Previous studies have revealed that patients with hypertrophic cardiomyopathy (HCM) exhibit differences in symptom severity and prognosis, indicating potential HCM subtypes among these patients. Here, 793 patients with HCM were recruited at an average follow-up of 32.78 ± 27.58 months to identify potential HCM subtypes by performing consensus clustering on the basis of their echocardiography features. Furthermore, we proposed a systematic method for illustrating the relationship between the phenotype and genotype of each HCM subtype by using machine learning modeling and interactome network detection techniques based on whole-exome sequencing data. Another independent cohort that consisted of 414 patients with HCM was recruited to replicate the findings. Consequently, two subtypes characterized by different clinical outcomes were identified in HCM. Patients with subtype 2 presented asymmetric septal hypertrophy associated with a stable course, while those with subtype 1 displayed left ventricular systolic dysfunction and aggressive progression. Machine learning modeling based on personal whole-exome data identified 46 genes with mutation burden that could accurately predict subtype propensities. Furthermore, the patients in another cohort predicted as subtype 1 by the 46-gene model presented increased left ventricular end-diastolic diameter and reduced left ventricular ejection fraction. By employing echocardiography and genetic screening for the 46 genes, HCM can be classified into two subtypes with distinct clinical outcomes.

Breast cancer is the most common cancer for Chinese women. Early screening is the best way to improve the rates of early diagnosis and early treatment of breast cancer. The peak ages of breast cancer in Chinese women are obviously different from those in the European and American countries. It is imperative to develop a guideline for breast cancer screening that is suitable for Chinese women. Based on the analysis and summary of breast cancer screening data in China, and the latest guidelines and consensus on breast cancer screening in Europe, the United States and East Asia, China Anti-Cancer Association and National Clinical Research Center for Cancer (Tianjin Medical University Cancer Institute and Hospital) has developed a population-based guideline for breast cancer screening in Chinese women. This guideline has provided detailed recommendations on the screening starting age, screening modalities, and screening interval in Chinese women with average risk and high risk of breast cancer, respectively. This article aims to interpret the above guideline, providing references for professionals in breast cancer screening.

AIM:To investigate the effect of microRNA-429 (miR-429) on the expression of occludin (Ocln) in intestinal epithelial cells ( IECs) and intestinal epithelial barrier function in diabetic mice.METHODS:Diabetes mel-litus mouse model was induced by intraperitoneal injection of streptozocin.The expression of miR-429 in IECs of diabetic mice was inhibited by antagomiRNA-429 injected via tail vein.The expression of miR-429 and mRNA expression of Ocln were detected by real-time PCR.The protein expression of Ocln was determined by Western blotting and immunohistochem-istry.The urinary lactulose/mannitol ratio was measured by gas chromatography.The plasma LPS concentrations in the mice were measured by chromogenic end-point TAL kit.RESULTS:The results of real-time PCR confirmed that the ex-pression of miR-429 in IECs of diabetic mice was remarkably inhibited by tail-vein administration of antagomiRNA-429, and resumed to similar level of normal mice on the 6th day after the administration.After suppressing the level of miR-429, the expression of Ocln in IECs of diabetic mice increased significantly (P<0.05), while the urinary lactulose/mannitol ra-tio and the plasma LPS concentration decreased obviously ( P<0.05 ) .CONCLUSION:AntagomiRNA-429 effectively suppresses miR-429 expression in IECs of diabetic mice, and then enhances the expression of Ocln and partially resumes the intestinal epithelial barrier function.

OBJECTIVETo explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application.

METHODSAccording to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 μg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle.

RESULTSThe duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 μg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581).

CONCLUSIONSIn patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms ; drug therapy ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cyclophosphamide ; administration & dosage ; adverse effects ; Epirubicin ; administration & dosage ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Incidence ; Induction Chemotherapy ; Lung Neoplasms ; drug therapy ; Neutropenia ; chemically induced ; epidemiology ; prevention & control ; Polyethylene Glycols ; Recombinant Proteins ; administration & dosage ; Taxoids ; administration & dosage ; adverse effects

