Liver fibrosis is the common pathological process in the progression of various chronic liver diseases to liver cirrhosis， and it greatly affects the prognosis of patients with chronic liver diseases. As a novel adipokine， Chemerin participates in the metabolism of glucose and lipids and inflammation， and various studies have shown that the expression level of Chemerin is correlated with the degree of liver fibrosis， suggesting that Chemerin may be involved in the process of liver fibrosis by regulating metabolism and inflammation. Chemerin has shown certain potential in the auxiliary diagnosis of liver fibrosis and the intervention against the progression of liver fibrosis. This article reviews the potential role and mechanism of action of Chemerin in the process of liver fibrosis， in order to provide new ideas for the diagnosis and treatment of liver fibrosis.

Acute pancreatitis (AP) is a life-threatening gastrointestinal disorder for which no effective pharmacological treatments are currently available. One of the pharmacological targets that merits further research is the neurokinin 1 receptor (NK1R), which is found on pancreatic acinar cells and responds to the neuropeptide substance P (SP) that participates in AP. Although a few studies have stated the involvement of SP/NK1R in neurogenic inflammation in AP development, the regulatory mechanism remains unclear. In this study, we found that following activation of NK1R by SP, β-arrestin1, a scaffold protein of NK1R, down-regulated transcription of Adss, Adsl, and Ampd in the purine nucleotide cycle, thereby inhibiting mitochondrial function through fumarate depletion. Interestingly, we identified magnolol as a new and natural NK1R inhibitor with a non-nitrogenous biphenyl core structure. It exhibited a beneficial effect on AP by restoring purine nucleotide cycle metabolic enzymes and fumarate levels. Our study not only provides new therapeutic strategies, leading compounds, and drug translation possibilities for AP, but also provides important clues for the study of downstream mechanisms driven by SP in other diseases.

Objective:To establish a rapid and accurate method for the detection of Klebsiella pneumoniae carbapenemase (KPC) carbapenemase gene based on recombinase aided amplification (RAA)-CRISPR-Cas13a (CRISPR-Cas13a) technology. Methods:Twenty-five clinical isolates of carbapenem-resistant Klebsiella pneumoniae (CRKP) and five carbapenem-sensitive Klebsiella pneumoniae (CSKP) strains preserved in 2020-2021 in Beijing Chuiyangliu Hospital were randomly collected, and the total DNA samples of the strains was extracted. RAA primers specific for KPC DNA and CRISPR RNA (crRNA) were designed to establish a rapid and accurate method for the detection of KPC carbapenemase gene based on RAA-CRISPR-Cas13a technology. The method was evaluated by plasmids and clinical sample strains, and the detection was also performed by Quantitative real-time PCR (qPCR) method to compare the detection rate and consistency of the two methods. Results:The RAA-CRISPR-Cas13a method can detect KPC plasmids and samples with a sensitivity of 1 copy/μl, which is higher than that of qPCR (10 1 copies/μl). Among the 30 clinical strains (including 25 CRKP strains and 5 CSKP strains), 23 strains were detected to carry KPC gene by both RAA-CRISPR-Cas13a method and qPCR method, and 7 strains were not detected with KPC gene. The detection rate of KPC gene in the 25 CRKP strains was 92% (23/25). The positive coincidence rate of the two methods was 100% (23/23). Conclusions:This study combined RAA amplification technology with CRISPR-Cas13a technology to establish a rapid and accurate method for detecting KPC carbapenemase gene. The method is useful for accurate screening of KPC carbapenemase-producing strains. It has a wide application prospect in drug resistance monitoring and infection control.

