BACKGROUND:Understanding the tracheal, bronchus, and lung (TBL) cancer burden caused by tobacco exposure in India can help local governments implement targeted measures for prevention and treatment of the disease. METHODS:The burden of TBL cancer deaths and disability-adjusted life years (DALYs) attributable to tobacco exposure from 2000 to 2021 were presented by age, sex, and region. A Joinpoint model was used to analyze temporal trends of the disease, while decomposition analysis was conducted to quantify the contributions of population growth, aging, and epidemiological changes. In addition, the age-period-cohort (APC) model was implemented to assess the effects of age, period, and cohort on tobacco-related TBL cancer deaths and DALYs burden. Finally, age-standardized deaths and DALYs rates for TBL cancer attributable to tobacco exposure were projected through 2035. RESULTS:In 2021, Mizoram recorded the highest age-standardized rates of TBL cancer deaths and DALYs attributable to tobacco exposure, regardless of sex. Uttar Pradesh and West Bengal consistently exhibited the highest number of deaths and DALYs associated with tobacco exposure across the three age groups analyzed. Population growth and aging are the primary drivers behind the increasing burden of TBL cancer. Overall, the risk of tobacco-related lung cancer death increased with age. There are differential period and cohort effects between male and female populations. In the future, the increase in age-standardized rates of deaths and DALYs attributable to secondhand smoke exposure will be more pronounced among males. CONCLUSION:Despite ongoing efforts to control the tobacco epidemic, the burden of TBL cancer related to tobacco remains high in India. Each state in India should adopt targeted measures based on local conditions to address the health threats posed by tobacco.

Renal fibrosis is the most common pathway in progressive kidney diseases. The unilateral ureteral obstruction (UUO) model is used to induce progressive renal fibrosis. We evaluated the effects of irisin on renal interstitial fibrosis in UUO mice. The GSE121190, GSE36496, GSE42303, and GSE96101 datasets were downloaded from the Gene Expression Omnibus (GEO) database. In total, 656 differentially expressed genes (DEGs) were identified in normal and UUO mouse renal samples. Periostin and matrix metalloproteinase-2 (MMP-2) were selected to evaluate the effect of irisin on renal fibrosis in UUO mice. In UUO mice, irisin ameliorated renal function, decreased the expression of periostin and MMP-2, and attenuated epithelial-mesenchymal transition and extracellular matrix deposition in renal tissues. In HK-2 cells, irisin treatment markedly attenuated TGF-β1-induced expression of periostin and MMP-2. Irisin treatment also inhibited TGF-β1-induced epithelial-mesenchymal transition, extracellular matrix formation, and inflammatory responses. These protective effects of irisin were abolished by the overexpression of periostin and MMP-2. In summary, irisin treatment can improve UUO-induced renal interstitial fibrosis through the TGF-β1/periostin/MMP-2 signaling pathway, suggesting that irisin may be used for the treatment of renal interstitial fibrosis.

Introduction: SOX4 plays an important role in tumorigenesis and cancer progression. The role of SOX4 in pan-cancer and its underlying molecular mechanism in liver hepatocellular carcinoma (LIHC) are not fully understood. In this study, a comprehensive analysis and experimental validation were performed to explore the function of SOX4 across tumor types. Methods: Raw data in regard to SOX4 expression in malignant tumors were downloaded from the TCGA and GTEx databases. The expression levels, prognostic values, genetic mutation, and DNA promoter methylation of SOX4 across tumor types were explored via systematic bioinformatics analysis. The ceRNA regulatory network, immune characteristics, and prognostic models were analyzed in LIHC. Finally, we conducted in vitro experiments including Western blotting, cell proliferative assay, trypan blue staining, and fluorescence microscopy to further explore the function of SOX4 in LIHC. Results: SOX4 expression was significantly upregulated in 24 tumor types. SOX4 expression level was strongly associated with unfavorable prognoses, genetic mutations, and DNA methylation levels across different tumor types. Especially in LIHC, LINC00152/hsa-miR-139-3p/SOX4 was identified as a crucial ceRNA network. Moreover, this study also provides insight into the roles of SOX4 expression in immune cell infiltration, macrophage polarization, immune subtype, molecular subtype, and immunomodulators, as well as the tumor immune microenvironment (TIME)-related prognosis, in LIHC. The study established six favorable prognostic models to predict LIHC prognosis based on the SOX4-associated genes. Finally, lenvatinib treatment can increase the expression of SOX4 in hepatocellular carcinoma cells and lead to drug resistance. Silencing SOX4 can effectively eliminate the drug resistance caused by lenvatinib treatment and inhibit the proliferation of cancer cells.Conclusions: This study highlights that SOX4 may serve as a promising therapeutic target for tumor treatment.

