Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

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.

Aim To analyze the anti-A549 and HI299 lung ade-nocarcinoma activities via using examples of baicalin, astragalo-side, hesperidin and cisplatin based on real time cellular analysis (RTCA) technology, and to build a new strategy for EC50 e-valuation reflecting the time-dimensional characteristic. Methods Using RTCA Software Pro for data analysis and GraphPad Prism and Origin Pro plotting, the in vitro anti-A549 and H1299 lung adenocarcinoma activities of baicalin, astragaloside, hesperidin, and cisplatin were characterized using the endpoint method and time dimension, respectively. Results (X) There were significant differences in EC50 values of A549 and H1299 cells at 24 h and 48 h endpoint methods. (2) The correlation coefficient of the curve fitted with the four-parameter equation was > 0. 9, and the dynamic change of EC50 remained relatively stable (the linear fitting of EC50 at adjacent 4 points I slope 1^1) used to calculate the EC50 value within this time dimension. The EC50 of baicalin, astragaloside, hesperidin and cisplatin on A549 cells was 52. 97 ±1.75 плпо! • L~1(16~48 h) , 62.88 ± 2.91 ijunol • L"1 (32.25 -48 h) , 78.84 ±0.33 плпо1 • L"1 (21.5 -29.75 h), 13.57 ±1.54 плпо1 • L_1(27.5 -48 h), respectively; the EC50 of baicalin, astragaloside, hesperidin and cisplatin on H1299 cells was 43. 71 ± 1. 26 |лто1 • L_1 ( 19. 5 -48 h), 47.23 ±1. 19 |лто1 • L_1(14 -48 h) , 39.45 ±0.24 плпо1 • L"1 (12.75 -46.25 h), 25.97 ±4.76 плпо1 • L"1 (10. 25 -48 h) , respectively. The results showed that the time window for the anti-tumor effect of the test solution/drug was different. Conclusions Based on RTCA technology, it is more accurate and reasonable to select EC50 data that exhibit better fitting, stable changes, and time-dimensional characteristics for the evaluation of anti-tumor activity. In addition, this method of distinguishing different effective time of antitumor drugs can provide a reference for the timing of clinical combination drugs, and this approach will also provide a reference for further related studies.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective:To analyze the effect of different gastric mucosa preparation programs on the quality of painless gastroscopy, so as to provide reference for developing mucosal preparation programs.Methods:This was a prospective, randomized controlled study. A total of 150 patients with painless gastroscopy from March 2021 to December 2022 in Shanxi Yuncheng Central Hospital were selected by convenience sampling in this study, they were assigned to control group, water group, and soda water group by random digits table method, each group contained 50 patients. All patients received oral administration of pronase + dimeticone + sodium bicarbonate solution. In addition, control group: prohibited from drinking 4 hours before examination; water group: drinking 200 ml of pure water 2 hours before examination; and soda water group: drinking 200 ml of soda water 2 hours before examination. The clarity score of gastric mucosa and the detection rate of small lesions were compared among the three groups.Results:There were 28 males and 22 females in the control group, aged (47.62 ± 13.83) years old. There were 30 males and 20 females in the water group, aged (44.68 ± 13.61) years old. There were 24 males and 26 females in the soda water group, aged (46.92 ± 12.79) years old. The difference of esophagus, gastric body, gastric antrum and total mucosal clarity scores among the three groups were statistically significant ( F values were 3.68-25.75, all P<0.05). Multiple comparison showed that the esophagus, gastric antrum and total mucosal clarity scores were (1.87 ± 0.58), (1.37 ± 0.34), (6.72 ± 0.92) points in the control group, which were higher than (1.47 ± 0.41), (1.18 ± 0.31), (5.97 ± 0.86) points in the water group, and (1.42 ± 0.41), (1.02 ± 0.22), (5.50 ± 0.79) points in the soda water group, the differences were statistically significant ( t values were 2.67-5.95, all P<0.05). The gastric antrum and total mucosal clarity scores in the water group were higher than in the soda water group, the differences were statistically significant ( t=7.11, 2.71, both P<0.05). The gastric body mucosal clarity score was (1.98 ± 0.74) points in the control group, which was higher than (1.64 ± 0.54) points in the soda water group, the difference was statistically significant ( t=2.66, P<0.05). The gastroscopy examination time and flushin times were (135.20 ± 21.60) s and (1.37 ± 0.43) times in the control group, while (115.52 ± 14.74) s, (0.90 ± 0.29) times and (107.48 ± 13.02) s, (0.62 ± 0.23) times in the water group and soda water group, the control group was higher than the water group and the soda water group, and the water group was also higher than the soda water group, the differences were statistically significant ( t values were 2.38-11.40, all P<0.05). However, there was no statistically significant difference in the detection rate of small lesions among the three groups (all P>0.05). Conclusions:Drinking soda water 2 hours before painless gastroscopy can significantly improve the clarity of patients′gastric mucosa, shorten the examination time and reduce flushing times, but it does not improve the detection rate of small lesions.

