A fast and non-invasive artificial intelligence olfactory-like system that aids diagnosis of Parkinson's disease.

BACKGROUND AND PURPOSE: Several previous studies have shown that skin sebum analysis can be used to diagnose Parkinson's disease (PD). The aim of this study was to develop a portable artificial intelligence olfactory-like (AIO) system based on gas chromatographic analysis of the volatile organic compounds (VOCs) in patient sebum and explore its application value in the diagnosis of PD. METHODS: The skin VOCs from 121 PD patients and 129 healthy controls were analyzed using the AIO system and three classic machine learning models were established, including the gradient boosting decision tree (GBDT), random forest and extreme gradient boosting, to assist the diagnosis of PD and predict its severity. RESULTS: A 20-s time series of AIO system data were collected from each participant. The VOC peaks at a large number of time points roughly concentrated around 5-12 s were significantly higher in PD subjects. The gradient boosting decision tree model showed the best ability to differentiate PD from healthy controls, yielding a sensitivity of 83.33% and a specificity of 84.00%. However, the system failed to predict PD progression scored by Hoehn-Yahr stage. CONCLUSIONS: This study provides a fast, low-cost and non-invasive method to distinguish PD patients from healthy controls. Furthermore, our study also indicates abnormal sebaceous gland secretion in PD patients, providing new evidence for exploring the pathogenesis of PD.

High-Pressure Induced Continuous Structural Evolution of Kagome Antiferromagnet MgMn3(OH)6Cl2: A Structural Analogue to Quantum Spin Liquid Herbertsmithite.

MgMn3(OH)6Cl2 serves readily as the classical Heisenberg kagome antiferromagnet lattice spin frustration material, due to its similarity to herbertsmithite in composition and crystal structure. In this work, nanosheets of MgMn3(OH)6Cl2 are synthesized through a solid-phase reaction. Low-temperature magnetic measurements revealed two antiferromagnetic transitions, occurring at ∼8 and 55 K, respectively. Utilizing high-pressure synchrotron radiation X-ray diffraction techniques, the topological structural evolution of MgMn3(OH)6Cl2 under pressures up to 24.8 GPa was investigated. The sample undergoes a second-order structural phase transition from the rhombohedral phase to the monoclinic phase at pressures exceeding 7.8 GPa. Accompanying the disappearance of the Fano-like line shape in the high-pressure Raman spectra were the emergence of new Raman active modes and discontinuities in the variations of Raman shifts in the high-frequency region. The phase transition to a structure with lower symmetry was attributed to the pressure-induced enhancement of cooperative Jahn-Teller distortion, which is caused by the mutual substitution of Mn2+ ions from the kagome layer and Mg2+ ions from the triangular interlayer. High-pressure ultraviolet-visible absorption measurements support the structural evolution. This research provides a robust experimental approach and physical insights for further exploration of classical geometrical frustration materials with kagome lattice.

Evidence for human infection with avian influenza A(H9N2) virus via environmental transmission inside live poultry market in Xiamen, China.

H9N2 avian influenza virus (AIV) has become prevalent in the live poultry market (LPM) worldwide, and environmental transmission mode is an important way for AIVs to infect human beings in the LPM. To find evidence of human infection with the influenza A(H9N2) virus via environmental contamination, we evaluated one human isolate and three environmental isolates inside LPMs in Xiamen, China. The phylogeny, transmissibility, and pathogenicity of the four isolates were sorted out systematically. As for the H9N2 virus, which evolved alongside the "Avian-Environment-Human" spreading chain in LPMs from the summer of 2019 to the summer of 2020, its overall efficiency of contact and aerosol transmissibility improved, which might contribute to the increasing probability of human infection. This study indicated that environmental exposure might act as an important source of human infection in LPMs.

Emerging Omicron subvariants evade neutralizing immunity elicited by vaccine or BA.1/BA.2 infection.

The newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2.75 and BA.2.76 subvariants contained 35 and 29 additional mutations in its spike (S) protein compared with the reference SARS-CoV-2 genome, respectively. Here, we measured the evasion degree of the BA.1, BA.2, BA.4, BA.5, BA.2.75, and BA.2.76 subvariants from neutralizing immunity in people previously infected with the Omicron BA.1 and BA.2, determined the effect of vaccination on immune evasion, and compared the titers of neutralizing antibodies in serums between acute infection and convalescence. Results showed that the neutralization effect of serums from patients with different vaccination statuses and BA.1/BA.2 breakthrough infection decreased with the Omicron evolution from BA.1 to BA.2, BA.4, BA.5, BA.2.75, and BA.2.76. This study also indicated that the existing vaccines could no longer provide effective protection, especially for the emerging BA.2.75 and BA.2.76 subvariants. Therefore, vaccines against emerging epidemic strains should be designed specifically. In the future, we can not only focus on the current strains, but also predict and design new vaccines against potential mutant strains. At the same time, we can combine the virus strains' infection characteristics to develop protective measures for virus colonization areas, such as nasal protection spray. Besides, further studies on the Y248N mutation of BA.2.76 subvariant were also necessary to explore its contribution to the enhanced immune evasion ability.

TaSINA2B, interacting with TaSINA1D, positively regulates drought tolerance and root growth in wheat (Triticum aestivum L.).

Wheat (Triticum aestivum L.) is an important food crop mainly grown in arid and semiarid regions worldwide, whose productivity is severely limited by drought stress. Although various E3 ubiquitin (Ub) ligases regulate drought stress, only a few SINA-type E3 Ub ligases are known to participate in such responses. Herein, we identified and cloned 15 TaSINAs from wheat. The transcription level of TaSINA2B was highly induced by drought, osmotic and abscisic acid treatments. Two-type promoters of TaSINA2B were found in 192 wheat accessions; furthermore wheat accessions with promoter TaSINA2BII showed a considerably higher level of drought tolerance and gene expression levels than those characterizing accessions with promoter TaSINA2BI that was mainly caused by a 64 bp insertion in its promoter. Enhanced drought tolerance of TaSINA2B-overexpressing (OE) transgenic wheat lines was found to be associated with root growth promotion. Further, an interaction between TaSINA2B and TaSINA1D was detected through yeast two-hybrid and bimolecular fluorescence complementation assays. And TaSINA1D-OE transgenic wheat lines showed similar drought tolerance and root growth phenotype to those observed when TaSINA2B was overexpressed. Therefore, the variation of TaSINA2B promoter contributed to the drought stress regulation, while TaSINA2B, interacting with TaSINA1D, positively regulated drought tolerance by promoting root growth.

Factors related to the mortality risk of severe hand, foot, and mouth diseases (HFMD): a 5-year hospital-based survey in Guangxi, Southern China.

BACKGROUND: To understand the factors influencing clinical outcomes of severe hand, foot, and mouth diseases (HFMD), and to provide scientific evidence for reducing the mortality risk of severe HFMD. METHODS: From 2014 to 2018, children diagnosed with severe HFMD cases in Guangxi, China, were enrolled in this hospital-based study. The epidemiological data obtained through face-to-face interviews with the parents and guardians. Univariate and multivariate logistics regression models were used to analyze the factors influencing the clinical outcomes of severe HFMD. The impact of the EV-A71 vaccination on inpatient mortality was analyzed by a comparison approach. RESULTS: A total of 1565 severe HFMD cases were enrolled in this survey, including 1474 (94.19%) survival cases and 91 (5.81%) death cases. The multivariate logistic analysis demonstrated that HFMD history of playmates in the last three months, first visit to the village hospital, time from the first visit to admission less than two days, no correct diagnosis for HFMD at the first visit, and having no rash symptoms were the independent risk factors for severe HFMD cases (all p < 0.05). While EV-A71 vaccination was a protective factor (p < 0.05). The EV-A71 vaccination group versus the non-vaccination group showed 2.23% of death in the vaccination group and 7.24% of death in the non-vaccination group. The EV-A71 vaccination protected 70.80% of the death of severe HFMD cases, with an effective index of 4.79. CONCLUSIONS: The mortality risk of severe HFMD in Guangxi was related to playmates had HFMD history in last 3 months, hospital grade, EV-A71 vaccination, patients visit hospital previously, and rash symptom. EV-A71 vaccination can significantly reduce mortality among severe HFMD. The findings are of great significance for the effective prevention and control of HFMD in Guangxi, southern China.

