1.Combination of the LPS/TLR4 Pathway and Fecal Metabolomics Analysis Reveals the Chronic Inflammatory Mechanism of Early Atherosclerosis in Tibetan Miniature Pigs
Qinqin YANG ; Songtao XU ; Yueqin CAI ; Yongming PAN ; Junjie HUANG ; Keyan ZHU ; Minli CHEN ; Xiaoping XU
Cardiology Discovery 2025;05(2):121-132
Objective::This study aimed to elucidate the effect of the lipopolysaccharides/toll-like receptor 4 (LPS/TLR4) pathway on early atherosclerosis (AS) development and its associated changes in fecal metabolites, thereby providing an experimental foundation for strategies to prevent and treat early AS.Methods::Twelve Tibetan miniature pigs aged 4-5 months were divided into normal control (NC) group and AS group (6 pigs in each). The group assignment was primarily based on body weight; Secondary criteria, including glucose, lipid profiles, and inflammatory indices, were considered to ensure balanced baseline characteristics between the 2 groups (all P > 0.05). AS group received a high-fat diet for 16 weeks to establish an AS model, while the NC group received a normal diet. Subsequently, serum levels of lipids and various inflammation and oxidative stress markers were measured. Pathological changes in the aorta and colon tissue, LPS/TLR4 pathway-associated protein expressions in the aorta, as well as occludin and zonula occludens-1 in the colon were also assessed. Proton nuclear magnetic resonance spectra technology was employed for the metabolomic analysis of fecal extracts. Results::The lipid metabolism was disrupted in AS group, with significantly higher total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels ((12.24 ± 5.24) mmol/L vs. (1.86 ± 0.27) mmol/L, P = 0.004,6; (2.39 ± 0.50) mmol/L vs. (0.83 ± 0.07) mmol/L, P = 0.000,5; (6.94 ± 2.87) mmol/L vs. (0.77 ± 0.18) mmol/L, P = 0.003,3), as compared to that in NC group. Serum factors, including LPS, tumor necrosis factor-α, and malondialdehyde levels of AS group were significantly higher than that of NC group ((1,230.00 ± 192.70) EU/L vs. (695.70 ± 213.70) EU/L), P = 0.001,1; (424.20 ± 176.90) ng/L vs. (51.20 ± 26.61) ng/L, P = 0.023,5; (3.60 ± 0.77) nmol/mL vs. (2.62 ± 0.21) nmol/mL, P = 0.025,4). Pathological evaluations revealed prominent lipid deposition area in the aortic arch, thoracic aorta, and abdominal aorta of the AS group compared with that of the NC group (4.17% ± 2.30% vs. 0, P = 0.006,7; 6.23% ± 2.95% vs. 0, P = 0.003,6; 3.78% ± 2.18% vs. 0, P = 0.008,1). TLR4, nuclear factor kappa-B p65, and tumor necrosis factor-α expression in the aorta tissue of the AS group were upregulated, whereas occludin and zonula occludens-1 expression in colon tissues was downregulated. Additionally, metabolomics identified significant differences in 21 metabolites in the feces of the AS group compared to the NC group, with further analysis linking these differences to amino acid metabolism. Conclusions::The Tibetan miniature pig model of early AS induced by high-fat intake displayed pronounced chronic inflammation. Preliminary findings suggest that the underlying mechanisms may be associated with the LPS/TLR4 pathway and intestinal metabolic disorders.
