OBJECTIVE To explore clinical characteristics and risk factors of drug-induced hypofibrinogenemia， providing a reference for rational clinical drug use. METHODS Retrospective case analyses literature on drug-induced hypofibrinogenemia were collected from domestic and international databases from their inception to December 31， 2024. The patients’ gender， age， fibrinogen （FIB） levels before and after treatment， drug types， the incidence of drug-induced hypofibrinogenemia， time of occurrence， bleeding rates， clinical manifestations， risk factors， and protective factors were all analyzed. RESULTS A total of 40 retrospective case analysis studies were included， involving 17 313 patients. Patient age ranged from 0.83 to 78.40 years， with males accounting for 16.90%-81.00%. The involved drugs comprised 5 categories and 13 specific agents， including tigecycline， snake venom hemocoagulase， tocilizumab， and alteplase， etc. The incidence of drug-induced hypofibrinogenemia ranged from 0 to 100%， occurring between 2 hours and 9 months after drug administration， and FIB levels rebounded in most patients after drug discontinuation. The bleeding rate varied from 0% to 91.30%， including epistaxis， airway bleeding， gastrointestinal bleeding， and cerebral hemorrhage. Risk factors included high drug dosage， prolonged treatment duration， abdominal infection， advanced age， and low baseline FIB levels. Protective factors were only mentioned in studies on tigecycline， including skin and soft tissue infections and high baseline FIB levels. CONCLUSIONS Drug-induced hypofibrinogenemia is commonly associated with tigecycline， hemocoagulase， and tocilizumab. Its clinical features vary depending on the drug， and risk factors include high drug dosage， prolonged treatment， low baseline FIB levels， and advanced age. For high-risk medications， individualized medication management and monitoring of FIB levels are recommended.

NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD⁺), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD⁺ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD⁺ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.
Humans ; NAD/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Nicotinamide Phosphoribosyltransferase/metabolism* ; Cytokines/metabolism* ; Quinones ; Oxidoreductases

Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.

In recent years, polysaccharides have received much attention because of their high safety and good immunological activity. The study of polysaccharide in vivo process is a key scientific problem that needs to be solved for polysaccharide drug development. Some progress has been made in the field of polysaccharide pharmacokinetics and immunomodulation. However, due to the lack of both chromogenic and light-absorbing groups and the complex molecular structure of polysaccharides, the in vivo processes and immunomodulatory mechanisms of polysaccharides have been slow to be investigated. The effective combination of multiple techniques can break the bottleneck of difficult tracing and unknown immunomodulatory mechanism of polysaccharides in vivo, and promote the development and utilization of polysaccharides. In this paper, we systematically summarize the key techniques in the study of polysaccharide in vivo processes and immunomodulatory mechanisms in order to provide technical references and research ideas for the study of polysaccharide in vivo processes and immunomodulatory mechanisms.

Objective To investigate the diagnostic efficiency of artificial intelligence(AI)in rib frac-ture under the computed tomography(CT)images with different reconstruction slice thickness.Methods The first CT images of 100 patients with rib fractures were selected,and the interval-free recon-struction was carried out with the thickness of 0.625 mm,1.250 mm,2.500 mm and 5.000 mm,respectively.The rib fracture screening function of AI was used to automatically detect the CT images of four groups,and the diagnostic efficiency of AI for rib fracture under different reconstruction thickness conditions was com-pared.Results The sensitivity of AI in the diagnosis of rib fracture at 0.625 mm,1.250 mm,2.500 mm and 5.000 mm thickness was 99.32%(436/439),98.41%(432/439),89.52%(393/439)and 83.60%(367/439),respectively.The false positive rate was 4.80%(22/458),0.92%(4/436),0.76%(3/396)and 0.27%(1/368).The diagnostic sensitivity of AI in 0.625 mm and 1.250 mm thickness was higher than that in 2.500 mm and 5.000 mm,and the difference was statistically significant(P<0.05),while there was no significant difference in the thickness of 0.625 mm and 1.250 mm.The false positive rate of AI in the diagnosis of 0.625 mm slice thickness was higher than that of 1.250 mm,2.500 mm and 5.000 mm,and the difference was sta-tistically significant(P<0.05),while there was no significant difference in the thickness of 1.250 mm,2.500 mm and 5.000 mm(P>0.05).Conclusion The diagnostic efficiency of AI in 1.250 mm CT images is better than that in 0.625 mm,2.500 mm and 5.000 mm CT images.

