Integrated transcriptomic and metabolomic analysis of the hepatotoxicity of dichloroacetonitrile.

Dichloroacetonitrile (DCAN), an emerged nitrogenous disinfection by-product (N-DBP) in drinking water, has garnered attention owing to its strong cytotoxicity, genotoxicity, and carcinogenicity. However, there are limited studies on its potential hepatotoxicity mechanisms. Understanding hepatotoxicity is essential in order to identify and assess the potential risks posed by environmental pollutants on liver health and to safeguard public health. Here, we investigated the viability, reactive oxygen species (ROS) levels, and cell cycle profile of DCAN-exposed HepG2 cells and analyzed the mechanism of DCAN-induced hepatotoxicity using both transcriptomic and metabolomic techniques. The study revealed that there was a decrease in cell viability, increase in ROS production, and increase in the number of cells in the G2/M phase with an increase in the concentration of DCAN. Omics analyses showed that DCAN exposure increased cellular ROS levels, leading to oxidative damage in hepatocytes, which further induced DNA damage, cell cycle arrest, and cell growth impairment. Thus, DCAN has significant toxic effects on hepatocytes. Integrated analysis of transcriptomics and metabolomics offers new insights into the mechanisms of DCAN-induced hepatoxicity.

Sinapic acid modulates oxidative stress and metabolic disturbances to attenuate ovarian fibrosis in letrozole-induced polycystic ovary syndrome SD rats.

Sinapic acid (SA) is renowned for its many pharmacological activities as a polyphenolic compound. The cause of polycystic ovary syndrome (PCOS), a commonly encountered array of metabolic and hormonal abnormalities in females, has yet to be determined. The present experiment was performed to evaluate the antifibrotic properties of SA in rats with letrozole-induced PCOS-related ovarian fibrosis. SA treatment successfully mitigated the changes induced by letrozole in body weight (BW) (p < .01) and relative ovary weight (p < .05). Histological observation revealed that SA reduced the number of atretic and cystic follicles (AFs) and (CFs) (p < .01), as well as ovarian fibrosis, in PCOS rats. Additionally, SA treatment impacted the serum levels of sex hormones in PCOS rats. Luteinizing hormone (LH) and testosterone (T) levels were decreased (p < .01, p < .05), and follicle-stimulating hormone (FSH) levels were increased (p < .05). SA administration also decreased triglyceride (TG) (p < .01) and total cholesterol (TC) levels (p < .05) and increased high-density lipoprotein cholesterol (HDL-C) levels (p < .01), thereby alleviating letrozole-induced metabolic dysfunction in PCOS rats. Furthermore, SA treatment targeted insulin resistance (IR) and increased the messenger RNA (mRNA) levels of antioxidant enzymes in the ovaries of PCOS rats. Finally, SA treatment enhanced the activity of peroxisome proliferator-activated receptor-γ (PPAR-γ), reduced the activation of transforming growth factor-ß1 (TGF-ß1)/Smads, and decreased collagen I, α-smooth muscle actin (α-SMA), and connective tissue growth factor (CTGF) levels in the ovaries of PCOS rats. These observations suggest that SA significantly ameliorates metabolic dysfunction and oxidative stress and ultimately reduces ovarian fibrosis in rats with letrozole-induced PCOS.

Impact of Liver Sympathetic Nervous System on Liver Fibrosis and Regeneration After Bile Duct Ligation in Rats.

