As a serine protease,thrombin can convert soluble fibrinogen into insoluble fibrin and plays a pivotal role in the coagulation cascade.Therefore,the accurate quantitative assay of thrombin levels is of great value in the evaluation of coagulation function,clinical screening and prognostic monitoring of coagulation-related diseases,and screening of drugs for targeted therapy.Existing methods for thrombin detection can be divided into two categories,e.g.,the assay of concentration levels using nucleic acid aptamers as the affinity elements and the assay of activity levels based on the hydrolytic cleavage of substrate peptides.In recent years,electrochemical biosensors have attracted much attention in thrombin detection due to high sensitivity,high selectivity,simple instrument,fast response,and good portability.In this review,the latest research progress in methods for electrochemical detection of thrombin was summarized,focusing on the detection principles and the applied signal amplification strategies of related electrochemical biosensors.In addition,the challenges with respect to the practical use of electrochemical thrombin biosensors and the prospects were discussed.

Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

Atherosclerosis caused by disorders of lipid metabolism is the main pathological basis of atherosclerotic cardiovascular disease.Statins are the cornerstone of lipid-modulating therapy for this type of disease,but in practice there are still some patients with suboptimal lipid management.Proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors have been gradually applied as a new class of lipid-modulating drugs for the treatment in patients with this type of disease,and recent studies have shown that in addition to regulating lipid metabolism,PCSK9 inhibitors also have potential anti-inflammatory and anti-platelet activation effects.This article sorts out the multiple pharmacological mechanisms of action of PCSK9 inhibitors and the current status of clinical research of PCSK9 inhibitors.Besides,it discusses the factors that may affect the efficacy of PCSK9 inhibitors,in order to provide a reference for the safe and rational medication of PCSK9 inhibitors.

Objective To observe the safety of low-intensity focused ultrasound(LIFU)for stimulating rat vagus nerve.Methods Twelve male SD rats were randomly divided into stimulation group A,B,C and sham stimulation(D)group(each n=3).A LIFU stimulation system equipped with a suitable collimator was used to stimulate rat left vagus nerve in A,B,C groups,with acoustic pressure of 1.05,3.87 and 4.25 MPa,respectively,with the same pulse repetition frequency,duty ratio and stimulation mode.For rats in group D,the ultrasonic transducer was positioned on the left side of the neck but no stimulation was performed.The changes of heart rate and local neck temperature were recorded before,during and after LIFU stimulation.After stimulation,neck MR T2WI were acquired for group C and D.Then pathological examination of vagus nerve was performed to observe whether there were abnormal changes after stimulation.Results No significant difference of heart rate 5 min before,during and 5 min after stimulation was found among 4 groups(all P>0.05).The local temperature beneath the transducer of rats in group A,B,C and D ranged from 28.1-30.1℃,28.3-30.3℃,27.9-30.4℃ and 27.8-30.2℃,respectively,and the temperature fluctuation all less than 2.5℃.T2WI showed no obvious abnormality of neck soft tissue in group C nor D,while no significant pathological changes of rat vagus nerve was detected.Conclusion LIFU with proper parameters was safe for stimulating rat vagus nerve.

As a long-standing research focus in electroanalytic chemistry,electrochemical biosensors have attracted immense interest in detection of biological targets such as small molecules,proteins,enzymes,nucleic acids,exosomes,circulating tumor cells (CTCs),bacteria,and viruses. etc. The highly sensitive and selective electrochemical detection of biological targets relies on the use of the specific biorecognition elements (BREs) and efficient signal amplification strategies. In this review,the typically used BREs and amplification strategies in electrochemical biosensing were summarized. On the basis of the interactions between BREs and targets,the enzyme/substrate-based and receptor/ligand-based electrochemical biosensors were first introduced,focusing on the BREs used in the electrochemical detection of nucleic acid targets and non-nucleic acid targets. Then,the representative use of various isothermal nucleic acid amplification technologies,catalytic reactions,functionalized nanocarriers,and polymer materials in amplified electrochemical detection of biological targets were introduced. The challenges with respect to the practical use of electrochemical biosensors and the prospect of electrochemical biosensing were discussed.

