OBJECTIVE To conduct a clinical comprehensive evaluation of five marketed thrombopoietin receptor agonists （TPO-RA） approved in China， providing quantitative evidence for drug selection and therapeutic decision-making in medical institutions. METHODS Relevant data on Romiplostim for injection， Eltrombopag olamine tablets， Herombopag olamine tablets， Avatrombopag maleate tablets， and Lusutrombopag tablets were collected. Based on the Chinese Rapid Guide for Drug Evaluation and Selection in Medical Institutions （Second Edition）， 12 formulations of these five TPO-RA were scored quantitatively and comparatively across five dimensions： pharmacological characteristics， efficacy， safety， cost-effectiveness， and other attributes. RESULTS The comprehensive scores of the 12 formulations ranged from 62.56 to 75.50 points， with most scoring ≥70 points. Using the highest-scoring formulation for each generic name as a representative， the overall rankings of the five TPO-RA were as follows： Lusutrombopag tablets （75.50 points）， Eltrombopag olamine tablets （75.10 points）， Avatrombopag maleate tablets （70.40 points）， Romiplostim for injection （63.93 points）， and Herombopag olamine tablets （63.52 points）. Lusutrombopag tablets scored relatively high in pharmacological characteristics， safety， and cost-effectiveness， while Eltrombopag olamine tablets performed well in efficacy and cost-effectiveness. The other formulations showed varying scores across evaluation dimensions. CONCLUSIONS The five TPO-RA demonstrate favorable overall clinical value， with Lusutrombopag tablets and Eltrombopag olamine tablets ranking higher in comprehensive scores， these two drugs should be prioritized in drug selection and formula optimization by medical institutions.

Background/Aims: Non-pharmacological treatments are crucial for managing irritable bowel syndrome (IBS), yet patient engagement remains a challenge. Understanding patients' knowledge, attitudes, and practices regarding these treatments is essential for improving care. Methods: A cross-sectional study was conducted across 5 hospitals, from October 2023 to February 2024. A self-designed knowledge, attitudes, and practices questionnaire along with the IBS quality of life and IBS severity scoring system was administered, and 496 valid responses were analyzed. Statistical analyses included correlation tests, multivariate linear regression, and mediation effect analysis. Results: The median scores for knowledge, attitude, and practice were 28, 25.5, and 21, respectively. Significant positive correlations were found between knowledge-attitude (r = 0.195), knowledge-practice (r = 0.364), and attitude-practice (r = 0.151). The multivariate linear regression analysis further indicated that knowledge (β = 0.399, P < 0.001) and attitude (β = 0.219, P = 0.022) positively correlated with the practical performance. SEM revealed that knowledge had a significant direct effect on both attitude (β = 0.186, P = 0.013) and practice (β = 0.356, P = 0.006). However, the direct effect of attitude on practice was not significant, and attitude did not mediate the relationship between knowledge and practice. Conclusions IBS patients exhibit a significant gap between their positive attitudes and their actual practices concerning non-pharmacological treatments. Knowledge is a direct driver of practice, but positive attitudes alone are insufficient to translate into behavior. Healthcare providers must move beyond simply fostering positive attitudes and focus on targeted educational interventions that provide actionable knowledge and skills to improve patient outcomes.