The sympathetic nervous system (SNS) affects many functions of the body. SNS fibers regulate many aspects of liver function, repair, and regeneration. However, in the model of bile duct ligation (BDL) in rats, the kind of impact caused by the regulation of liver SNS on liver fibrosis and liver regeneration is unclear. The main research objective of this experiment is to examine the effect of SNS on liver fibrosis and liver regeneration. Twenty-four male Sprague-Dawley (SD) rats were assigned randomly to four groups. These groups included the sham surgery group (sham), model group (BDL), 6-hydroxydopamine group (BDL+6-OHDA), and spinal cord injury group (BDL+SCI). In the sham group, only exploratory laparotomy was performed without BDL. In the 6-OHDA group, 6-OHDA was used to remove sympathetic nerves after BDL. In the spinal cord injury group, rats underwent simultaneous BDL and spinal cord injury. After 3 weeks of feeding, four groups of rats were euthanized using high-dose anesthesia without pain. Moreover, liver tissue and blood were taken to detect liver fibrosis and regeneration indicators. After intraperitoneal injection of 6-OHDA into BDL rats, liver fibrosis indicators decreased. The administration of the injection effectively alleviated liver fibrosis and inhibited liver regeneration. However, after SCI surgery in BDL rats, liver fibrosis indicators increased. This resulted in exacerbating liver fibrosis and activating liver regeneration. The SNS plays a role in contributing to the liver injury process in the rat BDL model. Therefore, regulating the SNS may become a novel method for liver injury treatment.

Intrahepatic Venous Collateral Circulation and Reverse Blood Flow After Main Hepatic Vein Obstruction: A Case Report with Literature Review.

BACKGROUND Alveolar echinococcosis, a lethal parasitic disease, can invade important vessels in the liver. A liver vascular anomaly causes compensatory changes in other blood vessels connected to it because of the close relationship between them. Obstruction of the retrohepatic inferior vena cava and the second hilum can form the intrahepatic venous network and the vertebral venous plexus pathway, which can be demonstrated by hepatic venography and anatomical and autopsy studies. CASE REPORT A Tibetan woman, age 31, with hepatic alveolar echinococcosis and unique intrahepatic hemodynamic features, was referred to our center and underwent successful ex vivo liver resection and autotransplantation. We report our experience and review the literature. In this clinical case, we performed an ex vivo liver resection and autotransplantation without hepatic inferior vena cava reconstruction. After surgery, the circulatory system hemodynamic remained stable, and blood flow in the liver and trunk was unhindered. The patient underwent an uneventful hospitalization and recovery. CONCLUSIONS This clinical case demonstrates the unique venous access, hemodynamic alterations, and surgical decision-making that follow the invasion of significant hepatic vessels by alveolar echinococcosis lesions. HAE exhibits unique collateral vessels, which are uncommon in other diseases. Additionally, this kind of therapy offers fresh perspectives for the surgical treatment of end-stage HAE.

Hepatic macrophages play critical roles in the establishment and growth of hydatid cysts in the liver during Echinococcus granulosus sensu stricto infection.

Cystic echinococcosis (CE) is a worldwide neglected zoonotic disease caused by infection with the larval stage of the tapeworm Echinococcus granulosus sensu lato (E. granulosus s.l.), which predominantly resides in the liver accompanied by mild inflammation. Macrophages constitute the main cellular component of the liver and play a central role in controlling the progression of inflammation and liver fibrosis. However, the role of hepatic macrophages in the establishment and growth of hydatid cysts in the liver during E. granulosus sensu stricto (E. granulosus s.s.) infection has not been fully elucidated. Here, we showed that CD68+ macrophages accumulated in pericystic areas of the liver and that the expression of CD163, a marker of anti-inflammatory macrophages, was more evident in active CE patients than in inactive CE patients. Moreover, in a mouse model of E. granulosus s.s. infection, the pool of hepatic macrophages expanded dramatically through the attraction of massive amounts of monocyte-derived macrophages (MoMFs) to the infection site. These infiltrating macrophages preferentially polarized toward an iNOS+ proinflammatory phenotype at the early stage and then toward a CD206+ anti-inflammatory phenotype at the late stage. Notably, the resident Kupffer cells (KCs) predominantly maintained an anti-inflammatory phenotype to favor persistent E. granulosus s.s. infection. In addition, depletion of hepatic macrophages promoted E. granulosus s.s. larval establishment and growth partially by inhibiting CD4+ T-cell recruitment and liver fibrosis. The above findings demonstrated that hepatic macrophages play a vital role in the progression of CE, contributing to a better understanding of the local inflammatory responses surrounding hydatid cysts and possibly facilitating the design of novel therapeutic approaches for CE.

Safety of high-carbohydrate fluid diet 2 h versus overnight fasting before non-emergency endoscopic retrograde cholangiopancreatography: A single-blind, multicenter, randomized controlled trial.

