Objective Narcolepsy type 1 （NT1） is known to be associated with low levels of hypocretin-1 （Hcrt-1） in cerebrospinal fluid （CSF）. The standard method for Hcrt-1 measurement is radioimmunoassay （RIA） with imported reagents， but this antibody-dependent method is limited to radiation safety-certified lab， gradual radioactivity degradation， and slow turn-around time. The purpose of this study is to explore a non-radioactive， faster， and antibody independent domestic method in China for Hcrt-1 detection. Methods Repeated testing of cerebrospinal fluid from 14 clinically diagnosed NT1 patients and 10 non-narcolepsy patients was performed using liquid chromatography-tandem mass spectrometry （LC-MS/MS）technology，including the establishment and optimization of fundamental methodological procedures. The main steps involved the addition of non-radioactive isotope-labeled internal standards to the cerebrospinal fluid， followed by solid-phase extraction， mass spectrometry signal acquisition， and quantitative analysis. The results were then compared with the corresponding radioimmunoassay（RIA） findings. Results The LC-MS/MS method showed faster speed， and good linearity across a wider range of synthesized standard（5~2 500 pg/ml）， and good repeatability. Although this absolute-quantitation-based LC-MS/MS method and RIA method have different reading values in Hcrt-1 quantitation， they both can segregate NT1 group from non-NT1 group well. Conclusion Although larger cohorts are needed to set up a standard method in China，LC-MS/MS method is proved to be an easier， safer， faster， and possibly more accurate method for Hcrt-1 quantitation and detection for NT1 diagnosis.
Narcolepsy ; Radioimmunoassay

To investigate the effect of Xuebijing injection (XBJ) on cGAS/STING pathway in alleviating sepsis-induced acute lung injury (ALI), the mouse sepsis-induced ALI model was established by cecal ligation and puncture (CLP), and the cell inflammation model was constructed by LPS stimulating RAW264.7 cells. The effects of XBJ on lung tissue injury and cGAS/STING pathway-related protein expression in septic mice were investigated by HE staining, ELISA, and Western blot. The results showed that XBJ intervention could alleviate lung tissue injury, reduce serum IL-6, TNF-α, IFN-β, IL-1-β levels, and the expression of cGAS, STING, p-TBK1, and p-IRF3 proteins in lung tissue in vivo, and reduce the mRNA level of related inflammatory factors in RAW264.7 cells and the expression of cGAS/STING pathway proteins in vitro. The results showed that XBJ could play a role in the prevention and treatment of sepsis-induced ALI by inhibiting the inflammatory response via inhibition of the activation of cGAS/STING pathway. This study provides a new molecular mechanism for the clinical prevention and treatment of sepsis-induced acute lung injury with XBJ.

OBJECTIVE To construct an evaluation index system for the core competencies of ethics committee members of drug clinical trial institution， providing a basis for optimizing the training system for committee members， improving the quality of ethical review， and fully safeguarding the safety and rights of subjects. METHODS Using methods such as literature research and expert consultation， a preliminary core competency evaluation index system was constructed. The Delphi method was employed to revise and validate it， ultimately forming an evaluation index system for the core competencies of ethics committee members. Based on this system， a questionnaire survey was conducted among 90 ethics committee members from 29 drug clinical trial institutions nationwide， comparing their importance rating and self-assessment scores of the core competency indexes. RESULTS The evaluation system constructed included 4 primary indicators （ethics and professional knowledge， ethics review ability， communication and expression ability， moral integrity and work style） and 39 secondary indicators （familiarity with the content of clinical trial-related laws and regulations， ability to complete project ethics review and identify ethical defects in research protocols within a short period of time， ability to judge the scientific value of clinical research， etc.）. The results of questionnaire survey showed that the interviewed ethics committee members had significant capability gaps in dimensions such as regulatory knowledge， ethical norms， review efficiency， risk judgment， and problem analysis. The differences between the importance rating scores of corresponding secondary indicators and the self-assessment scores were all no less than 0.38. CONCLUSIONS This study has developed a quantifiable and stratified core competency assessment tool for ethics committee members. It can provide a scientific framework for committee member training， qualification certification， and standardized management of ethics committees.