Objective: To analyze the survival time of reported HIV/AIDS and influencing factors of Yunnan Province from 1989 to 2021. Methods: The data were extracted from the Chinese HIV/AIDS comprehensive response information management system. The retrospective cohort study was conducted. The life table method was applied to calculate the survival probability. Kaplan-Meier was used to draw survival curves in different situations. Furthermore, the Cox proportion hazard regression model was constructed to identify the factors related to survival time. Results: Of the 174 510 HIV/AIDS, the all-cause mortality density was 4.23 per 100 person-years, the median survival time was 20.00 (95%CI:19.52-20.48) years, and the cumulative survival rates in 1, 10, 20, and 30 years were 90.75%, 67.50%, 47.93% and 30.85%. Multivariate Cox proportional risk regression model results showed that the risk of death among 0-14 and 15-49 years old groups were 0.44 (95%CI: 0.34-0.56) times and 0.51 (95%CI:0.50-0.52) times of ≥50 years old groups. The risk for death among the first CD4⁺T lymphocytes counts (CD4) counts levels of 200-349 cells/μl, 350-500 cells/μl and ≥501 cells/μl groups were 0.52 (95%CI: 0.50-0.53) times, 0.41 (95%CI: 0.40-0.42) times and 0.35 (95%CI: 0.34-0.36) times of 0-199 cells/μl groups. The risk of death among the cases that have not received antiretroviral therapy (ART) was 11.56 (95%CI: 11.26-11.87) times. The risk for death among the cases losing to ART, stopping to ART, both losing and stopping ART was 1.66 (95%CI:1.61-1.72) times, 2.49 (95%CI:2.39-2.60) times, and 1.65 (95%CI:1.53-1.78) times of the cases on ART. Conclusions: The influencing factors for the survival time of HIV/AIDS cases were age at diagnosis in Yunnan province from 1989 to 2021. The first CD4 counts levels, antiretroviral therapy, and ART compliance. Early diagnosis, early antiretroviral therapy, and increasing ART compliance could extend the survival time of HIV/AIDS cases.
Humans ; Middle Aged ; Retrospective Studies ; China/epidemiology* ; Acquired Immunodeficiency Syndrome/epidemiology* ; Anti-Retroviral Agents/therapeutic use* ; Asian People

The electrophysiological activity of the gastrointestinal tract and the mechanical anti-reflux structure of the gastroesophageal junction are the basis of the anti-reflux function of the stomach. Proximal gastrectomy destroys the mechanical structure and normal electrophysiological channels of the anti-reflux. Therefore, the residual gastric function is disordered. Moreover, gastroesophageal reflux is one of the most serious complications. The emergence of various types of anti-reflux surgery through the mechanism of reconstructing mechanical anti-reflux barrier and establishing buffer zone, and the preservation of, the pacing area and vagus nerve of the stomach, the continuity of the jejunal bowel, the original gastroenteric electrophysiological activity of the gastrointestinal tract, and the physiological function of the pyloric sphincter, are all important measures for gastric conservative operations. There are many types of reconstructive approaches after proximal gastrectomy. The design based on the anti-reflux mechanism and the functional reconstruction of mechanical barrier, and the protection of gastrointestinal electrophysiological activities are important considerations for the selected of reconstructive approaches after proximal gastrectomy. In clinical practice, we should consider the principle of individualization and the safety of radical resection of tumor to select a rational reconstructive approaches after proximal gastrectomy.
Humans ; Stomach Neoplasms/surgery* ; Gastrectomy ; Gastroesophageal Reflux ; Esophagogastric Junction/surgery* ; Pylorus/pathology*

Objective: To investigate the detection and diagnostic efficacy of chest radiographs for ≤30 mm pulmonary nodules and the factors affecting them, and to compare the level of consistency among readers. Methods: A total of 43 patients with asymptomatic pulmonary nodules who consulted in Cancer Hospital, Chinese Academy of Medical Sciences from 2012 to 2014 and had chest CT and X-ray chest radiographs during the same period were retrospectively selected, and one nodule ≤30 mm was visible on chest CT images in the whole group (total 43 nodules in the whole group). One senior radiologist with more than 20 years of experience in imaging diagnosis reviewed CT images and recording the size, morphology, location, and density of nodules was selected retrospectively. Six radiologists with different levels of experience (2 residents, 2 attending physicians and 2 associate chief physicians independently reviewed the chest images and recorded the time of review, nodule detection, and diagnostic opinion. The CT imaging characteristics of detected and undetected nodules on X images were compared, and the factors affecting the detection of nodules on X-ray images were analyzed. Detection sensitivity and diagnosis accuracy rate of 6 radiologists were calculated, and the level of consistency among them was compared to analyze the influence of radiologists' seniority and reading time on the diagnosis results. Results: The number of nodules detected by all 6 radiologists was 17, with a sensitivity of detection of 39.5%(17/43). The number of nodules detected by ≥5, ≥4, ≥3, ≥2, and ≥1 physicians was 20, 21, 23, 25, and 28 nodules, respectively, with detection sensitivities of 46.5%, 48.8%, 53.5%, 58.1%, and 65.1%, respectively. Reasons for false-negative result of detection on X-ray images included the size, location, density, and morphology of the nodule. The sensitivity of detecting ≤30 mm, ≤20 mm, ≤15 mm, and ≤10 mm nodules was 46.5%-58.1%, 45.9%-54.1%, 36.0%-44.0%, and 36.4% for the 6 radiologists, respectively; the diagnosis accuracy rate was 19.0%-85.0%, 16.7%-6.5%, 18.2%-80.0%, and 0%-75.0%, respectively. The consistency of nodule detection among 6 doctors was good (Kappa value: 0.629-0.907) and the consistency of diagnostic results among them was moderate or poor (Kappa value: 0.350-0.653). The higher the radiologist's seniority, the shorter the time required to read the images. The reading time and the seniority of the radiologists had no significant influence on the detection and diagnosis results (P>0.05). Conclusions: The ability of radiographs to detect lung nodules ≤30 mm is limited, and the ability to determine the nature of the nodules is not sufficient, and the increase in reading time and seniority of the radiologists will not improve the diagnostic accuracy. X-ray film exam alone is not suitable for lung cancer diagnosis.
Humans ; Retrospective Studies ; Solitary Pulmonary Nodule/diagnostic imaging* ; Radiography ; Multiple Pulmonary Nodules/diagnostic imaging* ; Tomography, X-Ray Computed/methods* ; Lung Neoplasms/diagnostic imaging* ; Sensitivity and Specificity ; Radiographic Image Interpretation, Computer-Assisted/methods*

