1.Liuwei Dihuang Erzhiwan Combination Regulate Myeloid-derived Suppressor Cells to Inhibit Breast Cancer Lung Metastasis
Lixiang ZHENG ; Zifeng GUO ; Huiwen GUO ; Xiaomin WANG ; Chuanming XU ; Yuliang HU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(20):37-45
ObjectiveTo investigate the mechanism by which Liuwei Dihuang Erzhiwan combination inhibit the lung metastasis of spontaneous breast cancer in mice by regulating the recruitment of myeloid-derived suppressor cells (MDSCs). MethodThree hundred and eighty SPF-grade 10-month-old female breeders of Kunming mouse were palpated at the mammary gland site once every 3 days. Mice that have not had a lump touched after being raised for 6 months are used as control group. After tumor development, the mice were randomized into model, positive control (paclitaxel, intraperitoneal injection at 0.01 g·kg-1 every other day for 22 d), Liuwei Dihuangwan (0.65 g·kg-1·d-1 by gavage), Erzhiwan (5.41 g·kg-1·d-1 by gavage), and Liuwei Dihuang Erzhiwan combination (6.05 g·kg-1·d-1 by gavage) groups. The mice were euthanised when the tumor reached a diameter of about 15 mm, and the tumor and lung tissues were collected. The survival time, tumor mass, and lung metastasis rate of tumor-bearing mice were recorded. Hematoxylin-eosin (HE) staining was used to observe the histopathological and morphological changes of mouse tumor and lung tissues. Immunofluorescence (IF) was used to detect the distribution of MDSCs in tissues of mice in each group by double-staining of MDSCs cells with lymphocyte antigen 6 complex site G6D (Ly6G) and CD11 antigen-like family member B (CD11b). Western blot was employed to determine the protein levels of matrix metalloproteinase-9 (MMP-9), transforming growth factor-β (TGF-β), zinc finger transcription factor 1 (Snail1), and E-cadherin in the tumor tissue and CC motif chemokine 9 (CCL9) and CC motif chemokine receptor 1 (CCR1) in the lung tissue. ResultDuring the modelling period, the paclitaxel group and Chinese medicine intervention groups had longer median number of days of survival and lower tumor weight, lung metastasis rate, and lung nodule than the model group (P<0.05, P<0.01). HE staining showed an increase in tumor cell necrosis in the paclitaxel group and the Liuwei Dihuang Erzhiwan combination group. The paclitaxel group and Chinese medicine intervention groups had lower fluorescence intensity of MDSCs in the tumor tissue than the model group (P<0.05, P<0.01). Compared with the normal control group, the model group showed increased fluorescence intensity of MDSCs in the metastatic lung tissue (P<0.01), which, however, was decreased in the paclitaxel group and Chinese medicine intervention groups (P<0.01). The model group showed higher protein levels of MMP-9, TGF-β, and Snail1 and lower protein level of E-cadherin in the tumor tissue than in the normal control group (P<0.01). Compared with model group, paclitaxel and Chinese medicine interventions downregulated the protein levels of MMP-9, TGF-β, and Snail1 (P<0.05, P<0.01) and upregulated the protein level of E-cadherin in the tumor tissue (P<0.01). Moreover, the Liuwei Dihuang Erzhiwan combination group had lower protein levels of TGF-β and Snail1 than the Liuwei Dihuangwan group and Erzhiwan group (P<0.05). In the metastatic lung tissue, the expression of CCL9 and CCR1 was higher in the model group than in the normal control group, paclitaxel group, and Chinese medicine intervention groups (P<0.05, P<0.01). ConclusionLiuwei Dihuang Erzhiwan combination inhibit tumor growth, prolong survival time, and reduce the occurrence of lung metastasis in the mouse model of spontaneous breast cancer by reducing the recruitment of MDSCs in the tumor and lung tissues and modulating the phenotypes of epithelial-mesenchymal transition (EMT)-related molecules and the expression of CCL9/CCR1.
