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BACKGROUND:Berberine has the potential to induce osteogenic differentiation of various mesenchymal stem cells under normal conditions and special conditions such as high glucose,infection and inflammation.It is a natural small molecule drug that can induce bone formation in seed cells instead of growth factors,and has great application prospect in bone tissue engineering. OBJECTIVE:To review and summarize the research progress in the osteogenic mechanism and efficacy of berberine,especially its osteogenic potential under high glucose,infection and inflammation conditions,and its biological safety,so as to provide theoretical basis for its development and application in bone tissue engineering. METHODS:PubMed,WanFang,and CNKI were searched for relevant literature using the keywords of"berberine,bone defects,bone repair,bone regeneration,osteoinductive,osteoporosis,osteoblast,osteoclast,bone tissue engineering,bone,high glucose,diabetes,inflam*,infect*"in English and Chinese,respectively.A total of 105 literatures were selected for review. RESULTS AND CONCLUSION:Berberine can be used to treat multiple diseases including bone diseases,and it has the ability to promote bone regeneration.This article systematically reviews the mechanism of berberine on bone regeneration and in vivo and in vitro studies.Studies have shown that it can play a role in bone repair by promoting osteogenesis,inhibiting osteoclast formation and activity,and preventing osteoporosis.It shows excellent osteogenic differentiation potential mainly via Wnt/β-catenin,PI3K/AKT,EGFR/MEK/p38MAPK,cAMP/PKA/CREB,ERK and other signaling pathways.Berberine can also relieve the inhibition of osteogenic differentiation caused by high glucose,infection and inflammation,which provides more possibilities for the treatment of bone defects in patients with diabetes or infection and inflammation in the bone defect site.Berberine also has the advantages of low toxicity,low price,easy access(currently it can be synthesized),which is a relatively ideal bone induction potential drug.In recent years,the application of berberine in the treatment of bone defect tends to be localized,mainly through the combination with bone tissue engineering technology to improve bioavailability,and has shown good bone repair effect and excellent biological safety in animal experiments.In addition,preclinical experiments have shown splendid bone regeneration potential in the conditions of diabetes,local infection and inflammation.In the future,more studies are needed to fully reveal the osteogenic mechanism and biological safety of berberine,and seek the most suitable controlled release loading system to make artificial bone replacement materials with good mechanical strength,efficacy and biological safety.
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Objective:To analyze the differences between trans-radial access (TRA) and trans-femoral access (TFA) in hepatic arterial perfusion chemotherapy (HAIC) in terms of patient experience, postoperative complications, and patient preferences; explore whether TRA in HAIC is associated with better patient experience and compliance; and determine whether it is safer than TFA.Methods:The study was a retrospective cohort study of patients with advanced hepatocellular carcinoma and liver metastases from colorectal cancer treated with HAIC. We enrolled a total of 91 patients with advanced liver malignancies treated with HAIC from November 2022 to May 2023 in the Department of Interventional Therapy and Hepatobiliary Medicine at Tianjin Medical University Cancer Hospital. The patients were divided into three groups: group TRA ( n=20, receiving TRA HAIC only), group TFA ( n=33, receiving TFA HAIC only), and crossover group [ n=19, receiving TFA HAIC (Cross-TFA group) first, followed by TRA HAIC (Cross-TRA group)]. Meanwhile, to facilitate the expression of partial results, all patients receiving TRA HAIC were defined as the TRA-HAIC group ( n=39, TRA+Cross-TRA group), and all patients receiving TFA HAIC were defined as the TFA-HAIC group ( n=52, TFA+Cross-TFA group). The primary research index was the Quality of Life (QOL) visualization scale score. The secondary research index included approach-related and catheter-related adverse events, duration of surgery, and mean length of patient stay. We used various statistical methods such as Mann-Whitney U test, t-test, Chi-square test, Fisher′s exact test, univariate logistic regression analysis, and