ObjectiveTo investigate the mechanism of salt processing of Psoraleae Fructus （PF） through modern analytical techniques and biotechnology， focusing on its effects related to hepatotoxicity and anti-osteoporosis activity. MethodsThe zebrafish model was utilized to evaluate the impact of PF and salt-processed Psoraleae Fructus （SPF） on the hepatotoxicity （using 134.17 ， 178.89， 268.34 mg·L^-1 as low， medium， and high dose groups of PF， 135.04， 180.06， 270.08 mg·L^-1 as low， medium， and high dose groups of SPF， respectively） and anti-osteoporotic activity （using 33.54 ， 67.08 and 134.17 mg·L^-1 as low， medium， and high dose groups of PF， 33.76， 67.52， 135.04 mg·L^-1 as low， medium， and high dose groups of SPF， respectively）， which was using alizarin red skull staining of zebrafish as an indicator of different batches of PF. The specific dosage of a batch of PF was taken as an example. Then ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry（UPLC-Q-TOF-MS） analysis was employed to identify the chemical composition of PF before and after salt processing， and PCA， OPLS-DA， and independent sample t-test were used to elucidating the compositional changes associated with the effects of salt processing on hepatotoxicity and anti-osteoporosis activity. ResultsUnder specific conditions， PF induced notable hepatotoxicity in zebrafish while simultaneously demonstrating protective effect against prednisolone-induced osteoporosis. In comparison to PF， SPF showed alleviated hepatotoxicity while retaining significant anti-osteoporosis activity. UPLC-Q-TOF-MS analysis revealed that after salt processing， the overall chemical composition of PF showed a downward trend， with 69 components showing a decrease in content， represented by psoralen， and 13 components showing an increase， represented by 4′-O-methyl psoralen B. Further multivariate statistical analysis revealed 11 key differential components before and after salt processing of PF， including psoralen and bakuchiol. ConclusionSalt processing effectively diminishes hepatotoxicity without impairing therapeutic efficacy against osteoporosis of PF， which may be related to the compositional changes before and after salt processing of PF and provides key evidence to reveal the scientific significance of salt processing of PF.

As a new type of model organism， zebrafish is gradually gaining prominence in the field of scientific research. The unique biological characteristics and advantages of zebrafish make them play an increasingly important role in the quality evaluation of traditional Chinese medicine. Compared with other common experimental animals， zebrafish have a fast reproductive and growth speed and high embryo transparency， making them an ideal model for evaluating the quality of traditional Chinese medicine. This provides a new perspective and method for research on traditional Chinese medicine. With the growing global interest in traditional Chinese medicine， it has become crucial to find scientific and accurate methods to evaluate the quality and effectiveness of traditional Chinese medicine. The introduction of the zebrafish model has brought new breakthroughs in the quality evaluation of traditional Chinese medicine. To further promote the application of zebrafish in evaluating the quality of traditional Chinese medicine， this article systematically searched and sorted out the previous studies related to the application of zebrafish for this purpose since 2023. The commonly used disease models and indicators of zebrafish in evaluating the effectiveness of traditional Chinese medicine， as well as the mechanism of zebrafish in exploring the active ingredients of traditional Chinese medicine， were primarily reviewed. The application of zebrafish in evaluating the safety of traditional Chinese medicine and the typical examples in ensuring the quality of traditional Chinese medicine were demonstrated. The limitations encountered by zebrafish models in evaluating the quality of traditional Chinese medicine were highlighted. The resolution of these problems will help further improve the accuracy and reliability of zebrafish in evaluating the quality of traditional Chinese medicine. The article discussed the evaluation of effectiveness， safety， and quality control of zebrafish applied in traditional Chinese medicine， so as to provide a reference for establishing standards for traditional Chinese medicine and promoting its modernization in the future.