Structural phase transformation of quantum spin liquid herbertsmithite via pressure induced enhancement of the cooperative Jahn-Teller effect and antisite disorder.

Herbertsmithite, Cu3Zn(OH)6Cl2, serves as one of the most promising candidates for quantum spin liquids with a perfect quantum kagome Heisenberg antiferromagnetic system. It can comprise an ideal model system for studying the compression response of the unique structure as well as exotic properties of kagome quantum spin liquid materials, which is of fundamental importance from both scientific and technological viewpoints. In this work, the structural evolution of herbertsmithite was investigated via in situ X-ray diffraction and Raman scattering techniques up to 30 GPa. The trigonal herbertsmithite structure transformed into a monoclinic clinoatacamite-like structure at 12.6 GPa. High pressure seems to act in a reverse way as Zn-doping for herbertsmithite, with the distortion degree of the system changing continuously. The occurrence of the displacive and reversible phase transition between the polymorphs is a consequence of the interplay between the external pressure and cooperative Jahn-Teller (JT) effect, aided by the presence of antisite mutual substitution of magnetic Cu2+ ions and nonmagnetic Zn2+ ions between the kagome layer and interlayer sites.

Genome-wide association study reveals the genetic variation and candidate gene for grain calcium content in bread wheat.

KEY MESSAGE: This study provides important information on the genetic basis of GCaC in wheat, thus contributing to breeding efforts to improve the nutrient quality of wheat. Calcium (Ca) plays important roles in the human body. Wheat grain provides the main diet for billions of people worldwide but is low in Ca content. Here, grain Ca content (GCaC) of 471 wheat accessions was determined in four field environments. A genome-wide association study (GWAS) was performed to reveal the genetic basis of GCaC using the phenotypic data form four environments and a wheat 660 K single nucleotide polymorphism (SNP) array. Twelve quantitative trait locus (QTLs) for GCaC were identified on chromosomes 1A, 1D, 2A, 3B, 6A, 6D, 7A, and 7D, which was significant in at least two environments. Haplotype analysis revealed that the phenotypic difference between the haplotypes of TraesCS6D01G399100 was significant (P ≤ 0.05) across four environments, suggesting it as an important candidate gene for GCaC. This research enhances our understanding of the genetic architecture of GCaC for further improving the nutrient quality of wheat.

Clinical data, survival, and prognosis of 426 cases of oropharyngeal cancer: a retrospective analysis.

OBJECTIVE: To determine factors influencing survival and prognosis of HPV-related and non-related oropharyngeal cancer. METHODS: Subjects were determined from the three hospitals in Anhui province of China between 2015 and 2020. Paraffin-embedded specimens from participants' tissues were analyzed, and the subjects were classified as P16 + and P16 - cases using immunohistochemical staining for P16 protein. RESULTS: A total of 426 patients with oropharyngeal cancer were recruited in this study; 108 cases were found to be P16 + . The subjects were treated with the three regimens: surgery/radiotherapy/chemotherapy (SRCT), radiotherapy/chemotherapy (RCT), and surgery/chemotherapy (SCT). There were no statistically significant differences in the survival rates within the P16 + or P16 - groups between the three treatment regimens (P > 0.05). The 1-, 3-, and 5-year survival rates for P16 + and P16 - groups were statistically different (P < 0.05). Multivariate analysis showed that age, physical health status, smoking, and alcohol abuse were independent risk factors affecting the prognosis of P16 + cases, while pathological grading and TNM staging were independent risk factors affecting the P16 - cases. CONCLUSION: The etiology, pathogenesis, survival status, and prognostic factors of HPV-related oropharyngeal cancer are very different from those of traditional oropharyngeal cancer. Thus, HPV-related oropharyngeal cancer could be classified as a separate type of disease. This distinction could be of great significance for treatment, prevention, and prognostication of oropharyngeal cancer.

BREAST-Q-Based Survey of the Satisfaction and Health Status of Patients with Breast Reconstruction.