multi-factor analysis. Results:TRA patients had significantly lower QOL scores than TFA patients (all P<0.001). The QOL scores of the Cross-TRA group were significantly lower than those of the Cross-TFA group (pain at the puncture site Z=-3.24, P=0.001, others P<0.001). The QOL scores of the Cross-TRA group were compared with those of the TRA group, which showed that the scores of the Cross-TRA group in overall discomfort ( Z=-3.07, P=0.002), postoperative toilet difficulty ( Z=-2.12, P=0.034), and walking difficulty ( Z=-2.58, P=0.010) were significantly lower than those of the TRA group. Satisfaction scores were significantly higher in the Cross-TRA group than in the Cross-TFA group ( Z=-3.78, P<0.001), and patients were more likely to receive TRA HAIC as the next procedure ( χ2=30.42, P<0.001). In terms of mean length of stay, patients receiving TRA HAIC had a significantly lower mean length of stay than those receiving TFA HAIC (50.1±3.2 h vs. 58.4±6.4 h, t=7.98, P<0.001). The incidence of radial artery occlusion (RAO) as an approach-related adverse event was 15.4% (6/39) in the TRA-HAIC group, which was significantly higher than that in the TFA-HAIC group (15.4% vs. 0, χ2=8.56, P=0.005). Notably, multifactorial analysis of RAO-related factors showed that intraoperative enoxaparin use and patency of radial artery flow during pressure were significantly associated with a reduced risk of postoperative RAO ( P=0.037 for enoxaparin use and P=0.049 for pressure). Conclusions:With respect to procedure approach, TRA was significantly better than TFA in terms of patient satisfaction and mean length of stay. Through further process optimization and prevention of adverse reactions, the incidence of adverse reactions can be maintained at a relatively low level, so that patients can benefit from TRA in future operations in terms of cost-effectiveness and medical efficiency.
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Objective:To investigate the expression of Macrophage migration-inhibitory factors (MIF) in hepatocellular carcinoma (HCC) tissues and its interaction with ERK1/2 signaling pathway, so as to establish a theoretical basis for further studying the molecular mechanism of MIF promoting HCC.Methods:From February 2020 to August 2021, 52 cases of hepatocellular carcinoma (HCC) tissues based on hepatitis B cirrhosis (HBV-LC) and 52 cases of adjacent tissues in Tianjin Medical University Cancer Hospital and 940th Hospital of Joint Logistic Support Force of PLA were collected as the experimental group, including 39 males and 13 females, aged 35-65 years. And 20 cases of normal liver tissue were selected as the control group. Immunohistochemistry was used to detect the expression of MIF, ERK1/2 and p-ERK1/2 proteins in liver tissues of the two groups, and in situ hybridization was used to detect the expression of ERK1/2 nucleic acid in liver tissues of the two groups.HepG2 HCC cells and L-02 normal hepatocytes were co-cultured with different concentrations of rMIF, the expression and phosphorylation levels of ERK1/2 and JNK1 proteins in the two kinds of liver cells were detected by Western-blot, and the expression levels of ERK1/2 nucleic acids in the two kinds of liver cells were detected by RT-PCR. One-way ANOVA was used for measurement data and χ 2 test was used for counting data. Results:The expressions of MIF, ERK1/2, p-ERK1/2 and ERK1/2 mRNA were significantly increased in HCC and para-cancer tissues (the expression of MIF in HCC group was 78.8%, and that in adjacent group was 75.0%; ERK1/2 80.8% in HCC group and ERK1/2 71.8% in paracancerous group. The expression of p-ERK1/2 75.0 % in HCC group and 46.2% in paracancerous group were respectively detected. ERK1/2 mRNA was expressed in HCC group 76.9%, ERK1/2 mRNA expression in paracancerous group 78.8%), and the differences were statistically significant compared with normal liver tissues ( P<0.05), but there was no significant difference between HCC and para-cancer tissues ( P>0.05). The expressions of ERK1/2, p-ERK1/2 and ERK1/2 mRNA in HepG2 HCC cells were significantly increased with the increase of rMIF concentration, and the increase was most obvious when rMIF concentration was 200 ng/ml, and the difference was statistically significant compared with L-02 normal hepatocytes ( P<0.05). Conclusion:MIF, ERK1/2 and p-ERK1/2 are highly expressed in HCC tissues and HepG2 HCC cells, suggesting that MIF promotes the occurrence and development of hepatocellular carcinoma through ERK1/2 signaling pathway.