ObjectiveBased on the zebrafish model， the hepatotoxicity and anti-osteoporotic activity of evodiamine （EVO） were studied. The mechanism of EVO in treating osteoporosis was explored by using network pharmacology and real-time polymerase chain reaction（Real-time PCR）. MethodsThree days after fertilization （3 dpf）， zebrafish were randomly selected and exposed to different concentrations of EVO solution for 96 hours. The mortality rate of zebrafish at different concentrations was calculated at the exposure endpoint， and a "dose-toxicity" curve was drawn. The 10% lethal concentration （LC₁₀） was calculated. Liver phenotype， acridine orange staining， and pathological tissue sections of liver-transgenic zebrafish ［CZ16 （gz15Tg.Tg （fabp 10a： ds Red； ela31： EGFP））］ were used to confirm hepatotoxicity of EVO. On this basis， prednisolone was used to create a model of osteoporosis in zebrafish. The skull development， area of the skull stained by alizarin red， and cumulative optical density were used as indicators to evaluate the anti-osteoporotic activity of EVO in a safe dose. Based on network pharmacology， the mechanism of action of EVO in the treatment of osteoporosis was predicted and verified through Real-time PCR. ResultsThe LC₁₀ of EVO on zebrafish （7 dpf） was determined to be 0.4 mg·L^-1. Compared with the control group， sublethal concentrations （10=0.36 mg·L^-1 and 1/2LC₁₀=0.18 mg·L^-1） significantly decreased the fluorescence area of zebrafish liver （P<0.05，P<0.01） and increased the number of liver cell apoptosis. The arrangement of liver tissue was disordered and loose， and the vacuole was obvious， especially in the 0.36 mg·L^-1 group. Compared with the control group， under safe dose conditions， 0.08 and 0.02 mg·L^-1 of EVO had no significant effect on the liver. Prednisolone administration significantly reduced the mineralization area and cumulative optical density of zebrafish skulls （P<0.01） compared with the control group. The mineralization area and cumulative optical density of zebrafish skulls in the 0.08 and 0.02 mg·L^-1 groups of EVO were significantly increased compared with the model group （P<0.01）. Network pharmacology prediction suggested that EVO may regulate key targets such as avian sarcoma viral oncogene homolog （SRC）， signal transducer and activator of transcription 3 （STAT3）， interleukin-8 （CXCL8） and tyrosine kinase receptor 2 （ERBB2） to regulate signaling pathways related to lipid and atherosclerosis in diabetic complications， as well as the regulation of inflammatory mediators of tryptophan （TRP） channels. Real-time PCR experiment results indicated that EVO could regulate the above-mentioned targets， as well as genes related to osteoblasts and osteoclasts. ConclusionExcessive doses of EVO can lead to hepatotoxicity in zebrafish. Under safe dosage conditions， EVO can regulate relevant targets to exert anti-osteoporotic activity， providing a reference for the clinical safe use of EVO and ideas for the development of new drugs for osteoporosis.

Objective: To identify the risk factors for pulmonary arterial hypertension(PAH) in maintenance peritoneal dialysis(MPD) patients and to develop and validate a nomogram-based risk-prediction model. Methods: A total of 168 hospitalized MPD patients from the Department of Nephrology were enrolled.Body-fluid composition was measured by bioelectrical impedance analysis,and pulmonary-artery systolic pressure(PASP) was assessed by echocardiography.Patients were randomly allocated into a training set and a validation set at 1:1 ratio.Variables with P< 0. 05 in multivariable Logistic regression in the training set were incorporated to construct a nomogram .The validation set was used to test the model ’s predictive performance . ROC curves , calibration curves , and decision-curve analysis were applied to evaluate accuracy , consistency , and clinical usefulness of the model . Results: Dialysis vintage ( OR : 1 . 038 , 95% CI: 1 . 008 - 1 . 069 , P = 0. 012) , hemoglobin level ( OR : 0. 961 , 95% CI: 0. 929 - 0. 994 , P = 0. 021) , and extracellular water/intracellular water ratio (E/I) (OR : 1 . 069 , 95% CI: 1 . 024- 1 . 115 , P = 0. 002) were independent risk factors for PAH . ROC analysis yielded area under curve as 0. 867 (95% CI: 0. 782 - 0. 953) and 0. 808 (95% CI: 0. 714 - 0. 902) in the training and validation sets , respectively .Calibration plots showed that the predicted curves for both the training and validation sets closely overlapped with the ideal reference line , indicating that the nomogram risk-prediction model had good predictive performance . Decision-curve analysis demonstrated that , within threshold ranges of 0. 13 - 0. 76 ( training set ) and 0. 20 - 0. 76 (val- idation set ) , clinical net benefit was substantial when interventions were guided by the nomogram . Conclusion Dialysis vintage , hemoglobin level , and fluid-overload index (E/I) are independent risk factors for PAH in MPD patients . The nomogram based on these parameters reliably predicts PAH risk and may aid clinical decision-making.

