Objective: To verify the inhibitory effect of a carbon monoxide hemoglobin-based oxygen carrier (CO-HBOC) on the fibrotic process in mice with idiopathic pulmonary fibrosis (IPF), clarify its efficacy difference compared with hemoglobin-based oxygen carriers (HBOCs), and elucidate its mechanism of action via proteomic analysis. Methods: CO-HBOC was prepared using gas loading technology. An IPF mouse model was established and the mice were randomly divided into a normal saline control group, an HBOC treatment group, and a CO-HBOC treatment group. The fibrotic area percentage was analyzed using Micro-CT; the degree of inflammatory infiltration and fibrosis in lung tissue was assessed by pathological section staining (e.g., HE and Masson staining); and differentially expressed proteins in lung tissue of IPF mice after CO-HBOC treatment were screened using proteomic technology. Results: Micro-CT results showed that the mean fibrotic area percentage in the CO-HBOC treatment group on day 21 was (8.89±0.98)%, which was better than that of the HBOC group (16.5±1.732)% and the normal saline group (30.75±6.45)% (P<0.05). HE and Masson staining results showed that the CO-HBOC group had reduced inflammatory cell infiltration and significantly decreased collagen fiber deposition in lung tissue, with a mean pathological score of 3.33±0.58, which was lower than that of the normal saline control group (8.33±1.53)(P<0.05); the mean collagen-positive area percentage was (3.33±1.53)%, significantly lower than that of the normal saline control group (14.00±3.61)% (P<0.05). Proteomic analysis identified 330 differentially expressed proteins, which were mainly enriched in inflammatory response regulatory pathways (such as the complement and coagulation cascades), and the expression changes of complement proteins may be the core target of CO-HBOC's anti-fibrotic effects. Conclusion: CO-HBOC can inhibit inflammatory responses and regulate fibrosis-related signaling pathways, there-by effectively inhibiting the fibrotic process in IPF mice, with superior efficacy to HBOC. Its mechanism of action involves the regulation of complement cascade-related signaling pathways and complement protein expression, providing an experimental and theoretical basis for targeted therapy of IPF.

OBJECTIVE To establish the UPLC fingerprint and the method for multi-component content determination in Jingangteng capsules， and to evaluate its quality by combining chemical pattern recognition analysis. METHODS An UPLC method was established. Separation was performed on a Zorbax SB-C 18 Rapid Resolution HD column， with acetonitrile-0.1% formic acid as the mobile phase for gradient elution.Using the Similarity Evaluation System for Chromatographic Fingerprints of Traditional Chinese Medicines （2012 edition）， UPLC fi ngerprints were established for 10 batches of Jingangteng capsules， and similarity was evaluated. SPSS 22.0 and SIMCA 14.1 software were used to perform hierarchial-cluster analysis and orthogonal partial least squares discriminant analysis （OPLS-DA）， respectively. The same UPLC method was employed to determine the contents of chlorogenic acid， 3，5-dihydroxy-2-methylbenzoic acid-3- O -glucoside （M1）， caffeic acid， astilbin， oxyresveratrol， quercitrin and resveratrol in the 10 batches of samples. RESULTS A total of 17 common peaks were identified in UPLC fingerprints of the 10 batches of samples， of which 7 were identified as chlorogenic acid， M1， caffeic acid， astilbin， oxyresveratrol， quercitrin， and resveratrol. The similarities of 10 batches of samples ranged from 0.820 to 0.985. The results of hierarchial-cluster analysis showed that 10 batches of samples were grouped into four categories： S1-S4 formed one group， S5 and S6 formed another， S7， S8 and S10 formed a third， and S9 formed a fourth， consistent with the OPLS-DA results； the variable importance projection values for peaks 7， 10， 2， 16 （resveratrol）， 13 （oxyresveratrol）， 11， 6 （caffeic acid）， 5 （M1） and 15 （quercitrin） were ＞1. Quantitative analysis results showed that the contents of chlorogenic acid， M1， caffeic acid， astilbin， oxyresveratrol， quercitrin， and resveratrol were 1.650 8-4.213 7， 0.636 2-2.161 7， 0.031 0-0.086 5， 0.239 1-1.069 3， 0.211 9-1.104 0， 0.488 8-2.399 2， and 0.164 0-0.699 8 mg/g， respectively. CONCLUSIONS UPLC fingerprint and content determination methods established in this study are simple to operate， accurate， reliable and reproducible； when combined with chemical pattern recognition analysis， they can be used to evaluate the quality of Jingangteng capsules. Nine components， such as resveratrol， oxyresveratrol， caffeic acid， M1 and quercitrin， may serve as markers of quality variation.