AIM:To observe the inhibitory effect of siRNA targeting to Wip1 gene on the Wip1 gene expression in the colon cancer cells and to investigate the influence of Wip1 gene silencing on the chemotherapy sensitivity of colon cancer cells.METHODS:Wip1-811 siRNA targeting to Wip1 gene was transfected into RKO colon cancer cells with high expression of Wip1 gene.The mRNA expression of Wip1 was measured by real-time PCR.The protein level of Wip1 was detected by Western blotting.The viability of RKO colon cancer cells was measured by MTS assay.The cell apoptosis and cell cycle were analyzed by flow cytometry.RESULTS: Wip1-811 siRNA efficiently inhibited the expression of Wip1 at mRNA and protein levels.The enhanced chemotherapy sensitivity of RKO colon cancer cells was observed after inhibition of Wip1 gene expression.The viability of RKO colon cancer cells was decreased from (89.4 ±6.6)%to (74.7 ±3.9)%af-ter treated with 5-fluorouracil (P<0.05) and decreased from (77.9 ±2.4)%to (66.7 ±2.9)%after treated with oxali-platin ( P<0.05 ) .The cell apoptotic rate was increased from ( 7.7 ±0.5 )% to ( 12.3 ±3.2 )% and from ( 14.7 ± 2.1)% to (34.0 ±2.1)% when RKO colon cancer cells were treated with 5-fluorouracil and oxaliplatin, respectively (P<0.05).CONCLUSION:Wip1 gene silencing enhances chemotherapy sensitivity of colon cancer cells.

[ ABSTRACT] AIM:To study the process of promoting mouse embryonic stem cells ( ESC) to specify to definitive endoderm by up-regulating of Nodal signal pathway in order to find the best cultivated systems of differentiation of mouse ESC to definitive endoderm cells.METHODS:The cells were divided into different groups based on the culture medium:ESC group ( serum-free medium +LIF) , natural differentiation group ( serum-free medium) and activin A group ( serum-free medium +50μg/L activin A).The cells and the sterilized coverslips with cells were collected at 1, 3, 5 and 7 d of the cultivation.The proportion of CXCR4 +cells was detected by flow cytometry.The expression of CXCR4 was determined by immunocytochemical method, and the protein expression of OCT4 and CXCR4 was detected by Western blot.RE-SULTS:The proportion of CXCR4 +cells showed no dramatic change in ESC group along with the extending of cultivation day, while there were gradually increased in natural differentiation group and activin A group and the highest level was ob-served at 5 d.Among the 3 groups, the proportion of CXCR4 +cells at 5 d was the highest in activin A group.The brown or tan staining in the cells observed under microscope was considered as positive CXCR4 by immunocytochemistry.The pro-tein levels of OCT4 and CXCR4 in ESC group along with the extending of cultivation days was observed.The expression levels of OCT4 were gradually decreased in the cells in natural differentiation group and activin A group, while those of CX-CR4 were gradually increased with the highest level at 5 d.It was highest in the cells in activin A group.CONCLUSION:The proportion of definitive endoderm was the highest at 5 d of the induction during in vitro mouse ESC differentiation.Up-regulation of Nodal signal pathway by adding activin A at the early stage of mouse ESC differentiation promotes mouse ESC to specify to definitive endoderm with CXCR4 molecular marker.

Objective To explore the efficacy and adverse reactions of diminishing scheme of cefaclor sustained re-lease tablets in the treatment of recurrent urinary tract infection(RUTI).Methods 60 RUTI patients in a hospital were divided into treatment group(n=30)and control group (n=30),patients in treatment group were treated with diminishing scheme of cefaclor sustained release tablets,patients in control group were treated with diminishing scheme of levofloxacin tablets,clinical therapeutic efficacy and adverse reactions of two groups were observed. Results The curative rate in treatment group was higher than control group ([80.00%,n =24]vs [53.33%,n =16])(χ2 =4.80,P =0.028).The incidence of RUTI in treatment group was lower than control group ([6.67%,n=2]vs [26.67%,n=8])(χ2 =4.32,P =0.038).Incidence of adverse reactions in treatment group was lower than control group (16.67% vs 50.00%)(χ2 =7.50,P =0.006).Conclusion The diminishing scheme of cefaclor sus-tained release tablets in the treatment of RUTI has good curative efficacy,low recurrence rate,fewer adverse reac-tions,and can be used for the treatment of recurrence of RUTI.