Polyphyllin Ⅰ(PPⅠ)and polyphyllin Ⅱ(PⅡ)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be elucidated.In this work,we found that PPⅠ and PⅡ exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent manner.The results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepa-totoxicity of PPⅡ and PⅡwas associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor lovastatin.Additionally,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the choles-terol synthesis,selected as the potential targets,were confirmed by the molecular docking,the over-expression,and knockdown of HMGCR or SQLE with siRNA.Finally,the pull-down and surface plasmon resonance technology revealed that PPⅠ could directly bind with SQLE but not with HMGCR.Collectively,these data demonstrated that PPⅠ-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis pathway.The findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future.

Objective : To investigate the status and influencing factors of home blood pressure monitoring (HBPM) among hypertensive patients, so as to provide the evidence for building and maintaining HBPM among hypertensive patients. Methods: Hypertensive patients hospitalized in the First Affiliated Hospital of Guangdong Pharmaceutical University were sampled from July to December 2022, and subjects' general data, HBPM behaviors and cognition were collected using self-designed questionnaires. In addition, factors affecting regular HBPM were identified using a multivariable logistic regression model. Results: Totally 440 questionnaires were allocated, and 422 valid questionnaires were recovered, with an effective recovery rate of 95.91%. The respondents included 234 males (55.45%) and 188 females (44.55%), and had a median age of 70 (interquartile range, 15) years. There were 239 respondents with regular HBPM (56.64%). Of 422 respondents, 68 had good cognition of blood pressure monitoring (16.11%), and 79.15% did not think regular changes of their blood pressure within 24 hours, while 72.04% did not think it necessary to measure blood pressure more than twice a day. Multivariable logistic regression analysis showed that recommendation of regular blood pressure monitoring by healthcare workers (OR=4.341, 95%CI: 2.493-7.560), number of blood pressure measurements according to real circumstances (OR=3.858, 95%CI: 1.358-10.961), recording of measurement results (OR=4.945, 95%CI: 1.863-13.129), provision of data to doctors at admission (OR=2.023, 95%CI: 1.173-3.488) and good cognition of blood pressure monitoring (good, OR=11.939, 95%CI: 3.972-35.886; general, OR=9.681, 95%CI: 5.157-18.172) resulted in a high possibility of regular HBPM among respondents. Conclusion Hypertensive patients with recommendation of regular blood pressure monitoring by healthcare workers, number of blood pressure measurements according to real conditions, recording of blood pressure measurement results, provision of blood pressure to doctors at admission and good cognition of blood pressure monitoring are more likely to have regular HBPM.

