Objective To design and synthesize derivatives of oleanolic acid and ursolic acid, and investigate their anti-hepatitis C virus （HCV） activity along with that of common triterpenoid acids. To explore the structure-activity relationship and provide a reference for the research of anti-HCV drugs derived from natural products through obtaining compounds with higher activity. Methods Oleanolic acid and ursolic acid were directly reacted with corresponding amines using PyBOP as a condensing agent in the presence of DIEA. Alternatively, the target compounds were prepared through PCC oxidation followed by the Baeyer-Villiger reaction catalyzed by m-CPBA. In vitro anti-HCV activity was tested using the HCVcc infection model. Molecular docking was performed by Autodock software to investigate the interaction between the active compounds and HCV NS5B. Results Oleanolic acid, glycyrrhetinic acid, ursolic acid, and asiatic acid all exhibited certain anti-HCV effects. Specifically, oleanolic acid derivatives OA2-OA4, OA6, and OA7, as well as ursolic acid derivatives UA1 and UA2, demonstrated superior anti-HCV activity compared to their parent compounds. Preliminary structure-activity relationship analysis revealed that introducing a bulky group to 28-COOH of oleanolic acid and ursolic acid enhanced their activity. Molecular docking results demonstrated that the active compounds could stably bind to HCV NS5B, thereby exhibiting antiviral activity. Conclusion Pentacyclic triterpenoids possessed anti-HCV effects, and their derivatives coud be synthesized to obtain more active compounds. The anti-HCV mechanism of these compounds may be associated with their inhibition of NS5B.

Objective This study aimed to analyze the characteristics and clinical significance of peripheral lymphocytic subsets and cytokine levels, including interleukin 1β(IL-1β), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, tumor necrosis factor α(TNF-α), interferon γ(IFN-γ) and IFN-α, in patients with primary biliary cholangitis (PBC), to provide some novel insights into the pathogenesis of PBC. Methods We retrospectively collected clinical features and laboratory data from hospitalized patients who were primarily diagnosed with PBC and from healthy physical examinees at the Third People's Hospital of Changzhou between January 1, 2023, and June 30, 2024. Results A total of 152 PBC patients and 96 healthy controls who met the inclusion and exclusion criteria were enrolled. Significant differences were observed in baseline characteristics and laboratory data between the two groups. After the propensity score matching (PSM) analysis, 61 PBC patients and 61 healthy controls were successfully matched, ensuring that the general characteristics (age and gender) of the two groups were balanced and comparable. Compared to the control group, the proportion of peripheral lymphocytes was significantly higher in the PBC group (31.9% vs. 17.8%), primarily due to an increase in CD4⁺ T cells (46.77% vs. 41.19%), while CD8⁺T cells were significantly decreased (19.73% vs. 22.07%). Notably, the proportions of CD4⁺ programmed cell death 1 (PD-1)⁺ T and CD8⁺PD-1⁺ T cells were elevated, with CD8⁺PD-1⁺ T cells showing a significant positive correlation with the severity of liver inflammation (r=0.41). Furthermore, the mitochondrial mass (MM) of CD4⁺ T cells was significantly increased in PBC patients, whereas no significant changes were observed in the MM of CD8⁺ T cells or the mitochondrial membrane potential (MMP) of CD3⁺ T cells. Additionally, the plasma levels of cytokines, such as IL-4, IL-8, IL-10 and IFN-α, were abnormally elevated. The plasma levels of IL-5 and IL-1β were negatively correlated with the stage of liver fibrosis in patients with PBC (r=-0.52). Conclusion The overactivation and proliferation of CD4⁺ T cells, along with the suppression of CD8⁺ T cell function and increased PD-1 expression leads to T cell exhaustion, indicating significant immunological alterations in PBC patients. These changes are closely associated with the disease progression. Additionally, cytokines are likely involved in the immune regulation process of PBC and may influence the pathogenic mechanisms of the disease. Regular monitoring of lymphocyte subsets and cytokine levels can help assess the immune status and disease activity in patients with PBC, thereby guiding the individualized treatment strategies.
Humans ; Male ; Female ; Middle Aged ; Liver Cirrhosis, Biliary/blood* ; Retrospective Studies ; T-Lymphocyte Subsets/immunology* ; Aged ; Cytokines/blood* ; Adult ; CD8-Positive T-Lymphocytes/immunology*

Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Objective To propose a method for abdominal multi-organ segmentation assisted by multi-phase CT synthesis.Methods Multi-phase CT synthesis for synthesizing high-quality CT images was used to increase the information details for image segmentation.A transformer block was introduced to help to capture long-range semantic information in cooperation with perceptual loss to minimize the differences between the real image and synthesized image.Results The model was trained using multi-phase CT dataset of 526 total cases from Nanfang Hospital.The mean maximum absolute error(MAE)of the synthesized non-contrast CT,venous phase contrast-enhanced CT(CECT),and delay phase CECT images from arterial phase CECT was 19.192±3.381,20.140±2.676 and 22.538±2.874,respectively,which were better than those of images synthesized using other methods.Validation of the multi-phase CT synthesis-assisted abdominal multi-organ segmentation method showed an average dice coefficient of 0.847 for the internal validation set and 0.823 for the external validation set.Conclusion The propose method is capable of synthesizing high-quality multi-phase CT images to effectively reduce the errors in registration between different phase CT images and improve the performance for segmentation of 13 abdominal organs.

Objective To propose a method for abdominal multi-organ segmentation assisted by multi-phase CT synthesis.Methods Multi-phase CT synthesis for synthesizing high-quality CT images was used to increase the information details for image segmentation.A transformer block was introduced to help to capture long-range semantic information in cooperation with perceptual loss to minimize the differences between the real image and synthesized image.Results The model was trained using multi-phase CT dataset of 526 total cases from Nanfang Hospital.The mean maximum absolute error(MAE)of the synthesized non-contrast CT,venous phase contrast-enhanced CT(CECT),and delay phase CECT images from arterial phase CECT was 19.192±3.381,20.140±2.676 and 22.538±2.874,respectively,which were better than those of images synthesized using other methods.Validation of the multi-phase CT synthesis-assisted abdominal multi-organ segmentation method showed an average dice coefficient of 0.847 for the internal validation set and 0.823 for the external validation set.Conclusion The propose method is capable of synthesizing high-quality multi-phase CT images to effectively reduce the errors in registration between different phase CT images and improve the performance for segmentation of 13 abdominal organs.

Objective To compare the effects of two different surgical methods in the treatment of female unilateral cT1N0-1a thyroid cancer and the satisfaction of incision cosmetics.Methods A retrospective analysis of the data of female patients with unilateral cT1N0-1a stage thyroid cancer in our hospital from October 2020 to September 2022 was conducted.They were divided into open group(65 cases)and oral group(55 cases)according to different surgical methods.Patients in open group were underwent traditional open thyroid surgery,and patients in oral group were underwent transoral vestibular approach laparoscopic thyroid surgery.Intraoperative conditions,postoperative complications and satisfaction degree of postoperative incision beauty between the two groups were comparded.Results The operation time was(124.40±11.59)minutes and the dissection time of the central lymph node was(26.44±5.33)minutes in the transoral group,which were longer than those in the open group[(65.91 ±11.44)minutes and(17.38±4.32)minutes,(P＜0.05)].Vancouver scar evaluation[(3.29± 0.96)points],patient scar evaluation[(8.62±1.57)points],observer scar evaluation[(6.67±1.17)points]and scar self-awareness score[(1.65±0.70)points]in the oral group were significantly lower than those in the open group[(5.29±1.20)points,(15.02±2.85)points,(19.57±2.94)points and(3.12±0.98)points,(P＜0.05)].There were no significant difference in the amount of blood loss,the amount of drainage,the number of days in hospital and the number of central lymph nodes dissection between the two groups(P＞0.05).There was no significant difference in total incidence of postoperative complications(hoarseness,cough after drinking water,postoperative bleeding,subcutaneous effusion)between oral group and open group(7.2％vs7.6％,P＞0.05).Conclusion The two surgical methods have their own advantages,the incidence of postoperative complications is low,safe and reliable,and the patients in the oral group are more satisfied with the cosmetology of the postoperative incision.In actual clinical work,the appropriate operation can be chosen according to the specific conditions of the patients.

