Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

OBJECTIVETo analyze a girl with moderate mental retardation and speech and language disorders with cytogenetics technique and next-generation sequencing (NGS).

METHODSG-banding chromosome analysis was used to ascertain the karyotype of the child and her parents, and NGS was used for determining the size and origin of the abnormal chromosome fragment. Mate-pair and PCR were used to determine its parental origin.

RESULTSThe karyotype of the child was determined to be 46,XX,add(1)(q44)dn, while her parents were both normal. NGS revealed that the child has harbored a partial trisomy of 6q24.3-q27, and the breakpoint was mapped to at 6q24.3q27. In addition, a 2.5 Mb microdeletion at 1q44 was found in the patient.

CONCLUSIONNo recognizable phenotype was associated with 1q44 deletion. The abnormal phenotypes presented by the child may be attributed to the 6q24.3-q27 triplication. Compared with conventional cytogenetic analysis, NGS has a much higher resolution and great accuracy.

Adult ; Child ; Chromosome Banding ; Chromosome Disorders ; genetics ; Chromosomes, Human, Pair 1 ; genetics ; Chromosomes, Human, Pair 6 ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Intellectual Disability ; genetics ; Male ; Monosomy ; genetics ; Trisomy ; genetics

Objective To investigate the distribution and antimicrobial resistance of multidrug‐resistant organisms(MDROs) . Methods The distribution and antimicrobial resistance of MDROs ,isolated from 2010 to 2014 ,were retrospectively analyzed . MDROs were identified according to international consensus .The WHONET5 .6 software was used to analyze data .Results A to‐tal of 5 709 strains of MDROs were isolated in five years ,in which 2 441 strains were Staphylococcus(42 .76% ) ,2 091 strains were non‐fermentive bacterial(36 .63% ) ,737 strains were Enterococcus(12 .90% ) ,440 strains were Enterobacter(7 .71% ) .Of the 5 709 MDROs isolates ,55 .04% were isolated from respiratory tract specimens .The resistant rate of multidrug‐resistant E .coli and K . pneumoniae against cefoperazone/sulbactam ,imipenem and meropenem was less than 30% .The resistance of multidrug‐resistant A . baumanii was higher than 90% ,except to minocycline and cefoperazone/sulbactam ,20 .2% and 50 .6% respectively .The resistant rate of multidrug‐resistant P .aeruginosa was 71 .4% -97 .0% against other antimicrobial agents ,except to polymyxin B .The resist‐ance of multidrug‐resistant E .faecium against the antimicrobials was higher than 90% ,except 13 .8% to minocycline and less than 3% to linezolid ,teicoplanin and vancomycin .Meanwhile ,1 linezolid resistant strain was identified in 1 914 methicillin resistant S .au‐reus(MRSA) strains and all MRSA strains were susceptible to vancomycin and teicoplanin .Conclusion MDROs could be predomi‐nated by A .bauman and MRSA in this hospital .Monitoring and control measures to healthcare‐associated infections should be in‐tensified to prevent the spread of MDROs .

Objective To observe the effects of adiponectin on mRNA and protein expressions of connective tissue growth factor (CTGF) in hepatic stellate cells (HSCs) and the levels of procollagen type Ⅲ (PC Ⅲ) and hyaluronic acid (HA).Methods Cultured rat HSCs were treated with different concentrations of adiponectin.CTGF mRNA and protein expressions were analyzed by reverse transcription polymerase chain reaction (RT-PCR) and Western Blot.The levels of PCⅢ and HA were detected by enzymelinked immunosorbent assay (ELISA).Results Compared with the control group,the result of RT-PCR showed that the four groups had different degrees of inhibitory effect,of which group D exhibited the strongest inhibitory effect.The absorbance ratio was 1.54 ±0.18,1.21 ±0.14,0.96 ±0.10,and 0.79 ± 0.08,respectively (t =2.42,P ＜0.05;t =2.73,P ＜0.05;t =3.28,P ＜0.01;t =4.67,P ＜0.01).Western Blot also indicated that four groups had different degrees of inhibitory effect,of which D group exhibited the strongest inhibitory effect.The ratio of integral absorption was 1.54 ± 0.18,1.21 ±0.14,0.96±0.10,and 0.79 ±0.08,respectively (t =2.84,P ＜0.01;t =4.05,P ＜0.01;t =6.25,P ＜0.01;t =9.72,P ＜0.01).The levels of PCⅢ and HA secreted in culture media were also decreased.It was significantly decreased with the concentration of adiponectin increased.Conclusion Adiponectin can inhibit the levels of PC Ⅲ and HA,which may be achieved through reducing CTGF mRNA and protein expressions.

Objective To study the expression of BCSG1 ,S100A4,VEGF in human breast cancer.Methods Immunohistochemistry technique SP method was used to examine breast fibroadenoma in 40 cases,breast invasive ductal carcinoma in 62 cases ( by armpit lymph node metastasis as 2 groups) and corresponding paratumor tissues in 48 cases. Results Among the 4 groups, there was significant difference ( P＜0.05 ) in the positive immunostaining rate of BCSG1 ,S100A4, VEGF. Conclusions In the breast invasive ductal carcinoma, the expression of BCSG1, S100A4 and VEGF increased. This suggested the invasive and metastasis ability of the neoplasm enhanced. The expression were in positive correlation with tumor pathology. Combined detection of BCSG1, S100A4, VEGF expression contributes to the early diagnosis and prognostic assessment of the carcinoma of the breast.