2.Combination of the LPS/TLR4 Pathway and Fecal Metabolomics Analysis Reveals the Chronic Inflammatory Mechanism of Early Atherosclerosis in Tibetan Miniature Pigs
Qinqin YANG ; Songtao XU ; Yueqin CAI ; Yongming PAN ; Junjie HUANG ; Keyan ZHU ; Minli CHEN ; Xiaoping XU
Cardiology Discovery 2025;05(2):121-132
Objective::This study aimed to elucidate the effect of the lipopolysaccharides/toll-like receptor 4 (LPS/TLR4) pathway on early atherosclerosis (AS) development and its associated changes in fecal metabolites, thereby providing an experimental foundation for strategies to prevent and treat early AS.Methods::Twelve Tibetan miniature pigs aged 4-5 months were divided into normal control (NC) group and AS group (6 pigs in each). The group assignment was primarily based on body weight; Secondary criteria, including glucose, lipid profiles, and inflammatory indices, were considered to ensure balanced baseline characteristics between the 2 groups (all P > 0.05). AS group received a high-fat diet for 16 weeks to establish an AS model, while the NC group received a normal diet. Subsequently, serum levels of lipids and various inflammation and oxidative stress markers were measured. Pathological changes in the aorta and colon tissue, LPS/TLR4 pathway-associated protein expressions in the aorta, as well as occludin and zonula occludens-1 in the colon were also assessed. Proton nuclear magnetic resonance spectra technology was employed for the metabolomic analysis of fecal extracts. Results::The lipid metabolism was disrupted in AS group, with significantly higher total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels ((12.24 ± 5.24) mmol/L vs. (1.86 ± 0.27) mmol/L, P = 0.004,6; (2.39 ± 0.50) mmol/L vs. (0.83 ± 0.07) mmol/L, P = 0.000,5; (6.94 ± 2.87) mmol/L vs. (0.77 ± 0.18) mmol/L, P = 0.003,3), as compared to that in NC group. Serum factors, including LPS, tumor necrosis factor-α, and malondialdehyde levels of AS group were significantly higher than that of NC group ((1,230.00 ± 192.70) EU/L vs. (695.70 ± 213.70) EU/L), P = 0.001,1; (424.20 ± 176.90) ng/L vs. (51.20 ± 26.61) ng/L, P = 0.023,5; (3.60 ± 0.77) nmol/mL vs. (2.62 ± 0.21) nmol/mL, P = 0.025,4). Pathological evaluations revealed prominent lipid deposition area in the aortic arch, thoracic aorta, and abdominal aorta of the AS group compared with that of the NC group (4.17% ± 2.30% vs. 0, P = 0.006,7; 6.23% ± 2.95% vs. 0, P = 0.003,6; 3.78% ± 2.18% vs. 0, P = 0.008,1). TLR4, nuclear factor kappa-B p65, and tumor necrosis factor-α expression in the aorta tissue of the AS group were upregulated, whereas occludin and zonula occludens-1 expression in colon tissues was downregulated. Additionally, metabolomics identified significant differences in 21 metabolites in the feces of the AS group compared to the NC group, with further analysis linking these differences to amino acid metabolism. Conclusions::The Tibetan miniature pig model of early AS induced by high-fat intake displayed pronounced chronic inflammation. Preliminary findings suggest that the underlying mechanisms may be associated with the LPS/TLR4 pathway and intestinal metabolic disorders.
3.Research progress of medication-related patient-reported outcome scales
Panpan LU ; Haixin LI ; Zhiling DENG ; Xujian LIANG ; Yiting LU ; Ming YAN ; Songtao CAI ; Wanchao LI ; Ruifeng ZENG ; Yi GUO ; Zhijie XU
Chinese Journal of Pharmacoepidemiology 2024;33(1):95-105
Drug therapy is a common method to cure diseases and relieve symptoms.The value of patient-reported outcome(PRO)in evaluating the effect of drug therapy has been increasingly paid attention.The PRO scale is a standardized questionnaire,which can scientifically evaluate the experiences and subjective effects of drug use from a patient-centered perspective,and help patients and clinicians make more reasonable medication decisions.By reviewing and sorting out relevant global literature,this paper found that the content of the PRO scales relevant to drug therapy focused on five fields:"medication satisfaction""medication adherence""drug treatment burden""medication-related quality of life"and"adverse drug reactions".This paper described the basic information,measurement characteristics and application of common scales in recent years respectively,and summarized and analyzed the problems and enlightenment of scale development,aiming to provide theoretical reference for the selection,application and development of PRO scales.