Objective To investigate the clinical characteristics and prognosis of patients with systemic lupus erythematosus (SLE) complicated with acute pancreatitis (AP) .Methods From January 1999 to December 2013 ,the clinical data of 16 patients with SLE complicated with AP among the total 2 526 cases of SLE was collected .A retrospective analysis was performed and the clinical data of patients was classified and documented ,which included general information ,past history ,clinical symptoms , laboratory findings ,imaging findings ,treatment and outcome .The rank sum test was performed for analysis of non‐normal distributed measurement data ,and the Fisher′s exact test was used for count data analysis .Results The incidence of SLE complicated with AP was 0 .63% (16/2 526) .Among them ,ten patients were mild acute pancreatitis (MAP) and six patients were severe acute pancreatitis (SAP) .All patients were treated with fasting ,gastrointestinal decompression ,nutritional support ,anti‐acid ,anti‐inflammatory ,glucocorticoid and somatostatin and so on . Six patients were cured , seven patients improved and three patients died (two SLE complicated with SAP ,one SLE complicated with MAP) . Compared with the SLE patients complicated with SAP ,the SLE patients complicated with MAP were more easily to have lupus nephritis(6/6 versus 5/10 ,Fisher′s exact test) ,hematological system injuries (6/6 versus 5/10 ,Fisher′s exact test) ,liver injuries (5/6 versus 0/10 ,Fisher′s exact test) ,more organs involved (mean 7 versus 3 ,Z= -3 .225) and higher SLE disease active indexes (DAI) score (mean 13 .5 versus 6 .5 ,Z= -2 .876);the differences were statistically significant (all P<0 .05) .Compared with the cured and improved SLE patients complicated with AP ,lupus encephalopathy (2/3 versus 1/13 ,Fisher′s exact test) ,more organs involved (mean 7 versus 5 ,Z= -2 .276) and higher SLE DAI score (mean 21 versus 12 ,Z= -2 .195) was more common in dead SLE patients complicated with AP;the differences were statistically significant (all P< 0 .05) .Conclusions SLE patients complicated with SAP are more easily to get lupus nephritis ,hematological system injuries ,liver injuries ,activity of SLE and multiple‐organ systems involved . The prognosis of SLE patients complicated with AP was poor in those with activity of SLE ,multiple‐organ involved and lupus encephalopathy .

Objective:To evaluate the efficacy and safety of palonosetron in preventing chemotherapy-induced vomiting. Meth-ods:A multi-center, randomized, double-blind, and self-cross-over positively controlled clinical trial design was used. All patients were randomized into two groups, as follows:Regiment A (61 cases) and Regiment B (64 cases). Regimen A with palonosetron hydrochlo-ride injection (test agent) was used in the treatment cycle A, whereas granisetron hydrochloride injection (control drug) was used in the cycle B. Treatments were randomly administered on the patients of the two groups. Regimen B was on the contrary, the control drug was used in the cycle A, and the test agent was used in the treatment cycle B. All patients treated with the test agent were classified as the test group, whereas those treated with the control drug were classified as the control group. Complete control rate and adverse reac-tion of acute and delayed vomiting in the two groups during the two cycles of chemotherapy regimen were compared. Results: In Group One, the complete control rate of delayed vomiting was significantly higher in the palonosetron administration cycles than in the granisetron cycles (76.92%vs. 55.38%, P=0.0110). In the same group, the frequency of vomiting was significantly less in palonosetron cycles than in the granisetron cycles during day 1 to day 5 (1.32±3.42 vs. 1.94±3.03, P=0.0096). The incidences of adverse effects were low in both groups. No grades 3 and 4 adverse effects were observed. Conclusion: Palonosetron showed efficacy in preventing the acute and delayed chemotherapy-induced vomiting. The drug is superior to granisetron, specifically in delaying vomiting in Group One. Palonosetron hydrochloride showed slight adverse effects. Hence, this drug can be used in clinic.

AIM:To investigate the role of side population ( SP) cells in multidrug resistance of colon cancer cells and microRNA biomarkers of SP cells in colon cancer cells .METHODS:SP cells in colon cancer cells were sorted by flow cytometry .The cell viability was measured by MTT method .MicroRNA expression profiles were detected by mi-croRNA chip.MicroRNA expression was verified by real-time PCR.RESULTS:The ratios of SP cells in HCT-15, HT-29 and LoVo colon cancer cell lines were 16.75%, 13.02%and 9.52%, respectively.In all 3 colon cancer cell lines, IC50 of the antitumor drugs including 5-fluorouracil , oxaliplatin and adriamycin for the SP cells were significantly higher than those for non-SP cells (P<0.05).MicroRNA profiling showed that miR-5000-3p, miR-5009-3p and miR-552 were all up-regulated in the SP cells of all 3 colon cancer cell lines .This result was verified by real-time PCR.CONCLUSION:miR-5000-3p, miR-5009-3p and miR-552 are all up-regulated in the SP cells of colon cancer cell lines , and may be the poten-tial microRNA biomarkers of SP cells in colon cancer .