Oxidative stress due to aberrant metabolism is considered as a crucial contributor to diabetes and its complications. Hyperglycemia and hyperlipemia boost excessive reactive oxygen species generation by elevated mitochondrial respiration, increased nicotinamide adenine dinucleotide phosphate oxidase activity, and enhanced pro-oxidative processes, including protein kinase C pathways, hexosamine, polyol, and advanced glycation endproducts, which exacerbate oxidative stress. Oxidative stress plays a significant role in the onset of diabetes and its associated complications by impairing insulin production, increasing insulin resistance, maintaining hyperglycemic memory, and inducing systemic inflammation. A more profound comprehension of the molecular processes that link oxidative stress to diabetes is crucial to new preventive and therapeutic strategies. Therefore, this review discusses the mechanisms underlying how oxidative stress contributes to diabetes mellitus and its complications. We also summarize the current approaches for prevention and treatment by targeting the oxidative stress pathways in diabetes.
Oxidative Stress/physiology* ; Humans ; Diabetes Mellitus/physiopathology* ; Diabetes Complications/metabolism* ; Reactive Oxygen Species/metabolism* ; Glycation End Products, Advanced/metabolism* ; Animals

Autophagy is a fundamental biological metabolic process involved in immune defense, material metabolism, and homeostasis and closely linked to immune regulation. Systemic lupus erythematosus (SLE) is a widespread connective tissue disorder primarily resulting from immune system imbalance. Due to the immune system's failure to recognize its own substances, it generates autoantibodies that can affect various tissues and organs, leading to diverse clinical manifestations. The pathogenesis and treatment of SLE are currently under extensive investigation. In normal metabolic processes, autophagy engages in both innate and adaptive immunity, regulates the immune response, and is crucial for maintaining normal immune function and the body's internal homeostasis. Research has indicated that SLE patients exhibit immune dysfunction and altered autophagy levels. Modulating autophagy expression can influence immune system functionality and alleviate SLE symptoms. Additionally, autophagy aids in the innate immune response and adaptive immunity by clearing metabolites and regulating the life cycle of immune cells. Studies suggest that drugs targeting autophagy can positively influence the progression of SLE. This article reviews advancements in research regarding the impact of autophagy on the pathogenesis of SLE through the regulation of immune system functions.
Lupus Erythematosus, Systemic/pathology* ; Autophagy/immunology* ; Humans ; Animals ; Immunity, Innate ; Adaptive Immunity ; Disease Progression ; Immune System/immunology*

The biological nitrogen removal technology utilizing heterotrophic nitrification-aerobic denitrification (HN-AD) bacteria has shown effectiveness in wastewater treatment. However, the nitrogen removal efficiency of HN-AD bacteria significantly decreases as the salinity increases. To tackle the challenge of treating high-salt and high-nitrogen wastewater, we isolated a moderately halophilic HN-AD strain 5505 from a salt lake in Xinjiang. The strain was identified based on morphological, physiological, and biochemical characteristics and the 16S rRNA gene sequence. Single-factor experiments were carried out with NH₄⁺-N, NO₃^--N, and NO₂^--N as sole or mixed nitrogen sources to study the nitrifying effect, denitrifying effect, and nitrogen metabolism pathway of the strain. The strain was identified as Halomonas sp.. It can grow in the presence of 1%-25% (W/V) NaCl and exhibited efficient nitrogen removal ability in the presence of 3%-8% NaCl. At the optimal NaCl concentration (8%), the strain showed the NH₄⁺-N, NO₃^--N and NO₂^--N removal rates of 100.0%, 94.11% and 74.43%, respectively. Strain 5505 removed inorganic nitrogen mainly by assimilation, which accounted for over 62.68% of total nitrogen removal. In the presence of mixed nitrogen sources, strain 5505 showed a preference for utilizing ammonia, with a potential HN-AD pathway of NH₄⁺→NH₂OH→NO₂^-→NO₃^-→NO₂^-→NO/N₂O/N₂. The findings provide efficient salt-tolerant bacterial resources, enhance our understanding of biological nitrogen removal, and contribute to the nitrogen removal efficiency improvement in the treatment of high-salt and high-nitrogen wastewater.
Halomonas/classification* ; Nitrogen/isolation & purification* ; Denitrification ; Nitrification ; Wastewater/microbiology* ; Aerobiosis ; Biodegradation, Environmental ; Salinity