目的 报道特殊临床表现多系统免疫相关不良事件个案,探讨本例免疫相关性不良反应发生的机制及危险因素,提高对该病的认识.方法 分析本例患者的临床病例资料及诊治过程,并复习相关文献进行讨论.结果 本例特殊临床表现多系统免疫相关不良事件患者,免疫相关性肺炎为G3,免疫相关性肝炎为G2,免疫相关性内分泌毒性G2.症状好转后仍死亡.结论 特殊临床表现多系统免疫相关不良事件临床罕见,发病机制、危险因素、治疗方法仍存争议,虽发生率低,但预后差,值得进一步研究.

BACKGROUND:Renal fibrosis is considered the pathway from almost all chronic kidney diseases (CKD) to end-stage renal diseases. The unilateral ureteral obstruction (UUO) model is a well-established experimental animal model to simulate renal fibrosis associated with obstructive nephropathy in an accelerated manner. In this study, in order to understand the development trends of research on UUO-induced renal fibrosis between 2005 and 2022 and predict prospects, we conducted a comprehensive bibliometric and visualized study using Web of Science (WoS).METHODS:The articles regarding UUO-induced renal fibrosis were culled from the "Core Collection" of the WoS database. VOSviewer software and the R-Bibliometrix Package were used in visual analysis of countries/regions, journals, authors, keywords, institutions, and highly cited articles in this field.RESULTS:The number of articles regarding UUO-induced renal fibrosis has obviously increased annually. China had the largest number of publications in this field. The most frequently used keywords were "inflammation," "transforming growth factor-beta1," "oxigative stress," "smad3," "beta-catenin," and "autophagy." Am J Physiol-Renal was the leading journal. The most highly influential documents were published by Higgins DF and his colleagues, with 46 local citations and 749 global citations. The leading institution was Nanjing Medical University. Furthermore, Zhang Y. was the author who contributed most to this field.CONCLUSION:Our results suggest that the molecular mechanism of UUO-induced renal fibrosis remains a research hot topic, especially on the inflammatory response and oxidative stress, and international cooperation is expected to expand and deepen in the future.

SLC16A1 plays an important role in the development of multiple cancer types. Pan-cancer analysis may have significant impacts on the exploration of the relationship between SLC16A1 gene expression, prognosis and the molecular mechanisms of tumorigenesis. In this study, through the analysis of TCGA and GEO datasets, we explored the expression level and survival prognosis of SLC16A1 in pan-cancer, and further explored the differences in SLC16A1 gene mutation, methylation, and phosphorylation between tumor and normal tissues. In addition, we focused on the biological function of this gene and the relationship between the prognosis and immune infiltration by immune infiltration analysis and enrichment analysis, in order to evaluate the diagnostic and prognostic significance of SLC16A1 in carcinomas. The study found that SLC16A1 was highly expressed in 14 kinds of tumors, and there were statistically significant differences in the prognosis of 9 tumors. The phosphorylation level of S467 increased in OV, RCC, and UCEC. There was a statistically negative correlation between the CD8+ T-cell infiltration level and the SLC16A1 expression in HNSC, LUSC, SARC, TGCT, and KIRC. The cancer-related fibroblasts were positively correlated with SLC16A1 expression in BLCA, BRCA, KIRC, KIRP, PAAD, PCPG, and THCA. The enrichment analysis indicated that the tumorigenesis mechanism of this gene was mainly related to "glycolysis and glucose metabolism synthesis." SLC16A1 was a promising prognostic and immunological biomarker in pan-cancer.

