OBJECTIVE To compare the anti-hepatitis mechanisms of Abrus pulchellus subsp. cantoniensis （Hance） Verdc. （AC） and Abrus pulchellus subsp. mollis（Hance） Verdc. （AM）. METHODS SD rats were randomly divided into blank group， AC- treated group， and AM-treated group， with each group consisting of 10 rats. The rats’ orbital venous blood was collected at 5， 15， 30 minutes， and 1， 1.5， 2， 4， 6， 8， 12 hours after gavage administration of 24 g/kg of the corresponding drug （calculated by crude drug） or water， respectively. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry technology was utilized to identify the prototype components present in the serum. The network pharmacology method was adopted to predict the anti-hepatitis active components， key targets， and signaling pathways of AC and AM. Additionally， molecular docking technology was utilized to verify the binding activity of the core active components with key targets. RESULTS A total of 35 prototype components migrating to the blood of AC and AM were identified in the serum of administered rats， among which 24 were common components. The active components in AC， such as acetylanguidine， physcion， soyasaponin A3 and soyasaponin Ⅰ， as well as those in AM， including vicenin 3， acetylanguidine，soyasaponin Ⅰ and schaftoside， all acted on key targets such as steroid receptor coactivator， phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit alpha， epidermal growth factor receptor （EGFR）， and protein kinase B1（Akt1）. These components modulated pathways in cancer， EGFR tyrosine kinase inhibitor resistance， and the phosphoinositide 3-kinase （PI3K） -Akt pathway， thereby exerting anti-hepatitis effects. Furthermore， the binding energies between these active components and their key targets were all less than －5 kJ/mol. CONCLUSIONS There are differences in the active components of AC and AM against hepatitis， but their mechanisms of action are similar. Both may exert their anti-hepatitis effects through pathways in cancer， EGFR tyrosine kinase inhibitor resistance， and the PI3K-Akt pathway.

BACKGROUND: Leukocyte telomere length (LTL) shortening, a biomarker of telomere attrition, has been linked to multiple diseases. However, the relationship between LTL and digestive diseases remains uncertain. This study aimed to investigate the association between LTL and the risk of digestive diseases. METHODS: A cohort analysis of over 500,000 participants from the UK Biobank (UKB) between 2006 and 2021 was conducted to estimate the associations of LTL with more than 90 common digestive diseases. LTL was quantified using multiplex quantitative polymerase chain reaction, and cases of each disease were determined according to inpatient and primary care data. Multivariable Cox proportional hazards regression analysis was used to evaluate the associations of LTL with the risk of digestive diseases. Furthermore, such associations were also evaluated after stratification by sex and ethnicity. RESULTS: After a mean follow-up time of 11.8 years, over 20 International Classification of Diseases, 10th Revision ( ICD-10 ) codes were showed to be associated with telomere attrition. LTL shortening is associated with an increased risk of several digestive diseases, including gastroesophageal reflux disease (K21: hazard ratio [HR] = 1.30, 95% confidence interval [95% CI]: 1.19-1.42), esophageal ulcer (K221: HR = 1.81, 95% CI: 1.22-2.71), Barrett's esophagus (K227: HR = 1.58, 95% CI: 1.14-2.17), gastritis (K29: HR = 1.39, 95% CI: 1.26-1.52), duodenal ulcer (K26: HR = 1.55, 95% CI: 1.14-2.12), functional dyspepsia (K30X: HR = 1.36, 95% CI: 1.06-1.69), non-alcoholic fatty liver disease (NAFLD) (K760: HR = 1.39, 95% CI: 1.09-1.78), liver cirrhosis (K74: HR = 4.73, 95% CI: 3.27-6.85), cholangitis (K830: HR = 2.55, 95% CI: 1.30-5.00), and hernia (K43: HR = 1.50, 95% CI: 1.17-1.94; K44: HR = 1.29, 95% CI: 1.17-1.42). The risk of rectal polyps (K621: HR = 0.77, 95% CI: 0.63-0.92) decreased per unit shortening of LTL. CONCLUSIONS This study suggests that LTL shortening is associated with an increased risk of most digestive diseases except for rectal polyps. These findings may provide some clues for understanding the pathogenesis of digestive diseases.
Humans ; Male ; Female ; Middle Aged ; Cohort Studies ; Leukocytes/metabolism* ; Telomere/genetics* ; Proportional Hazards Models ; Adult ; Digestive System Diseases/genetics* ; Aged ; Risk Factors ; Telomere Shortening

