Primary lung cancer is one of the most common malignant tumors in China. Approximately 60% of lung cancer patients have distant metastasis at the initial diagnosis, so it is necessary to find new ...tumor markers for early diagnosis and individualized treatment. Tumor markers contribute to the early diagnosis of lung cancer and play important roles in early detection and treatment, as well as in precision medicine, efficacy monitoring, and prognosis prediction. The pathological diagnosis of lung cancer in small biopsy specimens determines whether there are tumor cells in the biopsy and tumor type. Because biopsy is traumatic and the compliance of patients with multiple biopsies is poor, liquid biopsy has become a hot research direction. Liquid biopsies are advantageous because they are nontraumatic, easy to obtain, reflect the overall state of the tumor, and allow for real-time monitoring. At present, liquid biopsies mainly include circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. This review introduces the research progress and clinical application prospect of liquid biopsy technology for lung cancer.
Exhaustion of cytotoxic effector natural killer (NK) and CD8
T cells have important functions in the establishment of persistent viral infections, but how exhaustion is induced during chronic ...hepatitis C virus (HCV) infection remains poorly defined. Here we show, using the humanized C/O
mice permissive for persistent HCV infection, that NK and CD8
T cells become sequentially exhausted shortly after their transient hepatic infiltration and activation in acute HCV infection. HCV infection upregulates Qa-1 expression in hepatocytes, which ligates NKG2A to induce NK cell exhaustion. Antibodies targeting NKG2A or Qa-1 prevents NK exhaustion and promotes NK-dependent HCV clearance. Moreover, reactivated NK cells provide sufficient IFN-γ that helps rejuvenate polyclonal HCV CD8
T cell response and clearance of HCV. Our data thus show that NKG2A serves as a critical checkpoint for HCV-induced NK exhaustion, and that NKG2A blockade sequentially boosts interdependent NK and CD8
T cell functions to prevent persistent HCV infection.
Gut microbiota and its metabolites, short-chain fatty acids (SCFAs), play important roles in diarrheal diseases. Gegen Qinlian decoction (GQD), a Chinese herb formula, has been widely used to treat ...infectious diarrhea for centuries. However, little is known about the mechanism underlying its efficacy and whether it is mediated by gut microbiota and SCFAs. In this study, the composition of gut microbiota from bacterial diarrheal piglets was assessed using 16S rRNA analysis. The concentrations of fecal SCFAs were determined using a gas chromatography-mass spectrometer (GC-MS). The expression of mucosal pro-inflammatory cytokines in the colon was ascertained. Results showed that GQD reverses the reduction in the richness of gut microbiota, changes its structure, and significantly increases the relative abundances of SCFA-producing bacteria, including
, and
. Moreover, GQD increased the levels of fecal SCFAs, including acetic acid, propionic acid, and butyric acid. GQD thus attenuates diarrhea in piglets. Further, our results suggest that the SCFAs could help to attenuate mucosal pro-inflammatory responses following GQD treatment by inhibiting histone deacetylase and the NF-κB pathway. We thus suggseted that gut microbiota play an important role during diarrhea treatment, an effect may be promoted by the GQD-induced structural changes of the gut microbial community and production of SCFAs. The increased levels of SCFAs probably provide further help to attenuate mucosal inflammation and diarrhea. In conclusion, our study might provide evidence that GQD treats diarrhea maybe involved in modulating gut microbiota and increasing SCFA levels.
Rickettsia raoultii is frequently detected in multiple tick species, whereas human infection remains scarcely studied.
A surveillance study was performed at 3 sentinel hospitals in China, to recruit ...participants with suspected tick exposure. Rickettsia raoultii infection was identified through polymerase chain reaction, followed by sequencing, and confirmed serologically. Isolation by cell culture was performed and the isolates were genome sequenced.
Twenty-six subjects were determined to have R. raoultii infection, including 7 with asymptomatic infection, 15 with mild to moderate illness, and 4 with severe illness. Common nonspecific manifestations in the 19 patients with mild to moderate or severe illness included fever (100%), malaise (95%), myalgia (58%), lymphadenopathy (53%), and nausea (42%). Only 5% of them had rash, and 16% had eschar. Scalp eschar and neck lymphadenopathy after a tick bite syndrome was only seen in 2 patients. Of the 4 patients with severe complications, 3 developed pulmonary edema, and 1 developed clouding of consciousness and lethargy. Frequent abnormalities of laboratory testing included leukopenia, thrombocytopenia, lymphopenia, neutropenia, hypoproteinemia, and elevated levels of total bilirubin, hepatic aminotransferases, lactate dehydrogenase, and creatine kinase. All the 19 patients recovered without sequelae after receiving doxycycline treatment. Two R. raoultii strains were isolated, and a significantly less degraded genome was observed than other more virulent Rickettsia strains, indicating a low pathogenicity of the current strain.
