OBJECTIVE To explore the relationship between severe cardiotoxicity caused by oxaliplatin combined with capecitabine and genetic polymorphism， thereby providing references for safe clinical medication use. METHODS Clinical pharmacists conducted a correlation analysis on a case of severe cardiotoxicity in a rectal cancer patient at Qilu Hospital of Shandong University following first-time treatment with standard doses of oxaliplatin combined with capecitabine. Case reports of cardiotoxicity caused by oxaliplatin and capecitabine were retrieved from the Chinese and English databases such as CNKI and PubMed.Basic patient information， drug treatment plan， and cardiotoxic manifestations were extracted and summarized. Combined with the patient’s genetic polymorphism test results related to the metabolism and excretion of platinum-based and fluorouracil drugs， potential mechanisms and prevention strategies for cardiotoxicity induced by oxaliplatin and capecitabine were discussed. RESULTS The patient exhibited homozygous mutations in ABCB1 C3435T and G2677T/A， a heterozygous mutation in MTHFR A1298C， and a heterozygous mutation in GSTP1 A105G， indicating impaired metabolism and excretion of oxaliplatin and capecitabine. The pharmacists recommended discontinuing oxaliplatin and reducing capecitabine to 50% of the original dose for subsequent treatment. The physicians adopted this advice， and the patient experienced no further severe adverse reactions with stable disease progression. CONCLUSIONS Oxaliplatin and capecitabine may cause severe cardiotoxicity. Medical institutions with adequate resources should perform genetic polymorphism test related to drug metabolism and excretion in patients prescribed these agents. For patients with multiple gene mutations， close monitoring and appropriate dose reductions are recommended to ensure medication safety and efficacy.

Acute leukemias caused by mixed lineage leukemia(MLL)gene rearrangements(MLL-r)are characterized by high invasiveness and a poor prognosis,with few specific treatment options available.MLL protein is essential in embryonic development and hematopoiesis.It exhibits histone methyltransferase activity and can interact with various proteins through its functional domains,thus regulating downstream target gene expression through epigenetic modifications.MLL-r leads to the formation of MLL fusion proteins(MLL-FPs),in which the C-terminal is replaced by fusion partner proteins;over 100 such partner proteins have been identified to date.In numerous studies of the molecular mechanism,Menin serves as an important cofacter in the leukemogenesis of MLL-FPs and participates in forming the key complex when interacting with the N terminal of MLL protein,resulting in the disregulation of certain targeted genes,which makes the development of Menin-MLL inhibitors theoretically possible.To date,several small molecules have been identified that inhibit Menin-MLL interaction,including thienopyrimidine derivatives,piperidine derivatives,pyrimidine derivatives,and macrocyclic mimic peptides.Based on these prototypes,at least seven drugs are currently undergoing clinical evaluation,with some promising preliminary data regarding safety,tolerability,and efficacy.This review summarizes the structure and function of MLL,the mechanism of the occurrence of MLL-r leukemia,and current Menin-MLL inhibitors tested in MLL-r leukemia.