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Objective:To explore the risk factors and preventive strategies of pancreatitis after percutaneous transhepatic biliary drainage (PTBD) in patients with pancreatic cancer and obstructive jaundice.Methods:A total of 241 patients were retrospectively analyzed from May 2001 to October 2014 in Tianjin Medical University Cancer Institute and Hospital. The possibly correlated 9 factors were analyzed, including gender, age, hemoglobin level, total bilirubin level, degree of pancreatic duct dilatation, degree of pancreatic atrophy, degree of biliary stenosis, the pancreatic duct visualization, and drainage mode.Results:Univariate analysis suggested that pancreatic duct dilatation, pancreatic atrophy, visualized pancreatic duct and drainage mode were associated with the incidence of pancreatitis after PTBD ( P<0.05). Logistic regression analysis showed that visualization of pancreatic duct ( OR=6.33) was a risk factor for pancreatitis, while pancreatic duct dilatation ( OR=0.14), pancreatic atrophy ( OR=0.12) and external drainage ( OR=0.11) were protective factors for pancreatitis. Conclusion:In pateints with pancreatic cancer and obstructive jaundice, pancreatic duct dilatation and pancreatic atrophy predict low risk of pancreatitis after PTBD,while intraoperative pancreatic duct visualization and internal or external drainage may increase the incidence of postoperative pancreatitis.
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Objective To evaluate the efficacy and safety of CT-guided percutaneous argon-helium cryoablation in treating hepatic metastases from nasopharyngeal carcinoma. Methods The clinical data of 16 patients with hepatic metastases from nasopharyngeal carcinoma, who had received percutaneous argonhelium cryoablation therapy, were retrospectively analyzed. The quality of life before and after therapy, and the postoperative complications were recorded. After argon-helium cryoablation therapy, the progression-free survival (PFS), the overall survival (OS), and the one-month, 3-month, 6-month, 12-month postoperative tumor local control rates were calculated. Results In all 16 patients, no severe complications occurred and the quality of life was significantly improved after argon-helium cryoablation therapy. The one-month, 3-month, 6-month, 12-month postoperative tumor local control rates were 100%, 87.5%, 80.0% and 58.3%respectively. The median PFS was 11 months (95%CI: 8.4-13.6 months), and the median survival time was19 months (95%CI: 9.2-28.8 months) . After argon-helium cryoablation therapy, the half-year, one-year and2-year survival rates were 93.8%, 75% and 43.8% respectively. Conclusion For the treatment of hepatic metastases from nasopharyngeal carcinoma, CT-guided percutaneous argon-helium cryoablation is minimally-invasive, safe and effective with reliable curative effect.
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Objective To evaluate the curative effect and safety of percutaneous argon-helium knife cryoablation in treating patients with liver metastases from gastric cancer.Methods The clinical data of 24 patients with liver metastases from gastric cancer,who had received percutaneous argon-helium knife cryoablation therapy,were retrospectively analyzed.A total of 33 metastatic lesions could be used for evaluation.CT-guided percutaneous argon-helium knife cryoablation of liver metastases was carried out in all patients.The 3-month,6-month and 12-month local control rate,overall survival (OS) rate,progression -free survival (PFS),incidence of recurrence,preoperative and postoperative quality of life,and complications were documented.Results The median follow-up time was 14 months (6-48 months).After cryoablation therapy,the quality of life was improved significantly.The 3-month,6-month and 12-mouth local control rates were 91.7%,73.9% and 52.6% respectively.Mter cryoablation therapy,the median PFS was 8 months (1-16 months),the median survival time was 16 months,and the one-year and 2-year survival rates were 75.0% and 37.5% respectively.No severe complications occurred.Conclusion For the treatment of liver metastases from gastric cancer,percutaneous argon-helium knife cuoablation is safe and effective with reliable short-term curative effect,the patient's quality of life can be well improved.