Lung cancer is one of the malignant tumors with the highest mortality and the fastest growing incidence,which seriously threatens human life and health.With the popularization of low-dose spiral CT and the enhancement of public awareness of physical examination,more and more ground-glass nodules have been detected.Accumulating studies have shown that for patients with nodules diameter≤2 cm and ground-glass opacity≥50% ,under the condition of ensuring the cutting edge,thoracoscopic sublobectomy or subsegmentectomy can more effectively preserve the lung function of patients,and has gradually become the recommended surgical method.In recent years,with the continuous improvement of thoracoscopic surgery technology,thoracoscopic subsegmentectomy and combined subsegmentectomy have been gradually carried out.Compared with lobectomy and segmentectomy,subsegmental resection can retain more normal lung tissue and reduce the loss of lung function under the condition of ensuring the safe cutting edge.However,thoracoscopic subsegmental resection requires a higher level of surgical technique and anatomical knowledge for the operator,and is rarely reported in relevant literature.Therefore,this article reviews the progress of anatomical subsegmentectomy and combined subsegmentectomy in the treatment of early non-small cell lung cancer.

Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6％),Mycobacterium tuberculosis 249(20.0％),other bacteria 150(12.0％),fungi 68(5.5％),parasites 18(1.4％),Treponema pallidum 18(1.4％)and rickettsia 1(0.1％).The number of cases increased by 177 cases(33.1％)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ￥29,500(￥16,000,￥59,200).The mortality rate from CNS infectious diseases is 1.6％.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.

RNA editing, an essential post-transcriptional reaction occurring in double-stranded RNA (dsRNA), generates informational diversity in the transcriptome and proteome. In mammals, the main type of RNA editing is the conversion of adenosine to inosine (A-to-I), processed by adenosine deaminases acting on the RNAs (ADARs) family, and interpreted as guanosine during nucleotide base-pairing. It has been reported that millions of nucleotide sites in human transcriptome undergo A-to-I editing events, catalyzed by the primarily responsible enzyme, ADAR1. In hematological malignancies including myeloid/lymphocytic leukemia and multiple myeloma, dysregulation of ADAR1 directly impacts the A-to-I editing states occurring in coding regions, non-coding regions, and immature miRNA precursors. Subsequently, aberrant A-to-I editing states result in altered molecular events, such as protein-coding sequence changes, intron retention, alternative splicing, and miRNA biogenesis inhibition. As a vital factor of the generation and stemness maintenance in leukemia stem cells (LSCs), disordered RNA editing drives the chaos of molecular regulatory network and ultimately promotes the cell proliferation, apoptosis inhibition and drug resistance. At present, novel drugs designed to target RNA editing(e.g., rebecsinib) are under development and have achieved outstanding results in animal experiments. Compared with traditional antitumor drugs, epigenetic antitumor drugs are expected to overcome the shackle of drug resistance and recurrence in hematological malignancies, and provide new treatment options for patients. This review summarized the recent advances in the regulation mechanism of ADAR1-mediated RNA editing events in hematologic malignancies, and further discussed the medical potential and clinical application of ADAR1.

Tranexamic acid is widely used in joint orthopedic surgery.At the same time,it has high safety and few adverse drug reactions.It can effectively improve intraoperative bleeding and promote early functional recovery of patients.This article reviews the mode of administration,safe dose,administration time and adverse drug reactions of tranexamic acid in the perioperative period of joint replacement and arthroscopic surgery,in order to provide reference for the clinical application of tranexamic acid.

Objective To analyze the safety of idarubicin or daunorubicin combined with cytarabine in the treatment of patients with acute myeloid leukemia.Methods The Chinese Biomedical Database,Chinese Journal Full-text Database,Chinese Science and Technology Journal Full-text Database,Wanfang Database,Embase,PubMed,Cochrane Library were searched.The randomized controlled trials(RCTs)of idarubicin combined with cytarabine(treatment group)and daunorubicin combined with cytarabine(control group)were collected.The search time was from 2014-01-01 to 2024-02-23.RevMan 5.4 software was used to perform meta-analysis,sensitivity analysis and publication bias analysis on adverse drug reactions of the included studies.Results A total of 11 RCTs involving 1 818 patients were included in the Meta-analysis.The treatment and control groups were enrolled 912 and 906 cases,respectively.The results of meta-analysis showed that the total incidence of adverse drug reactions in the treatment group and the control group was 22.9％(56 cases/245 cases)and 42.9％(105 cases/245 cases),respectively,and the difference was statistically significant[relative risk(RR)=0.53,95％confidence interval(CI)=0.41-0.69,P＜0.001)].In the specific adverse drug reactions,there were no statistically significant differences in the incidence of hematological toxicity,digestive system toxicity,cardiac toxicity,liver and kidney toxicity,infection,bleeding between the two groups(all P＞0.05).Sensitivity analysis showed that the results were stable and reliable.The results of publication bias analysis showed that this study was less likely to have publication bias.Conclusion The incidence of adverse drug reactions of idarubicin combined with cytarabine in the treatment of patients with acute myeloid leukemia is significantly lower than that of daunorubicin combined with cytarabine,so the former has better safety.