Background. Triple-negative breast cancer (TNBC) is the worst prognosis subtype of breast cancer due to lack of specific targets. Recent studies have shown that immunotherapy may solve that problem by targeting folate receptor-alpha (FRα). Methods. Gene modified γδ T cells were manufactured to express FRa specific chimeric antigen receptor (FRa CAR) and secrete interleukin-7 (IL-7) and chemokine C–C motif ligand 19 (CCL19). CAR-γδT cells that secrete IL-7 and CCL19 (7 × 19 CAR-γδT) were evaluated for their antitumor activity both in vitro and in vivo. Results. 7 × 19 CAR-γδT showed remarkable antitumor activity in vitro. Combined with PBMC, 7 × 19 CAR-γδT inhibited TNBC xenograft model growth superiorly compared with single-application or conventional CAR-γδT cells. Histopathological analyses showed increased DC or T cells infiltration to tumor tissues. Conclusion. Taken together, our results showed that 7 × 19 CAR-γδT have remarkable anti-TNBC tumor activity and showed a broad application prospect in the treatment of incurable TNBC patients.

Objectives:To evaluate the effect of Metformin therapy on patients of breast cancer with complications of Type-2 diabetes. Methods:Altogether 102 cases of breast cancer complicated with Type-2 diabetes admitted into Hebei General Hospital from January 2019 to December 2020 were included in the study. They were divided into two groups per whether Metformin was administered in the regimen, namely Metformin group and non-Metformin group. In the meanwhile, 106 cases of breast cancer without Type-2 diabetes admitted in the same period were selected to form a control group. Three groups were compared in terms of general data (incl. age, body mass, family history, menopause or not), clinical staging, tumor histological differentiation, molecular subtyping (Incl. Luminal A, Luminal B, ERBB2+, Basal-like) and prognosis. Results:Compared with the control group, Metformin group and non-Metformin group presented more patients with an older age and post-menopause state (P<0.05), but the latter two groups were not significantly different (P > 0.05). Patients in Metformin group and non-Metformin group had higher clinical staging and histological differentiation and more cases of Basal-like subtype than those in the control group (P < 0.05), without significant difference between those two groups (P > 0.05). More cases of local relapse, lymphatic and distant metastasis were seen in Metformin and non-Metformin groups, but the differences were not significant (P > 0.05). Both groups had lower 5-year survival rates than the control group (P < 0.05). Metformin group had a higher overall survival rate as well as a survival rate free of other lethal reasons than the non-Metformin group (P < 0.05) but was not significantly different from the control group in the survival rate free of other lethal reasons (P > 0.05). Conclusions:Type-2 diabetes remains one of the risk factors affecting breast cancer development, progress and prognosis, which could lower the 5-year overall survival rate among breast cancer patients. This is especially evident among menopaused women. Metformin therapy may improve the prognosis of patients of breast cancer complicated with Type-2 diabetes.

目的 探讨程序性死亡受体1(PD-1)/程序性死亡配体1(PD-L1)抑制剂在非黑色素瘤治疗中所致白癜风的临床特点.方法 检索中国知网、万方医学、PubMed、Embase、Web of Science建库至2022年7月31日收录的PD-1/PD-L1抑制剂在非黑色素瘤中所致白癜风的病例报告类文献进行描述性统计分析.结果 纳入分析的患者共25例,其中男性18例,女性7例;年龄32～79岁;25例患者首次使用PD-1/PD-L1抑制剂至发生白癜风最短时间为6 d,最长时间为5年,中位发生时间为用药后5个月.白癜风主要分布在头皮、面部、手部、四肢和躯干,可伴有其他免疫相关性不良事件,以甲状腺居多;皮肤活检表现为病变及病灶周围皮肤黑色素细胞及黑色素的缺失.20名患者进行了疗效评估,完全缓解6例,部分缓解3例,疾病稳定8例,疾病进展3例.结论 白癜风是PD-1/PD-L1抑制剂在非黑色素瘤治疗中的一种罕见不良反应,白癜风的发生可能与良好的临床结果相关.