2.Clinical application of DSA-guided infusion port implantation via internal jugular vein,subclavian vein and axillary vein
Xinchun GUO ; Xinjian XU ; Dongqing REN ; Feng GAO ; Xiangzhong HUANG
Journal of Interventional Radiology 2023;32(12):1211-1216
Objective To investigate the clinical application and safety of DSA-guided infusion port implantation via internal jugular vein,subclavian vein and axillary vein.Methods A total of 827 patients with malignant tumors,who underwent DSA-guided intravenous infusion port implantation at the Jiangyin Municipal People's Hospital of China between March 28,2016 and June 28,2018,were enrolled in this study.According to the used approach in the port implantation,the patients were divided into internal jugular vein group(group A,n=125),subclavian vein group(group B,n=87),and axillary vein group(group C,n=615).The success rate of puncturing and the incidence of complications were compared between each other among the three groups.Results The success rates of the DSA-guided first-time puncturing in group A,B and C were 98.40%(123/125),94.25%(82/87),and 97.89%(602/615)respectively,the difference was statistically significant(P<0.05);the success rate of puncturing in group B was lower than that in group C,and among the other groups there was no statistically significant difference(P>0.05).All patients were followed up for a mean period of(15.56±2.91)months(range of 3-26 months).The overall incidence of postoperative early complications was 3.75%,which in group A was 4.00%(5/125),in group B was 9.20%(8/87),and in group C was 2.93%(18/615),and the incidence of complications in group B was obviously higher than that in group C(P<0.0167).There was no statistically significant difference in the incidence of various complications between each other among the three groups(P>0.05).The overall incidence of postoperative long-term complications was 4.72%(39/827),which in group A was 4.80%,in group B was 14.95%,and in group C was 3.25%,and the incidence of complications in group B was strikingly higher than that in group A and group C,the difference was statistically significant(P<0.05).Comparison of groups for the rates of various complications showed that the incidence of catheter fracture in group B was higher than that in group C,and the clipping syndrome occurred only in group B,the difference was statistically significant(P<0.0167).There was no significant difference in the incidence of other complications between each other among the three groups(P>0.05).The abnormal port-taking rate was 1.45%,including 3 patients in group A,7 patients in group B,and 2 patients in group C.The postoperative abnormal port-taking rate in group B was the highest(8.05%),which was significantly different from that in group C(P<0.0167).Conclusion For intravenous infusion port implantation,axillary vein approach is clinically safe,comfortable,minimally-invasive and highly-efficient method,it is superior to internal jugular vein approach and subclavian vein approach in effectively reducing the incidence of complications and improving the postoperative abnormal port-taking rate of patients.Therefore,this technique can be regarded as a first choice in clinical practice.(J Intervent Radiol,2023,32:1212-1216)
3.A study on mechanism of lncRNA-mediated SNHG5/miR-26a-5p/MTDH signal axis promoting metastasis of colorectal cancer
Junling YE ; Xiaoying ZHENG ; Xinjian GUO ; Ruihui CHEN ; Liu YANG ; Xiaodan GOU ; Hanmei JIANG
China Oncology 2023;33(7):673-685
Background and purpose: Long non-coding RNA small nucleolar RNA host gene 5 (lncRNA SNHG5) plays a cancer-promoting role in many cancers, however its effect on colorectal cancer (CRC) and its regulatory mechanism are not clear. This study aimed to explore the mechanism of lncRNA SNHG5/miR-26a-5p/metadherin (MTDH) signal axis promoting metastasis of CRC. Methods: The data of The Cancer Genome Atlas (TCGA) database was analyzed, the abnormal expression of lncRNA in CRC was explored and analyzed the survival. Samples of CRC, paracancerous tissues and complete clinical data of patients who underwent surgical resection from October 2020 to October 2021 were collected. The expression levels of SNHG5 and miR-26a-5p in lncRNA were detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR), and the expression level of MTDH was detected by immunohistochemistry. The relationship between the relative