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.

Objective To evaluate the clinical value of epicardial echocardiographic examination in cardiac valve surgery.Methods Epicardial echocardiography were performed in 46 patients undergoing valvular plasty or valvular replacement surgery to estimate the function of valve and left ventricle and residual shunt during cardiac surgery.Results Twelve cases of 46(26.1％)showed abnormality during cardiac surgery.Two cases of 15 patients performed valvuloplasty were changed to valvular replacement because of remarkable regurgitation of native valves.There was 1 case of periprosthetic leakage,3 cases of left atrial appendage thrombus,1 case of patent foramen ovale and 5 cases of low ejection of left ventricle in all 31 cases of valvular replacement.Conclusions Epicardial echocardiograpyc examination is an effective examination in cardiac valve surgery with clearly image,simplicity operation and promptness.

OBJECTIVETo investigate the effectiveness and the safety of clinical use of rhGH in the management of severe burn patients.

METHODSTwo hundred burn patients aged 20 - 25 yrs with TBSA from 20% to 50% and admitted within 5 postburn days (PBD) were enrolled in this study. The patients were divided into operation and non-operation groups. Furthermore, each group was randomly divided into control (N), treatment with rhGH in dosage 0.2 IU/Kg/d (A) and treatment with rhGH in dosage 0.4 IU/kg/d (B) groups. The general data, the metabolism of protein and glucose, the immune function, the urine biochemistry, the wound healing rate and hospital stay days recorded and compared among all groups.

RESULTSPlasma protein was increased, the immune function recovered early, the wound healing time was shortened obviously, the wound healing rate was increased evidently and the hospital stay days were decreased significantly in the treatment groups (A and B groups) compared with the N group. The body weight of burn patients remained unchanged in N group. Nevertheless, the plasma levels of glucose and insulin were increased and the urine output of potassium, sodium and chloride decreased in N group compared with those in A and B groups. Moreover, the levels of all these indices in B group were higher than those in A group, whereas side effects were more common in B group than in A group. In addition, the incidence of adverse reaction was higher in operation group than that in non-operation group.

CONCLUSIONrhGH could effectively promote protein synthesis, enhance systemic immune function, accelerate wound healing and shorten hospital stay days in severely burned patients. But attention should be paid to appropriate dosage and duration of use.

Adult ; Burns ; drug therapy ; immunology ; CD4-CD8 Ratio ; Dose-Response Relationship, Drug ; Growth Hormone ; therapeutic use ; Humans ; Middle Aged ; Wound Healing