Renal fibrosis is characterized by glomerulosclerosis and tubulointerstitial fibrosis in diabetic nephropathy (DN). We aimed to evaluate the effects of PP2 on renal fibrosis of DN. GSE33744 and GSE86300 were downloaded from the GEO database. Firstly, 839 DEGs were identified between nondiabetic and diabetic mice renal glomerular samples. COX-2 was selected to assess the effects of PP2 on renal glomerulosclerosis. In db/db mice, PP2 decreased the expression of COX-2, phosphorylated p65, and fibrotic proteins, accompanied with attenuated renal glomerulosclerosis. In cultured glomerular mesangial cells, high glucose- (HG-) induced p65 phosphorylation and COX-2 expression were attenuated by PP2 or NF-κB inhibitor PDTC. PP2, PDTC, or COX-2 inhibitor NS-398 ameliorated abnormal proliferation and expression of fibrotic proteins induced by HG. Secondly, 238 DEGs were identified between nondiabetic and diabetic mice renal cortex samples. UCP2 was selected to assess the effects of PP2 on renal tubulointerstitial fibrosis. In db/db mice, PP2 decreased the expression of PPARγ and UCP2, accompanied with attenuated renal tubulointerstitial fibrosis and EMT. In cultured proximal tubular cells, HG-induced PPARγ and UCP2 expression was inhibited by PP2 or PPARγ antagonist GW9662. PP2, GW9662, or UCP2 shRNA ameliorated HG-induced EMT. These results indicated that PP2 ameliorated renal fibrosis in diabetic mice.

Background: Hypertension is a highly prevalent disorder. A nomogram to estimate the risk of hypertension in Chinese individuals is not available. Methods: 6201 subjects were enrolled in the study and randomly divided into training set and validation set at a ratio of 2:1. The LASSO regression technique was used to select the optimal predictive features, and multivariate logistic regression to construct the nomograms. The performance of the nomograms was assessed and validated by AUC, C-index, calibration curves, DCA, clinical impact curves, NRI, and IDI. Results: The nomogram140/90 was developed with the parameters of family history of hypertension, age, SBP, DBP, BMI, MCHC, MPV, TBIL, and TG. AUCs of nomogram140/90 were 0.750 in the training set and 0.772 in the validation set. C-index of nomogram140/90 were 0.750 in the training set and 0.772 in the validation set. The nomogram130/80 was developed with the parameters of family history of hypertension, age, SBP, DBP, RDWSD, and TBIL. AUCs of nomogram130/80 were 0.705 in the training set and 0.697 in the validation set. C-index of nomogram130/80 were 0.705 in the training set and 0.697 in the validation set. Both nomograms demonstrated favorable clinical consistency. NRI and IDI showed that the nomogram140/90 exhibited superior performance than the nomogram130/80. Therefore, the web-based calculator of nomogram140/90 was built online. Conclusions: We have constructed a nomogram that can be effectively used in the preliminary and in-depth risk prediction of hypertension in a Chinese population based on a 10-year retrospective cohort study. Funding: This study was supported by the Hebei Science and Technology Department Program (no. H2018206110).

Increasing evidence demonstrates that long noncoding RNAs (lncRNAs) play critical roles in human breast cancer (BC) tumorigenesis. However, the mechanisms by which lncRNA and N 6 -methyladenosine (m 6 A) regulate BC tumorigenesis are still unclear. In the present research, LINC00958 was markedly overexpressed in BC tissue and cells, and LINC00958 upregulation promoted the tumor progression of BC cells. Mechanistically, m 6 A methyltransferase-like 3 (METTL3) gave rise to the upregulation of LINC00958 by promoting its RNA transcript stability. Moreover, LINC00958 acted as a competitive endogenous RNA for miR-378a-3p to promote YY1. Overall, these data provide novel insight into how m 6 A-mediated LINC00958 regulates BC tumorigenesis.

