1.Correlation between the expression of nuclear factor-kappa B,monocyte chemoattractant protein-1 and CD68 in lupus nephritis
Jianping WEI ; Xiaofen ZHANG ; Shulei YAO ; Xiaoqin ZHANG ; Liran WU ; Chen WANG
Chinese Journal of Rheumatology 2010;14(2):91-93,后插一
Objective To observe the expression of nuclear factor-kappa B(NF-κ3)and monocyte chemnattractant protein-1(MCP-1),and the infiltration of mononuclear macrophage CD68 in lupus nephritis (LN).The association between NF-κB,MCP-1 and MΦ with kidney pathology and clinical manifestations is explored.MethodsNF-κB,MCP-1 and MΦ in renal biopsy specimens from 49 cases of LN were detected using immunohistochemical techeniques.Forty-nine cases of renal tissues were examined for NF-κB by in situ hybridization.The relationship between NF-κB,MCP-1 and MΦ with kidney pathology and clinical manifestations were analyzed.Results ①Compared with the control group ,the expression of NF-κB,MCP-1 and MΦ in LN was significantly higher(P<0.01).The expression of MCP-1 positively correlated with MΦinfiltration and NF-κB(P<0.01)in glomeruli and renal tubule and renal interstitium of LN.The expression of NF-κB,MCP-1 and the infiltration of MΦ in LN Ⅳ was significandy higher than non LN Ⅳ and the control group(P<0.01,P<0.05).There was no significant difference between renal NF-κB positive group and negative groups in the degree of the immunohistochemical and in situ hybridization examination(P>0.05).②The histological activity index,urine protein volume(24 h)and serum creatinine in LN were significantly higher than the control group(P<0.01),and the expression of NF-κB in LN was correlated with histological activity index,urine protein volume(24 h)and serum creatinine(P<0.01,P<0.01,P<0.05).MCP-1 and CD68 expression in LN were correlated with histological activity index and urine protein volume(24 h),but not correlated with serum creatinine(P>0.05).Conclusion NF-κB induced MΦ by activating MCP-1 may be one cause of kidney injury of LN.NF-κB signal pathway may act as a new therapeutic target for MΦinfiltration and proliferation inhibition in kidney.
2.Analysis of gene characteristics and therapeutic effect of cblC type methylmalonic acidemia with hydrocephalus
Yu LI ; Hongwu ZHANG ; Yangxu GAO ; Hui LI ; Haibo YANG ; Lixue SHEN ; Shulei WANG ; Hongxin YAO
Chinese Journal of Applied Clinical Pediatrics 2021;36(8):593-596
Objective:The clinical manifestations, types of gene mutations, therapeutic effects and prognostic characteristics of 15 children with cblC type methylmalonic acidemia (MMA) and hydrocephalus were analyzed to improve the clinical understanding of the disease, so as to provide a basis for the treatment of the disease.Methods:From April 2015 to January 2019, 15 patients with MMA and hydrocephalus in Department of Pediatric Surgery, Peking University First Hospital were enrolled, and all gene detection showed clbC type.All the 15 patients underwent ventriculoperitoneal shunt.After surgery, the clinical manifestations and imaging findings were applied as the basis to adjust the pressure of the diverter valve appropriately.Clinical data and gene mutation characteristics of 15 children with cblC type and hydrocephalus were retrospectively analyzed, and the therapeutic effects and prognosis were summarized and analyzed as well.Results:There were 8 males (53.3%) and 7 females (46.7%), aged from 2 to 33 months.All the cases were followed up from 11 to 55 months, without death case and serious postoperative complications of hydroce-phalus.The head circumference of 3 cases (20.0%) was in the normal range, 1 case (6.7%) was greater than the normal range, and 11 cases (73.3%) were less than the normal range.Four patients (26.7%) were transferred to the pediatric intensive care unit after surgery.c.609G>A mutation was the most common in this study, with 7 cases (46.7%) of c. 609G>A homozygous mutation, and 5 cases (33.3%) of c. 609G>A heterozygous mutation.Clinical symptoms of intracranial hypertension were relieved or disappeared.The head circumference progressive enlargement was stopped.The anterior fontanelle tension greatly decreased, all " setting-sun" sign of eyes disappeared, and vision loss and hearing loss were better compared with the pre-operation.Four cases (26.7%) displayed normal intelligence and exercise, and 11 cases (73.3%) were left with mild to severe psychomotor retardation.During the follow-up pe-riod, the head CT showed that the ventricle was remarkably narrowed, and interstitial brain edema obviously improved.Conclusions:Ventriculoperitoneal shunt in the treatment of cblC type MMA with hydrocephalus has positive effects.The head circumference of most cblC type MMA with hydrocephalus is less than the normal range.c.609 G>A is the most common mutation in cblC type MMA with hydrocephalus.Perioperative " metabolic crisis" can result in serious complications.