ObjectiveGastric cancer (GC) seriously affects human health and life, and research has shown that it is closely related to the serine/glycine metabolism. The proliferation ability of tumor cells is greatly influenced by the metabolism of serine and glycine. The aim of this study was to investigate the molecular mechanism of serine/glycine metabolism can affect the proliferation of gastric cancer cells. MethodsIn this work, a stable metabolic dynamic model of gastric cancer cells was established via a large-scale metabolic network dynamic modeling method in terms of a potential landscape description of stochastic and non-gradient systems. Based on the regulation of the model, a quantitative analysis was conducted to investigate the dynamic mechanism of serine/glycine metabolism affecting the proliferation of gastric cancer cells. We introduced random noise to the kinetic equations of the general metabolic network, and applied stochastic kinetic decomposition to obtain the Lyapunov function of the metabolic network parameter space. A stable metabolic network was achieved by further reducing the change in the Lyapunov function tied to the stochastic fluctuations. ResultsDespite the unavailability of a large number of dynamic parameters, we were able to successfully construct a dynamic model for the metabolic network in gastric cancer cells. When extracellular serine is available, the model preferentially consumes serine. In addition, when the conversion rate of glycine to serine increases, the model significantly upregulates the steady-state fluxes of S-adenosylmethionine (SAM) and S-adenosyl homocysteine (SAH). ConclusionIn this paper, we provide evidence supporting the preferential uptake of serine by gastric cancer cells and the important role of serine/glycine conversion rate in SAM generation, which may affect the proliferation ability of gastric cancer cells by regulating the cellular methylation process. This provides a new idea and direction for targeted cancer therapy based on serine/glycine metabolism.

Objective To analyze a case of hyperhemolytic syndrome(HHS)and explore the laboratory diagnostic method and clinical treatment strategy.Methods Serological tests such as blood typing,direct antiglobulin test(DAT),an-ti-screening and antibody identification were performed,The complete blood count(CBC),as well as hemolysis indicators such as lactate dehydrogenase(LDH)and bilirubin were tested,and the changes and progression of hemolysis were moni-tored.By using genotyping methods to test 32 common rare blood type antigens in clinical practice,the accuracy of antibody identification results was supported.Results The patient had anti-E antibodies and autoantibodies in her serum.After blood transfusion,LDH and bilirubin increased significantly,but hemoglobin dropped sharply,far lower than before transfusion,presenting with unique manifestations such as hemoglobinuria.The patient made a full recovery after treatment with high-dose intravenous immunoglobulin and corticosteroids.Conclusion HHS is a rare and potentially fatal diseases,which is mainly manifested by hemolysis and severe anemia,and the hemoglobin level after blood transfusion is often lower than that before blood transfusion.This patient had typical clinical manifestations of post-transfusion hyperhemolytic reaction.After timely and correct treatment,the patient recovered completely and was discharged,accumulating valuable clinical experience for the diagnosis and treatment of such disease.