expression level of lncRNA SNHG5 in CRC and clinicopathological features and survival time was analyzed. The effects of lncRNA SNHG5 on the proliferation, migration and invasion of CRC cells were detected by cell counting kit-8 (CCK-8), clone formation, scratching assays, transwell test and in vivo xenotransplantation. The relationship between CRC cell metastasis, the expression level of epithelial-mesenchymal transition related molecules and lncRNA SNHG5 expression level by Western blot and immunohistochemical detection were explored. The physical interaction between SNHG5 and miR-26a-5p, MTDH and miR-26a-5p was studied by RNA pull-down test, double luciferase reporter gene detection and RNA co-immunoprecipitation. The functional relationship among the three was verified by CCK-8, EdU and transwell experiments. The effect of SNHG5, miR-26a-5p and MTDH expression on migration and invasion related molecules was analyzed by Western blot. Results: The results of TCGA database analysis showed that lncRNA SNHG5 was significantly upregulated in CRC. The results of RTFQ-PCR and immunohistochemistry showed that the levels of lncRNA SNHG5 and MTDH in CRC tissues were significantly upregulated (P<0.05), the level of miR-26a-5p was decreased (P<0.05), and the level of MTDH in samples with high expression of SNHG5 was also increased. The expression of lncRNA SNHG5 in CRC tissues with serosa and extraserosal invasion, distant metastasis, lymph node metastasis and TNM stage Ⅲ was significantly higher compared with subserosal invasion, no distant metastasis and lymph node metastasis and TNM stage Ⅰ-Ⅱ (P<0.05). The results of survival analysis showed that the high expression of lncRNA SNHG5 was significantly correlated with overall survival rate (P<0.05). Overexpression of lncRNA SNHG5 could enhance the proliferation, clone formation, migration and invasion of CRC cells, promote the growth and lung metastasis of transplanted tumor, increase the relative expression level of Ki-67 proliferation index and vimentin (P<0.05), and decrease the relative expression level of E-cadherin (P<0.05). However, the development of CRC cells was inhibited after inhibition of lncRNA SNHG5 expression. RNA pull-down test, double luciferase reporter gene detection and RNA co-immunoprecipitation confirmed the physical interaction between SNHG5 and miR-26a-5p, MTDH and miR-26a-5p. Upregulation of miR-26a-5p or downregulation of MTDH expression in lncRNA SNHG5 overexpressed cells partially reversed the effects of lncRNA SNHG5 on proliferation, migration, invasion and expression of related molecules in CRC cells. Conclusion: LncRNA SNHG5 is upregulated in CRC tissues and cells, and its high expression is related to tumor progression and poor survival. It can be used as a molecular sponge of miR-26a-5p to regulate the expression of MTDH to promote the proliferation and metastasis of SW620 cells.
5.Effectiveness and safety of submaximal angioplasty and stenting for patients with severe carotid artery stenosis before CABG
Xu GUO ; Chengzhe FAN ; Yudong MA ; Lifeng WANG ; Nan ZHANG ; Yang WANG ; Lei YU ; Xiaofen HE ; Xinjian YANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2021;37(4):250-254
Objective:To investigate the feasibility and safety of submaximal balloon dilation and to perform small-diameter stent for symptomatic carotid artery severely stenosis before coronary artery bypass grafting(CABG).Methods:From January 2016 to December 2019, 30 patients of the Department of Neurointervention in Beijing Anzhen Hospital with symptomatic carotid artery stenosis(≥70%) and the left main trunk or triple-vessel of coronary artery disease were analyzed retrospectively. General information, clinical characteristics, and imaging data of all cases were collected. All patients underwent submaximal balloon dilation and small-diameter stent implantation. Preoperative comorbidities or risk factors included hypertension 23 cases(76.7%), diabetes 10 cases(33.3%), hyperglycemia 14 cases(46.7%), moking 13 cases(43.3%). Left main trunk disease 6 cases(20.0%), three-vessels disease 24 cases(80.0%), mitral regurgitation 1 case(3.3%), stable angina 25 cases(83.3%), myocardial infarction 8 cases(26.7%), cerebral infarction 24 cases(80.0%) and transient ischemia attack(TIA) 6 cases(20.0%) caused by ipsilateral carotid artery stenosis. The median National Institutes of Health Stroke Scale(NIHSS) score was 2(0-3), and the median modified Rankin Scale(mRS) score was 1(0-1) before the operation. The mean interval between carotid artery intervention and CABG was(23.4±8.2)days.Results:29 cases(96.7%, 29/30) underwent CAS-CABG operation successfully. In one case of carotid artery extreme tortuosity, the emboli protective device could not place the distal carotid artery. In the operative procedure, 27 cases(90.0%, 27/30) underwent with 3mm diameter balloon, only 3 cases(10.0%) with 3 mm balloon after pre-dilatation with 2 mm diameter balloon because of severely high-grade stenosis(99%). 