Human infection with R. raoultii has a wide clinical spectrum that ranged from subclinical infection to severe complications. Physicians need to be aware of the high potential and clinical complexity of R. raoultii infection, to ensure appropriate testing and treatment in endemic regions.
A NaI-promoted sequential double carbon
-
sulfur bond formation was developed to afford sulfur-bridged imidazopyridines, using Deoxofluor as the sulfur source and requiring only 15 min at room ...temperature. Using this process, imidazo1,5-
a
pyridines could also be transformed to 1,2,4-thiadiazoles in the presence of ammonium salt with the formation of both carbon
-
sulfur and nitrogen
-
sulfur bonds. This mechanistically unique method is distinguished by its wide substrate scope, lack of requirement for transition metals and mild conditions.
Iodide-promoted transformations of imidazopyridines into sulfur-bridged imidazopyridines or 1,2,4-thiadiazoles have been developed using Deoxofluor as a novel sulfur source at room temperature.
To explore the possible clues for the extra dimension from the Event Horizon Telescope (EHT) observations, we study the shadow of the rotating 5D black string in General Relativity (GR). Instead of ...investigating the shadow in the effective 4D theory, we concern the motion of photons along the extra dimension
z
with a conserved momentum
P
z
, which appears as an effective mass in the geodesic equations of photons. The existence of
P
z
enlarges the photon regions and the shadow of the rotating 5D black string while it has slight impact on the distortion. The EHT observations of M87* and SgrA* can rule out the black string model with an infinite length along the extra dimension, and support the hypothesis that the extra dimension is compact to avoid the Gregory-Laflamme (GL) instability, where the length of the black string/the compact extra dimension can be constrained as
2.03125
mm
≲
ℓ
≲
2.6
mm
and
2.28070
mm
≲
ℓ
≲
2.6
mm
respectively.
Astragali Radix
(
A. Radix
) is the dried root of
Astragalus membranaceus var. mongholicus
(Bge) Hsiao or
Astragalus membranaceus
(Fisch.) Bge., belonging to the family Leguminosae, which is mainly ...distributed in China.
A. Radix
has been consumed as a tonic in China for more than 2000 years because of its medicinal effects of invigorating the spleen and replenishing qi. Currently, more than 400 natural compounds have been isolated and identified from
A. Radix
, mainly including saponins, flavonoids, phenylpropanoids, alkaloids, and others. Modern pharmacological studies have shown that
A. Radix
has anti-tumor, anti-inflammatory, immunomodulatory, anti-atherosclerotic, cardioprotective, anti-hypertensive, and anti-aging effects. It has been clinically used in the treatment of tumors, cardiovascular diseases, and cerebrovascular complications associated with diabetes with few side effects and high safety. This paper reviewed the progress of research on its chemical constituents, pharmacological effects, clinical applications, developing applications, and toxicology, which provides a basis for the better development and utilization of
A. Radix
.
Background
Atrial esophageal fistula (AEF) is a lethal complication that can occur post atrial fibrillation (AF) ablation. Esophageal injury (EI) is likely to be the initial lesion leading to AEF. ...Endoscopic examination is the gold standard for a diagnosis of EI but extensive endoscopic screening is invasive and costly. This study was conducted to determine whether fecal calprotectin (Fcal), a marker of inflammation throughout the intestinal tract, may be associated with the existence of esophageal injury.
Methods
This diagnostic study was conducted in a cohort of 166 patients with symptomatic AF undergoing radiofrequency catheter ablation from May 2020 to June 2021. Fcal tests were performed 1–7 days after ablation. All patients underwent endoscopic ultrasonography 1 or 2 days after ablation.
Results
The levels of Fcal were significantly different between the EI and non‐EI groups (404.9 µg/g (IQR 129.6–723.6) vs. 40.4 µg/g (IQR 15.0–246.2), p < .001). Analysis of ROC curves revealed that a Fcal level of 125 µg/g might be the optimal cut‐off value for a diagnosis of EI, giving a 78.8% sensitivity and a 65.4% specificity. The negative predictive value of Fcal was 100% for ulcerated EI.
Conclusions
The level of Fcal is associated with EI post AF catheter ablation. 125 µg/g might be the optimal cut‐off value for a diagnosis of EI. Negative Fcal could predict the absence of ulcerated EI, which could be considered a precursor to AEF.