3.Analysis of risk factors of lymph node metastasis and clinical significance of deep submucosal invasion in 64 cases of T1 stage colorectal cancer
Haiyan JING ; Chunfang TIAN ; Qingshan PEI ; Shulei ZHAO ; Zhigang YAO ; Xichao SUN ; Yejun QIN ; Xiaolong ZHU
Chinese Journal of Digestion 2021;41(11):770-774
Objective:To investigate the risk factors of lymph node metastasis and the clinical significance of deep submucosal invasion in patients with T1 stage colorectal cancer.Methods:From January 30, 2010 to December 31, 2019, at Shandong Provincial Hospital Affiliated to Shandong First Medical University, among patients with T1 stage colorectal cancer, 41 patients underwent radical surgery for colorectal cancer (surgery group) and 23 patients received endoscopic submucosal dissection (ESD) (ESD group) were enrolled. The tumor gross type, maximum diameter, histologically poorly differentiated components, degree of invasion (the type of mucosal muscle destruction, the width and depth of invasion), the budding grade of tumor, and whether with vascular tumor thrombus were recorded. The additional treatment and prognosis of patients were collected by telephone follow-up. The risk factors of lymph node metastasis in stage T1 colorectal cancer, the correlation between the complete muscularis mucosa destruction and the width and depth of invasion in the ESD group, and the effects of additional treatment after operation on the prognosis of patients were analyzed. Independent sample t test and chi-square test were used for statistical analysis. Results:The rate of lymph node metastasis in patients with poorly differentiated components or vascular tumor thrombus was higher than that in patients without poorly differentiated components or vascular tumor thrombus (3/6 vs. 12.1%, 7/58; 3/4 vs. 11.7%, 7/60), and the differences were statistically significant ( χ2=5.934 and 11.409, both P<0.05). All patients in the surgery group had complete muscularis mucosa destruction. In ESD group, the width of tumor invasion was ≥ 2 mm in 16 cases, including complete destruction of muscularis mucosa in 15 cases and partial destruction in one case; the width of tumor invasion was <2 mm in seven cases, including complete destruction of muscularis mucoa in two cases and partial destruction in five cases; the depth of infiltration was ≥ 2 000 μm in 14 cases, including complete destruction of muscularis mucosa in 13 cases and partial destruction in one case; the depth of infiltration was <2 000 μm in nine cases, including complete destruction of muscularis mucosa in four cases and partial destruction in five cases. The complete muscularis mucosa destruction was related with tumor of invasion width ≥ 2 mm and invasion depth ≥ 2 000 μm (15/16 vs.2/7, 13/14 vs. 4/7), and the differences were statistically significant ( χ2=10.729, 6.659, both P<0.05). Among the 64 patients with T1 stage colorectal cancer in this study, six cases (9.4%) had poor prognosis; five cases (7.8%) died, and three of them (4.7%) were tumor-related deaths. Adjuvant therapy was added in 10 cases in surgery group and 10 cases in ESD group, and there were no poor prognosis in those patients. There were no significant difference in the incidences of poor prognosis of patients without additional treatment and patients with additional treatment of the two groups (9.7% (3/31) vs. 0 (0/10) and 23.1% (3/13) vs. 0 (0/10)) (both P>0.05). Conclusion:When T1 stage colorectal cancer with tumor submucosal invasion, clinicians should comprehensively evaluate the prognostic risk based on various pathological characteristics such as the degree of tumor differentiation, vascular tumor thrombus and mucosal muscle destruction.