程序性死亡受体1(PD-1,programmed death1)或程序性死亡配体1(PD-L1,programmed death-ligand 1)免疫检查点抑制剂目前广泛用于恶性肿瘤的免疫治疗中,但治疗效果不一.生物标记物有助于预测患者应用PD-1/PD-L1抑制剂后的疗效,起疗效预测作用.PD-1/PD-L1抑制剂疗效相关的正向预测因子主要有PD-L1、微卫星高度不稳定性和/或错配修复缺陷、肿瘤突变负荷等,提示在人群中应用PD-1/PD-L1抑制剂治疗获益率高.PD-1/PD-L1抑制剂疗效相关的负向预测因子主要有调节性T细胞、β2-微球蛋白及JAK1基因等,提示PD-1/PD-L1抑制剂治疗疗效较差,或者耐药.EGFR、ALK、MDM2/MDM4等基因突变可能提示在应用PD-1/PD-L1抑制剂治疗后人群中出现疾病超进展的比例较高.

cir-ITCH, a well-known tumor-suppressive circular RNA, plays a critical role in different cancers. However, its expression and functional role in prostate cancer (PCa) are unclear. Herein, we explored the potential mechanism and tumor-inhibiting role of cir-ITCH in PCa. Using reverse transcriptase polymerase chain reaction assay, we analyzed the expression of cir-ITCH in PCa and paired adjacent nontumor tissue samples resected during surgical operation, as well as in two cell lines of human PCa (LNCaP and PC-3) and the immortalized normal prostate epithelial cell line (RWPE-1). Cell viability and migration of PCa cell lines were evaluated using CCK-8 and wound-healing assays. Expression of key proteins of the Wnt/β-catenin and PI3K/AKT/mTOR pathways was detected using western blotting. We found that cir-ITCH expression was typically downregulated in the tissues and cell lines of PCa compared to that in the peritumoral tissue and in RWPE-1 cells, respectively. The results showed that cir-ITCH overexpression significantly inhibits the proliferation, migration, and invasion of human PCa cells and that reciprocal inhibition of expression occurred between cir-ITCH and miR-17. Proteins in the Wnt/β-catenin and PI3K/AKT/mTOR pathways were downregulated by overexpression of cir-ITCH both in androgen receptor-positive LNCaP cells and androgen receptor-negative PC-3 cells. Taken together, these data demonstrated that cir-ITCH plays a tumor-suppressive role in human PCa cells, partly through the Wnt/β-catenin and PI3K/AKT/mTOR pathways. Thus, cir-ITCH may serve as a novel therapeutic target for the treatment of PCa, especially castration-resistant prostate cancer.

Objective To explore correlations between body mass index (BMI), preoperative systemic immune-inflammation index (SII) and endocrine therapy resistance, and evaluate BMI and SII as predictors of resistance, in patients with luminal breast cancer. Methods This retrospective study included patients with luminal breast cancer who underwent endocrine therapy at Hebei General Hospital. Relationships between BMI and SII subgroups, and clinicopathological parameters were analysed using χ 2 -tests. Disease-free survival was assessed using Log-rank statistics. Multivariate analysis of factors related to disease progression were analysed using Cox proportional hazards model. Results Out of 161 patients, those with normal BMI and low SII had significantly lower endocrine resistance rates versus those with high BMI and SII, and BMI was significantly positively correlated with SII. High BMI or SII was associated with significantly lower disease-free survival rates. Hazard ratios for disease progression risk were 6.036, 3.508 and 1.733, for SII, BMI and TNM stage, respectively. Conclusion In patients with luminal breast cancer, high BMI (>23 kg/m 2 ) and SII (>518 × 10 9 /L) levels may predict high endocrine resistance rates. BMI, SII and TNM stage were independent prognostic factors for endocrine therapy resistance.

Introduction: Drug-induced liver injury is one of the most common adverse drug reactions in clinical. Sorafenib is a widely used in hepatoma patients, while diclofenac sodium in patients suffering from cancer pain. Both of the two drugs showed mild and unfrequented liver damage. However, taking both drugs orally at the same time may cause severe liver function abnormity and there are few reports at present. Case report: We'll expatiate on an unusual case of a patient with kidney cancer who takes sorafenib and diclofenac sodium simultaneously and suffered from severe and acute liver failure about nearly two months. Conclusion: Sorafenib and diclofenac are likely to have some interactions. Clinically, the combination of the two should be carefully considered to reduce the potential risk of liver damage and avoid liver failure or even liver necrosis.