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Objective To discuss the clinical significance of peripheral neutrophil-to-lymphocyte ratio (NLR) changes in patients with castration-resistant prostate cancer (CRPC) after receiving argon-helium cryoablation.Methods A total of 33 CRPC patients,who were treated with argon-helium cryoablation at Tianjin Medical University Cancer Hospital,were included in this study.The clinical and pathological data were collected and analyzed.The following factors that might affect the postoperative overall survival (OS) of patients were analyzed with univariate and multivariate analysis:age,baseline PSA level,hemoglobin,white blood cell count,platelet count,albumin,alkaline phosphatase,NLR,platelet-to-lymphocyte ratio (PLR),hormone sensitive time,chemotherapy,bone metastasis,Gleason score,ECOG score,PSA effective rate.Results A total of 33 patients were enrolled in this study,the average age was 69 years (50-82 years) and the median survival time was 28 months (6-55 months).Univariate analysis showed that the baseline PSA level,alkaline phosphatase,NLR,hormone sensitive time,chemotherapy,bone metastases,Gleason score and PSA effective rate were significantly correlated with OS of CRPC patients after receiving cryoablation (P<0.05).Multivariate analysis showed that the baseline PSA level (P=0.003),NLR (P=0.009),Gleason score (P<0.001) were independent predictive factors for OS of CRPC patients after cryoablation therapy.Conclusion NLR can be used as a prognostic predictor for CRPC patients undergoing argon-helium cryoablation,and the increased NLR indicates a poor prognosis.(J Intervent Radiol,2017,26:237-242)
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Objective To investigate the effect of incomplete cryoablation on the biological behavior of prostatic cancer RM-1 cells and its mechanism.Methods RM-1 cells of prostatic cancer were placed in -20℃ icebox to be frozen for 5 min.After the recovery of the cell state,the RM-1 cells were frozen again for 10 min and 15 min successively.After culture for one day,the cellular morphology was microscopically examined.A total of 20 C57/BL mice were used to establish the tumor-bearing models,which were randomly and equally divided into the control group and the incomplete cryoablation group with 10 mice in each group.At scheduled time points the tumor lesion size was measured for all mice.The mice were sacrificed at 14 days,the lung tissues were collected and were stained with lE;the numbers of metastatic lesions in the lung were calculated.Transwell assay was used to test the cell migration and invasion,immuno-blotting method was adopted to determine the epithelial-mesenchymal transition-related (EMT-related) protein expression level,and the enzyme-linked immunosorbent assay (ELISA) was employed to check the secretion volume of transforming growth factor-beta (TGF-β).Results After incomplete cryoablation,RM-1 cells became disorderly arranged,their morphology was changed,and antenna structure might be formed.At 3 and 7 days after cryoablation,the tumor size in the incomplete cryoablation group was slightly smaller than that in the control group,but only the difference at 7 days after cryoablation was statistically significant between the two groups (P=0.019).At 10 and 14 days after cryoablation,the tumor volume of the two groups was almost equal.The pulmonary metastatic lesions in the incomplete cryoablation group were obviously much more than those in the control group (P<0.001).Transwell assay indicated that the cell migration and invasion ability in the incomplete cryoablation group was stronger than that in the control group (P<0.05).Immuno-blotting test revealed that,when compared with the control group,in the incomplete cryoablation group the expressions of N-cadherin,MMP-9 and Vimentin were up-regulated,while the expression of E-cadherin was downregulated.ELISA test showed that increased secretion of TGF-β was observed in the incomplete cryoablation group.Conclusion Incomplete cryoablation can enhance the migration and invasion ability of RM-1 cells,increase the number of pulmonary metastatic lesions in tumor-bearing mice,and affect the EMT-related protein expression level.