Objective To investigate the effect of acacetin on oxidative stress injury in diabetic cataract(DC)rats and its regulation of sirtuin 1(Sirt1)/adenosine monophosphate-activated protein kinase(AMPK)/nuclear factor-erythroid 2-related factor 2(Nrf2)signaling pathway.Methods Sixty SD rats were randomly divided into the control group,model group,low-dose acacetin group,high-dose acacetin group,and acacetin+Sirt1 inhibitor(EX527)group.DC rat models were constructed except for the control group.Rats in the low-dose and high-dose acacetin groups were injected with 10 mg·kg-1 and 20 mg·kg-1 acacetin subcutaneously through the neck,twice a day,respectively.Rats in the acacetin+EX527 group were injected with 20 mg·kg-1 acacetin subcutaneously through the neck,twice a day;additionally,3.5 mg·kg-1 EX527 was administered subcutaneously through the osmotic micro-pump for 4 weeks.The same amount of nor-mal saline was pumped into rats in the rest groups for 4 weeks.After administration,blood pressure and fasting blood glu-cose(FBG)were measured.The lens opacity was observed under the slit lamp irradiation,and the histopathological chan-ges in the lens were observed after hematoxylin-eosin staining.Enzyme-linked immunosorbent assay was performed to de-termine the serum levels of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),in-terleukin(IL)-6,and IL-1 β.Western blot was applied to detect the expression levels of Sirt1,phosphorylated AMPK(p-AMPK),AMPK,and Nrf2 proteins.Results Compared with the control group,the lens epithelial cells(LECs)of rats in the model group showed patchy and striped shapes,and migration and aggregation occurred;the systolic blood pres-sure(SBP),FBG,lens opacity score,and the levels of MDA,IL-6 and IL-1 β increased,while the expression levels of SOD,GSH-Px,Sirt1,p-AMPK/AMPK,and Nrf2 proteins decreased(all P＜0.05).Compared with the model group,the migration and aggregation of LECs improved in the low-dose and high-dose acacetin groups,the SBP,FBG,lens opacity score,and the levels of MDA,IL-6 and IL-1 β decreased,while the expression levels of SOD,GSH-Px,Sirt1,p-AMPK/AMPK,and Nrf2 proteins increased(all P＜0.05).Compared with the high-dose acacetin group,the morphological chan-ges and aggregation of LECs in the acacetin+EX527 group were more significant,the SBP,FBG,lens opacity score,and the levels of MDA,IL-6 and IL-1 β increased,while the expression levels of SOD,GSH-Px,Sirt1,p-AMPK/AMPK,and Nrf2 proteins decreased(all P＜0.05).Conclusion Acacetin may protect DC rats from oxidative stress injury by activating the Sirt1/AMPK/Nrf2 pathway.