25 cases(83.3%) with 7mm diameter stents and 5 cases(16.7%) with 6 mm diameter stents, including 22 cases(73.3%) with a closed-cell stent and 8 cases(26.7%) with an open-cell stent. In the perioperative period, the heart rate of two patients was lower than 50 BPM during operation and returned to normal after using atropine immediately. Another patient presented with chest tightness during interventional therapy. TNI elevation was examined urgently. After oxygen inhalation and intravenous infusion of Nitroglycerin, the patient's symptoms improved rapidly. No cardiac and cerebrovascular complications occurred during the perioperative period of CABG, no cardiac-related complications occurred within 30 days of follow-up, one case of TIA and 1 case of cerebral infarction. After intensive anti-platelet aggregation and lipid-lowering treatment, two patient's symptoms improved. There were no death cases in all patients during carotid artery interventional therapy, perioperative CABG and 30-day follow-up. Thirty days later, we performed a clinical follow-up of 23 cases, median 4.5(3.0-7.9) months, mRS Score Median 1(0-1). One patient presented with TIA, any patient had no symptoms of the cardiac or nervous system. Image follow-up of 17 cases, median 3.5(2.8-4.5) months, carotid artery ultrasound showed in-stent restenosis(stenosis rate>50%) in 1 case, the patient was asymptomatic restenosis, continue treatment of aggressive anti-platelet and lipid-lowering drugs.Conclusion:Submaximal balloon dilation and performing small-diameter stent for symptomatic carotid artery severely stenosis before CABG is safe and feasible, which could not only reduce the incidence of vagus reflex resulted in acute coronary syndrome during carotid artery stenosis intervention but also morbidity of acute ischemic stroke events during CABG.
6.Diagnosis and treatment of hepatic alveolar echinococcosis with intraperitoneal implantable metastasis
Jican YAN ; Zhiyu CHEN ; Wenhao YU ; Xinjian GUO ; Haijiu WANG ; Qian LU ; Liuxin ZHOU ; Haining FAN ; Zhixin WANG
Chinese Journal of Digestive Surgery 2021;20(9):1007-1010
Hepatic alveolar echinococcosis is a zoonotic parasitic disease caused by echinococcus multilocularis infection. The growth pattern of the lesions of hepatic alveolar echinococcosis is similar to that of liver malignant tumor showing invasive growth. Hepatic alveolar echinococcosis can not only directly invade the adjacent tissue structure, but also metastasize through the lymphatic tracts and blood vessels. Hepatic alveolar echinococcosis with intraperitoneal implantable metastasis is extremely rare. The authors introduce the diagnosis and treatment of 1 patient who had hepatic alveolar echinococcosis with intraperitoneal implantable metastasis.
7.Meta-analysis of the effects of triamcinolone acetonide alone and in combination with 5-fluorouracil for treating keloids
Xinjian LIU ; Zhengjun CUI ; Shutang ZHANG ; Weiguo SU ; Qingnan MENG ; Pengfei GUO ; Aizhou WEI ; Jian ZHOU ; Changyin WANG ; Shibo ZOU ; Jialin SUN ; Xu WANG
Chinese Journal of Burns 2020;36(12):1191-1198
Objective:To compare the efficacy and safety of triamcinolone acetonide (TA) alone and in combination with 5-fluorouracil (5-FU) for treating keloids using meta-analysis.Methods:Databases including PubMed, Embase, and Cochrane Library were retrieved with the search terms of " triamcinolone acetonide, 5-fluorouracil, glucocorticoid, fluorouracil, keloid, scar, TAC, 5-FU, hypertrophic scar " and databases including Chinese Journal Full- Text Database, Chinese Biomedical Database, and Wanfang Data were retrieved with the search terms of "曲安奈德,瘢痕疙瘩, 5-氟尿嘧啶,糖皮质激素,增生性瘢痕" in Chinese to obtain the publicly published randomized controlled trials about the effects of TA alone and in combination with 5-fluorouracil for