4.Expert Concensus on Triune Personalized Treatment of Pelvic Tumor Based on Three-Dimensional Printing
Songtao AI ; Zhengdong CAI ; Feiyan CHEN ; Kerong DAI ; Yang DONG ; Lingjie FU ; Yongqiang HAO ; Yingqi HUA ; Wenbo JIANG ; Jiong MEI ; Yuhui SHEN ; Wei SUN ; Rong WAN ; Yichao WANG ; Zhiwei WANG ; Haifeng WEI ; Wen WU ; Jianru XIAO ; Wangjun YAN ; Xinghai YANG ; Chunlin ZHANG ; Weibin ZHANG
Journal of Medical Biomechanics 2021;36(1):E001-E005
The adjacent anatomy of the pelvis is complicated, with digestive, urinary, reproductive and other organs as well as important blood vessels and nerves. Therefore, accurate resection of pelvic tumors and precise reconstruction of defects after resection are extremely difficult. The development of medical 3D printing technology provides new ideas for precise resection and personalized reconstruction of pelvic tumors. The “triune” application of 3D printing personalized lesion model, osteotomy guide plate and reconstruction prosthesis in pelvic tumor limb salvage reconstruction treatment has achieved good clinical results. However, the current lack of normative guidance standards such as preparation and application of 3D printing personalized lesion model, osteotomy guide plate and reconstruction prosthesis restricts its promotion and application. The formulation of this consensus provides normative guidance for 3D printing personalized pelvic tumor limb salvage reconstruction treatment.
5.Establishment of LINC01018 overexpression colon cancer cell line and study on its biological characteristics
Hongwei CHEN ; Jiahong CAI ; Xiaochen ZENG ; Bingjie PAN ; Zhoujing LIU ; Songtao CHEN
Journal of Chinese Physician 2021;23(11):1663-1667
Objective:To establish a colon cancer cell line which overexpressing LINC01018 stably and study its biological characteristics.Methods:The expression of LINC01018 in HCoEpiC and HT-29 cells were detected by real time fluorescence quantitative polymerase chain reaction (qRT-PCR). HT-29 cells were infected with LINC01018 overexpression lentivirus to screen and establish HT-29 cell lines which overexpressing LINC01018 stably. The effect of LINC01018 on the proliferation, invasion and migration of HT-29 cells were detected by cell counting kit-8 (CCK-8) assay and Transwell assay separately. The expression of CDK6 and matrix metalloproteinase-2 (MMP-2) in HT-29 cells was detected by Western blot.Results:The expression of LINC01018 in HT-29 cells was significantly lower than that in the human colonic epithelial cells (HCoEpiC). HT-29-L18 cell lines which overexpressing LINC01018 stably was screened successfully. Overexpression of LINC01018 significantly inhibited the cell proliferation, invasion and migration, and reduced the protein expression of CDK6 and MMP-2 in HT-29 cells.Conclusions:The expression of LINC01018 was decreased abnormally in colon cancer cells. Up-regulation of LINC01018 expression can inhibit the proliferation, invasion and migration of colon cancer cells, which may be related to CDK6 and MMP-2.
6.Effects of tranexamic acid on the drainage duration after total knee arthroplasty
Jinliang WANG ; Zhe LI ; Xiaofei LUO ; Songtao CAI ; Xuan WEI
Chinese Journal of Orthopaedics 2020;40(10):635-643
Objective:To investigate the effects of tranexamic acid on the drainage duration after primary unilateral total knee arthroplasty (TKA).Methods:From June 2017 to December 2018, a total of 182 patients (42 males and 140 females) who underwent primary TKA were included. The age of patients was 68.1±7.1 years (60-76 years). According to the random number table, the subjects were divided into four groups: 45 cases in tranexamic acid group 1 (TXA1), 46 cases in tranexamic acid group 2 (TXA2), 46 cases in tranexamic acid group 3 (TXA3) and others in none tranexamic acid group (NTXA). The patients in TXA1-3 groups received intravenous infusion combined with local application of tranexamic acid. The patients in NTXA group were locally perfused in the joint cavity with 100 ml normal saline after surgery. The drainage volume, total blood loss, invisible blood loss, degree of postoperative joint swelling, Hospital for Special Surgery (HSS) and visual analogue scale (VAS) of pain were compared among the four groups.Results:The postoperative drainage volume of TXA1-3 groups was 85.5±34.3 ml, 189.4±72.3 ml and 215.3±93.4 ml, respectively, which were less than that of the NTXA group (351.3±113.5 ml) with significant difference ( F=11.5, P=0.005). The postoperative drainage volume of TXA1 group was less than that of TXA2-3 groups. The total postoperative blood loss was 699.0±255.7 ml, 710.4±296.1 ml, and 715.8±248.2 ml in the TXA1-3 groups, respectively, which were less than that of the NTXA group (1 130.5±354.2 ml) with significant difference ( F=13.1, P=0.001). At the 4th day after TKA, the knee swelling degree of TXA1-3 groups was 1.25±0.07, 1.13±0.12, and 1.12±0.13, respectively, which were less severe than that of the NTXA group (1.43±0.22) with significant difference ( F=8.23, P=0.015). There were 2 cases with positive bacterial culture in NTXA group and TXA3, 3 cases with hematoma and 1 case with delayed wound healing in the NTXA group. Conclusion:The application of tranexamic acid after TKA can reduce postoperative drainage volume, latent blood loss and total blood loss. The removal of the drainage at 18 h after the operation can not only drain completely, relieve pain and promote knee joint function, but also effectively reduce the risk of infection associated drainage.