Objective:To compare the efficacy of gasless robotic surgery via transaxillary approach and combined axillary-retroauricular approach for unilateral N1b PTC, and to explore the safety and effectiveness of gasless robotic surgery via transaxillary approach for unilateral N1b PTC. Methods:Unilateral N1b PTC patients who underwent surgery in the Department of Otolaryngology, Sun Yat Sen Memorial Hospital, Sun Yat sen University between July 2016 and December 2024 were included and analyzed. According to the inclusion and exclusion criteria and the differences of surgical approaches, the patients were divided into the transaxillary approach（TA） group and the combined axillary-retroauricular approach（TARA） group. The demographic data, operation time, intraoperative blood loss, postoperative drainage volume, postoperative complications, shoulder function evaluation, postoperative visual analogue scale（VAS） of neck aesthetics and recurrence of the two groups were statistically analyzed. Results:A total of 88 patients undergoing gasless robotic surgery were included in this study, including 23 cases in the TA group and 65 cases in the TARA group. The proportion of males in the TA group was significantly higher than that in the TARA group（56.5% vs 21.5%, χ²=9.776, P=0.002）. The total operation time in the TA group was significantly lower than that in the TARA Group（180.00[155.00, 220.00]min vs 220.00[177.50, 272.50]min, z=-2.775, P=0.006）, and the postoperative blood loss in the TA group was significantly lower than that in the TARA Group（30.00[20.00, 50.00]ml vs 50.00[30.00, 60.00]ml, Z=-2.127, P=0.033）. The proportion of area Ⅱ-Ⅴ in the TA group and the TARA group was 87.0% and 70.8%, respectively, and there was no significant difference between the two groups（P>0.05）. There was no significant difference in lateral cervical lymph node dissection and central lymph node dissection between the two groups（P>0.05）. During the follow-up period, no recurrence was found in the two groups, and there was no significant difference in the incidence of complications between the two groups（P>0.05）. According to the stratification of dynamic recurrence risk assessment, it can be seen that the proportion of curative effect satisfaction in the TA group was as high as 95.7%, and that in the TARA group was as high as 81.5%, with no significant difference between the two groups. There was no significant difference in VAS score of neck, Constant Shoulder Score and NDⅡ scale between the two groups（P>0.05）. Conclusion:Gasless robotic surgery via transaxillary approach for unilateral N1b PTC is safe and feasible, and the amount postoperative lymph node acquisition is equivalent to that of combined axillary-retroauricular approach, which can provide a new choice for the treatment of unilateral N1b PTC patients.
Humans ; Robotic Surgical Procedures/methods* ; Axilla/surgery* ; Male ; Female ; Operative Time ; Middle Aged ; Adult ; Treatment Outcome ; Postoperative Complications

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective:To analyze and summarize the efficacy and safety of thalidomide in the treatment of refractory systemic juvenile idiopathic arthritis（sJIA）.Methods:The clinical data of ten patients with refractory sJIA admitted to Department of Nephrology and Immunology in Children's Hospital of Hebei Province from January 2015 to March 2022 were collected，and the clinical manifestations，efficacy and safety of thalidomide in the treatment of refractory sJIA were analyzed retrospectively. Systemic juvenile arthritis disease activity score（sJADAS）was used to evaluate the efficacy of the treatment. Statistical analysis was performed by repeated measurements using general linear models.Results:Among the 10 children（4 males and 6 females）with refractory sJIA，the average age of onset was（7.5±3.3）years. Seven patients were complicated with macrophage activation syndrome at an early stage of disease.The average course of disease was（4.4±1.7）years，and the longest course of disease was 8.3 years. Before the application of thalidomide，all the 10 children experienced relapses（ranging from 2 to 10 times）. The indices of 10 children treated with thalidomide at 6 months and 12 months were compared with those before treatment. Peripheral blood leukocytes［（10.19±3.67）×10 9/L，（8.53±2.83）×10 9/L vs.（16.11±7.81）×10 9/L， F=7.918，11.084， P=0.020，0.009］，C-reactive protein［19.13（0.38，35.21）mg/L，8.05（0.10，18.00）mg/L vs. 59.34（24.20，131.90）mg/L， F=7.030，12.731， P=0.026，0.006］，sJADAS scores［6.00（1.50，12.50）scores，3.00（0，12.50）scores vs. 20.00（11.50，28.00）scores， F=14.710，17.870， P=0.004，0.002］were decreased significantly. The doses of prednisone［0.13（0，0.45）mg/（kg·d），0.02（0，0.06）mg/（kg·d）vs. 0.42（0.16，1.47）mg/（kg·d）， F=5.890，7.623， P=0.041，0.022］were significantly decreased.All the differences were statistically significant. Prednisone was successfully discontinued in 7 cases. Tocilizumab was gradually withdrawn in 3 cases，and tocilizumab administration interval was prolonged in 1 case. None of the 10 children had serious adverse reactions. Conclusion:Thalidomide is clinically effective in the treatment of sJIA，and can reduce the required dose of prednisone and prolong the tocilizumab free remission.