BACKGROUND:The micro/nanostructured gradient biomimetic surface of implant materials can simulate the structure of the extracellular environment in human bone tissue,thereby achieving perfect bone integration function.However,further research is needed on the mechanisms by which the surface microstructure of bone implant materials regulates cell function and promotes osteogenesis. OBJECTIVE:To analyze the effect of titanium sheet microstructure surface on osteogenic differentiation of MC3T3-E1 osteoblasts. METHODS:(1)At a constant voltage of 5 V or 20 V,nanotube arrays of different diameters were prepared on the surface of titanium sheets by acid etching and anodic oxidation techniques,and were recorded as group R5 and group R20,respectively.The surface morphology,roughness,and hydrophilicity of pure titanium sheet(without acid etching or anodizing treatment)were measured in group R5 and group R20.(2)MC3T3-E1 osteoblasts of logarithmic growth stage were inoculated on the surface of pure titanium sheets,R5 group and R20 group respectively.After 24 hours of osteogenic induction culture,the expression of mechanical sensitive channel protein 1 was analyzed by RT-PCR and immunofluorescence staining.Osteoblast inducible base with or without the mechanosensitive channel protein 1 activator Yada1 was added,and alkaline phosphatase staining was performed after 7 days of culture.Alizarin red staining was performed after 14 days of culture. RESULTS AND CONCLUSION:(1)The surface of pure titanium sheets was smooth under scanning electron microscope.Relatively uniform and orderly nanotube arrays with average diameters of about 30 nm and 100 nm were observed on the surface of titanium sheets of groups R5 and R20,respectively.The results of scanning electron microscope were further verified by atomic force microscopy.The surface roughness of titanium sheet of group R5 was higher than that of pure titanium(P<0.05),and the water contact angle was lower than that of pure titanium(P<0.05).The surface roughness of titanium sheet in group R20 was higher than that in group R5(P<0.05),and the water contact angle was lower than that in group R5(P<0.05).(2)RT-PCR and immunofluorescence staining showed that the expression of mechanosensitive channel protein 1 in group R5 was higher than that in pure titanium group(P<0.05),and the expression of mechanosensitive channel protein 1 in group R20 was higher than that in group R5(P<0.05).Under the osteogenic induction,compared with the condition without Yada1,there were no significant changes in the activity of alkaline phosphatase and the deposition of calcified nodules in pure titanium group after Yada1 addition,while the activity of alkaline phosphatase and the deposition of calcified nodules in groups R5 and R20 after Yada1 addition were significantly increased(P<0.05).With or without Yada1,the alkaline phosphatase activity and calcified nodule deposition in group R5 were higher than those in pure titanium group(P<0.05),and the alkaline phosphatase activity and calcified nodule deposition in group R20 were higher than those in group R5(P<0.05).(3)The results show that the surface microstructure of titanium sheet can promote the osteogenic differentiation of osteoblast MC3T3-E1 by activating mechanosensitive channel protein 1.

OBJECTIVE To investigate the regulatory effect of vitamin D3(VD3)-mediated TIPE2 on macrophage function and phenotype in chronic rhinosinusitis with nasal polyps(CRSwNP).METHODS Peripheral blood samples were collected from 100 CRSwNP patients and 100 patients with simple nasal septum deviation.RT-qPCR and Western blot were used to measure the expression of TIPE2 and Arg-1,and chemiluminescence was used to measure VD3 concentration.In the J774A.1 macrophage cell line,TIPE2 was silenced,and in CRSwNP model mice,TIPE2 was overexpressed,followed by treatment with overexpressed TIPE2 combined with VD3.Western blot was used to measure the expression of TIPE2 and Arg-1,and ELISA was used to measure the expression of IL-4 and IL-13.RESULTS In the CRSwNP group,VD3 levels decreased,while TIPE2 and Arg-1 levels increased(all P<0.05).Arg-1 and TIPE2 were positively correlated(r2=0.994,P<0.05),and both were negatively correlated with VD3 levels(r2=0.652,P<0.05;r2=0.745,P<0.05).Silencing TIPE2 in J774A.1 cells led to a decrease in Arg-1,IL-4,and IL-13 levels(all P<0.05).In CRSwNP mice,overexpression of TIPE2 resulted in decreased VD3 and increased Arg-1,IL-4,and IL-13 levels,which were reversed by VD3 treatment(all P<0.05).CONCLUSION VD3 inhibits the expression of Arg-1,IL-4,and IL-13 in CRSwNP by downregulating TIPE2 expression.

Objective To observe the clinical efficacy of Shujin Tougu Wash Recipe in the treatment of knee osteoarthritis and to analyze the changes in patients'serum metabolites before and after treatment.Methods A total of 30 patients with knee osteoarthritis were randomly divided into the observation group and the control group.Patients in the control group were treated with Glucosamine Hydrochloride Tablets.Patients in the observation group were treated with Shujin Tougu Wash Recipe.Two groups were treated for 3 weeks.The clinical efficacy was evaluated by observing the changes in the Visual Analogue Scale(VAS),Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC),and knee joint activity before and after treatment.Serum was collected from five patients from the observation group before and after treatment,and the changes in serum metabolites were detected by UPLC-MS untargeted metabolomics technology.Metabolic pathways were analyzed through the KEGG database.Results Compared with before treatment,the VAS and WOMAC scores of patients were reduced after treatment(P＜0.05),and the activity of the knee joint was increased(P＜0.05).Tthe Observation Group is better than the control group.There were 15 differential metabolites before and after treatment,among which the content of valproic acid,N-methylundecanamide,arachidonamide,spironolactone,propylene glycol,lysophosphatidylcholine,dehydroisoproporphyrinogen,and marcoticin increased after treatment,while the content of arginine,glycine,aspartic acid,pipecolate,fexofenadine,perindopril,alfuzosin,2-aminohexanoic acid,and all-trans-heptaprenyl diphosphate decreased.The metabolic pathways involved were mainly choline metabolism,retrograde endocannabinoid signaling pathway,linoleic acid metabolism,glycerophospholipid metabolism,α-linolenic acid metabolism,and arachidonic acid metabolism.Conclusion The treatment of knee osteoarthritis patients with Shujin Tougu Wash Recipe can significantly improve the clinical symptoms of patients,improve the quality of life of patients,and can regulate the levels of arginine,valproic acid,and lysophosphatidylcholine metabolites in patients'serum,affecting multiple metabolic pathways,and improving the inflammatory level of patients through correcting d lipid metabolism,and playing an analgesic effect.