Objective To develop a preoperative question prompt list(QPL)for older patients with benign prostatic hyperplasia(BPH)and evaluate its effectiveness in application.Methods This trial adopted a randomized controlled design.The QPL was developed by literature review,expert discussions,and Delphi consultation.Convenience sampling was used to subject 76 older BPH inpatients treated in our department,and then they were randomly divided into control(routine communication,n=38)and intervention(QPL-assisted communication,n=38)groups.Number of the questions patient asking,communication duration,information recall,and communication quality were compared between the 2 groups.Results In the 2 rounds of expert consultation,the response rate of questionnaire was 94.44%and 100%,the authority coefficient was 0.89 and 0.93,the coefficient of variation was 0.05～0.22 and 0～0.11,and Kendall's coefficients was 0.645(Chi-square=87.782,P<0.001)and 0.733(Chi-square=74.789,P<0.001),respectively.The final QPL included 3 themes and 7 questions.The intervention group asked more questions(4.03±1.89 vs 2.11±1.27,P<0.05)but spent similar time for communication(8.18±2.11 vs 7.67±1.72 min,P>0.05).At 1 d before discharge,better information recall(8.74±1.12 vs 6.49±1.68,P<0.001)and communication quality(60.06±6.25 vs 54.86±7.98,P<0.05)were observed in the intervention group when compared with the control group.Conclusion Our developed preoperative communication QPL is of scientificalness and effectiveness for elderly BPH patients.This tool can not only encourage question-asking behavior,but also improve information recall and communication quality in the patients.

Objective To establish a rapid analysis method for cyanide based on a ratiometric fluores-cent probe,providing a quantitative strategy for on-site visual and rapid detection of cyanide.Methods A dual-emission ratiometric fluorescent probe(AuNCs-FL)was constructed by using bovine serum al-bumin(BSA)-stabilized gold nanoclusters(AuNCs,fluorescence emission at 660 nm)as the responsive signal unit and fluorescein(FL,emission at 515 nm)as the internal reference.Results The etching effect of cyanide on AuNCs resulted in fluorescence quenching at 660 nm,while the fluorescence inten-sity of FL at 515 nm remained unchanged,enabling a rapid response analysis of cyanide shift from red to green fluorescence.The developed probe enabled rapid analysis of cyanide within 3 min,with a limit of detection(LOD)of 3.4 mg/L and a visual detection range of 10-100 mg/L.Conclusion The AuNCs-FL fluorescent probe is structurally simple,low-cost,and easy to operate,delivering rapid and accurate results.It also avoids the interference from sulfides encountered in commercial cyanide test kits,making it suitable for the on-site rapid detection of suspected powder samples in cyanide poisoning cases.

Objective To investigate the relationship of mindful attention awareness with sleep quality and occupational stress of soldiers.Methods A questionnaire survey was conducted on 1 100 soldiers by using the mindful attention awareness scale(MAAS),occupational stress scale(OSS),and Pittsburgh sleep quality index(PSQI).Results The PSQI of the soldiers was negatively correlated with mindful attention awareness(r=-0.446,P<0.01),and positively correlated with occupational stress(r=0.569,P<0.01).Mindful attention awareness and occupational stress were effective predictors for sleep quality,accounting for 34.7%of variance.And the mediating effect of occupational stress between mindful attention awareness and sleep quality accounted for 58.86%.Conclusion The mindful attention awareness in soldiers can not only directly affect the sleep quality,but also indirectly affect the sleep quality through their occupational stress.