Objective:To evaluate the survival, complications and prognostic factors in patients with stageⅠb2 and Ⅱa2 cervical squamous cell carcinoma treated by primarily radical surgery with or without postoperative adjuvant therapy.Methods:The clinical and pathological data of patients with stageⅠb2 and Ⅱa2 cervical squamous cell carcinoma treated in the Cancer Hospital of the University of Chinese Academy of Sciences from January 2015 to January 2018 were retrospectively analyzed. All patients underwent Querleu-Morrow classification (Q-M classification) C2 radical surgery, including extensive hysterectomy+pelvic lymphadenectomy with or without adjuvant therapy based on postoperative risk factors. Survival rate was calculated by Kaplan-Meier method and survival curve was drawn. Univariate analysis was performed by using the log-rank test to analyze the clinicopathological factors related to the prognosis of patients. Multivariate analysis was performed by using Cox regression method to analyze independent risk factors affecting survival prognosis.Results:(1) The median age of 643 patients with cervical squamous cell carcinoma was 50 years old (45-58 years old). Clinical stage: 260 cases (40.4%, 260/643) of stage Ⅰb2, 383 cases (59.6%, 383/643) of stage Ⅱa2. (2) Among 643 cases underwent Q-M classification C2 surgery, 574 cases (89.3%, 574/643) of them received adjuvant therapy and 184 cases (28.6%, 184/643) of them had grade 3-4 complications after treatment, including 134 cases (20.8%, 134/643) early complications and 66 cases (10.3%, 66/643) late complications. The incidence of grade 3-4 complications in 574 patients received postoperative adjuvant therapy was 30.1% (173/574), which was significantly different from that in 69 patients who received surgery alone (15.9%, 11/69; χ2=6.08, P=0.014). (3) All 643 cases were followed up, and the median follow-up time was 40 months (3-76 months). During the follow-up period, 117 cases (18.2%, 117/643) recurred, including 45 cases (7.0%, 45/643) of local recurrence, 54 cases (8.4%, 54/643) of distant metastasis, and 18 cases (2.8%, 18/643) of local recurrence and distant metastasis. The 5-year progression-free survival (PFS) and 5-year overall survival (OS) rates of patients with stage Ⅰb2 and Ⅱa2 cervical squamous cell carcinoma were 79.9% and 85.5%, respectively. Univariate analysis showed that pelvic lymph node metastasis, para-aortic lymph node metastasis, deep stromal infiltration, and lymph-vascular space invasion were significantly associated with 5-year PFS in patients with stage Ⅰb2 and Ⅱa2 cervical squamous cell carcinoma (all P<0.05). The maximum diameter of tumor, pelvic lymph node metastasis and para-aortic lymph node metastasis were significantly associated with the 5-year OS of cervical squamous cell carcinoma in stages Ⅰb2 and Ⅱa2 (all P<0.05). Multivariate analysis showed that pelvic lymph node metastasis and para-aortic lymph node metastasis were independent factors affecting 5-year PFS and 5-year OS in patients with stage Ⅰb2 and Ⅱa2 cervical squamous cell carcinoma (all P<0.01). Conclusion:Radical surgery is a feasible and effective primary treatment for stagesⅠb2 and Ⅱa2 cervical squamous cell carcinoma, with a high 5-year survival rate and an acceptable complication rate.

The delay of diabetic foot not only brings painful experience to patients, but also increases the care time and caregiver burden, which seriously affects quality of life of patients and caregivers. This article summarized the definition, research tools, current situation, influencing factors, positive feelings of caregivers and intervention measures of caregivers for diabetic foot patients, aiming to provide a theoretical basis for adoption of targeted intervention measures.

Objective:To compare the expression level of exosomal miR-503 in peritoneal dialysis effluent (PDE) from patients of different peritoneal transport characteristics, predict the target genes of miR-503 and provide bioinformatic data for researches of peritoneal transport characteristics.Methods:Twenty-four stable peritoneal dialysis (PD) patients were selected and divided into high transport group (H group, n=12) and low transport group (L group, n=12) according to the results of peritoneal equilibration tests (PET). The 500 ml PDE that was left on the patient's abdomen overnight was collected and concentrated using ultrafiltration cell. Exosomes in PDE were resuspended in phosphate buffered saline (PBS) after ultracentrifugation and the characteristics of PDE exosomes were identified by transmission electron microscope (TEM), nanoparticle tracking analysis (NTA), Western blotting and fluorescent staining. MicroRNAs were extracted from PDE exosomes. The expression levels of PDE exosomal miR-503 in the two groups were detected by quantitative real-time PCR. Then the relations between the relative quantity of PDE exosomal miR-503 and PET values or 24 h ultrafiltration volume (UF) were analyzed. Targetscan and miRDB databases were used to predict the target genes of miR-503. Gene ontology (GO) functional enrichment and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analysis were relied on DAVID (https://david.ncifcrf.gov/). Results:The exosomes in PDE showed a round and cup-shaped morphology under TEM, and the diameters were approximately 100 nm measured by NTA. The specific biomarkers of exosomes, CD63, CD81 and heat shock protein -70 (HSP-70) were all detected by Western blotting. The internalization and uptake of the exosomes was observed after fluorescent staining. The relative expression level of PDE exosomal miR-503 in H group was found to be significantly higher than that in L group ( P=0.002), and the relative quantity of PDE exosomal miR-503 was significantly positively correlated with PET values ( r=0.547, P=0.006), but not 24 h UF ( r=-0.297, P=0.159). There were 156 target genes of miR-503 in total that could be predicted by two different databases at the same time. GO analysis of these 156 target genes was mainly focused on kinase binding, regulation of protein modification and catabolic process as well as regulation of epithelial cell proliferation. KEGG enriched many tumor associated or classical signaling pathways, including transforming growth factor-β (TGF-β) signaling pathway and vascular endothelial growth factor (VEGF) signaling pathway. The prediction showed that vascular endothelial growth factor A (VEGFA) was a direct target gene of miR-503 and it was also related to many proteins involved in fibrosis mechanism. Conclusions:The expression level of PDE exosomal miR-503 is significantly higher in H group, and positively correlates with PET values, which may regulate the angiogenesis of peritoneal vessels by targeting VEGFA.