Objective:To analyze the changes of diagnosis and treatment before and after renal biopsy in adult patients with acute kidney disease (AKD), and to explore the value of renal biopsy in the diagnosis and treatment of AKD.Methods:It was a single-center retrospective observational study. The adult patients with AKD who underwent renal biopsy in the Department of Nephrology of the First Affiliated Hospital of Nanjing Medical University from January 1, 2017 to December 31, 2021 were enrolled. Demographic data, general clinical data, laboratory tests, and diagnosis and treatment data before and after renal biopsy were collected to analyze the concordance rate between clinical and pathological diagnoses, changes in treatment after renal biopsy, and bleeding complication.Results:A total of 575 patients diagnosed with AKD by renal biopsy were included in this study, with age of 51 (36, 63) years old and 359 males (62.4%). Among them, there were 293 patients (51.0%) of acute kidney injury, 348 patients (60.5%) of hypertension and 124 patients (21.6%) of diabetes. The peak serum creatinine was 272 (190, 477) μmol/L. The hemoglobin was 106 (86, 126) g/L. The 24-hour urine protein was 2.15 (0.79, 4.82) g. There were 347 patients (60.3%) of acute glomerular diseases, 136 patients (23.7%) of acute interstitial nephritis, 47 patients (8.2%) of thrombotic microangiopathy, and 45 patients (7.8%) of acute tubular necrosis. The most common types of acute glomerular diseases were IgA nephropathy and anti-neutrophil cytoplasmic antibody-associated glomerulonephritis, accounting for 22.3% (128/575) and 12.2% (70/575), respectively. The clinical diagnoses before renal biopsy were consistent with the renal histopathological diagnoses in 454 patients, with an accuracy rate of 79.0%. Following the renal biopsy, the treatment plan involving glucocorticoids or immunosuppressants was adjusted in 394 patients (68.5%). Significant post-biopsy bleeding occurred in 15 patients (2.6%), with 12 patients requiring blood transfusion and 1 patient requiring surgical intervention.Conclusions:Twenty-one clinical diagnoses do not match the pathological diagnoses in adult AKD patients, 68.5% of patients have changes in their treatment plans, and 2.6% of patients have significant hemorrhagic complications after renal biopsy. Clinicians need to carefully consider the benefits and risks and make individualized decisions about renal biopsy.

Objective To establish a method for the simultaneous determination of aconitine,neoaconitine,hypaconitine,benzoyl aconitine,benzoyl mesaconine and benzoylhypacoitine in Xiaozhong ointment by UPLC-TQD-MS.Methods ACQUITY UPLC BEH C18 column(50 mm ×2.1 mm,1.7 μm),mobile phase 0.1％formic acid water(A)-acetonitrile(B),gradient elution,column temperature 40 ℃,flow rate 0.3 mL·min-1,injection volume 5 μL;electrospray ionization source(ESI+)and multiple reaction monitoring(MRM)were used for mass spectrometry analysis.Results The concentration of aconitine,new aconitine,hypaconitine,benzoyl aconitine,benzoyl new aconitine and benzoyl hypaconitine were 1.0-100.0 ng·mL-1,respectively,the average recovery were 98.62％-101.24％.The mass fractions of the six components were 0.18,0.33,0.38,0.43,0.28,0.06μg·g-1.Conclusion The method can be used to determine the content of 6 aconitine-type alkaloids in Xiaozhong ointment,and provide reference for the quality evaluation and clinical safe use of Xiaozhong ointment.

Objective To develop the functions and optimize the automatic monitoring module for arrhythmias of the adverse drug event active surveillance and assessment system-Ⅱ,in order to continuously improve the performance,enhance the monitoring efficiency,and explore the ways to optimize the module.Methods Expand and optimize the functions of the module,increase the customized configuration,and determine the optimal setting conditions;compare the optimized test data with the results of the evaluation studies on the automatic monitoring of drug-induced arrhythmias in large samples of medicated population previously,and verify the optimization extent as well as the accuracy of the module.Results In the new module optimized according to the characteristics of the monitoring population,the function of"mandatory medical order keywords"was added,and it was determined that the inclusion of 6 electrocardiogram examination-related medical order keywords with a frequency of not less than 2 occurrences was the optimal configuration condition for the optimization of the module;combining the results of the previous automatic monitoring and evaluation researches,the system functions were verified and compared under the conditions of using the whole drugs and 2 kinds of single drug.While there was no loss of true positive cases,the number of cases with system alarms decreased by 30.75％,80.13％and 90.82％,respectively,compared with that before the optimization of the module,and the positive predictive value was significantly improved.Conclusion After the function expansion and optimization,the automatic monitoring module of drug-induced arrhythmias significantly reduces the labor cost of case evaluation and keeps the accuracy of monitoring results constant;the new module can better adapt to the demands of different automatic monitoring modes and operates stably,which is more generalizable and flexible,and provides a new way of considering for the research and development of automatic monitoring modules.