Objective To study the relationship between the changes of diffusion tensor imaging(DTI)and diffusion tensor tractography(DTT)of optic radiation and the defect of visual field.Methods DTI and DTT were performed in 37 patients with invasion of the optic radiation by intracranial lesions and in 20 normal control group at 3.0T MR scanner,the visual fields of all cases were examined.The relativity between FA values,ADC values and mean sensitivity(MS)values,mean defect(MD)values of visual field and the relativity between the morphological change of optic radiation and the defect of visual field were analysed.Results In comparison with control group,FA values decreased and ADC values increased in subject group,there were statistically significant differences(P＜0.001)between them.In disordered group,FA values were positive correlation with MS values(r=0.718)and negative correlation with MD values(r=-0.694);ADC values were negative correlation with MS values(r=-0.625)and positive correlation with MD values(r=0.538).DTT showed that the ventral tracts of optic radiation were damaged which oppeared as the defect of ditto quadrant of bilateral field vision in 9 cases,the dorsal tracts and the lateral tracts of optic radiation were damaged which appeared as the defect of inferior quadrant of bilateral field vision in 7 cases,the optic radiations were damaged extensively that caused symmetric or asymmetric congruous hemianopia of bilateral field vision in 21 cases.Conclusion DTI and DTT of optic radiation are intimately correlated with the examined results of visual field,it will be a objective index to extimate the function and the morphological changes of optic radiation.

Objective In attempt to improve the reconstruction of small defects in the facial and frontal regions, we developed a modified radial artery perforator-based free flap. Methods The free proxi-mal radial forearm flap was based on the distal perforator of the radial artery and the concomitant radial vein. The vascular pedicle passed through deep fascia. The free flap was transferred to repair the defects of the fa-cial and frontal regions. Results In 6 patients with frontal defects and 4 patients with facial defects, all flaps survived completely. After following up for 6-12 months, flaps underwent plastic surgery to become thin-ner. The flaps of 10 cases were good in skin texture and color at recipient sites. The scars were cosmetically acceptable. The superficial sensibility recovered well. Conclusion A modified radial artery perforator-based free flap was useful in coveting small defects of the facial and frontal regions.

OBJECTIVE To understand flora distribution and four antifungal drugs′in vitro antifungal activity of deep fungi in nosocomial infection in order to provide help to clinics.METHODS Fungi were cultured and isolated by routine procedure which identified by VITEK microbe automatic system.Drug susceptibility test used Rosco paper disk diffusion and broth dilution method with NCCLS M27-A.RESULTS Totally 156 strains with 9 species of deep fungi that main fungi were Candida albicans,and C.tropicalis with 57.69%,and 31.41%,respectively,were isolated from nosocomial infection.The major isolating rates of clinical infection specimens were from respiratory,cardiovascular surgery,and neurological departments with 26.28%,12.18%,and 9.62%,respectively.The main infection specimens were from respiratory tract and urinary tract with 71.15% and 16.67%,respectively.Drug resistance rates to fluconazole,amphotericin B,itraconazole,and ketoconazole with Rosco paper disk diffusion were 23.08%,2.56%,12.18%,and 17.36%,MIC90 were 64.0,2.0,8.0,and 16.0mg/L,respectively.CONCLUSIONS The main deep fungi are C.albicans and C.tropicalis.Antifungal activity of amphotericin B is the highest than others.The drug resistance rate to fluconazole is more and more higher.Clinics should use antifungal drug rationally in accordance with drug susceptibility test results.

Objective To evaluate the toxic effects and efficacy of the intra-arterial chrono-chemotherapy on patients with liver metastasis arised from colorectal cancer. Methods Chemotherapy of 42 patients were randomly divided into group A (n = 20) with continuously constant arterial infusion, and group B (n = 22) with arterial chrono-modulated infusion. And the toxic effects and efficacy of two groups were compared. Results A significant difference was found in the toxic effects of digestive system between the two groups. The treatment response was similar in the two groups. Conclusions Intra-arterial chrono-chemotherapy may decrease the toxic effects and improve the life quality of these patients.

Objective To investgate the value of interventional therapy in inferior vena cava stenosis or obstruction caused by tumor and management after the operation. Methods 53 patients with IVC stenosis caused by tumor had detailed information. After the guide wire passed through the stenosised part and then undergoing balloon expansion, Gianturco Z stents or wallstents were implanted to undergo venography and measuring pressure after that. Results Technical success was attained in 50 patients, 3 cases was failure because the guide wire couldn't pass through the obstructed region.The technical success rate is 94.3%. 2 patients with IVC stenosis over 10 cm length was placed two stents. In other 48 patients,everyone was placed one stent. The pressure of IVC dropped from (28.66?4.08)cm H 2O (1 cm H 2O =0.098 kPa) before operation to (17.65?4.18)cm H 2O after operation. Through t examination, the difference of IVC pressure before and after treatment has statistic significance( t =3.261, P