treating keloids from the establishment of each database to august 2019. The outcome indexes included effective proportion of treatment, incidence proportion of adverse reactions, and recurrence proportion of keloids. RevMan 5.3 and Stata 14.0 statistical software were used to conduct a meta-analysis of eligible studies. Results:A total of 1 326 patients with keloids were included in 14 studies, including 668 patients in TA+ 5-fluorouracil group whose keloids were injected with TA and 5-fluorouracil and 658 patients in TA alone group whose keloids were injected with TA alone. A total of 7 articles achieved 1 to 3 points in modified Jadad score, while 7 articles achieved 4 to 7 points in modified Jadad score. Patients in TA+ 5-fluorouracil group had a higher effective proportion of treatment than that of TA alone group (relative risk=1.28, 95% confidence interval=1.16-1.41, P<0.01). Subgroup analysis showed that the quality of the included literature and ethnic factors might be the source of heterogeneity in effective proportion of treatment. Patients in TA+ 5-fluorouracil group had a lower incidence proportion of adverse reactions than that of TA alone group (relative risk=0.44, 95% confidence interval=0.25-0.75, P<0.01). Patients in TA+ 5-fluorouracil group had a lower recurrence proportion of keloids than that of TA alone group (relative risk=0.25, 95% confidence interval=0.14-0.44, P<0.01). There was no publication bias in incidence proportion of adverse reactions ( P>0.05), while the effective proportion of treatment and recurrence proportion of keloids had publication bias ( P<0.05). Conclusions:TA combined with 5-fluorouracil is more effective than TA alone for treating keloids, with less incidence of adverse reactions and recurrence.
8.Efficacy of minimally invasive pulmonary surfactant administration in preterm infants with neonatal respiratory distress syndrome: a multicenter clinical trial
Huiqiang LIU ; Xiaomei TONG ; Tongyan HAN ; Hui ZHANG ; Ming GUO ; Xuefeng ZHANG ; Xinjian LIU ; Xiang ZHANG ; Mingtao ZHANG ; Fang LIU ; Lisha BAO ; Jun ZHENG ; Xiuying TIAN ; Qi GAO ; Wanxian ZHANG ; Yang DUAN ; Fuqiang SUN ; Wei GUO ; Ling LI ; Min XIAO ; Weili LIU ; Rui JIANG
Chinese Journal of Pediatrics 2020;58(5):374-380
Objective:To explore the feasibility and safety of minimally invasive surfactant administration (MISA) in preterm neonates with respiratory distress syndrome (NRDS).Methods:In this multicenter prospective randomized controlled trial, 92 preterm infants with gestation age ≤30 weeks and diagnosed with NRDS were enrolled in 8 level Ⅲ neonatal intensive care units (NICU) in Beijing-Tianjin-Hebei Region from 1 st July 2017 to 31 st December 2018. They were randomly assigned to minimally invasive surfactant administration (MISA) group or endotracheal intubation surfactant administration (EISA) group according to random number generated by computer. Infants in both groups received calf pulmonary surfactant preparation at a dose of 70-100 mg/kg. The data of demography, perinatal situation, medication administration, complications, clinical outcomes in the two groups were compared with Chi-square test, Student′s t-test, Mann-Whitney U test or Fisher′s exact test. Results:Among the 92 preterm infants, 53 were males, 39 were females; 47 were in the MISA group (25 males), and 45 were in the EISA group (28 males). The gestational age and birth weight were (29.5±1.2) weeks and (1 271±242) g in all patients, (29.5±1.4) weeks and (1 285±256) g in the MISA group, and (29.6±0.9) weeks and (1 255±227) g in the EISA group. The duration of surfactant infusion and the length of whole procedure in the MISA group were significantly longer than that in the EISA group (60 (18, 270) s vs. 50 (30, 60) s, Z=3.009, P=0.003; 90 (60, 300) s vs. 60 (44, 270) s, Z=3.365, P=0.001). For the outcomes, the incidence of hemodynamically significant patent ductus arteriosus (hsPDA) and bronchopulmonary dysplasia (BPD) were lower in the MISA group than in the EISA group (36% (17/47) vs. 67% (30/45), χ 2=8.556, P=0.003; 26% (12/47) vs. 47% (21/45), χ 2=4.464, P=0.035). Conclusions:Minimally invasive surfactant administration is applicable in preterm infants ≤30 weeks gestational age with NRDS. Although the length of whole procedure is longer than route endotracheal administration, the benefit of decreasing the incidences of hsPDA and BPD outweighs this demerit.