BACKGROUND: Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients' recovery. METHODS: This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group (n = 665) and fasting group (n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. RESULTS: The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t = 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26-0.71, P <0.001) and 0.76 (95% CI: 0.57-0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05-0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39-0.95, P = 0.028) in the multivariable models. CONCLUSION: Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery. TRAIL REGISTRATION: ClinicalTrials.gov, No. NCT03075280.

Complex inferior vena cava reconstruction during ex vivo liver resection and autotransplantation: A case report.

BACKGROUND: Ex vivo liver resection and autotransplantation (ELRA) is an essential approach for treating patients with end-stage hepatic alveolar echinococcosis (AE), and its surgical indications involve severe invasion of important hepatic vessels, which makes in vivo resection impossible. Revascularization is a major step in the process of ELRA, which is extremely challenging when the invaded vessels have huge defects. CASE SUMMARY: Herein, we have reported the case of a 26-year-old patient with hepatic AE in an autologous liver graft who underwent complex inferior vena cava (IVC) reconstruction using disease-free IVC, autologous portal vein fragments, and umbilical vein within the ligamentum teres hepatis. The patient showed good surgical recovery without vascular-related complications during the long-term follow-up. CONCLUSION: We reviewed three studies that have reported complex revascularization of the IVC. This case report and systematic review showed that the use of autologous perihepatic vessels prevents donor-area trauma, immune rejection, and other adverse reactions. When the blood vessel is severely invaded and a single vascular material cannot repair and reconstruct the defect, ELRA may provide a safe and feasible surgical approach, which has good prospects for clinical application.

Potassium cobalt hexacyanoferrate as a peroxidase mimic for electrochemical immunosensing of Lactobacillus rhamnosus GG.

In this paper, the potassium cobalt hexacyanoferrate (II), K2CoFe(CN)6, with peroxidase-like activity was used for the fabrication of a novel label-free Lactobacillus rhamnosus GG (LGG) electrochemical immunosensor. The K2CoFe(CN)6 nanocubes were made by a simple hydrothermal method and followed by low-temperature calcination. In addition to structural characterization, the peroxidase-mimicking catalytic property of the material was confirmed by a chromogenic reaction. It is known that H2O2 can oxidize electroactive thionine molecules under the catalysis of horseradish peroxidase (HRP). In this nanozyme-based electrochemical immunoassay, due to the steric hindrance, the formation of immune-complex of LGG and LGG antibody on the modified GCE inhibits the catalytic activity of the peroxidase mimics of K2CoFe(CN)6 and thus reduced the current signal. Therefore, the developed electrochemical immunosensor achieved quantitative detection of LGG. Under optimal conditions, the linear range of the sensor was obtained from 101 to 106 CFU mL-1 with a minimum detection limit (LOD) of 12 CFU mL-1. Furthermore, the immunosensor was successfully applied in the quantitative detection of LGG in dairy product samples with recoveries ranging from 93.2% to 106.8%. This protocol presents a novel immunoassay method, which provides an alternative implementation pathway for the quantitative detection of microorganisms.

ERCP management of acute cholangitis caused by rupture of Echinococcus hepaticus into the biliary tract.

Background: Hepatic cystic echinococcosis (HCE) rupture into the biliary tract, one of the most common and refractory complications, is treated by laparotomy to remove hydatid lesions. The aim of this article was to investigate the role of endoscopic retrograde cholangiopancreatography (ERCP) in the treatment of this particular disease. Patients and Methods: This was is a retrospective analysis of 40 patients with HCE ruptured into the biliary tract in our hospital from September 2014 to October 2019. They were divided into two groups, ERCP group (group A, n = 14) and conventional surgery group (group B, n = 26). Group A was treated with ERCP first to control infection and improve the general condition before undergoing laparotomy at an optional stage while group B was treated with laparotomy directly. First, the infection parameters and liver, kidney and coagulation functions of group A patients before and after ERCP were compared to evaluate treatment effectiveness. Second, the intraoperative and post-operative parameters during the laparotomy of group A were compared with group B to evaluate the impact of ERCP treatment on laparotomy. Results and Conclusions: White blood cell, NE%, platelet, procalcitonin, C-reactive protein, interleukin-6, Total bilirubin (TBIL), alkaline phosphatase, gamma-glutamyl transpeptidase, aspartate transaminase, alanine transaminase (ALT), ALT and Cr in group A significantly improved by ERCP (P < 0.05); during laparotomy, the bleeding amount and hospital stay in group A were better (P < 0.05); moreover, concerning the post-operative complications, the incidence of acute renal failure and coagulation dysfunction in group A was significantly less (P < 0.05). ERCP, which not only quickly and effectively controls infection and improves the patient's systemic condition but also provides good support for subsequent radical surgery, enjoys good prospects for clinical application.