OBJECTIVE: To examine the expressions of JMJD3, matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in invasive ductal breast carcinoma, their association with the clinicopathological features of the patients and the effect of JMJD3 overexpression on proliferation and MMP-2 and VEGF expressions in breast cancer cells. METHODS: The protein and mRNA expressions of JMJD3, MMP-2, and VEGF in invasive ductal breast carcinoma and paired adjacent tissues were detected by immunohistochemistry and RT-PCR, respectively, and their correlation with the clinicopathological characteristics of the patients was analyzed. Kaplan-Meier survival analysis was used to evaluate the correlation of JMJD3, MMP-2 and VEGF expression levels with the survival of the patients. In breast cancer MDA-MB-231 cells transfected with a JMJD3-expression plasmid, the expression of Ki67 was examined immunohistochemically, the cell proliferation was assessed with CCK8 assay, and the mRNA expressions of MMP-2 and VEGF were detected with RT-PCR. RESULTS: Breast cancer tissues had significantly lower JMJD3 expression and higher MMP-2 and VEGF expressions at both the mRNA and protein levels than the adjacent tissue ( CONCLUSIONS The expressions of JMJD3, MMP-2 and VEGF in invasive ductal breast carcinoma are closely correlated to tumor proliferation, invasion, metastasis and prognosis and can be used for prognostic evaluation of breast cancer.
Breast Neoplasms/genetics* ; Carcinoma, Ductal, Breast/genetics* ; Humans ; Jumonji Domain-Containing Histone Demethylases ; Lymphatic Metastasis ; Matrix Metalloproteinase 2 ; Prognosis ; Vascular Endothelial Growth Factor A

Objective To understand the risk factors of hospital-acquired pneumonia(HAP) due to Carbapenem-resistant Kleb-siella pneumonia (CRKP) ,and propose prevention and control measures to reduce the incidence of hospital infection rate .Methods A total of Klebsiella pneumonia infection 73 patients with HAP ,who were treated in the ICU of a tertiary hospital in Chongqing from January 2014 to March 2016 were included .The 27 cases with CRKP were assigned as case group ,46 cases with Carbapenem-susceptible Klebsiella pneumonia(CSKP) were included as control group .Univariate and the multivariate Logistic regression analy-sis was performed for the risk factors .Results Univariate analysis showed that ,before infection ,the use of antimicrobial agents≥7 days ,Carbopenems ,mechanical ventilation ≥7 days ,APACHE Ⅱ score ,and at least 11 factors were the risk factors for CRKP HAP .Multivariate Logistic regression analysis showed that ,Carbapenems ,and mechanical ventilation≥7 days before infection and APACHE Ⅱ score was an independent risk factor of CRKP HAP .Conclusion Carbapenems ,and mechanical ventilation≥7 days before infection and APACHE Ⅱ score are the independent risk factors for CRKP HAP .Rational use of antibiotics ,reducing me-chanical ventilation and doing good hand hygiene are effective measures to reduce the incidence of CRKP HAP .

OBJECTIVETo explore the effect of a Chinese medicine, Xiaoaiping, in combination with cisplatin on the proliferation, invasion and apoptosis in human ovarian cancer HO-8910PM cells in vitro and vivo.

METHODSCCK-8 assay was used to detect the inhibitoty effect of Xiaoaiping alone or in combination with cisplatin on the proliferation of human ovarian cancer HO-8910PM cells. Flow cytometry was used to detect the apoptosis and cell cycle distribution. Transwell migration test was used to assay the effect of drugs on the cell invasive capability. Changes of the tumor volume in nude mice were observed to evaluate the antitumor effects in vivo.

RESULTSCCK-8 assay Xiaoaiping alone or combined with cisplatin could inhibit the proliferation of HO-8910PM cells with a dose-dependent manner. The inhibition rates of Xiaoaiping combined with cisplatin were (53.4±3.0)%, significantly increased than those with single drug (P<0.05). Flow cytometry showed that G0/G1 fraction was increased respectively from (64.2±1.6)% to (74.1±1.6)% and (68.6±1.6)%. The percentages of apoptotic cells were increased from (2.2±1.6)% to (16.1±1.6)%, (35.6±1.6)% after treated with Xiaoaiping, Cisplatin and combination drugs (P<0.05 for all). Transwell chamber with matrigel assay showed that number of cells penetrating through membrane in HO-8910PM cells was (89.2±20.7)/HPF in the drug combination group, significantly less than that in the control group(187.2±24.6)/HPF, Xiaoaiping(141.8±13.7 )/HPF or cisplatin group (155.8±19.4)/HPF (P<0.01 for all). The inhibition rate of drug combination group in the nude mouse transplanted tumors, compared with that of single Xiaoaiping and cisplatin group, was increased significantly (59.0% vs. 23.4% and 34.2%), (P<0.01 for both).