Objective To investigate the effect of total flavone of Cydonia oblonga on oxidative damage of human lens epithelial cells induced by high glucose and its mechanism.Methods A cell injury model was established by inducing human lens epithelial cells with high glucose.Human lens epithelial cells were cultured in the medium containing 30 mmol·L-1 glucose for 24 h,which was recorded as the high glucose group.Cells in the control group were cultured in a medium con-tainning 5.5 mmol·L-1 glucose for 24 h.Human lens epithelial cells were inoculated into 96-well plates with 5 × 103 cells per well,and treated with mediums containing 10 mmol·L-1,20 mmol·L-1,and 40 mmol·L-1 total flavone of Cydonia ob-longa combined with 30 mmol·L-1 glucose for 24 h.They were recorded as high glucose+low total flavone of Cydonia oblonga group,high glucose+medium total flavone of Cydonia oblonga group,and high glucose+high total flavone of Cydonia oblonga group.Human lens epithelial cells were transfected with anti-miR-NC and anti-miR-370 with Lipo-fectamine2000 transfection reagent,and treated with 30 mmol·L-1 glucose for 24 h,which were recorded as high glucose+anti-miR-NC group and high glucose+anti-miR-370 group.Human lens epithelial cells were transfected with miR-NC and miR-370 mimics,and treated with medium containing 30 mmol·L-1 glucose and 40 mmol·L-1 total flavone of Cydonia oblonga for 24 h,which were labeled as high glucose+total flavone of Cydonia oblonga+miR-NC group and high glucose+total flavone of Cydonia oblonga+miR-370 group.The activities of superoxide dismutase(SOD)and cata-lase(CAT),and the content of malondialdehyde(MDA)were measured by Enzyme-linked immunosorbent assay;flow cy-tometry was applied to detect apoptosis rate;quantitative reverse transcription polymerase chain reaction was applied to detect the expression level of miR-370;Western blot was applied to detect the expression of apoptosis-related proteins.Results Compared with the control group,the activities of SOD and CAT decreased and the content of MDA increased in the human lens epithelial cells of the high glucose group,and the differences were statistically significant(all P＜0.05);compared with the high glucose group,the activities of SOD and CAT significantly increased and the content of MDA signifi-cantly decreased in the high glucose+low total flavone of Cydonia oblonga group,the high glucose+medium total fla-vone of Cydonia oblonga group and the high glucose+high total flavone of Cydonia oblonga group(all P＜0.05).Com-pared with the control group,apoptosis rate,and protein expressions of Caspase-3 and Caspase-9 of human lens epithelial cells in the high glucose group significantly increased(all P＜0.05);compared with the high glucose group,the apoptosis rate,Caspase-3 and Caspase-9 protein expressions of human lens epithelial cells in the high glucose+low total flavone of Cydonia oblonga group,high glucose+medium total flavone of Cydonia oblonga group,and high glucose+high total fla-vone of Cydonia oblonga group significantly decreased(all P＜0.05).The expression levels of miR-370 in human lens epi-thelial cells were 1.00±0.00,4.04±0.36,3.22±0.24,2.42±0.23 and 1.62±0.14 in the control group,high glucose group,high glucose+low total flavone of Cydonia oblonga group,high glucose+medium total flavone of Cydonia oblon-ga group,and high glucose+high total flavone of Cydonia oblonga group,respectively.There was a statistically different significance among the five groups(F=256.138,P＜0.05).Compared with the high glucose+anti-miR-NC group,the ex-pression of miR-370 significantly decreased,the activities of SOD and CAT significantly increased,and the content of MDA significantly decreased in human lens epithelial cells of the high glucose+anti-miR-370 group(all P＜0.001).Compared with the high glucose+anti-miR-NC group,apoptosis rate,and protein expressions of Caspase-3 and Caspase-9 of the hu-man lens epithelial cells in the high glucose+anti-miR-370 group significantly decreased(all P＜0.001).Compared with the high glucose+total flavone of Cydonia oblonga+miR-NC group,the activities of SOD and CAT significantly de-creased,and the content of MDA,apoptosis rate,and protein expressions of Caspase-3 and Caspase-9 significantly in-creased in the human lens epithelial cells of high glucose+total flavone of Cydonia oblonga+miR-370 group(all P＜0.001).Conclusion The expression of miR-370 increases in high glucose-induced human lens epithelial cells.Total fla-vone of Cydonia oblonga can inhibit the oxidative stress and apoptosis of high glucose-induced human lens epithelial cells,and the mechanism may be related to the decreased expression of miR-370.