Objective:To explore the surgical strategies and clinical efficacy of open partial nephrectomy in the treatment of renal angiomyolipoma (AML) with inferior vena cava tumor thrombus.Methods:A retrospective analysis was conducted on the clinical data of 5 patients with renal AML and inferior vena cava tumor thrombus who underwent partial nephrectomy at Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine from October 2014 to December 2022. There were 2 male and 3 female patients, with a median age of 37 years, ranged from 33 to 45 years. All patients were identified during routine physical examinations. Four patients presented with right-sided lesions, while one had a left-sided lesion. The diameter of the primary tumor within the kidney ranged from 3.0 to 7.0 cm, with a median diameter of 5.5 cm.The length of the tumor thrombus within the inferior vena cava ranged from 1.0 to 6.0 cm, with a median length of 1.5 cm. Among them, 2 patients underwent laparoscopic nephrectomy combined with extracorporeal workbench tumor resection and autologous kidney transplantation (the workbench surgery group), while 3 patients underwent open in-situ partial nephrectomy combined with removal of inferior vena cava tumor thrombus (the in-situ nephron-sparing surgery group). The surgical method of the workbench surgery group: The patients first underwent laparoscopic nephrectomy on the affected side combined with inferior vena cava tumor thrombus removal, then the incision was extended to remove the affected kidney, and table partial nephrectomy was performed. After completely removing the tumor and tumor thrombus within the affected kidney and renal vein, autologous kidney transplantation was performed in the iliac fossa. The surgical method of the in-situ kidney preservation surgery group: The affected kidney, renal artery and vein on the affected side, inferior vena cava, and contralateral renal vein were dissected and exposed. The distal end of the inferior vena cava, the contralateral renal vein, the proximal end of the inferior vena cava, and the renal artery on the affected side were blocked respectively. The venous wall was opened in the middle of the renal vein, and the tumor thrombus was gradually pulled out. According to the pre-marked tumor boundary, the tumor within the kidney was gradually removed by alternate blunt and sharp dissection combined with suction, and the wound surface was sutured layer by layer. The perioperative conditions, complications, and follow-up results of the patients were analyzed.Results:All 5 surgeries were successfully completed, with a median operation time of 100 to 450 minutes and a median operation time of 200 minutes. The intraoperative bleeding volume was 100 to 600 ml, with the median of 150 ml. In the in-situ nephron-sparing surgery group, the renal artery occlusion time was 28 to 41 minutes, and the median occlusion time was 34 minutes. All patients were discharged safely after surgery, and there were no serious perioperative complications. The postoperative pathology of all 5 patients was renal angiomyolipoma, without any epithelioid components. The patients were followed up for 12 to 90 months, with a median follow-up duration of 24 months. None of the 5 patients had tumor recurrence or metastasis, and no patient developed chronic kidney dysfunction during follow-ups.Conclusions:Renal AML with venous tumor thrombus is a challenging clinical problem. In situ open partial nephrectomy or the combined approach through the workbench and autologous kidney transplantation can effectively remove the tumor thrombus and maximize the protection of renal function. For cases of ① multiple or complex renal AML; ② complex vascular system structure within the renal sinus requiring precise anatomy; ③ renal AML with a previous history of hemorrhage, complex adhesions around, and difficult dissociation, table partial nephrectomy combined with inferior vena cava tumor thrombus removal and autologous kidney transplantation can be selected. For cases where the expected surgical operation is simple, in situ open partial nephrectomy can significantly shorten the operation time and reduce surgical trauma.