Objective:To compare the antiplatelet effects of vicagrel and clopidogrel in patients with different cytochrome P450 (CYP) 2C19 genotypes.Methods:This is a post-hoc analysis of a phase Ⅱ clinical trial of vicagrel, which included patients with coronary heart disease who underwent percutaneous coronary intervention from August 2018 to June 2019 in 18 centers. Patients were categorized based on the presence of CYP 2C19 *2 or *3 loss-of-function (LOF) alleles into LOF carrier group ( n=111) and non-LOF carrier group ( n=90). Each group included patients received vicagrel 5 mg, 6 mg, 7.5 mg, or clopidogrel 75 mg for 28 days per study protocol. P2Y 12 reaction units (PRU) were measured using VerifyNow at baseline, 6 to 8 hours after loading dose, 7 to 10 days after randomization, and 28 days after randomization and the percentage inhibition of platelet aggregation (%IPA) was calculated. The primary endpoint was %IPA on day 28. Within the patients from the General Hospital of Northern Theater Command, 8 to 12 patients in each study arms were enrolled in a prespecified pharmacokinetic sub-study, measuring the time to reach maximum plasma concentration (T max), peak plasma concentration (C max), and area under the plasma concentration-time curve (AUC). Results:Among 201 patients, the age was (58.8±8.5) years, and 139 (69.2%) were male. In non-LOF carriers, there was no significant differences in PRU values and %IPA between the vicagrel 5 mg, 6 mg, 7 mg, and clopidogrel groups at all time points (all P>0.05). In LOF carriers, %IPA was significantly higher in the vicagrel-treated groups than in the clopidogrel group at 6-8 hours after loading dose (22.9 (14.2, 31.5)% vs. 19.8 (11.0, 28.6)% vs. 29.5 (20.9, 38.0)% vs. 12.9 (3.9, 21.9)%, P=0.038) and 7-10 days after randomization (22.4 (14.2, 30.5)% vs. 34.4 (26.1, 42.6)% vs. 39.8 (31.8, 47.9)% vs. 24.7 (16.3, 33.2)%, P=0.001), with a trend towards higher %IPA in the vicagrel-treated groups at day 28 (30.4 (21.3, 39.6)% vs. 36.5 (27.2, 45.7)% vs. 40.8 (31.8, 49.8)% vs. 30.7(21.2, 40.2)%, P=0.056). Pharmacokinetic results of 35 patients showed that the C max and AUC of the active metabolite M15-2 of vicagrel was similar to that of clopidogrel in non-LOF carriers, but AUC between vicagrel 5 mg, 6 mg, 7 mg and clopidogrel were significantly different in LOF carriers ((5.6±0.6) h·μg -1·L -1 vs. (6.8±2.7) h·μg -1·L -1 vs. (9.2±3.3) h·μg -1·L -1 vs. (4.2±1.9) h·μg -1·ml -1, P=0.020). Conclusion:Vicagrel and clopidogrel have similar antiplatelet effects in non-LOF carriers, but vicagrel exhibits superior antiplatelet effects in LOF carriers.

Objective:To investigate the predictive value of cardiopulmonary exercise test (CPET) indexes for major adverse cardiovascular events (MACE) in patients with coronary heart disease (CHD).Methods:This study was a retrospective cohort study. CHD patients were consecutively enrolled who procedure CPET before discharge from the Department of Cardiology, General Hospital of Northern Theater Command from November 2015 to September 2021 were enrolled. Demographic information, past medical history, CPET indexes and other baseline data were collected and the patients were followed up. Patients were divided into a MACE group and a control group according to the presence or absence of MACE. A multivariate Cox proportional hazard regression model was used to analyze the CPET indexes with predictive value for MACE in CHD patients.Results:A total of 3 800 patients were eligible for the criterion, age (57.2±8.8) years, 2 920 (76.84%) males. During a follow-up of 1 237 (695, 1 596) days, 390 (10.26%) patients were in MACE group, and 3 410 (89.74%) patients were in control group. In adjusted multivariable analysis, higher metabolic equivalent of tasks (MET) at anaerobic threshold (AT) is an independent protective factor for MACE in patients with CHD ( HR=0.75, 95% CI 0.62-0.90, P=0.002), higher VE/VCO 2 is an independent risk factor for MACE in CHD patients ( HR=1.05, 95% CI 1.02-1.07, P=0.001). Conclusion:In CPET, high MET at AT is an independent protective factor for MACE in patients with CHD, and high VE/VCO 2 is an independent risk factor for MACE in CHD patients.

Objective:To investigate the changes in cardiopulmonary exercise testing (CPET) characteristics before and after the outbreak of COVID-19 in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI).Methods:This is a cross-sectional study that included ACS patients who underwent PCI at the General Hospital of the Northern Theater Command from July 2018 to February 2023. Based on the timeline of the COVID-19 pandemic, patients were divided into two groups: the pre-pandemic group and the during-pandemic group, with January 2020 as the dividing line. Clinical data were collected from both groups, and a comparative analysis was performed on their postoperative CPET outcomes, including peak oxygen uptake (peak VO 2), peak metabolic equivalents (peak MET), and other indicators. Weber′s classification was used to assess cardiac function. In addition, the 7-tiem generalized anxiety disorder scale (GAD-7) and the patient health questionnaire-9 (PHQ-9) were used to assess the patients′ psychological anxiety and depression states, respectively. Multivariate logistic regression was used to analyze the influencing factors of CPET after PCI. Results:A total of 4 310 post-PCI ACS patients were included, with an average age of (58.7±9.1) years, and 3 464 (80.37%) were male. There were 1 698 patients in the pre-pandemic group and 2 612 patients in the during-pandemic group. The main indicator of the CPET, peak VO 2 (15.04±3.93) ml·min -1·kg -1 in the during-pandemic group, was lower than that in the pre-pandemic group (15.52±3.68) ml·min -1·kg -1, and the difference was statistically significant ( P<0.001). Multivariate logistic regression analysis showed that advanced age, female gender, high body mass index, elevated high-sensitivity C-reactive protein, reduced high-density lipoprotein cholesterol, smoking history, history of myocardial infarction, more severe ACS classification, and mild to moderate degree of depression were related to poor cardiopulmonary outcomes ( P<0.05). Conclusion:The COVID-19 pandemic had a negative impact on the cardiopulmonary outcomes of ACS patients after PCI. Reduced physical activity, and increased psychological stress should be given consideration and attention regarding their impact on patients′ cardiopulmonary function.

