic retinopathy (DR) causes irreversible visual impairment in diabetes mellitus (DM) patients. Immunity played a crucial role in DR. Nevertheless, the triggering mechanism of DR was not yet thorough enough. Herein, we aim to identify the immune-associated genes as biomarkers associated with immune scores that can distinguish early DR from DM without DR. Methods: In this study, total RNA of peripheral blood mononuclear cell (PBMC) samples from 15 non-proliferative DR patients and 15 DM patients without DR were collected and the transcriptome sequencing data were extracted. Firstly, the target genes were obtained by intersecting the differentially expressed genes (DEGs), which were screened by "limma", and the module genes (related to immune scores), which were screened by "WGCNA". In order to screen for the crucial genes, three machine learning algorithms were implemented, and a receiver operating characteristic (ROC) curve was used to obtain the diagnostic genes. Moreover, the gene set enrichment analysis (GSEA) was performed to understand the function of diagnostic genes, and analysis of the proportions of immune cells and their association with diagnostic genes was performed to analyze the pathogenesis of DR. Furthermore, the regulatory network of TF-mRNA-miRNA was built to reveal the possible regulation of diagnostic genes. Finally, the quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the mRNA level of diagnostic genes. Results: A total of three immune-associated diagnostic genes, namely, FAM209B, POM121L1P, and PTGES, were obtained, and their expression was increased in PBMC samples of DR, and qRT-PCR results confirmed these results. Moreover, the functions of these genes were associated with immune response. The expression of POM121L1P and PTGES was significantly negatively associated with naive B cells, and the expression of FAM209B was significantly negatively associated with immature dendritic cells. Moreover, ESR1 could regulate both FAM209B and PTGES. Conclusion: This study identified three immune-associated diagnostic genes, FAM209B, POM121L1P, and PTGES, as biomarkers associated with immune scores in DR for the first time. This finding might proffer a novel perspective of the triggering mechanism of DR, and help to understand the role of immune-associated genes in the molecular mechanism of DR more deeply.

Genome-Wide Profiling of Transcriptome and DNA Methylome in Human Embryonic Stem Cells Exposed to Extractable Organic Matter from PM2.5.

Increasing evidence indicates that PM2.5 exposure disrupts early embryonic development, but the mechanisms remain unclear. We hypothesized that PM2.5 cause abnormal embryonic development by interfering with DNA methylation and mRNA expression. In this study, we observed that human embryonic stem cells (hESCs) treated with extractable organic matters (EOM) from PM2.5 concentrations above 100 µg/mL exhibited reduced viability. While EOM within non-cytotoxicity concentrations did not affect the expression levels of pluripotency genes, it did enhance cellular proliferation, as indicated by increased Edu incorporation and the upregulation of cell cycle genes (Cdk2, Mdm2). Additionally, EOM significantly influenced the transcriptome patterns in hESCs. Notably, the differentially expressed genes were found to be significantly enriched in processes such as extracellular matrix organization, cell-cell junction organization, chromatin organization, and DNA methylation. Furthermore, we observed whole genomic-wide DNA methylation changes. Through a cross-analysis of changes in DNA methylation and mRNA expression, we identified an enrichment of terms related to the VEGFR signaling pathway and extracellular matrix. The gene signal transduction networks revealed that crucial hubs were implicated in cell growth and division. In conclusion, our findings demonstrate that PM2.5 induce significant alterations in transcriptome and DNA methylome in hESCs, leading to aberrant cell proliferation. This research provides novel insights into the molecular mechanisms underlying the developmental toxicity of PM2.5.

TGFB1 induces fetal reprogramming and enhances intestinal regeneration.