Objective To evaluate the efficacy,safety,and economy of tislelizumab(TIS)as a first-line treatment for advanced non-small cell lung cancer(NSCLC).Methods PubMed,Embase,Cochrane Library,CNKI,WanFang Data,SinoMed databases and health technology assessment(HTA)websites were electronically searched to collect the HTA report,systematic review/Meta-analysis and pharmacoeconomic research of TIS as a first-line treatment for advanced NSCLC from the inception to April 30,2024.Two reviewers independently screened literature,extracted data,and evaluated quality,and qualitative descriptive methods were used for rapid health technology assessment(rHTA).Results A total of 9 articles were included,in which 7 systematic review/Meta-analysis and 2 pharmacoeconomic studies.In terms of effectiveness,compared with chemotherapy(CT),TIS+CT could improve the progression free survival(PFS)and objective response rate(ORR)of advanced NSCLC patients.It could also improve PFS in patients with advanced NSCLC who have the any expression of programmed cell death receptor ligand-1(PD-L1),with or without liver metastasis,aged＞65 years or＜65 years,and with a history of smoking;Compared with CT,TIS+CT could improve the PFS of advanced non squamous NSCLC patients,and could increase the PFS of advanced non squamous NSCLC patients with PD-L1＞50％;Compared with CT,TIS+CT could improve the PFS of patients with advanced squamous cell carcinoma NSCLC in stages ⅢB and IV,with PD-L1 being 1％-49％,PD-L1＞50％,male,age＞65 years old,smoking history,ECOG score of 1 point.In terms of safety,compared with camrelizumab+CT and atezolizumab+bevacizumab+CT,TIS+CT could reduce the incidence of serious adverse reactions.In terms of economics,for non squamous NSCLC without epidermal growth factor receptor(EGFR)mutations and gradual lymphoma kinase(ALK)rearrangements,TIS+CT had certain cost-effectiveness advantages compared to CT in China.The subgroup analysis results showed that the first-line TIS+CT regimen had greater survival benefits in non squamous NSCLC patients with PD-L1 expression＞50％,liver metastasis,and a history of smoking.Conclusion TIS+CT first-line treatment for advanced NSCLC has good efficacy,safety,and economy.

Objective This study was to develop a HPLC-MS/MS method for determination of etomidate and etomidate acid in blood samples.Methods The blood samples were deproteinized with acetonitrile and supernatant was achieved by shake,sonication,centrifuge and filtration using 0.22 μm membrane.Then,supernatant was performed on an analytical column Poroshell 120 EC-C18(150 mm×3.0 mm,2.7 μm)and flowed with 0.1%formic acid(mobile phase A)and acetonitrile(mobile phase B).The gradient elution at a flow rate of 0.8 mL/min was determined using an electrospray ionization source in positive ion mode and multiple reaction monitoring mode.Results The linearities of etomidate and etomidate acid in blood samples were good within the corresponding range and the correlation coefficients(r)were over 0.9988.The limit of detection(LOD)of etomidate and etomidate acid were 19.94 and 40.25 ng/mL,and the limit of quantitation(LOQ)of them were 50 and 100 ng/mL,respectively.Moreover,matrix effects were ranged from 1.47%to 10.34%and recoveries ranged from 82.81%to 90.07%.The detection of a positive case using our method was successfully determined to be 1 138.89 and 3 126.41 ng/mL for the contents of etomidate and etomidate acid,respectively.Conclusion Our study has further confirmed that this method with simple pretreatment,little sample usage and wide linear range,can be successfully applied to the detection of forensic sciences on etomidate and etomidate acid.