7. The preliminary report of a registration clinical trial of proton and heavy ion irradiation
Jiade LU ; Ming YE ; Xiaomao GUO ; Shen FU ; F. Michael MOYERS ; Qing ZHANG ; Jingfang MAO ; Lin KONG ; Wen Chien HSI ; Kambiz SHAHNAZI ; Jingfang ZHAO ; Zhen ZHANG ; Xiumei MA ; Songtao LAI ; Xiaomeng ZHANG ; Ningyi MA ; Yunsheng GAO ; Xin CAI ; Xiyin GUAN ; Junhua ZHANG ; Bin WU ; Jingyi CHENG ; Yin-xiang-zi SHENG ; Wei REN ; Jun ZHAO ; Lining SUN ; Guoliang JIANG
Chinese Journal of Oncology 2018;40(1):52-56
Objective:
To verify the safety and efficacy of IONTRIS particle therapy system (IONTRIS) in clinical implementation.
Methods:
Between 6.2014 and 8.2014, a total of 35 patients were enrolled into this trial: 31 males and 4 females with a median age of 69 yrs (range 39-80). Ten patients had locally recurrent head and neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with non-metastatic prostate carcinomas. Phantom dose verification was mandatory for each field before the start of radiation.
Results:
Twenty-two patients received carbon ion and 13 had proton irradiation. With a median follow-up time of 1 year, all patients were alive. Among the 16 patients with head and neck, thoracic, and abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response, partial response, stable disease, or disease progression, respectively. Progression-free survival rate was 93.8% (15/16). Among the 19 patients with prostate cancer, biological-recurrence free survival was 100%. Particle therapy was well tolerated in all 35 patients. Twenty-five patients (71.4%) experienced 33 grade 1 acute adverse effects, which subsided at 1 year follow-up. Six (17.1%) patients developed grade 1 late adverse effects. No significant change in ECOG or body weight was observed.
Conclusions
IONTRIS is safe and effective for clinical use. However, long term follow-up is needed to observe the late toxicity and long term result.
8.The preliminary report of a registration clinical trial of proton and heavy ion irradiation
Jiade LU ; Ming YE ; Xiaomao GUO ; Shen FU ; F.Michae MOYERS ; Qing ZHANG ; Jingfang MAO ; Lin KONG ; Chien Wen HSI ; Kambiz SHAHNAZI ; Jingfang ZHAO ; Zhen ZHANG ; Xiumei MA ; Songtao LAI ; Xiaomeng ZHANG ; Ningyi MA ; Yunsheng GAO ; Xin CAI ; Xiyin GUAN ; Junhua ZHANG ; Bin WU ; Jingyi CHENG ; Yin?xiang?zi SHENG ; Wei REN ; Jun ZHAO ; Lining SUN ; Guoliang JIANG
Chinese Journal of Oncology 2018;40(1):52-56
Objective To verify the safety and efficacy of IONTRIS particle therapy system ( IONTRIS) in clinical implementation. Methods Between 6.2014 and 8.2014, a total of 35 patients were enrolled into this trial:31 males and 4 females with a median age of 69 yrs ( range 39?80) . Ten patients had locally recurrent head and neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with non?metastatic prostate carcinomas. Phantom dose verification was mandatory for each field before the start of radiation. Results Twenty?two patients received carbon ion and 13 had proton irradiation. With a median follow?up time of 1 year, all patients were alive. Among the 16 patients with head and neck, thoracic, and abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response, partial response, stable disease, or disease progression, respectively. Progression?free survival rate was 93.8% (15/16). Among the 19 patients with prostate cancer, biological?recurrence free survival was 100%. Particle therapy was well tolerated in all 35 patients. Twenty?five patients (71.4%) experienced 33 grade 1 acute adverse effects, which subsided at 1 year follow?up. Six ( 17.1%) patients developed grade 1 late adverse effects. No significant change in ECOG or body weight was observed. Conclusions IONTRIS is safe and effective for clinical use. However, long term follow?up is needed to observe the late toxicity and long term result.