4.Study on Huangqi Jiedu Decoction for Wnt/β-catanin signaling pathway inhibiting EMT against lung metastasis of breast cancer
Shulei LIU ; Lifang LIU ; Lihong ZENG ; Yao ZHOU ; Dan ZHAO ; Jie GONG ; Hailin CAO
International Journal of Traditional Chinese Medicine 2023;45(9):1113-1118
Objective:To observe the inhibitory effects of Huangqi Jiedu Decoction on lung metastasis of breast cancer in nude mice; To explore the mechanism of intervening epithelial mesenchymal transformation (EMT) induced by Wnt/β-catenin signaling pathway.Methods:Totally 30 nude mice were divided into model group, adriamycin group and Huangqi Jiedu Decoction low-, medium-, and high-dosage groups according to random number table method. Each group was injected subcutaneously with mouse breast cancer 4T1 cells to construct tumor - bearing nude mice model. Huangqi Jiedu Decoction low-, medium- and high-dosage groups were intragastrically administrated with Huangqi Jiedu Decoction 17.82, 35.64 and 71.28 g/kg; adriamycin group was injected intraperitoneally adriamycin 0.05 g/kg; model group was intragastrically administrated with normal saline of the same volume for 21 d. Tumor volume was measured at 9, 15, and 21 days after modeling. After the end of administration, the tumor tissue was separated, the tumor weight was measured, and the tumor inhibition rate was calculated. The lung tissue was Isolated,, the number of lung metastatic nodules and the inhibition rate of lung metastasis was counted. HE staining was used to observe the tissue morphology and evaluate the effectiveness of the model. The protein expressions of β-catenin, E-Cadherin and Vimentin in lung tissue were detected by Western Blot. The mRNA levels of β-catenin, E-Cadherin and Vimentin in lung tissue were detected by real-time fluorescent quantitative PCR.Results:Compared with the model group, the tumor volume and mass of Huangqi Jiedu Decoction low-, medium- and high-dosage groups decreased ( P<0.01); the number of pulmonary metastasis nodules in Huangqi Jiedu Decoction high-dosage group significantly decreased ( P<0.01); the mRNA and protein expressions of β-catenin and Vimentinm decreased in the Huangqi Jiedu Decoction low-, medium- and high-dosage groups ( P<0.01), and the protein and mRNA expressions of E-Cadherin increased in the Huangqi Jiedu Decoction high-dosage group ( P<0.01). Conclusion:Huangqi Jiedu Decoction can effectively inhibit the growth and lung metastasis of breast cancer transplanted tumor, and the mechanism may be to down-regulate the expression of key molecules in the Wnt/β-catanin signaling pathway, thereby inhibiting the EMT process, so as to inhibit the lung metastasis of breast cancer.
5.Mechanism of Chaihu Qinggantang in Intervening NLRP3/IL-1β Pathway to Treat Granulomatous Lobular Mastitis in Rat Model
Yao ZHOU ; Lifang LIU ; Jialu LIU ; Jie GONG ; Shulei LIU ; Dan ZHAO ; Jie LING ; Hongqiao FAN
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(15):1-7
ObjectiveTo investigate the mechanism of Chaihu Qinggantang (CHQGT) in the treatment of granulomatous lobular mastitis (GLM) in the rat model. MethodSixty female rats were divided into a normal group, a model group, a prednisolone group (0.001 8 g·kg-1), and three CHQGT low-dose, medium-dose, and high-dose groups (4.5, 8.9, 17.8 g·kg-1). The tissue homogenates mixed with GLM lesion tissue and Fritner's reagent were used for modeling. After modeling, the treatment groups were given corresponding treatment factors, and the normal group and the model group were given the equal volume of normal saline. The changes in mammary gland of rats were observed after 14 d. Hematoxylin-eosin (HE) staining was used to observe the histopathological changes in breast samples. The mRNA expressions of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, Caspase-1, and interleukin-1β (IL-1β) were detected by real-time quantitative fluorescence polymerase chain reaction (Real-time PCR). The protein expressions of NLRP3, Caspase-1, IL-1β, and IL-18 were detected by Western bolt. ResultAs compared with the normal group, the breasts of rats in the model group were obviously swelling, and mammary gland inflammation index was significantly increased (P<0.01). Pathological changes included the formation of granuloma centered on the lobule of mammary gland with a large number of inflammatory cells such as lymphocytes and plasma cells. The mRNA expressions of NLRP3, Caspase-1, and IL-1β, and the protein expressions of NLRP3, Caspase-1, IL-1β, and IL18 in the model group were significantly increased (P<0.01). Compared with the model group, the treatment groups improved breast swelling, and the CHQGT medium and high-dose groups and the prednisolone group reduced inflammation index to some extent after treatment (P<0.05, P<0.01). The inflammation degree of mammary gland was significantly improved, and inflammatory cells such as macrophages, lymphocytes, and plasma cells were reduced to varying degrees in pathological aspects. The mRNA expressions of NLRP3, Caspase-1, and IL-1β, and the protein expressions of NLRP3, Caspase-1, IL-1β, and IL-18 in the CHQGT high-dose group and the prednisolone group were significantly down-regulated (P<0.05, P<0.01). ConclusionCHQGT inhibits inflammation and treats GLM in rats. The mechanism is possibly related to the inhibition of NLRP3/IL-1β signaling pathway, which provides a new target for the prevention and treatment of GLM by Qingxiao method.