Objective:To analyze the problems and risk factors of the investigator initiated out-of-range trial, propose countermeasures and suggestions, and provide reference for improving project standardization and quality, and preventing research risks.Methods:Through literature analysis and field research, combined with personal work experience, this study sorted and analyzed the problems in the regulation of out-of-range IIT conducted in hospital, and proposed countermeasures.Results:Through analysis, it was found that the current out-of-range IIT trial in China faces 5 problems: imperfect management regulations, incomplete IIT management organizational system in medical institutions, insufficient scientificity of research protocols, insufficient ethical review, and insufficient research funds.Conclusions:Out-of-range IIT is of great significance in promoting pharmaceutical innovation. Standardized management of such projects requires the efforts of regulatory authorities, medical institutions, and ethics committees, as well as the continuous improvement of researchers' awareness and research capabilities to promote the orderly, high-quality, and rapid development of IIT. Based on the above analysis, this article proposed countermeasures and suggestions: at the national level, summarize practical experience from various regions as soon as possible, improve IIT management regulations and technical guidelines; establishing clinical research and design guidance departments in medical institutions and strengthening scientific review; the ethics committee formulates ethical review standards and processes for out-of-range IIT projects to enhance review capabilities; establish a normalized clinical research training mechanism in hospitals; expand and standardize the channels for IIT funding.

Objective: To analyze the influencing factors for hospitalization costs among stroke patients with different subtypes, so as to provide the reference for reducing the economic burden of patients. Methods: Data of patients with hemorrhagic or ischemic stroke who were discharged from hospitals in Nanshan District, Shenzhen City from January 1, 2016 to December 31, 2021 were collected through Hospital Information System. Hospitalization costs were analyzed between hemorrhagic and ischemic stroke patients, and factors affecting hospitalization costs among stroke patients with different subtypes were identified using a structural equation model. Results: A total of 10 298 patients with stroke were recruited, including 2 820 patients with hemorrhagic stroke (27.38%) and 7 478 patients with ischemic stroke (72.62%). The patients with hemorrhagic stroke had a median duration of hospital stay of 19.00 (interquartile range, 18.00) d, and a median hospitalization cost of 26 759.48 (interquartile range, 51 000.87) Yuan. The patients with ischemic stroke had a median duration of hospital stay of 12.00 (interquartile range, 10.00) d, and a median hospitalization cost of 12 199.87 (interquartile range, 13 290.20) Yuan. Structural equation model analysis showed that department of hospitalization, discharge status, ways of leaving hospital, surgery and hypertension had direct effects on hospitalization costs and indirect effects on hospitalization costs through duration of hospital stay among hemorrhagic stroke patients, and duration of hospital stay had the highest total effect (0.684), followed by surgery (0.632). Employment status, admission route, department of hospitalization, ways of leaving hospital, payment mode, surgery and dyslipidemia had direct effects on hospitalization costs and indirect effects on hospitalization costs through duration of hospital stay among ischemic stroke patients, and duration of hospital stay (0.746), surgery (0.424) and department of hospitalization (0.151) ranked the top three in total effects. Conclusion The hospitalization cost is relatively high among stroke patients in Nanshan District, and duration of hospital stay and surgery have great influence on hospitalization costs among stroke patients with different subtypes.