Poor water solubility is the primary obstacle preventing the development of many pharmacologically active compounds into oral preparations. Self-nanoemulsifying drug delivery systems(SNEDDS) have become a widely used strategy to enhance the oral bioavailability of poorly soluble drugs by inducing a supersaturated state, thereby improving their apparent solubility and dissolution rate. However, the supersaturated solutions formed in SNEDDS are thermodynamically unstable systems with solubility levels exceeding the crystalline equilibrium solubility, making them prone to drug precipitation in the gastrointestinal tract and ultimately hindering drug absorption. Therefore, maintaining a stable supersaturated state is crucial for the effective delivery of poorly soluble drugs. Incorporating polymers as precipitation inhibitors(PPIs) into the formulation of supersaturated self-nanoemulsifying drug delivery systems(S-SNEDDS) can inhibit drug aggregation and crystallization, thus maintaining a stable supersaturated state. This has emerged as a novel preparation strategy and a key focus in SNEDDS research. This review explores the preparation design of SNEDDS and the technical challenges involved, with a particular focus on polymer-based S-SNEDDS for enhancing the solubility and oral bioavailability of poorly soluble drugs. It further elucidates the mechanisms by which polymers participate in transmembrane transport, summarizes the principles by which polymers sustain a supersaturated state, and discusses strategies for enhancing drug absorption. Altogether, this review provides a structured framework for the development of S-SNEDDS preparations with stable quality and reduced development risk, and offers a theoretical reference for the application of S-SNEDDS technology in improving the oral bioavailability of poorly soluble drugs.
Solubility ; Administration, Oral ; Polymers/chemistry* ; Drug Delivery Systems/methods* ; Humans ; Emulsions/chemistry* ; Biological Availability ; Animals ; Pharmaceutical Preparations/administration & dosage*

Automatic classification of medical questions is of great significance in improving the quality and efficiency of online medical services, and belongs to the task of intent recognition. Joint entity recognition and intent recognition perform better than single task models. Currently, most publicly available medical text intent recognition datasets lack entity annotation, and manual annotation of these entities requires a lot of time and manpower. To solve this problem, this paper proposes a medical text classification model, bidirectional encoder representation based on transformer-recurrent convolutional neural network-entity-label-semantics (BRELS), which integrates medical entity label semantics. This model firstly utilizes an adaptive fusion mechanism to absorb prior knowledge of medical entity labels, achieving local feature enhancement. Then in global feature extraction, a lightweight recurrent convolutional neural network (LRCNN) is used to suppress parameter growth while preserving the original semantics of the text. The ablation and comparison experiments are conducted on three public medical text intent recognition datasets to validate the performance of the model. The results show that F1 score reaches 87.34%, 81.71%, and 77.74% on each dataset, respectively. The results show that the BRELS model can effectively identify and understand medical terminology, thereby effectively identifying users' intentions, which can improve the quality and efficiency of online medical services.
Semantics ; Neural Networks, Computer ; Humans ; Natural Language Processing