Collateral circulation caused by end-stage hepatic alveolar echinococcosis.

BACKGROUND: Hepatic alveolar echinococcosis (HAE), as a benign parasitic disease with malignant infiltrative activity, grows slowly in the liver, allowing sufficient time for collateral vessels to emerge in the process of vascular occlusion. METHODS: The portal vein (PV), hepatic vein and hepatic artery were observed by enhanced CT and the inferior vena cava (IVC) by angiography, respectively. Analysis of the anatomical characteristics of the collateral vessels helped to look into the pattern and characteristics of vascular collateralization caused by this specific etiology. RESULTS: 33, 5, 12 and 1 patients were included in the formation of collateral vessels in PV, hepatic vein, IVC and hepatic artery, respectively. PV collateral vessels were divided into two categories according to different pathways: type I: portal -portal venous pathway (13 cases) and type II: type I incorporates a portal-systemic circulation pathway (20 cases). Hepatic vein (HV) collateral vessels fell into short hepatic veins. The patients with IVC collateral presented with both vertebral and lumbar venous varices. Hepatic artery collateral vessels emanating from the celiac trunk maintains blood supply to the healthy side of the liver. CONCLUSIONS: Due to its special biological nature, HAE exhibited unique collateral vessels that were rarely seen in other diseases. An in-depth study would be of great help to improve our understanding related to the process of collateral vessel formation due to intrahepatic lesions and its comorbidity, in addition to providing new ideas for the surgical treatment of end-stage HAE.

LncRNA Regulation Mechanism in Hepatic Alveolar Echinococcosis with Nanosecond Pulse.

BACKGROUND: The mortality of patients infected with hepatic alveolar echinococcosis (HAE) was higher. The aim of this study was to investigate the therapeutic effect of nanosecond pulsed electric fields (nsPEFs) on HAE in rats and explore the related molecular mechanisms. METHODS: Establishment of HAE rat model and the lesions were treated with nsPEFs. The RNA of lesions in the high voltage nsPEFs treatment group and model group were extracted, and lncRNA and mRNA sequence analyses was performed. After obtaining the differentially expressed lncRNAs and mRNAs between the two groups, enrichment analysis was performed for mRNAs. The target genes of lncRNAs were predicted through co-location and co-expression. The expression of important lncRNAs and target genes in lesions was detected by qPCR. RESULTS: The HAE rat model was successfully established. After nsPEFs treatment, the size of lesions was improved significantly. Then, we identified 270 differentially expressed lncRNAs and 1659 differentially expressed mRNAs between the high voltage nsPEFs treatment group and model group. Enrichment analysis showed that the differentially expressed mRNAs were mainly enriched in metabolism and inflammation. Five important lncRNAs regulatory networks were identified, then Cpa1, Cpb1, Cel, Cela2a, and Cela3b were identified as key target genes. Importantly, the expression of 5 lncRNAs and 5 target genes was verified in the lesions. CONCLUSIONS: Preliminary results had shown that HAE treatment with nsPEFs can inhibit the growth of lesions. NsPEFs treatment altered gene expression in the lesions, and some genes were regulated by lncRNAs. The therapeutic mechanism may involve metabolism and inflammation.

An ultrasensitive bacterial imprinted electrochemical sensor for the determination of Lactobacillus rhamnosus GG.