Long term retention of hemodialysis catheters in blood vessels can lead to the formation of fibrin sheath, which is one of the main reasons causing catheter dysfunction. This study aims to explore a new in situ tube replacement technique that breaks through the binding of fibrin sheath. The tunnel-cuffed catheters of right internal jugular vein due to dysfunction were reimplanted with a double guide wire combined with balloon catheter sheathing technique in seven patients. The surgery successfully broke through the fibrin sheath constraint, and postoperative catheter dialysis proceeded smoothly, and none had catheter dysfunction during 6 months of follow-up. The double guide wire combined with balloon catheter sheathing technique is a safe and effective method in situ catheterization.

ObjectiveBy exploring the volatile components， polysaccharide composition and changes in the contents of five carbohydrate components of Polygonatum cyrtonema rhizoma before and after processing， and then the effect of yellow rice wine on the odour formation of P. cyrtonema rhizoma was investigated. MethodThe volatile components of P. cyrtonema rhizoma before and after processing were detected by headspace gas chromatography-mass spectrometry（HS-GC-MS）， and sample data were subjected to principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） using SIMCA 14.1， then the differences between these components of P. cyrtonema rhizoma before and after processing were screened according to the principle of variable importance in the projection（VIP） value>1. Crude carbohydrate components in raw and wine-processed P. cyrtonema rhizoma were subjected to oxime and silylation， the carbohydrate components were analyzed by gas chromatography-mass spectrometry（GC-MS/MS）， and the relative contents of various components were calculated by peak area normalization， then quantitative analysis of four carbohydrate components was also carried out. ResultA total of 23 volatile components were identified from the raw products and the wine-processed products， including 15 components in raw products and 20 components in wine-processed products. Among them， 2-methylbutyraldehyde and isovaleraldehyde had a sweet odor and their contents increased after processing， but the contents of hexanal and caproic acid decreased， new components such as 2-acetylfuran and 5-methylfuranal were produced after processing. PCA and OPLS-DA results showed that there were significant differences between raw products and the wine-processed products， a total of 13 differential compounds were screened out， of which 7 showed an upward trend in relative content and 6 showed a downward trend. A total of 7 carbohydrate components， including 5 monosaccharides and 2 disaccharides， were identified in raw products and the wine-processed products. The results of determination showed that the contents of fructose， glucose， mannose and sucrose in P. cyrtonema rhizoma increased after wine-processing， and their increases were 4.54， 1.51， 2.93， 3.66 times， respectively. ConclusionAfter processing， the increase of aromatic flavor of P. cyrtonema rhizoma may be related to the increase of the contents of aldehydes such as 2-methylbutyraldehyde and isovaleraldehyde， while the decrease of raw flavor may be related to the decrease of the contents of volatile components such as hexanal and hexanoic acid， the increase of sweet flavor may be related to the increase of the contents of monosaccharides and oligosaccharides such as fructose and sucrose.

Animals ; Mice ; Motor Neurons/physiology* ; Spinal Cord

Objective:To investigate the expression and role of asparte-specific cysteine protease (Caspase)-1, inflammasomes key molecule, in hepatitis B virus (HBV)-related diseases.Methods:HBV-related liver disease patients' serum (438 cases) and liver tissue (82 cases) samples were collected from Beijing You'an Hospital affiliated with Capital Medical University. The mRNA expression level of caspase-1 in liver tissue was detected by real-time fluorescence quantitative PCR (qRT-PCR). The protein expression level of Caspase-1 in liver tissue was detected by the immunofluorescence method. The activity of Caspase-1 was detected using the Caspase-1 colorimetric assay kit. The level of Caspase-1 in the serum was detected by an ELISA kit.Results:The results of qRT-PCR showed that the mRNA level of Caspase-1 was downregulated in patients with chronic hepatitis B (CHB), cirrhosis (LC), and hepatocellular carcinoma (HCC), while up-regulated in patients with acute-on-chronic liver failure (ACLF) ( P＜0.01) compared with normal subjects. Immunofluorescence assays showed that Caspase-1 protein levels were elevated in ACLF patients, decreased in HCC and LC patients, and slightly elevated in CHB patients. The activity of Caspase-1 was slightly higher in liver tissue from CHB, LC, and HCC patients than in the normal control group, and there was no statistically significant difference between the groups. Additionally, compared with the control group, Caspase-1 activity was significantly reduced in the ACLF group ( P＜0.01). Serum Caspase-1 levels were significantly lower in patients with CHB, ACLF, LC, and HCC than in normal subjects, and serum Caspase-1 levels were lowest in patients with ACLF ( P＜0.001). Conclusion:Caspase-1, a key molecule of inflammasomes, plays an important role in HBV-related diseases and has significant differences, showing distinct features for ACLF than other HBV-related diseases.