9. Clinicopathologic characterization of malignant mixed tumor of the skin accompanied by eccrine porocarcinoma
Xiaofeng ZHOU ; Qingguo YAN ; Xinjian GUO ; Xiaodan GOU ; Jingqi HAN ; Junling YE ; Haiyan ZHANG ; Fengmei WANG
Chinese Journal of Pathology 2018;47(7):536-541
Objective:
To investigate the clinicopathologic features, immunophenotype, pathological diagnosis and treatment of malignant mixed tumor (MMT).
Methods:
Clinical and pathological features including immunohistochemical phenotypes were analyzed in a case of MMT accompanied with eccrine porocarcinoma (EP) involving both hands, diagnosed definitely in January 2018 along with review of relevant literature.
Results:
A 64-year-old man presented with multiple rash on both hands for 4 years. Three lesions of 0.5 to 2.2 cm were removed for pathological evaluation. The pathological changes on little finger of left and right hands were MMT with EP, whereas that removed from the right ring finger was EP. MMT showed infiltrative growth with vascular wall invasion and consisted of epithelial (glandular or tube differentiation) and mesenchymal components (mucinous and/or cartilage stroma). The endothelial cells showed moderate to severe cytological atypia, nuclear pleomorphism and increased mitotic activity. The glandular component had histological characteristics of syringocarcinoma with moderately atypical chondrocytes but without myoepithelium. EP was composed of basal cells with visible vacuoles in cytoplasm and the presence of tubular and squamous differentiation, along with obvious atypia. Immunohistochemically cavosurface epithelium of glandular differentiation of MMT showed positivity for CK7, EMA and CD117. Myoepithelium showed S-100, CK5/6 and p63 positivity and stromal cells were positive for S-100. Differential diagnoses included metaplastic carcinoma, malignant myoepithelioma and atypical mixed tumor of skin.
Conclusions
MMT with EP is extremely rare.The diagnosis of MMT depends on the morphologic features. Immunohistochemical staining is helpful for differential diagnosis. Surgical excision with safety margins is the treatment of choice. Complementary radiotherapy and/or chemotherapy is still controversial. The clinical course of MMT is deemed unpredictable and long-term follow-up is necessary.
10.Microsurgery of spinal cord Intramedullary cavernous hemangioma
Weijie DONG ; Xinman LIU ; Yuejiao SU ; Kun CHEN ; Shaolei GUO ; Xinjian WU
Chinese Journal of Microsurgery 2018;41(2):105-108
Objective To investigate the microsurgical effect of spinal cord Intramedullary cavernous hemangioma.Methods The clinical data of 23 patients with spinal cord Intramedullary cavernous henangioma from January,2003 to March,2017 were analyzed retrospectively.McCormick clinical neurological function classification method and MRI examination were used to analyze the changes of neurological function and imaging changes beforeand-after operation.MRI and assess nerve function were reviewed 6-12 months after discharge.Results Twentytwo cases were totally resected,and subtotal excised in 1 case.The symptoms improved and even disappeared completely in 17 cases.There was no obvious improvement in 4 cases,2 cases were worse and no death cases.Twentyone cases were followed-up.The follow-up time was 3 months-9 years,and no tumor recurrence was found.Among the 14 cases of clinical neurological function Ⅰ-Ⅱ,10 cases recovered rapidly and most of the symptoms improved or even disappeared.Three cases had no obvious change.The other 1 case aggravated symptoms;Six cases of Ⅲ-Ⅳ patients in 7 cases of postoperative recovery,and 1 case of no change.According to preoperative neurological function grade Ⅰ-Ⅱ and Ⅲ-Ⅳ,the treatment effect of patients was compared,the difference was significant (x2=5.25,P<0.05).Conclusion Microsurgical resection of spinal cord Intramedullary cavernous hemangioma is safe and effective.The preoperative nerve function,the relationship between the tumor and the spinal cord,and the surgical skill and the degree of resection are the important factors that affect the prognosis.

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