Colorectal cancer is one of the most common malignancies worldwide, as it is often diagnosed at an advanced stage. Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable success and emerged as one of the most promising therapeutic strategies in multiple malignancies. The purpose of this study was to investigate the anti-tumor activity of NKG2D CAR-T cells against human colorectal cancer cells. A non-viral thirdgeneration NKG2D CAR was constructed, and subsequently transduced into T cells to obtain the NKG2D CAR-T cells. In vitro, NKG2D CAR-T cells showed cytotoxicity against human colorectal cancer cells in a dose-dependent manner compared with untransduced T cells. In addition, IL-2 and IFN-γ secreted by these cells were significantly higher than those by untransduced T cells. In vivo, NKG2D CAR-T cells significantly suppressed tumor growth, reduced tumor sizes and extended overall survival of mice in a xenograft model of HCT-116 cells. Furthermore, human NKG2D-positive lymphocytes infiltration could be found in the tumor sections of NKG2D CAR-T cells-treated mice. There were no severe pathological changes found in vital organs in any of the treatment groups. NKG2D CAR-T cells showed excellent killing effect and represented a promising immunotherapeutic strategy against human colorectal cancer.

目的 研究微小RNA-150(miR-150)在膀胱尿路上皮癌细胞BC-6中的作用机制.方法 (1)将膀胱尿路上皮癌细胞株BC-6分为3组:空白对照组、miR-150抑制剂组和阴性对照组.miR-150抑制剂组和阴性对照组分别用Lipofectamine 2000将浓度均为100 nmol·L-1的miR-150 inhibitors和无意义序列转染至细胞,空白对照组不做处理.(2)在空白对照组中,加入磷脂酰肌醇3-激酶(PI3K)/丝苏氨酸蛋白激酶(Akt)信号通路抑制剂——LY294002,作为LY294002组.以细胞毒性检测试剂盒检测细胞增殖能力,流式细胞术检测细胞凋亡,蛋白免疫印迹法检测Cleaved caspase-3、PI3K、Akt和磷酸化丝苏氨酸蛋白激酶(p-Akt)相对表达量.结果 (1)48 h,miR-150抑制剂组、阴性对照和空白对照组细胞增殖率分别为(23.97±3.28)％,(98.14±1.34)％ 和(99.86±1.15)％;上述这3组的细胞凋亡率分别为(16.32±3.19)％,(1.86±0.24)％ 和(0.79±0.15)％;上述这3组的PI3K相对表达量分别为0.21±0.03,0.53±0.12和0.56±0.11;上述这3组的Akt相对表达量分别为0.08±0.01,0.21±0.05和0.23±0.04;上述这3组的p-Akt相对表达量分别为0.70±0.10,0.69±0.12和0.72±0.11;上述这3组的Cleaved caspase-3相对表达量分别为0.58±0.11,0.23±0.04和0.24±0.03.阴性对照组和miR-150抑制剂组与空白对照组比较,上述指标的差异均有统计学意义(均P<0.01).(2)48 h,LY294002组和空白对照组的细胞增值率分别为(27.02±3.13)％,(99.86±1.15)％;LY294002组和空白对照组的细胞凋亡率分别为(12.31±3.07)％,(0.79±0.15)％;LY294002组与空白对照组比较,上述指标的差异均有统计学意义(均P<0.01).结论 干扰miR-150表达能够抑制膀胱尿路上皮癌BC-6细胞株的增殖,并通过上调Cleaved caspase-3促进细胞凋亡,其调控作用可能与PI3K/Akt信号通路有关.