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Symptomatic venous thromboembolism (VTE) has a six-to seven-fold risk of occurring in cancer patients compared with non-cancer patients. VTE is the second most common cause of death among patients with cancer, and cancer-associated VTE is be-coming increasingly prevalent. Therefore, early diagnosis and treatment of cancer-associated VTE is particularly important. This study presents a pancreatic cancer-associated deep vein thrombosis (DVT) patient who engaged in a multidisciplinary comprehensive discus-sion in the Interventional Therapy Department, Tianjin Medical University Cancer Hospital to enhance concern, interdisciplinary com-munication, and cooperation in terms of cancer-associated VTE diagnosis and treatment strategies.
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Objective: To analyze the effect of Argon-Helium cryosurgery (AHCS) on CD4+ CD25+ regulatory T cells (Treg) and its implication in patients with advanced renal carcinoma.Methods:,Peripheral venous blood samples were ob-tained from 32 patients with advanced renal cell carcinoma before and after AHCS.The proportions of Treg cells and T lym-phocyte subsets (CD3+ T, CD4+ T, CD8+ T, CD4+ T/CD8+ T, and NK cells) in the peripheral blood were measured by flow cytometry.Enhanced CT or enhanced MRI was used to observe the necrosis of tumor at 1 month after AHCS.The areas with no imaging enhancement in tumor were regarded as tumor necrosis.The necrosis rate was measured by Cavalieri method and the tumor burden was evaluated.Results: At 3 months after AHCS, the percentages of Treg cells were gradual-ly decreased from 4.18%±1.58% to 1.96%±0.54%, with a significant difference (P=0.001).At 3 months after AHCS, the pro-portions of CD3+ T, CD4+ T, NK and CD4+ T/CD8+ T were gradually increased from 19.26%±7.52%, 43.54%±12.99%, 1.15%±0.57%, and 17.49%±8.36% to 30.83%±5.69%, 49.58±10.76%, 1.84%±0.12%, and 27.63%±8.20%, with a statistical significance (P=0.000, P=0.003, P=0.02, and P=0.001).The proportion of CD8 + T was decreased from 40.86%±8.89% to the lowest ratio (26.74%±4.29%) at 3 months after AHCS, with a significant difference (P=0.000).At 3~6 months after cryo-therapy, there was only a slight change in the proportions of CD3 + T, CD4 + T, CD4 + T/CD8 + T, NK, CD8 + T, and Treg cells, with no significant difference (P>0.05).Correlation analysis showed that the decrease in tumor burden was positively correlated with the decrease of the proportion of Treg cells (r=0.793, P<0.01).Conclusion: After AHCS, the distribution of T-lymphocyte subsets can be improved and the anti-tumor immune response was strengthened.The percentage of Treg cells is correlated with tumor burden.
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Objective To analyze the clinical and pathological factors which can influence the occurrence of the recurrent occlusion of metallic stents in patients with malignant biliary obstruction. Methods The clinical data of 50 patients with malignant biliary obstruction, who suffered repeated metallic stents obstruction and were admitted to authors" hospital during the period of March 2006-September 2008, were retrospectively analyzed. Of 50 patients, liver carcinoma was diagnosed in 12, pancreatic carcinoma in 17 and carcinoma of bile duct in 21. The relevant factors which might bear a relation to the occurrence of repeated metallic stents obstruction were evaluated. Results Single factor analysis of variance indicated that the denomination of carcinoma, clinical stage of carcinoma, location of obstruction, whether infection being accompanied or not, and the anti-tumor therapy after biliary stenting treatment were the significant factors closely linked to the occurrence of repeated metallic stents obstruction in patients with malignant biliary obstruction, Logistic regression analysis demonstrated that clinical stage of carcinoma, location of obstruction and whether infection being accompanied or not were the important factors that determined the occurrence of repeated metallic stents obstruction. Conclusion Clinical stage of carcinoma, location of obstruction and whether infection being accompanied or not are important reference factors for judging the occurrence of occlusion of metallic stents in malignant biliary obstruction.