AIMS: To explore the patients' satisfaction and health-related quality of life (HRQOL) of patients who received reconstruction after breast cancer surgery using the BREAST-Q questionnaire and further investigate the influencing risk factors. METHODS: This cross-sectional study enrolled patients who underwent first-ever breast reconstruction after unilateral or bilateral mastectomy at the Breast Surgery Department of First Affiliated Hospital of Zhengzhou University or People's Hospital of Zhengzhou between January 2016 and December 2021. Multivariable linear regression analysis was used to analyze the risk factors. RESULTS: A total of 202 participants were included. Age of >45 years (vs.≤35 years, ß = - 3.74, P < 0.001) was an independent risk factor influencing the satisfaction degree score. Age between 36 and 45 years (vs. ≤35 years, ß = - 0.26, P < 0.001), age of >45 years (vs. ≤35 years, ß = - 0.45, P < 0.001), nipple-preserving mastectomy (NSM)/ skin-preserving mastectomy (SSM) + sentinel lymph node dissection + prosthesis implantation + contralateral breast augmentation (vs. NSM/SSM + sentinel lymph node dissection + prosthesis implantation, ß = - 0.16, P=0.012), and the use of small intestinal submucosa (SIS) matrix (ß = 0.13, P = 0.044) were independent risk factors influencing the HRQOL scores. CONCLUSION: Age, the surgical procedure, and the use of matrix were associated with the satisfaction degree and HRQOL after breast reconstruction in patients receiving mastectomy. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Spinocerebellar ataxia type 8 presents as progressive supranuclear palsy.

Spinocerebellar ataxia type 8 is a progressive neurodegenerative disease induced by expansion of CTA/CTG repeats in an untranslated region of the ATXN8/ATXN8OS gene. We report an elderly female patient presenting with rigidity, bradykinesia, ataxia and oculomotor defect at the disease onset age of 65 years old without family history, and hummingbird sign in cranial MRI, initially diagnosed as progressive supranuclear palsy (PSP). But genetic test showed that one allele of ATXN8OS gene had more than 131 CTA/CTG repeats which was a full penetrance mutant. It's possible that this is a case of PSP with an ATXN8OS gene mutation that doesn't contribute to the phenotype. Whether the ATXN8OS gene CTA/CTG repeats cause PSP phenotype needs further investigation with larger samples and pathological findings.

[Characteristics of the left heart structure and function in 86 term neonates with intrauterine growth restriction]. / 86ä¾‹å®«å† ç”Ÿé•¿å—é™è¶³æœˆæ–°ç”Ÿå„¿çš„å·¦å¿ƒç»“æž„åŠåŠŸèƒ½åˆ†æž.

OBJECTIVES: To study the left heart structure and functional characteristics of term neonates with intrauterine growth restriction (IUGR). METHODS: This study included 86 term neonates with IUGR admitted to the Neonatal Ward of Beijing Friendship Hospital, Capital Medical University from January 2019 to January 2022 as the IUGR group, as well as randomly selected 86 term neonates without IUGR born during the same period as the non-IUGR group. The clinical data and echocardiographic data were compared between the two groups. RESULTS: The analysis of left heart structure and function showed that compared with the non-IUGR group, the IUGR group had significantly lower left ventricular mass, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left atrial diameter, end-diastolic interventricular septal thickness, left ventricular posterior wall thickness, left ventricular end-diastolic volume, left ventricular end-systolic volume, and stroke volume (P<0.05) and significantly higher ratio of end-diastolic interventricular septal thickness to left ventricular posterior wall thickness, proportion of neonates with a mitral peak E/A ratio of ≥1, and cardiac index (P<0.05). The Spearman correlation analysis suggested that stroke volume was positively correlated with birth weight and body surface area (rs=0.241 and 0.241 respectively; P<0.05) and that the ratio of end-diastolic interventricular septal thickness to left ventricular posterior wall thickness was negatively correlated with birth weight and body surface area (rs=-0.229 and -0.225 respectively; P<0.05). CONCLUSIONS: The left ventricular systolic function of neonates with IUGR is not significantly different from that of neonates without IUGR. However, the ventricular septum is thicker in neonates with IUGR. This change is negatively correlated with birth weight and body surface area. The left ventricular diastolic function may be impaired in neonates with IUGR.

Identification of the circ_PRKDC/miR-20a-3p/RASA1 axis in regulating HaCaT keratinocyte migration.