患者男,63岁,于2017年4月前后无明确诱因出现颈部疼痛,并逐渐加重. 2017年9月初于外院查颈部CT提示颈3～5椎体受压,考虑占位. 进一步完善胸腹部CT及颈部MRI等检查,考虑多发骨转移癌,发现右肾下极占位. 查无禁忌,于2017年9月22日行颈前路减压病灶清除术,术后病理提示转移性透明细胞癌,考虑肾来源. 因患者拒绝行姑息性放疗,后于2017年10月中旬开始口服索拉非尼(起始剂量为0.2 g,1 次/d),10 d后耐受可,逐渐加量至0.4 g, 2次/d,至入院前半月自行减为0.2 g,2次/d. 服药期间患者颈部无明显疼痛,间断有腹泻,予对症治疗后可改善. 靶向治疗1个月余后复查肾MRI及颈椎CT等提示右肾及骨转移灶基本稳定. 2个月后患者自觉颈部疼痛,疼痛评分3～4分,拒绝行局部放疗,自行间断口服双氯芬酸钠75 mg止痛,疼痛控制可. 于入院前2d患者发现皮肤黄染,小便为深黄色,外院化验提示转氨酶及胆红素明显增高,患者为求进一步诊治于2018年2月20日入我院肿瘤四科. 患者初步诊断为右肾癌(Ⅳ期)骨转移,入院后查凝血功能:凝血酶原时间19.1 s,凝血酶原时间活动度36.3,凝血酶原比率1.66,凝血酶原国际标准化比率1.66,活化部分凝血活酶时间57.4 s,部分凝血活酶比率 2.31,纤维蛋白原含量1.11 g/L;血生化:总胆红素:195.5 μmol/L,直接胆红素:117.2 μmol/L,间接胆红素:78.30 μmol/L,丙氨酸转氨酶( ALT):1640.8 U/L,天冬氨酸转氨酶( AST):1522.5 U/L.血常规、病毒七项、肝炎全项无异常. 进一步查CT:胸骨、T9椎体及附件、L2椎体、骶骨多发转移. 右肾下部占位,考虑恶性可能性大. 下腔静脉肝段及门静脉分支静脉期可见"套袖征",符合肝功能受损后改变. 综合相关检查及消化科会诊意见,考虑为急性药物性肝损伤、肝细胞性黄疸,给予异甘草酸镁、谷胱甘肽等保肝治疗,停用索拉非尼、双氯芬酸钠, 1周后复查生化提示转氨酶下降( ALT:463.3 U/L;AST:266.1 U/L) ,胆红素逐渐升高(总胆红素:391.3μmol/L) ,因凝血功能异常无法行血浆置换,继续给予保肝治疗40余天,复查转氨酶、胆红素明显下降( ALT:20 U/L;AST:30 U/L;总胆红素:58 μmol/L)后出院.

目的:观察GKLF基因在胃癌组织和细胞株中的表达情况及与耐药基因P-糖蛋白(P-gp)、多药耐药相关蛋白1(MRP-1)表达的相关性.方法:采用免疫组织化学SP法、Real time-PCR和Western-blot检测胃癌组织和细胞株中GKLF、P-gp、MRP-1表达情况,分析GKLF蛋白表达与临床病理特征及P-gp、MRP-1蛋白表达的相关性.分别将携带GKLF基因的重组慢病毒颗粒或靶向GKLF基因的特异性siRNA转染耐药人胃癌细胞SGC7901/VCR.Real time-PCR和Western-blot检测过表达或敲低GKLF后P-gp变化.结果:胃癌组织GKLF蛋白阳性表达率及mRNA表达水平显著低于癌旁组织,P-gp、MRP-1蛋白阳性表达率及mRNA表达水平显著高于癌旁组织(P<0.05);且GKLF蛋白表达与TNM临床分期、淋巴结是否转移密切相关,并与P-gp、MRP-1蛋白表达具有负相关性(P<0.05).在多种胃癌细胞中均存在GKLF基因表达显著下调和P-gp、MRP-1基因表达上调,尤其在胃癌耐药SGC7901/VCR细胞表达变化更为显著(P<0.05).过表达GKLF后SGC7901/VCR细胞P-gp、MRP-1 mRNA和蛋白表达、存活率、穿膜数显著下调,而沉默GKLF后SGC7901/VCR细胞P-gp、MRP-1 mRNA和蛋白表达、存活率、穿膜数显著上调(P<0.05).结论:GKLF基因在胃癌组织和细胞系中表达下调,且与耐药相关基因P-gp、MRP-1表达具有负相关性.上调GKLF表达可能通过调控P-gp、MRP-1表达逆转胃癌对化疗药物的耐药性.