Objective:To systematically analyze and integrate the psychological experience of heart failure patients using mobile medical applications (App) for self-management.Methods:Qualitative research on the self-management experience of heart failure patients using mobile medical App was retrieved through computer on PubMed, Web of Science, Embase, Cochrane Library, CINAHL, PsycINFO, Australian Joanna Briggs Evidence-Based Health Care Center Database, China National Knowledge Infrastructure, WanFang Data, VIP, and China Biomedical Literature Database. The search period was from the establishment of the database to December 30, 2022. The quality of literature was evaluated in accordance with the quality evaluation criteria for qualitative research of the Joanna Briggs Institute Evidence-Based Health Care Center (2016) . The results were integrated using the aggregative integration method.Results:A total of 14 articles were included, 32 research results were extracted, and 7 new categories were summarized. Finally, three integrated results were obtained (positive experience of heart failure patients using mobile medical App, risks and challenges of heart failure patients using mobile medical App, and preferences and expectations of heart failure patients towards mobile medical App) .Conclusions:The mobile medical App provides new ideas for self-management of heart failure patients, and its effectiveness is recognized by most heart failure patients, who perceive significant benefits. Future research should enrich the functionality and participation forms of the App based on the personalized needs of patients and their families, explore remote health management intervention models at home, and promote the promotion and application of mobile medical App.

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

Objective To study urodynamic changes of urine at different degrees of hydronephrosis based on computational fluid dynamics (CFD) method, so as evaluate the influence of hydronephrosis degree on kidneys’ ability to discharge stones. Methods Twelve models, including the branched pelvis Model A (normal hydronephrosis A1, mild hydronephrosis A2, medium hydronephrosis A3, severe hydronephrosis A4 models), mature ampullary pelvis Model B (normal hydronephrosis B1, mild hydronephrosis B2, medium hydronephrosis B3, severe hydronephrosis B4 models), and embryo pot abdominal pelvis Model C (normal hydronephrosis C1, mild hydronephrosis C2, medium hydronephrosis C3, severe hydronephrosis C4 models) were established. The urine flow velocity and velocity vector at the neck of the kidney, the outlet of the renal pelvis were calculated by CFD method. Results As the degree of hydronephrosis increased, the flow velocity of urine at the neck of the kidney and the outlet of the renal pelvis decreased. The urinary shearing force of the stones and the kidney’s ability to discharge stones gradually decreased, whereas the circulatory stagnation zone and the velocity boundary layer in kidney aggregate system gradually increased. Conclusions Hydronephrosis can cause changes in urodynamics of the urine. Therefore, the effect of hydronephrosis with different degrees on the patient’s ability to discharge stones after surgery should be fully considered， so as to choose an appropriate treatment method for kidney stones in clinic.

Objective:To explore the effect of improved urethral irrigation on urethral stricture in patients with closed bulbar urethral injury.Methods:The clinical data of 65 male patients with closed bulbar urethral injury complicated with difficult catheterization from January 2014 to January 2018 in the First Hospital of Shanxi Medical University were retrospectively analyzed. Among them, 30 cases were treated with flexible cystoscope-guided catheterization and external urethral orifice nursing (routine group), and 35 cases were treated with flexible cystoscope-guided catheterization and urethral drug flushing (improved group). The incidence of urethral stricture 1 and 6 months after catheter removal, number of urethral dilatation and maximum urinary flow rate 6 months after catheter removal, visual analogue score (VAS) during indwelling catheter were compared between 2 groups.Results:Both groups indwelled the catheters successfully. During indwelling catheter, the inflammatory secretion in improved group was less and thinner than that in routine group. There was no significant difference in the incidence of urethral stricture 1 month after catheter removal and VAS during indwelling catheter between 2 groups ( P>0.05); the incidence of urethral stricture and number of urethral dilatation 6 months after catheter removal in improved group were significantly lower than those in routine group: 5.7% (2/35) vs. 26.7% (8/30) and (7.1±1.0) times vs. (11.4±1.8) times, the maximum urinary flow rate 6 months after catheter removal was significantly higher than that in routine group: (19.8 ± 2.9) ml/s vs. (16.3±2.3) ml/s, and there were statistical differences ( P<0.05 or <0.01). Conclusions:The system of improved urethral irrigation can be easily fabricated and can achieve convenient application. This improved treatment can facilitate the discharge of urethral secretions, alleviate the urethral inflammation, reduce the urethral scar formation, and can prevent the incidence of bulbar urethral stricture effectively.