An ultrasensitive label-free electrochemical sensor based on a homemade imprinted polypyrrole (PPy) polymer film was prepared to achieve quantitative determination of Lactobacillus rhamnosus GG (LGG). The LGG-imprinted polymer (LIP) film was deposited on a portable screen-printed electrode (SPE) via electropolymerization, which constituted an independent integrated system. The main preparation parameters of the LIP sensor were investigated to obtain optimal performance. Under optimized conditions, the peak current response of the LIP sensor showed a linear relationship with the logarithmic value of LGG concentration in the range from 101 to 109 CFU mL-1 and a detection limit of 5 CFU mL-1. The proposed LIP sensor has achieved efficient, ultrasensitive, highly selective, and cost-effective detection of LGG and can be further developed for practical applications in the quality inspection and development of probiotic products.

Interactions between polycyclic musks and human lactoferrin: Multi-spectroscopic methods and docking simulation.

Galaxolide (1,3,4,6,7,8-hexahydro-4,6,6,7,8-hexamethylcyclopenta-γ-2-benzopyrane; HHCB) and Tonalide (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene; AHTN) are "pseudo-persistent" pollutants that can cause DNA damage, endocrine disruption, organ toxicity, and reproductive toxicity in humans. HHCB and AHTN are readily enriched in breast milk, so exposure of infants to HHCB and AHTN is of concern. Here, the molecular mechanisms through which HHCB and AHTN interact with human lactoferrin (HLF) are investigated using computational simulations and spectroscopic methods to identify indirectly how HHCB and AHTN may harm infants. Molecular docking and kinetic simulation studies indicated that HHCB and AHTN can interact with and alter the secondary HLF structure. The fluorescence quenching of HLF by HHCB, AHTN was static with the forming of HLF-HHCB, HLF-AHTN complex, and accompanied by non-radiative energy transfer and that 1:1 complexes form through interaction forces. Time-resolved fluorescence spectroscopy indicated that binding to small molecules does not markedly change the HLF fluorescence lifetime. Three-dimensional fluorescence spectroscopy indicated that HHCB and AHTN alter the peptide chain backbone structure of HLF. Ultraviolet-visible absorption spectroscopy, simultaneous fluorescence spectroscopy, Fourier-transform infrared spectroscopy, and circular dichroism spectroscopy indicated that HHCB and AHTN change the secondary HLF conformation. Antimicrobial activity experiments indicated that polycyclic musks decrease lactoferrin activity and interact with HLF. These results improve our understanding of the mechanisms involved in the toxicities of polycyclic musks bound to HLF at the molecular level and provide theoretical support for mother-and-child health risk assessments.

Application of hepatic lobe hyperplasia techniques in the treatment of advanced hepatic alveolar echinococcosis: a single-centre experience.

BACKGROUND: This study was designed to investigate clinical efficiency and application indications of hepatic lobe hyperplasia techniques for advanced hepatic alveolar echinococcosis (AE) patients. METHODS: A retrospective case series covering 19 advanced hepatic AE patients admitted to the First Affiliated Hospital of Xinjiang Medical University from September 2014 to December 2021 and undergoing hepatic lobe hyperplasia techniques due to insufficient remnant liver volume were analyzed. Changes of liver function, lesions volume, remnant liver volume, total liver volume before and after operation have been observed. RESULTS: Among the patients, 15 underwent portal vein embolization (PVE). There was no statistical difference in total liver volume and lesions volume before and after PVE (P > 0.05). However, the remnant liver volume was significantly increased after PVE (P < 0.05). The median monthly increase rate in future liver remnant volume (FLRV) after PVE stood at 4.49% (IQR 3.55-7.06). Among the four patients undergoing two-stage hepatectomy (TSH), FLRV was larger than that before the first stage surgery, and the median monthly increase rate in FLRV after it stood at 3.34% (IQR 2.17-4.61). Despite no statistical difference in total bilirubin (TBil), albumin (Alb), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT) in all patients with PVE, four patients who underwent TSH showed a decrease in ALT, AST and GGT. During the waiting process before the second stage operation, no serious complications occurred in all patients. CONCLUSIONS: For patients suffering from advanced hepatic AE with insufficient FLRV, PVE and TSH are safe and feasible in promoting hepatic lobe hyperplasia.