Migration of keratinocytes plays a crucial role in the re-epithelialization phase during wound healing. Circular RNA (circRNA) protein kinase, DNA-activated, catalytic subunit (circ_PRKDC, hsa_circ_0084443) has been identified as a regulator of keratinocyte migration. However, the molecular basis governing it remains unclear. The levels of circ_PRKDC, microRNA (miR)-20a-3p, and RAS p21 protein activator 1 (RASA1) were assessed by quantitative real-time PCR (qRT-PCR) or western blot. Subcellular localization, Actinomycin D, and Ribonuclease (RNase) R assays were performed to characterise circ_PRKDC. Cell migration was gauged by transwell and wound-healing assays. A direct relationship between miR-20a-3p and circ_PRKDC or RASA1 was verified by dual-luciferase reporter and RNA pull-down assays. Circ_PRKDC expression was reduced in wound skin during wound healing. Circ_PRKDC modulated migration of HaCaT keratinocytes. Mechanistically, circ_PRKDC directly targeted miR-20a-3p. The regulation of circ_PRKDC on HaCaT keratinocyte migration was mediated by miR-20a-3p. RASA1 was identified as a direct and functional target of miR-20a-3p, and miR-20a-3p-mediated inhibition of RASA1 impacted HaCaT keratinocyte migration. Circ_PRKDC acted as a post-transcriptional modulator of RASA1 expression through miR-20a-3p. Moreover, circ_PRKDC modulated migration of HaCaT keratinocytes by RASA1. Our findings demonstrated a novel molecular basis, the miR-20a-3p/RASA1 axis, for the regulation of circ_PRKDC on HaCaT keratinocyte migration.

Genome-Wide Association Study on Root System Architecture and Identification of Candidate Genes in Wheat (Triticum aestivum L.).

The root tissues play important roles in water and nutrient acquisition, environmental adaptation, and plant development. In this study, a diversity panel of 388 wheat accessions was collected to investigate nine root system architecture (RSA) traits at the three-leaf stage under two growing environments: outdoor pot culture (OPC) and indoor pot culture (IPC). Phenotypic analysis revealed that root development was faster under OPC than that under IPC and a significant correlation was observed between the nine RSA traits. The 660K single-nucleotide polymorphism (SNP) chip was used for a genome-wide association study (GWAS). Significant SNPs with a threshold of -log10 (p-value) ≥ 4 were considered. Thus, 36 quantitative trait loci (QTLs), including 13 QTL clusters that were associated with more than one trait, were detected, and 31 QTLs were first identified. The QTL clusters on chromosomes 3D and 5B were associated with four and five RSA traits, respectively. Two candidate genes, TraesCS2A01G516200 and TraesCS7B01G036900, were found to be associated with more than one RSA trait using haplotype analysis, and preferentially expressed in the root tissues. These favourable alleles for RSA traits identified in this study may be useful to optimise the root system in wheat.

Therapeutic mechanisms of mesenchymal stem cells in acute respiratory distress syndrome reveal potentials for Covid-19 treatment.

The mortality rate of critically ill patients with acute respiratory distress syndrome (ARDS) is 30.9% to 46.1%. The emergence of the coronavirus disease 2019 (Covid-19) has become a global issue with raising dire concerns. Patients with severe Covid-19 may progress toward ARDS. Mesenchymal stem cells (MSCs) can be derived from bone marrow, umbilical cord, adipose tissue and so on. The easy accessibility and low immunogenicity enable MSCs for allogeneic administration, and thus they were widely used in animal and clinical studies. Accumulating evidence suggests that mesenchymal stem cell infusion can ameliorate ARDS. However, the underlying mechanisms of MSCs need to be discussed. Recent studies showed MSCs can modulate immune/inflammatory cells, attenuate endoplasmic reticulum stress, and inhibit pulmonary fibrosis. The paracrine cytokines and exosomes may account for these beneficial effects. In this review, we summarize the therapeutic mechanisms of MSCs in ARDS, analyzed the most recent animal experiments and Covid-19 clinical trial results, discussed the adverse effects and prospects in the recent studies, and highlight the potential roles of MSC therapy for Covid-19 patients with ARDS.