Objectives:This study aimed to explore the association between perceived mental stress (MS), lymphocyte subset variations, and coronary lesion severity in patients with coronary artery disease (CAD).Methods:Patients with CAD were enrolled in this study from September 2023 to May 2024. Perceived Stress Scale-14 (PSS-14) was used to evaluate MS during the last 1 month. Lymphocyte subsets were analyzed, including the percentage and absolute counts of CD3 +, CD3 +CD4 +, CD3 +CD8 +, CD3 -CD19 +, CD3 -CD56 +16 +, and the Th/Ts ratio. Statistical analysis was conducted using SPSS 24.0. Results:This study recruited patients with 323 CAD, with an average age of 61 (56, 68) years, including 203 males and 120 females. According to the PSS-14, a score of 14-42 and 43-70 were categorized as normal and increased MS, respectively. Patients with CAD with increased MS had significantly higher Gensini scores than those with normal MS [37(19,64) vs. 28(12,50), Z=-2.19, P=0.029]. Male CAD patients with increased MS exhibited significantly higher Gensini scores [39(20, 58) vs. 26(12, 45), Z=-2.37, P=0.018], levels of CD3 +CD8 +%[28.3%(23.6%,36.6%) vs. 25.9%(21.0%,32.4%), Z=-2.05, P=0.041], and CD3 +CD8 +absolute value [485 (346, 675) vs. 396 (309, 510) cells/μl, Z=-2.55, P=0.011] than those with normal MS. In male patients with CAD, a positive correlation was observed between Gensini scores (correlation coefficient: 0.181, P=0.011), PSS-14 scores, and CD3 +CD8 +absolute value (correlation coefficient: 0.162, P=0.038). Conclusion:This study reveals a positive correlation between MS and coronary stenosis severity, with notable sex differences. In male patients with CAD, higher levels of MS are associated with more severe coronary stenosis. The potential underlying mechanism may involve the regulation of lymphocyte subsets .

Objective To analyze the influencing factors of health behaviors in stroke patients,and explore the chain mediating effects of self-efficacy and e-health literacy between the perception of stroke recurrence risk and health behaviors in stroke patients,providing a reference for strengthening the health behavior and reducing recurrence risk in stroke patients.Methods 249 stroke patients were selected as the research objects from March to September 2024 in a tertiary hospital in Shanghai,China.Patients were surveyed using General Information Questionnaire,Stroke Recurrence Risk Perception Scale,Stroke Health Behavior Scale(HBS-SP),Chronic Disease Self-Efficacy Scale(CDSES),and the e-health Literacy Scale(e-HEALS).Pearson correlation analysis was used to explore the correlations among various variables,and SPSS 26.0 software macro program Process Model 6 was used to conduct chain mediation model test.Results The scores of Recurrence Risk Perception,HBS-SP,CDSES and e-HEALS of stroke patients were(42.88±6.48)scores,(68.32±14.13)scores,(6.87±1.55)scores and(27.76±6.06)scores,and all the variables were positively correlated(P<0.01).The mediating effect model showed that self-efficacy and e-health literacy played a chain mediating role in the recurrence risk perception and health behavior in stroke patients,with an effect size of 0.488,accounting for 37.22%of the total effect.Conclusions The recurrence risk perception and health behavior of stroke patients are both at a moderate level.In the future,we can establish a mobile management platform to provide comprehensive health management for stroke patients.Further exploration of strategies to enhance stroke patients'self-efficacy and channels for online health education could be pursued to improve their health behaviors.

Objective:To explore the potential mechanisms of autophagy suppressing the activation of pro-inflammatory macro-phages.Methods:Macrophage-specific knockout mice(Atg5△mye)was generated by the hybridization of Lyz2-Cre mice and Atg 5flox/+mice.Bone marrow cells were differentiated into bone marrow-derived macrophages(BMDMs)induced by monocyte colony-stimulating factor.The expressions of endoplasmic reticulum stress(ER stress)-related proteins,such as glucose regulatory protein 78(GRP78),autophagy-related marker LC3-Ⅱ and p62,and pro-inflammatory iNOS,were detected by Western blot.GO analysis was performed on BMDMs from Atg5flox/flox and Atg5△mye mice stimulated by LPS.Tauroursodeoxycholate(TUDCA)or ATF6 inhibitor Ceapin-A7 was used to suppress the ER stress in BMDMs.Results:LPS promoted the expression of ER stress-related proteins and the activation of pro-in-flammatory macrophages,while inhibiting autophagy in BMDMs.By utilizing proteomic detection and GO enrichment analysis,it was found that the autophagy deficiency in BMDMs caused changes in the ATF6 pathway,a key downstream pathway of ER stress.Inhibi-tion of ER stress by TUDCA significantly down-regulated the expression of iNOS and the secretion of inflammatory cytokines IL-18 and IL-1β in autophagy-deficient BMDMs.ATF6-specific inhibitor(Ceapin-A7)was used to exculpate LPS-stimulated BMDMs,and it was found that Ceapin-A7 significantly down-regulated the elevated expression of iNOS and inflammatory factors caused by Atg5 deletion in BMDMs.Conclusion:Autophagy inhibits the activation of pro-inflammatory macrophages by suppressing ATF6 pathway.