Diversity and temporal dynamics of breast milk microbiome and its influencing factors in Chinese women during the first 6 months postpartum.

Human breast milk (HBM) plays an important role in providing nutrients, beneficial microorganisms and bioactive components for infants, helping maturation of their immune system and gastrointestinal development. Here, we present a study aiming to investigate the diversity and temporal dynamics of the milk microbiome across the first 6 month postpartum in Chinese healthy breastfeeding women, and to investigate to what extent other variables (e.g., sampling location, infant sex, and mode of delivery) might also be related to variations in the human milk microbiome, and the association with maternal diet and nutrients. Fifty-three healthy pregnant women from four cities were recruited from a China Maternal and Infant Health Cohort Study and breast milk samples were collected and analyzed using 16S rRNA metagenomic sequencing. We illustrated the diversity and temporal dynamics during lactation (Adonis p-value = 3e-04). Firmicutes and Proteobacteria were the most abundant phyla, and Streptococcus, Staphylococcus, Serratia, and Corynebacterium were the core genera. Partitioning around medoids clustering identified two major internal clusters of breast milk microbiota. Cluster 1 was dominated by Acinetobacter and Pseudomonas, while Cluster 2 was dominated by Streptococcus and Staphylococcus. Among other environmental variables, sampling location showed significant influence on breast milk microbiome (Adonis p-value = 4e-04), while infant sex (Adonis p-value = 0.33) and mode of delivery (Adonis p-value = 0.19) were less related to variations in the human milk microbiome. Maternal diet such as tuber was significantly correlated with the relative abundance of Neisseria (rho = 0.34, adjusted p-value = 0.01) and Cutibacterium (rho = -0.35, adjusted p-value = 0.01), and nutrients such as carbohydrates were significantly correlated with the relative abundance of Aquabacterium (rho = -0.39, adjusted p-value = 0.0027), and vitamin B12 was significantly correlated with the relative abundance of Coprococcus (rho = 0.40, adjusted p-value = 0.0018), etc. These results illustrated the dynamic changes of composition and diversity during the lactation phases of the Chinese breast milk microbiome and addressed the importance of geographic location on milk microbiota, and associations with maternal diet consumption, which have potential benefits on the establishment and future health of breastfeeding infants.

Single-Cell Heterogeneity of the Liver-Infiltrating Lymphocytes in Individuals with Chronic Echinococcus multilocularis Infection.

Human alveolar echinococcosis (AE) is a tumor-like disease predominantly located in the liver. The cellular composition and heterogeneity of the lesion-infiltrating lymphocytes which produce an "immunosuppressive" microenvironment are poorly understood. Here, we profiled 83,921 CD45+ lymphocytes isolated from the peripheral blood (PB), perilesion (PL), and adjacent normal (AN) liver tissue of four advanced-stage AE patients using single-cell RNA and T-cell receptor (TCR) sequencing technology. We identified 23 large clusters, and the distributions and transcriptomes of these cell clusters in the liver and periphery were different. The cellular proportions of exhausted CD8+ T cells and group 2 innate lymphoid cells (ILC2s) were notably higher in PL tissue, and the expression features of these cell subsets were related to neoplasm metastasis and immune response suppression. In the 5 CD8+ T-cell populations, only CD8+ mucosa-associated invariant T (MAIT) cells were enriched in PL samples and the TRAV1-2_TRAJ33_TRAC TCR was clonally expanded. In the 11 subsets of CD4+ T cells, Th17 cells and induced regulatory T cells (iTregs) were preferentially enriched in PL samples, and their highly expressed genes were related to cell invasion, tumor metastasis, and inhibition of the inflammatory immune response. Exhaustion-specific genes (TIGIT, PD-1, and CTLA4) were upregulated in Tregs. Interestingly, there was a close contact between CD8+ T cells and iTregs or Th17 cells, especially for genes related to immunosuppression, such as PDCD1-FAM3C, which were highly expressed in PL tissue. This transcriptional data set provides valuable insights and a rich resource for deeply understanding the immune microenvironment in AE, which could provide potential target signatures for AE diagnosis and immunotherapies.