A novel clinical model for predicting malignancy of solitary pulmonary nodules: a multicenter study in chinese population.

BACKGROUND: This study aimed to establish and validate a novel clinical model to differentiate between benign and malignant solitary pulmonary nodules (SPNs). METHODS: Records from 295 patients with SPNs in Sun Yat-sen University Cancer Center were retrospectively reviewed. The novel prediction model was established using LASSO logistic regression analysis by integrating clinical features, radiologic characteristics and laboratory test data, the calibration of model was analyzed using the Hosmer-Lemeshow test (HL test). Subsequently, the model was compared with PKUPH, Shanghai and Mayo models using receiver-operating characteristics curve (ROC), decision curve analysis (DCA), net reclassification improvement index (NRI), and integrated discrimination improvement index (IDI) with the same data. Other 101 SPNs patients in Henan Tumor Hospital were used for external validation cohort. RESULTS: A total of 11 variables were screened out and then aggregated to generate new prediction model. The model showed good calibration with the HL test (P = 0.964). The AUC for our model was 0.768, which was higher than other three reported models. DCA also showed our model was superior to the other three reported models. In our model, sensitivity = 78.84%, specificity = 61.32%. Compared with the PKUPH, Shanghai and Mayo models, the NRI of our model increased by 0.177, 0.127, and 0.396 respectively, and the IDI changed - 0.019, -0.076, and 0.112, respectively. Furthermore, the model was significant positive correlation with PKUPH, Shanghai and Mayo models. CONCLUSIONS: The novel model in our study had a high clinical value in diagnose of MSPNs.

Flavonoid 3'-hydroxylase of Camellia nitidissima Chi. promotes the synthesis of polyphenols better than flavonoids.

Camellia nitidissima Chi. is an ornamental plant of the genus Camellia L. Its flowers contain a lot of flavonoids and polyphenols. Flavonoid 3'-hydroxylase (F3'H) plays an important role in the synthesis of flavonoids, polyphenols and anthocyanins. We used PCR amplification, quantitative PCR, High-performance liquid chromatography, subcellular localization, and agrobacterium-mediated leaf disk method to study the the function of CnF3'H. The full length of CnF3'H was 1859 bp (GenBank code: HQ290518.1), with an open reading frame of 1577 bp, and encoded 518 amino acid. A phylogenetic tree analysis showed that CnF3'H was closely related to Camellia sinensis L. and C. sinensis cultivar Zhonghuang. CnF3'H was expressed in flowers, leaves, fruits, sepals, petals and stamens of C. nitidissima, and during the flowering process the expression level in flower decreased initially and then increased. CnF3'H expression was significantly positive correlated with polyphenol contents in C. nitidissima. A CnF3'H-EGFP expression vector was constructed to do the subcellular localization, we found that CnF3'H was obviously localized in the nuclear envelope and cytomembrane. In transgenic tobacco flowers, the total polyphenol content and various polyphenol constituents were significantly increased with high CnF3'H expression level, while total flavonoid contents and some flavonol constituents were increased slightly. These findings suggest that CnF3'H promotes the synthesis of polyphenols better than flavonoids.

Response of Wheat DREB Transcription Factor to Osmotic Stress Based on DNA Methylation.

Dehydration-responsive element-binding protein (DREB) plays an important role in response to osmotic stress. In this study, DREB2, DREB6 and Wdreb2 are isolated from wheat AK58, yet they belong to different types of DREB transcription factors. Under osmotic stress, the transcript expression of DREB2, DREB6 and Wdreb2 has tissue specificity and is generally higher in leaves, but their expression trends are different along with the increase of osmotic stress. Furthermore, some elements related to stresses are found in their promoters, promoters of DREB2 and Wdreb2 are slightly methylated, but DREB6's promoter is moderately methylated. Compared with the control, the level of promoter methylation in Wdreb2 is significantly lower under osmotic stress and is also lower at CG site in DREB2, yet is significantly higher at CHG and CHH sites in DREB2, which is also found at a CHG site in DREB6. The status of promoter methylation in DREB2, DREB6 and Wdreb2 also undergoes significant changes under osmotic stress; further analysis showed that promoter methylation of Wdreb2 is negatively correlated with their expression. Therefore, the results of this research suggest the different functions of DREB2, DREB6 and Wdreb2 in response to osmotic stress and demonstrate the effects of promoter methylation on the expression regulation of Wdreb2.

