Primary biliary cholangitis (PBC) is an immune-mediated chronic cholestasis, in which T cell homeostasis plays an important role. Lysosomal-associated membrane protein 2 isoform A (LAMP-2A) has been implicated in the regulation of CD4
T cell responses.
We comprehensively evaluated the immunobiology of CD4
T cells in patients with PBC (PBC, n=42), chronic hepatitis B (CHB, n=20), and healthy control subjects (HC, n=20) by flow cytometry including activation status and LAMP-2A expression. Additionally, we investigated the activation responses of PBC-naïve CD4
T cells by stimulation
and tested the changes caused by deleting the gene encoding LAMP-2A.
Firstly, we found an increased activation status of circulating CD4
T cells from PBC patients compared to the HC subjects, and PBC-naïve CD4
T cells showed enhanced responses after stimulation
. Secondly, PBC-naïve CD4
T cells expressed a significantly higher level of LAMP-2A compared to the HC and CHB groups [PBC
HC, 1,954.74 (1,254.28-3,057.14)
1,542.12 (961.18-2,277.98), P=0.03;
CHB, 1,153.59 (726.87-1,275.48), P=0.02], and the overreactions of PBC-naïve CD4
T cells could be reversed by interfering with LAMP-2A expression
. Thirdly, the LAMP-2A expression level of PBC-naïve CD4
T cells was related to disease severity and drug response.
An abnormally increased LAMP-2A expression of PBC-naïve CD4
T cells might be related to excessive activation responses. LAMP-2A could be a novel therapeutic target for the treatment of PBC by reversing excessive responses and consequently reducing biliary injury.
An abnormally increased LAMP-2A expression of PBC-naïve CD4+T cells might be related to excessive activation responses. LAMP-2A could be a novel therapeutic target for the treatment of PBC by reversing excessive responses and consequently reducing biliary injury.
To investigate the temporal pattern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presence on ocular surfaces using conjunctival swabs in coronavirus disease 2019 (COVID-19) patients.
This study included 59 patients (32 newly admitted and 27 hospitalized for ≥2 weeks) with a COVID-19-confirmed diagnosis at the Shanghai Public Health Clinical Center from March 3, 2020, to March 21, 2020. Conjunctival swab samples were collected from both eyes of all the 59 patients and were tested by reverse transcription polymerase chain reaction (RT-PCR) assay. The range of sampling time lies widely between 1 and 50 days since symptom onset.
Among the 32 newly admitted patients, positive RT-PCR results for SARS-CoV-2 in conjunctival swab samples were reported in 2 patients (one eye for each) without ocular discomfort, but 1 positive case had conjunctival congestion. The positive results were detected on Day 5 for 1 patient and Day 7 for the other, but repeated tests after 1 week were negative for both patients. All 27 patients who had been hospitalized for ≥2 weeks had negative test results. The mean time from symptom onset to sampling of 2 positive cases was significantly less than that of 57 negative cases (P<0.001).
SARS-CoV-2 on the ocular surface can be detected in the early phase of COVID-19. https://www.selleckchem.com/products/evobrutinib.html The risk of ocular transmission remains and might be higher in the early phase.
SARS-CoV-2 on the ocular surface can be detected in the early phase of COVID-19. The risk of ocular transmission remains and might be higher in the early phase.
The hyperplastic patterns of parathyroid glands (PTGs) in secondary hyperparathyroidism (SHPT) are critical for surgical indication and deciding on the approach. Earlier histopathological investigations have suggested the occurrence of an initial increase in the parathyroid cells, with a normal lobular structure (diffuse hyperplasia, DH). After this, the PTGs become hyperplastic with some nodules (nodular hyperplasia, NH). The current study aimed to explore the relationship between the intraoperative measurements of weight, volume, and maximal diameter of dissected PTGs and the histopathological diagnosis of SHPT patients with end-stage renal disease.
A total of 182 SHPT patients who received parathyroidectomy (PTX) were retrospectively enrolled. Altogether 21 patients were selected as having at least one diffuse polyclonal hyperplasia PTG. Intraoperative measurements of weight, volume, and maximal diameter of dissected PTGs were compared between tissues with DH and NH.
Intraoperative dissected PTGs were verified histologically. The differences in the intraoperative measurements of weight, volume, maximal diameter, and the combination of the three measurements between the DH and the NH PTGs groups were significant (P=0.000), and the values of area under the ROC curve (AUCs) were 0.824 (95% CI 0.731-0.918), 0.812 (95% CI 0.716-0.908), 0.746 (95% CI 0.633-0.860), and 0.851 (95% CI 0.768-0.935), respectively, with cut-off values of the three parameters being 0.19 g, 206.3 mm
, and 10.5 mm, respectively.
The measurement of weight, volume, and maximal diameter of dissected PTGs is a possible alternative to assess the hyperplasia patterns of the dissected PTGs. It is a promising reference for the ultrasound prediction of pathological patterns of PTGs.
The measurement of weight, volume, and maximal diameter of dissected PTGs is a possible alternative to assess the hyperplasia patterns of the dissected PTGs. It is a promising reference for the ultrasound prediction of pathological patterns of PTGs.
The initial response to islet transplantation and the subsequent acute inflammation is responsible for significant attrition of islets following both autologous and allogenic procedures. This multicentre study compares this inflammatory response using cytokine profiles and complement activation.
Inflammatory cytokine and complement pathway activity were examined in two cohorts of patients undergoing total pancreatectomy followed either by autologous (n=11) or allogenic (n=6) islet transplantation. Two patients who underwent total pancreatectomy alone (n=2) served as controls.
The peak of cytokine production occurred immediately following induction of anaesthesia and during surgery. There was found to be a greater elevation of the following cytokines TNF-alpha (P<0.01), MCP-1 (P=0.0013), MIP-1α (P=0.001), MIP-1β (P=0.00020), IP-10 (P=0.001), IL-8 (P=0.004), IL-1α (P=0.001), IL-1ra (0.0018), IL-10 (P=0.001), GM-CSF (P=0.001), G-CSF (P=0.0198), and Eotaxin (P=0.01) in the allogenic group compared to autografts and controls.