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Objective To investigate the expression and signficance of secretory phospholipase A2(sPLA2>) in gastric adenocareinoma. Methods Sixty-five samples of gastric adenocarcinoma (11 with high differentiation, 10 with median differentiation and 44 with low differentiation) and 11 samples of normal gastric mucosa had been obtained from the Second Affiliated Hospital of Jilin University from January 2006 to April 2007. Fifty samples of gastric adenocarcinoma were found with lymph node metastasis. The expression of sPLA2> in gastric adenocarcinoma and normal gastric mucosa was detected. The relationship between sPLA2> and the differentiation of gastric adenoearcinoma, lymph node metastasis and helicobacter pylori infection was detected. All the data were processed with chi-square test or Spearman rank correlation. Results The positive rates of the sPLA2> expression in normal gastric mucosa and gastric adenocarcinoma were 36% (4/11) and 78% (51/65). The positive rates of sPLA2> expression in low, median and high differentiated gastric adenocarcinoma were 84% (37/44), 70% (7/10) and 64% (7/11), respectively. The expression of sPLA2> was positively correlated with the malignancy of gastric adenocarcinoma (r =0.272, P <0.05). The positive rates of sPLA2> expression in gastric adenocarcinoma with and without lymph node metastasis were 88% (44/50) and 47% (7/15), respectively. The expression of sPLA2> was correlated with lymph node metastasis (X2 = 9. 347, P < 0.05). The positive rates of sPLA2> expression in gastric adenocarcinoma with and without helicobacter pylori infection were 79% (38/48) and 76% (13/17), respectively. The expression of sPLA2> was not correlated with helicobacter pylori infection (X2 = 0. 000, P > 0.05). Conclusions The activation of sPLA2> gene may be correlated with the genesis of gastric adenocarcinoma. sPLA2> may influence the invasion of gastric adenocarcinoma, and can be used as an indicator in predicting poor prognosis.
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Objective To evaluate the effectiveness and safety of rectal ultrasound-guided agon- hilium percutaneous cryoablation in treatment of patients with median and or late-stage prostate cancer patients. Methods Retrospectively analysis of 42 cases of with stage C and D prostate cancer patients treated by rectal ultrasound-guided argon&ilium percutaneous cryoablation during the follow-up of 1--12 months. The prostate specific antigen (PSA), biochemical progression-free survival (bPFS), PSA objective response, transrectal ultrasound of the prostate (TRUS), TRUS-guided biopsy of the prostate, the maximum urinary flow rate(MFR), MRI examination at before, and 3,6,12 months after cryoablatian were recorded and evaluated. The results were statistically evaluated by using variance analysis. Results The PSA value at before and 3, 6, 12 months after cryoablation were (4.48±1.35), (3.54±1.67), (3.18±1.76), (2.87±1.89) ug/L, respectively; TRUS-messured prostate volumes at before and 3, 6,12 months after cryoablation were (59.7± 8.2),(46.9±8.3),(26.2±3.9),(25.9±3.7)mm3, respectively; MFR before and 3, 6,12 months after cryoablation were (10.4±0.8), (14.3±1.2), (18.3±1.3), (18.9±1.3) ml/s, respectively; Compared with before cryoablation, the differences between before and after cryoablation was statistically significant( F = 53.93,747.92,3843.03,respectively, P<0.01). The bPFS rates in 3 months,6 months and 12 months were 95.2% (40/42), 95. 2% (40/42), and 90.5% (38/42), respectively. According to the PSA response, the total effective rate (CR 16 cases, PR 15 cases) at 12 months was 73. 8%, and SD was 16.7% (7/42), PD was 9.5% (4/42). Complications included temporary incontinence 2.4% (1/42), Penile tingling/numbness 2.4% (1/42), pelvic pain 4.9% (2/41) and Scrotum Edema 2.4% (1/42). There was no case with severe complications such as severe infection or urethrorectal fistula, etc. Condusions Rectal ultrasound-guided agon-hilium percutaneous cryoablation showed is a well tolerated and has better early clinical efficacy to the treatment of stage C and D prostate cancer.