Emperipolesis mediated by CD8+ T cells correlates with biliary epithelia cell injury in primary biliary cholangitis.

Primary biliary cholangitis (PBC) is an autoimmune disease characterized by chronic destruction of the bile ducts. A major unanswered question regarding the pathogenesis of PBC is the precise mechanisms of small bile duct injury. Emperipolesis is one of cell-in-cell structures that is a potential histological hallmark associated with chronic hepatitis B. This study aimed to clarify the pathogenesis and characteristics of emperipolesis in PBC liver injury. Sixty-six PBC patients, diagnosed by liver biopsy combined with laboratory test, were divided into early-stage PBC (stages I and II, n = 39) and late-stage PBC (stages III and IV, n = 27). Emperipolesis was measured in liver sections stained with haematoxylin-eosin. The expressions of CK19, CD3, CD4, CD8, CD20, Ki67 and apoptosis of BECs were evaluated by immunohistochemistry or immunofluorescence double labelling. Emperipolesis was observed in 62.1% of patients with PBC, and BECs were predominantly host cells. The number of infiltrating CD3+ and CD8+ T cells correlated with the advancement of emperipolesis (R2  = 0.318, P < .001; R2  = 0.060, P < .05). The cell numbers of TUNEL-positive BECs and double staining for CK19 and Ki67 showed a significant positive correlation with emperipolesis degree (R2  = 0.236, P < .001; R2  = 0.267, P < .001). We conclude that emperipolesis mediated by CD8+ T cells appears to be relevant to apoptosis of BEC and thus may aggravate the further injury of interlobular bile ducts.

SARS-CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19.

Background & Aims: Liver enzyme abnormalities are common in patients with coronavirus disease 2019 (COVID-19). Whether or not severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to liver damage per se remains unknown. Herein, we reported the clinical characteristics and liver pathological manifestations of COVID-19 patients with liver enzyme abnormalities. Methods: We analyzed 156 patients diagnosed with COVID-19 from 2 designated centers in China and compared clinical features between patients with or without elevated aminotransferases. Postmortem liver biopsies were obtained from 2 cases who had elevated aminotransferases. We investigated the patterns of liver impairment by electron microscopy, immunohistochemistry, TUNEL assay and pathological studies. Results: Sixty-four out of 156 (41.0%) patients with COVID-19 had elevated aminotransferases. The median levels of alanine aminotransferase were 50 U/L vs. 19 U/L, respectively, aspartate aminotransferase were 45.5 U/L vs. 24 U/L, respectively in abnormal and normal aminotransferase groups. Liver enzyme abnormalities were associated with disease severity, as well as a series of laboratory tests including higher alveolar-arterial oxygen partial pressure difference, higher gamma-glutamyltransferase, lower albumin, decreased CD4+ T cells and B lymphocytes. Ultrastructural examination identified typical coronavirus particles, characterized by spike structures, in the cytoplasm of hepatocytes in 2 COVID-19 cases. SARS-CoV-2-infected hepatocytes displayed conspicuous mitochondrial swelling, endoplasmic reticulum dilatation and glycogen granule decrease. Histologically, massive hepatic apoptosis and some binuclear hepatocytes were observed. Taken together, both ultrastructural and histological evidence indicated a typical lesion of viral infection. Immunohistochemical results showed scarce CD4+ and CD8+ lymphocytes. No obvious eosinophil infiltration, cholestasis, fibrin deposition, granuloma, massive central necrosis, or interface hepatitis were observed. Conclusions: SARS-CoV-2 infection in the liver directly contributes to hepatic impairment in patients with COVID-19. Hence, a surveillance of viral clearance in liver and long-term outcome of COVID-19 is required. Lay summary: Liver enzyme abnormalities are common in patients with coronavirus disease 2019 (COVID-19). We reported the clinical characteristics and liver pathological manifestations of COVID-19 patients with elevated liver enzymes. Our findings suggested that SARS-CoV-2 infection of the liver is a crucial factor contributing to hepatic impairment in patients with COVID-19.