ObjectiveTo compare the contents and relative molecular weight distributions of proteins and polypeptides in Naoxuekang dropping pills， Huoxue Tongmai capsules and Maixuekang capsules of Hirudo single medicinal preparations， to evaluate the in vitro anticoagulant， antiplatelet and fibrinolytic activities of the three preparations， and to investigate the effects of temperature， pH and digestive enzymes on the anticoagulant activities of the three preparations. MethodsThe contents of soluble proteins and polypeptides in the three preparations were determined by bicinchoninic acid assay（BCA） and Bradford method， and the relative molecular weight distributions of the three preparations were determined by electrophoresis combined with gel chromatography. The antithrombin activity of the three preparations was evaluated by fibrinogen-thrombin time（Fibg-TT） method， and their anticoagulant activities were further assessed by the elongations of activated partial thromboplastin time（APTT）， prothrombin time（PT） and thrombin time（TT）. The antiplatelet aggregation activities of the three preparations were measured by turbidimetry and the fibrinolytic activities were measured by fibrin plate method. Relative TT was used as index to investigate the effects of temperature， pH and digestive enzyme buffer on anticoagulant activities of the three preparations. ResultsAt the lowest single dosage， the contents of proteins and polypeptides were in the order of Maixuekang capsules>Huoxue Tongmai capsules>Naoxuekang dropping pills. Both Huoxue Tongmai capsules and Maixuekang capsules had 11 electrophoretic bands between 4.0 kDa and 90 kDa， the bands of Maixuekang capsules were more clear in the range of >25 kDa， and there was 1 obvious band at 14 kDa for the two capsules. Huoxue Tongmai capsules had one specific band at 9.0 kDa and Maixuekang capsules had one specific band at 48.0 kDa. Naoxuekang dropping pills only had 2 electrophoretic bands at 6.5 kDa and 8.5 kDa， primarily containing peptides below 2 kDa， most of which were oligopeptides. The anticoagulant activity concentrations of the three preparations exhibited a certain dose-dependent effect. At the lowest single dosage， The anticoagulant activity concentrations were ranked as Naoxuekang dropping pills>Huoxue Tongmai capsules>Maixuekang capsules. The prolongation effect of the three preparations on coagulation time was dose-dependent. At the same concentration， the prolongation effect of Naoxuekang dropping pills and Huoxue Tongmai capsules was APTT prolongation rate>TT prolongation rate>PT prolongation rate， whereas for Maixuekang capsules， the sequence was TT prolongation rate>APTT prolongation rate>PT lengthening rate. At the single minimum dosage， the order of APTT prolongation rate was Maixuekang capsules>Huoxue Tongmai capsules≈Naoxuekang dropping pills， the order of PT prolongation rate was Naoxuekang dropping pills≈Maixuekang capsules>Huoxue Tongmai capsules， and the order of TT prolongation rate was Maixuekang capsules>Huoxue Tongmai capsules>Naoxuekang dropping pills. The three preparations showed dose-dependent effects on platelet aggregation induced by adenosine diphosphate（ADP） and arachidonic acid（AA）， and the effect induced by ADP was stronger than that induced by AA. The anti-platelet aggregation effect of Naoxuekang dropping pills was significantly stronger than that of Maixuekang capsules（P<0.01）， whereas Huoxue Tongmai capsules had the effect of promoting platelet aggregation. None of the three preparations had the ability to dissolve fibrin. The anticoagulant activity of Naoxuekang dropping pills was least affected by heating， while the activities of the two capsules decreased significantly within 5 min above 80 ℃， and continued to decrease within 2 h. Compared with pure water， the anticoagulant activities of the three preparations could be increased by 1-3 times under strong acidity（pH 1-3）. In the pepsin buffer， the anticoagulant activity of Naoxuekang dropping pills could be increased by 1-3 times， while the anticoagulant activities of Huoxue Tongmai capsules and Maxuekang capsules were significantly decreased， the lowest levels were about 60% and 20%， respectively. In trypsin buffer， the anticoagulant activities of Naoxuekang dropping pills， Huoxue Tongmai capsules and Maixuekang capsules decreased significantly， and the lowest levels decreased to about 41%， 41% and 35%， respectively. ConclusionThe contents of proteins and polypeptides and relative molecular weights of the preparations derived from lyophilized fresh Hirudo powder， dried Hirudo powder and reflux extract of Hirudo decrease sequentially， and the anticoagulant activity decrease gradually， but the anticoagulant pathway is different. And the anti-platelet aggregation activity of the reflux extract is significantly enhanced. The heat resistance and gastrointestinal stability of the three preparations increase successively， and the first two are suitable for enteric-soluble preparations， while the latter is suitable for routine oral administration. The above results can provide data reference for the rationality of different preparation methods， active substances， pharmacodynamics and mechanism of Hirudo preparations.

Deactivation of the mitochondrial pyruvate dehydrogenase complex (PDC) is important for the metabolic switching of cancer cell from oxidative phosphorylation to aerobic glycolysis. Studies examining PDC activity regulation have mainly focused on the phosphorylation of pyruvate dehydrogenase (E1), leaving other post-translational modifications largely unexplored. Here, we demonstrate that the acetylation of Lys 488 of pyruvate dehydrogenase complex component X (PDHX) commonly occurs in hepatocellular carcinoma, disrupting PDC assembly and contributing to lactate-driven epigenetic control of gene expression. PDHX, an E3-binding protein in the PDC, is acetylated by the p300 at Lys 488, impeding the interaction between PDHX and dihydrolipoyl transacetylase (E2), thereby disrupting PDC assembly to inhibit its activation. PDC disruption results in the conversion of most glucose to lactate, contributing to the aerobic glycolysis and H3K56 lactylation-mediated gene expression, facilitating tumor progression. These findings highlight a previously unrecognized role of PDHX acetylation in regulating PDC assembly and activity, linking PDHX Lys 488 acetylation and histone lactylation during hepatocellular carcinoma progression and providing a potential biomarker and therapeutic target for further development.
Humans ; Acetylation ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/genetics* ; Pyruvate Dehydrogenase Complex/genetics* ; Gene Expression Regulation, Neoplastic ; Animals ; Mice ; Cell Line, Tumor ; Protein Processing, Post-Translational ; Histones/metabolism* ; Disease Progression

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*