[Objective]To summarize the characteristics of MA Shi's refutations of WANG Bing's annotations in Suwen Zhuzheng Fawei(Commentaries and Discussions on Suwen of Yellow Emperor's Inner Canon),and analyze the relationship between MA's annotations and WANG's annotations.[Methods]After consulting the annotations of MA Shi refuting WANG Bing in Suwen Zhuzheng Fawei,this paper analyzes MA Shi's critical views on WANG's annotations,compares the different understandings of MA Shi and WANG Bing on scriptures,and summarizes the characteristics of MA's annotations from three aspects:expression of terms,method of interpreting scriptures and elucidation of medical theory.Finally it sums up the relationship between MA's annotations and WANG's annotations.[Results]When refuting WANG's annotations,MA Shi often used three types of words to express different degrees of refutation on WANG's annotations,which contained"opposed""superficial"and"lacking".The methods of interpreting scriptures can be summarized into five kinds of citation analysis and four levels of literary analysis,and the scriptures of Suwen and Lingshu were mostly cited as evidence.In the elucidation of medical theory,MA's annotations differed from WANG's in the understanding of theoretical scope,the analysis of theoretical connotation and the determination of acupoint position.[Conclusion]MA Shi used the more comprehensive interpretation methods,interpreted the scriptures from the broader theoretical level and refuted WANG's annotations,which not only formed a systematic way of interpreting the scriptures,but also inspired more possibilities of the meaning of the scriptures.MA's annotations had both critical inheritance and innovative development to WANG's annotations,which promoted the study of Suwen.

Objective To investigate the effect of core decompression combined with bone-morphogenetic proteins(BMP)activity inducing rod implantation in the treatment of early-stage femoral head necrosis.Methods Retrospective analysis of 116 patients with early-stage femoral head necrosis from June 2018 to June 2022 were divided into core decompression combined with BMP activity inducing rod group(BMP group)and allograft bone group.Sixty cases in the BMP group were treated with core decompression combined with implantation of BMP-activated induced rods,and 56 cases in the allograft group were treated with core decompression combined with bone grafting of the allograft bone by punching and compression.The differences in hip Harris scores and visual analogue scores(VAS)of pain between the two groups at preoperative,6 months postoperative and 1 year postop-erative,and the patient treatment response and femoral head survival rate at 1 year postoperative were compared.Results All patients were followed-up,and the difference between the preoperative VAS score and Harris score of the two groups was not statistically significant(P＞0.05),and the VAS score and Harris score of the two groups were significantly improved at 6 months and 1 year after operation,and the BMP group was better than the allograft bone group,with significant difference(P＜0.05).At 1 year after surgery,the Harris hip score excellence rate of the BMP group was higher than that of the allograft bone group,and the difference was statistically significant(P＜0.05);the femoral head survival rate of the BMP group was higher than that of the allograft bone group,and the difference was statistically significant(P＜0.05).Conclusions Core decompression combined with BMP activity induced rod implantation was effective in the treatment of early femoral head necrosis,which accelerated the induction of new bone formation,improved the quality of new bone,provided biomechanical support for the femoral head,and effectively avoided femoral head collapse.Moreover,it has good biocompatibility and couldbe degraded and absorbed in the body,which is worthy of clinical promotion.

Objective To observe the value of spectral CT parameters for evaluating T staging of advanced gastric cancer(AGC).Methods Totally 155 AGC patients were collected and divided into T2 stage(n=40)and T3/4a stage(n=115)according to postoperative pathology.CT values,water concentration(WC)and iodine concentration(IC)of AGC lesions on 40-140 keV arteriovenous phase single energy level images were measured,and the standardized IC(nIC)and spectral curve slopes k1 and k2 were calculated.Clinical variables and spectral quantitative parameters were compared between groups,and receiver operating characteristic curve was plotted,the area under the curve(AUC)was calculated to evaluate the value of each parameter and model for identifying T2 and T3/4a stage AGC.Results Tumor thickness,proportion of low differentiation degree,CT100kev,CT140kev,and WC values in T3/4a group were all significantly higher than those in T2 group(all P＜0.05).CT140keV of AGC lesions on venous phase images presented the highest discrimination efficacy among single parameters,with AUC of 0.782.AUC of clinical-arterial phase-venous phase model was 0.848,higher than that of clinical model and arterial phase model alone(both P＜0.05)but not significantly different compared with AUC of venous phase model(P＞0.05).Conclusion Spectral CT quantitative parameters,especially venous phase parameters could be used to effectively identify T stage of AGC.Multi-parameter combined models had higher diagnostic value.