CONCLUSIONThe results of our in vitro and vivo experiments indicate that Xiaoaiping can inhibit cell proliferation, increase G0/G1 arrest, promote apoptosis, inhibit cell migration of human ovarian cancer HO-8910 PM cells, and can synergistically enhance the antitumor activity of cisplatine.

Animals ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cisplatin ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Female ; Humans ; Mice, Nude ; Neoplasm Invasiveness ; Ovarian Neoplasms ; drug therapy ; pathology

Objective To discuss the clinicopathologic characteristics and risk factors for lung metastasis of early-stage cervical cancer after radical hysterectomy. Methods The complete clinicopathologic data of patients with lung metastasis of cervical cancer after radical surgery from January 2008 to December 2013 admitted in Zhejiang Cancer Hospital were retrospectively analyzed by univariate and multivariate analysis. Results (1)There were 38 cases of early cervical cancer suffered from lung metastasis after radical hysterectomy during the period. The median age at diagnosis of cervical cancer was 46 years, the average lung metastasis time was 13 months after operation, 50.0%(19/38) cases occurred in the first year. Thirty-one cases were squamous cell carcinoma and 7 cases were non-squamous cell carcinoma.(2)Univariate analysis showed that age,clinical stage, manner of tumor growth, tumor grade, perineuronal invasion, para-aortic lymph node metastasis were not significant effect on postoperative lung metastasis(all P>0.05). But tumor size, histologic types, depth of stromal invasion, uterine body infiltration, lympho-vascular space invasion,pelvic lymph node metastasis, positive margin and abnormal tumor markers were significantly correlated with postoperative lung metastasis(all P<0.05). Multivariate analysis showed that only tumor size, histologic types and pelvic lymph node metastasis were independent risk factors for lung metastasis of cervical cancer(P<0.05). Conclusions Patients of early-stage cervical cancer with lung metastasis mostly occurs within 1 year after radical hysterectomy. Local large tumor lesions (tumor size>4 cm), non-squamous cell carcinoma and pelvic lymph node metastasis were more likely to have lung metastasis.

[ ABSTRACT] AIM:To explore the role of superoxide dismutase ( SOD) and malondialdehyde ( MDA) in chronic pancreatitis ( CP) induced by dibutyltin dichloride ( DBTC) combined with ethanol, and the mechanisms for prevention and treatment of pancreatic fibrosis by Chaihushugansan.METHODS: The KM mice were randomly divided into control group, CP group ( DBTC combined with ethanol) and Chaihushugansan group ( CP+Chaihushugansan) .Except for control group, the mice in other groups were intravenously injected in tail with DBTC (8 mg/kg) and drank 10% ethanol.The mice in Chaihushugansan group were administered intragastrically with Chaihushugansan (6 g· kg-1 · d-1 ) at the follow-ing experimenal period.Before modeling and 1 week, 2 weeks, 4 weeks and 8 weeks after modeling, the mice were anes-thetized and sacrificed.The activity of amylase and the content of hyaluronic acid in the serum were measured.The mor-phology and the degree of fibrosis in the pancreas were observed by HE staining.The activity of SOD and the level of MDA in the pancreas homogenate were analyzed.The protein of pancreas was extracted to detect the expression of type I collagen by Western blotting.RESULTS:DBTC combined with ethanol induced CP with increased serum amylase and hyaluronic acid levels, while the serum amylase and hyaluronic acid levels in Chaihushugansan group were significantly lowered ( P<0.05).In 1 week, 2 weeks, 4 weeks and 8 weeks, the pancreas were obviously injured and appeared different degrees of fibrosis.The content of MDA and the expression of type I collagen in the increased significantly, but the SOD was de-creased.In Chaihushugansan group, the pathological damage and the degree of fibrosis of the pancreas were improved.The level of MDA and type I collagen expression in the pancreas were significantly reduced, but the SOD was increased.CON-CLUSION:The oxidative stress may take part in the development of CP.Inhibition of oxidative stress in the pancreas is one of the mechanisms that Chaihushugansan attenuates the development of CP.