Objective:To predict the molecular mechanism of Biminkang Granules in the treatment of allergic rhinitis using network pharmacological methods combined with animal experiments.Methods:Active component targets and allergic rhinitis targets were screened from TCMSP, OMIM, GeneCards, TTD, DrugBank and PharmGKB databases; R language software was used to map the intersection of drug and disease targets; Cytoscape software and String platform were used to construct intersection target PPI network and conduct network topology analysis; DAVID platform was used to perform GO enrichment and KEGG pathway analysis, and perform molecular docking verification on the main active components and key targets. 32 rats were divided into a blank group of 8 and a model group of 24 using a random number table method. Model rats were induced by ovalbumin to establish an allergic rhinitis model. 24 SD rats that were successfully modeled and were randomly divided into model group, Western medicine group, and Biminkang Granules group using a random number table method, with 8 rats in each group. The Western medicine group was gavaged with 1 mg/kg of loratadine solution, the Biminkang Granules group was gavaged with 4.1 g/kg of Biminkang Granules solution, and the blank group and model group rats were gavaged with the same volume of physiological saline once a day for 2 consecutive weeks. The symptoms of rhinitis in each group of rats for 30 minutes were observed and recorded, and the pathological changes of the rat nasal mucosa were observed using HE staining. ELISA method was used to detect the levels of IL-17 and IL-6 in rat serum, and Western blot method was used to determine the expressions of TNF and STAT3 proteins in rat tissues.Results:A total of 41 target proteins of BiMinKang Dranule in the treatment of allergic rhinitis were predicted, and TNF, STAT3 and other core target proteins were obtained by PPI network topology analysis. The biological process of GO involved drug response, inflammatory response, cytokine response, etc.KEGG enrichment is involved in Th17 cell differentiation, lipid and atherosclerosis, IL-17, toll-like receptor and other pathways. Molecular docking results indicated that the main active components had good binding activity to key target proteins.Animal experiments showed that BiMinKang Dranule could improve the inflammatory symptoms of allergic rhinitis rats, down-regulate the expression of IL-17 and IL-6 in blood, and inhibit the expression of TNF and STAT3 proteins.Conclusion:Biminkang Granules can treat allergic rhinitis through multiple active components, multiple target proteins and multiple pathways, and the mechanism may be related to the regulation of Th17 cell differentiation pathway related proteins.

Objective To optimize the spray drying process of Banlangen(Isatidis Radix)formula granules based on quality by design(QbD)concept.Methods Using powder yield and the contents of uridine,adenosine,guanosine,and(R,S)-goitron as the critical quality attributes(CQAs),Plackett-Burman design was used to screen out critical process parameters(CPPs)for inlet temperature,spray pressure,liquid temperature,pump speed,and liquid relative density.The central-composite design(CCD)test was used to optimize the CPPs,which were screened.Based on the quadratic polynomial regression model,the design space of spray drying process of Banlangen(Isatidis Radix)formula granules was established,and further validated by experiments.Results Plackett-burman test results show that liquid relative density and inlet velocity are the key parameters for the study.The variance analysis results of CCD test showed that the constructed model in a good prediction ability,since the P-values of model was less than 0.01 and P-values of items lack of fit was more than 0.05.The optimized design space of CPPs was the liquid relative density 1.05-1.08,and pump speed 30%-40%.Conclusion Based on the QbD concept,the design space for the spray drying process of Banlangen(Isatidis Radix)formula granules can improve the stability of its process and help ensure the consistency of product quality.

BACKGROUND:Tyrosine kinase inhibitors,as well as other types of small-molecule cancer drugs,can cause severe cardiotoxicity. OBJECTIVE:To perform a heart safety re-evaluation by observing the effects of antitumor drugs on isolated heart electrocardiograph,cardiac action potential and associated ion channels and cytotoxicity. METHODS:Extracorporeal cardiac perfusion was given to the isolated rabbit heart using Langendorff perfusion:Sunitinib(0.3,3,10 μmol/L),Crizotinib(0.3,1,3 μmol/L),and Doxorubicin(1,30 μmol/L)were perfused sequentially for 120 minutes to record electrocardiograph and left ventricular pressure.A blank control group was set for comparison.Manual patch clamp was used to record the effects of Crizotinib,Sunitinib,Doxorubicin on hERG,Cav1.2,Nav1.5 channel currents and action potential in human induced pluripotent stem cell derived cardiomyocytes.Adenosine triphosphate level in human induced pluripotent stem cell derived cardiomyocytes was detected by CellTiter-Glo luminescent cell viability assay. RESULTS AND CONCLUSION:Isolated rabbit heart using Langendorff perfusion:Compared with the blank ontrol group,Sunitinib and Crizotinib at≥3 μmol/L decreased heart rate(P<0.01)and prolonged QT/QTc interval(P<0.01),and reduced left ventricular pressure to different extents.Manual patch clamp recording:Compared with the blank control group,Sunitinib and Crizotinib at 3 μmol/L inhibited the activities of hERG,Nav1.5 and Cav1.2 channels and significantly prolonged the duration of action potential(P<0.01).According to the analysis of the test article,the difference between the labeled concentration and the measured concentration of the recovered solution was not significant.Cell viability assays:Compared with the blank control group,adenosine triphosphate content in human induced pluripotent stem cell derived cardiomyocytes significantly decreased after treatment with Sunitinib(IC50=4.64 μmol/L),Doxorubicin(IC50=4.21 μmol/L)and Crizotinib(IC50=2.87 μmol/L),indicating that cell viability significantly decreased(P<0.01).To conclude,this study successfully established an early cardiac safety evaluation method for antitumor drugs,which provides good support and help for the subsequent development of antitumor drugs.