MYBIOTA: A birth cohort on maternal and infant microbiota and its impact on infant health in Malaysia.

Background: The microbiota plays a key role in early immunity maturation that affects infant health and is associated with the development of non-communicable diseases and allergies in later life. Objective: The MYBIOTA is a prospective mother-infant cohort study in Malaysia aiming to determine the association between gut microbiota with infant health (temperament, gastrointestinal disorders, eczema, asthma, and developmental delays) in Selangor, Malaysia. Methods: Pregnant mothers will be enrolled in their first trimester of pregnancy, and follow-ups will be done for infants during their first year of life. Maternal-infant biological samples (blood, feces, saliva, urine, and breast milk), anthropometric, dietary, and clinical information will be collected at different time points from early pregnancy to 12 months postpartum. Discussion: This study could provide a better understanding of the colonization and development of the gut microbiome during early life and its impact on infant health. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT04919265.

Approaches to reconstruction of inferior vena cava by ex vivo liver resection and autotransplantation in 114 patients with hepatic alveolar echinococcosis.

BACKGROUND: Hepatic alveolar echinococcosis (AE) is most commonly found in retrohepatic inferior vena cava (RHIVC). Ex vivo liver resection and autotransplantation (ELRA) can better realize the radical resection of end-stage hepatic AE with severely compromised hepatocaval confluences, and reconstruction of the affected vessels. Currently, there is a scarcity of information regarding RHIVC reconstruction in ELRA. AIM: To propose reasonable RHICV reconstruction strategies for ex vivo liver resection and autotransplantation. METHODS: We retrospectively summarized the clinical data of 114 patients diagnosed with hepatic AE who treated by ELRA in our department. A total of 114 patients were divided into three groups according to the different reconstruction methods of RHIVC: Group A with original RHIVC being repaired and reconstructed (n = 64), group B with RHIVC being replaced (n = 43), and group C with RHIVC being resected without reconstruction (n = 7). The clinical data of patients, including the operation time, anhepatic phase, intraoperative blood loss, complications and postoperative hospital stay, were analyzed and the patients were routinely followed up. The normally distributed continuous variables were expressed as means ± SD, whereas the abnormally distributed ones were expressed as median and analyzed by analysis of variance. Survival curve was plotted by the Kaplan-Meier method. RESULTS: All patients were routinely followed up for a median duration of 52 (range, 12-125) mo. The 30 d mortality rate was 7.0% (8/114) and 7 patients died within 90 d. Among all subjects, the inferior vena cava (IVC)-related complication rates were 17.5% (11/63) in group A and 16.3% (7/43) in group B. IVC stenosis was found in 12 patients (10.5%), whereas thrombus was formed in 6 patients (5.3%). Twenty-two patients had grade III or higher complications, with the complication rates being 17.2%, 16.3%, and 57.1% in the three groups. The average postoperative hospital stay in the three groups was 32.3 ± 19.8, 26.7 ± 18.2, and 51.3 ± 29.4 d (P = 0.03), respectively. CONCLUSION: ELRA can be considered a safe and feasible option for end-stage hepatic AE patients with RHIVC infiltration. The RHIVC reconstruction methods should be selected appropriately depending on the defect degree of AE lesions in IVC lumen. The RHIVC resection without any reconstruction method should be considered with caution.

A cohort study of vitamins contents in human milk from maternal-infant factors.

Human milk vitamin content is an important indicator to evaluate the nutritional composition of human milk. This paper investigates the influence of maternal and infant factors on the dynamics of human milk vitamin content. A total of 147 mother-infant pairs from 3 different cities (north-south distribution) in China were selected and 9 major vitamins were measured in 332 human milk samples. The three vitamins (vitamin A, ß-carotene, and pantothenic acid) showed significant downward trends with lactation period (| r | > 0.3, p < 0.05). The lactation period factor could explain the negative variation of vitamin A (21.2%) and pantothenic acid (9.5%). The factors of lactation period and oils intake could jointly explain variations of ß-carotene (11.8%). (Registration number: NCT02658500).