The gut epithelium has a remarkable ability to recover from damage. We employed a combination of high-throughput sequencing approaches, mouse genetics, and murine and human organoids and identified a role for TGFB signaling during intestinal regeneration following injury. At 2 days following irradiation (IR)-induced damage of intestinal crypts, a surge in TGFB1 expression is mediated by monocyte/macrophage cells at the location of damage. The depletion of macrophages or genetic disruption of TGFB signaling significantly impaired the regenerative response. Intestinal regeneration is characterized by the induction of a fetal-like transcriptional signature during repair. In organoid culture, TGFB1 treatment was necessary and sufficient to induce the fetal-like/regenerative state. Mesenchymal cells were also responsive to TGFB1 and enhanced the regenerative response. Mechanistically, pro-regenerative factors, YAP/TEAD and SOX9, are activated in the epithelium exposed to TGFB1. Finally, pre-treatment with TGFB1 enhanced the ability of primary epithelial cultures to engraft into damaged murine colon, suggesting promise for cellular therapy.

Anatomic versus non-anatomic resection for early-stage intrahepatic cholangiocarcinoma: a propensity score matching and stabilized inverse probability of treatment weighting analysis.

BACKGROUND: Radical resection is still the most cost-effectiveness curative strategy for intrahepatic cholangiocarcinoma (ICC), but it remains controversial on the survival benefit of anatomic resection (AR). In this study, we sought to compare the oncologic outcomes between AR versus non-AR (NAR) as the primary treatment for early-stage ICC patients. METHODS: Data of ICC patients who underwent hepatectomy and staged at AJCC I were retrospectively collected from 12 hepatobiliary centers in China between Dec 2012 and Dec 2015. Propensity score matching (PSM) and stabilized inverse probability of treatment weighting (IPTW) analysis were performed to minimize the effect of potential confounders, and the perioperative and long-term outcomes between AR and NAR groups were compared. RESULTS: Two hundred seventy-eight ICC patients staged at AJCC I were eligible for this study, including 126 patients receiving AR and 152 patients receiving NAR. Compared to the NAR group, the AR group experienced more intraoperative blood loss before and after PSM or stabilized IPTW (all P > 0.05); AR group also experienced more intraoperative transfusion after stabilized IPTW (P > 0.05). In terms of disease-free survival (DFS) and overall survival (OS), no significant differences were observed between the two groups before and after PSM or stabilized IPTW (all P > 0.05). Multivariable Cox regression analyses found that AR was not an independent prognostic factor for either DFS or OS (all P > 0.05). Further analysis also showed that the survival benefit of AR was not found in any subgroup stratified by Child-Pugh grade (A or B), cirrhosis (presence or absence), tumor diameter (≤ 5 cm or > 5 cm) and pathological type (mass-forming or non-mass-forming) with all P > 0.05. CONCLUSION: Surgical approach does not influence the prognosis of patients with stage I primary ICC, and NAR might be acceptable and oncological safety.

Evaluation of vaccination status of children with special health care needs in Suzhou, China, 2020-2022: A retrospective survey study.

Children with special health care needs (CSHCNs) are at an increased risk of vaccine-preventable infections (VPDs), but they also face the dilemma of vaccine hesitancy. We obtained information on pediatric visits from the Referral and Assessment Information System for Vaccination (RAISV) and information on vaccination from the Jiangsu Province Immunization Information System (JSIIS). We followed the occurrence of Adverse Events Following Immunization (AEFIs) and VPDs by actively calling and querying the China Information System for Disease Control and Prevention (CISDCP). The Poisson test was used to compare the incidence of AEFIs between groups. A total of 5,037 children who visited a vaccination assessment clinic were followed-up in this study. The majority were children with developmental anomalies (28.5%), certain conditions originating in the perinatal period (12.1%), and nervous system disorders (9.0%). Most CSHCNs (66.9%) were advised to have all vaccines according to routine practice, 29.0% were advised to have partial vaccination, and 4.1% were advised to delay all vaccines and wait for future assessment. A total of 201 (4.0%) CSHCNs were not vaccinated, although they were assessed to be eligible for vaccination. By querying the immunization planning module in CISDCP, we observed 55 AEFI cases, which amounted to an incidence rate of 1.2 per 1,000, and the occurrence of abnormal reactions was not significantly different compared with the general population. The vaccination program following the designed workflow for CSHCNs was safe and could be recommended in other areas.