9.The preliminary report of a registration clinical trial of proton and heavy ion irradiation
Jiade LU ; Ming YE ; Xiaomao GUO ; Shen FU ; F.Michae MOYERS ; Qing ZHANG ; Jingfang MAO ; Lin KONG ; Chien Wen HSI ; Kambiz SHAHNAZI ; Jingfang ZHAO ; Zhen ZHANG ; Xiumei MA ; Songtao LAI ; Xiaomeng ZHANG ; Ningyi MA ; Yunsheng GAO ; Xin CAI ; Xiyin GUAN ; Junhua ZHANG ; Bin WU ; Jingyi CHENG ; Yin?xiang?zi SHENG ; Wei REN ; Jun ZHAO ; Lining SUN ; Guoliang JIANG
Chinese Journal of Oncology 2018;40(1):52-56
Objective To verify the safety and efficacy of IONTRIS particle therapy system ( IONTRIS) in clinical implementation. Methods Between 6.2014 and 8.2014, a total of 35 patients were enrolled into this trial:31 males and 4 females with a median age of 69 yrs ( range 39?80) . Ten patients had locally recurrent head and neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with non?metastatic prostate carcinomas. Phantom dose verification was mandatory for each field before the start of radiation. Results Twenty?two patients received carbon ion and 13 had proton irradiation. With a median follow?up time of 1 year, all patients were alive. Among the 16 patients with head and neck, thoracic, and abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response, partial response, stable disease, or disease progression, respectively. Progression?free survival rate was 93.8% (15/16). Among the 19 patients with prostate cancer, biological?recurrence free survival was 100%. Particle therapy was well tolerated in all 35 patients. Twenty?five patients (71.4%) experienced 33 grade 1 acute adverse effects, which subsided at 1 year follow?up. Six ( 17.1%) patients developed grade 1 late adverse effects. No significant change in ECOG or body weight was observed. Conclusions IONTRIS is safe and effective for clinical use. However, long term follow?up is needed to observe the late toxicity and long term result.
10.Treatment of periprosthetic femoral fractures with unstable prosthesis by replacement of long-stem femoral prosthesis
Jinliang WANG ; Xiaofei LUO ; Xuan WEI ; Shaohua WANG ; Yingzhou HOU ; Songtao CAI ; Jingtao SUN
Chinese Journal of Orthopaedic Trauma 2016;18(2):169-171
Objective To discuss the treatment of periprosthetic femoral fractures (PFF) with unstable prosthesis by replacement of long-stem femoral prosthesis and internal fixation.Methods From December 2005 to December 2014,15 PFF patients with unstable prosthesis (15 hips) following were treated at our department.They were 10 men and 5 women,aged from 64 to 89 years (mean,76.2 years).Their primary surgeries included total hip arthroplasty in 13 cases and biological bi-polar replacement of femoral head in 2.Two prostheses were cement and 13 biological.By Vancouver classification,9 cases were type B2,and 6 type B3.The unstable prostheses in the 15 cases were replaced by long-stem femoral ones,followed by internal fixation.At the last follow-ups,clinical outcome were evaluated by Harris scoring and images of PFF by Beals & Tower criteria.Complications were documented.Results One died 4 months after operation.The other 14 patients were followed up for an average of 4.5 years (from 6 months to 9 years).Fracture union was achieved in 12 cases after an average of 3.9 months (from 3 to 9 months).Nonunion occurred in 2 cases.Imaging evaluation revealed 9 excellent cases,3 good ones and 2 poor ones.The Harris scores at the last follow-up averaged was 82.3 points (from 50 to 100 points).Deep vein thrombosis occurred preoperatively in one case and posterior tibial vein thrombosis occurred in 2 cases respectively on day 3 and day 10 postoperatively.No such complications occurred as malunion,fixation failure,dislocation or prosthesis loosening.Conclusion Satisfactory outcomes can be achieved by replacement of long-stem femoral prosthesis combined with appropriate fixation for treatment of PFF with unstabrosthesis.

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