Lu Dangshen, a traditional authentic medicinal material of Codonopsis Radix is mainly produced in Shangdang (Changzhi) area of Shanxi Province. Baitiao Dangshen is mainly produced in Gansu Province. Codonopsis Radix contains many kinds of components such as phenylpropanoids, polyalkynes, alkaloids, terpenes, fatty acids, flavonoids, and so on. At present, the effect of producing areas on its chemical compositions has not been systematically studied. This study analyzed the differences of metabolites among Codonopsis pilosula from different producing areas by UPLC-HRMS. PCA, OPLS-DA coupled with Thermo mzcloud online and local databases were used to compare the overall differences of metabolites among Codonopsis pilosula from different producing areas, and the chemical constituents were identified to further screen and find out the different metabolites and analyze the metabolic pathways by information retrieval in HMDB, PubChem, Chemspider and KEGG databases. The results showed that 72 differential metabolites were identified in this study. There were 15 kinds of up-regulated and 57 kinds of down-regulated metabolites of Lu Dangshen compared with Baitiao Dangshen. The top 30 metabolic pathways were analyzed by KEGG enrichment, and the most important metabolic pathways were phenylpropanoid biosynthesis, which was demonstrated that phenylpropanoid biosynthesis pathway and related intermediate metabolites could be used as the characteristics of distinguishing Lu Dangshen from different habitats of Codonopsis pilosula. The present study provided a basis for analyzing the influence of producing areas on the chemical components of Codonopsis pilosula and reasonably evaluating the quality of Codonopsis Radix, and also provided a new idea for expounding the authenticity of Lu Dangshen.

Objective: To analyze the course of disease and epidemiological parameters of COVID-19 and provide evidence for making prevention and control strategies. Methods: To display the distribution of course of disease of the infectors who had close contacts with COVID-19 cases from January 1 to March 15, 2020 in Guangdong Provincial, the models of Lognormal, Weibull and gamma distribution were applied. A descriptive analysis was conducted on the basic characteristics and epidemiological parameters of course of disease. Results: In total, 515 of 11 580 close contacts were infected, with an attack rate about 4.4%, including 449 confirmed cases and 66 asymptomatic cases. Lognormal distribution was fitting best for latent period, incubation period, pre-symptomatic infection period of confirmed cases and infection period of asymptomatic cases; Gamma distribution was fitting best for infectious period and clinical symptom period of confirmed cases; Weibull distribution was fitting best for latent period of asymptomatic cases. The latent period, incubation period, pre-symptomatic infection period, infectious period and clinical symptoms period of confirmed cases were 4.50 (95%CI:3.86-5.13) days, 5.12 (95%CI:4.63-5.62) days, 0.87 (95%CI:0.67-1.07) days, 11.89 (95%CI:9.81-13.98) days and 22.00 (95%CI:21.24-22.77) days, respectively. The latent period and infectious period of asymptomatic cases were 8.88 (95%CI:6.89-10.86) days and 6.18 (95%CI:1.89-10.47) days, respectively. Conclusion: The estimated course of COVID-19 and related epidemiological parameters are similar to the existing data.
COVID-19 ; Cohort Studies ; Contact Tracing ; Humans ; Incidence ; Prospective Studies