[Choice of immediate breast reconstructive methods after modified radical mastectomy].

OBJECTIVE: To investigate the choice of immediate breast reconstructive methods and asso-ciated outcomes after modified radical mastectomy. METHODS: Retrospective analysis of patients undergoing immediate breast reconstruction after modified radical mastectomy in Peking University Third Hospital from January 2009 to May 2019. The reconstructive methods were summarized, and the clinical outcomes and the safety of immediate breast reconstruction were evaluated. RESULTS: One hundred and twenty-three patients were enrolled in this study. Different reconstructive methods were applied according to the clinical stage, the amount of skin removal, the size of contralateral breasts, the physical condition and the preference of the patients. Seventy-nine cases were performed with tissue expander/implant two-stage reconstruction, twenty-three cases received direct breast implant insertion, seven cases were applied for latissimus dorsi (LD) myocutaneous flap transfer combined with implant insertion, five cases were provided transverse rectus abdominis myocutaneous (TRAM) flap transfer, six cases underwent tissue expander/implant combined with endoscopic LD muscle flap transfer, and three cases chose tissue expander/deep inferior epigastric artery perforator (DIEP) flap transfer. The average follow-up time was (12.3±9.0) months (3.5-41.0 months). One patient with direct implant insertion had partial blood supply distur-bance of the mastectomy flap. One case had necrosis of distal end of TRAM zone Ⅳ. One patient with expander/DIEP reconstruction had partial fat liquefaction. And two cases had expander leakage at the end of the expansion period. The tumor local recurrence occurred in one patient, and the implant was finally removed. The outcomes were evaluated by Harris method, and 90.2% patients were good or above in shape evaluation. Among the patients with implant based reconstruction, there was no obvious capsular contracture, and most of the implants had good or fair mobility. CONCLUSION: It is safe and feasible of immediate breast reconstruction after modified radical mastectomy for appropriate cases. The reconstructive methods can be individualized according to the individual's different conditions. The appropriate reconstructive methods could achieve satisfactory results.

[Techniques enhancement for tissue expander/implant two-stage breast reconstruction].

OBJECTIVE: To investigate the outcomes of breast reconstruction with employing improved techniques throughout the tissue expander/implant two-stage breast reconstructed process, which involved the tissue expander placement, the saline filling intraoperatively and postoperatively, the implant selection, and the permanent implant replacement. METHODS: In this study, 68 patients who had been provided immediate or delayed tissue expander/implant two-stage breast reconstruction with autologous fat injection post-mastectomy in Peking University Third Hospital from April 2014 to September 2018 were involved, and the relevant information was analyzed retrospectively. The enhancements of the techniques, involving the incision selection, the expander placement, the principle of expansion, the management of capsule, the prosthesis selection, and the assisted reconstruction method were summarized, and the reconstruction outcomes were evaluated objectively through three-dimensional surface imaging. RESULTS: Among the 68 patients in this study, immediate reconstruction was conducted in 25 patients and 43 patients underwent delayed reconstruction. The median time of tissue expansion was 7.0 (3.0, 20.0) months, and the average volume of expansion was (372.8±87.2) mL. The median size of breast implant was 215 (100, 395) mL. The median number of injections for fat grafting was 1 (1, 3), and the average volume of fat grafting was (119.3±34.1) mL. The median follow-up time was 7.0 (4.0, 24.0) months. During the process of breast reconstruction, the tissue expander leakage was observed in two patients, and one of them underwent expander replacement due to the secondary infection. In the immediate reconstruction cases, the volume symmetry of bilateral breasts after reconstruction got even better than that before mastectomy (t=4.465, P<0.01). And in the delayed reconstruction cases, the volume between bilateral breasts also achieved good symmetry after reconstruction (t=0.867, P>0.1). CONCLUSION: Good results of tissue expander/implant two-stage breast reconstruction could be achieved through the techniques enhancement, which involved the preferred transverse incision, the downward placement of expander, the rapid expansion of chest soft tissue, the release of capsule tension, the application of sizer in prosthesis selection, and the assisted autologous fat grafting.

Mechanisms of glucocorticoid action and insensitivity in airways disease.

Glucocorticoids are the mainstay for the treatment of chronic inflammatory diseases including asthma and chronic obstructive pulmonary disease (COPD). However, it has been recognized that glucocorticoids do not work well in certain patient populations suggesting reduced sensitivity. The ultimate biologic responses to glucocorticoids are determined by not only the concentration of glucocorticoids but also the differences between individuals in glucocorticoid sensitivity, which is influenced by multiple factors. Studies are emerging to understand these mechanisms in detail, which would help in increasing glucocorticoid sensitivity in patients with chronic airways disease. This review aims to highlight both classical and emerging concepts of the anti-inflammatory mechanisms of glucocorticoids and also review some novel strategies to overcome steroid insensitivity in airways disease.

Plasminogen-stimulated airway smooth muscle cell proliferation is mediated by urokinase and annexin A2, involving plasmin-activated cell signalling.

BACKGROUND AND PURPOSE: The conversion of plasminogen into plasmin by interstitial urokinase plasminogen activator (uPA) is potentially important in asthma pathophysiology. In this study, the effect of uPA-mediated plasminogen activation on airway smooth muscle (ASM) cell proliferation was investigated. EXPERIMENTAL APPROACH: Human ASM cells were incubated with plasminogen (0.5-50 µg·mL(-1) ) or plasmin (0.5-50 mU·mL(-1) ) in the presence of pharmacological inhibitors, including UK122, an inhibitor of uPA. Proliferation was assessed by increases in cell number or MTT reduction after 48 h incubation with plasmin(ogen), and by earlier increases in [(3) H]-thymidine incorporation and cyclin D1 expression. KEY RESULTS: Plasminogen (5 µg·mL(-1) )-stimulated increases in cell proliferation were attenuated by UK122 (10 µM) or by transfection with uPA gene-specific siRNA. Exogenous plasmin (5 mU·mL(-1) ) also stimulated increases in cell proliferation. Inhibition of plasmin-stimulated ERK1/2 or PI3K/Akt signalling attenuated plasmin-stimulated increases in ASM proliferation. Furthermore, pharmacological inhibition of cell signalling mediated by the EGF receptor, a receptor trans-activated by plasmin, also reduced plasmin(ogen)-stimulated cell proliferation. Knock down of annexin A2, which has dual roles in both plasminogen activation and plasmin-signal transduction, also attenuated ASM cell proliferation following incubation with either plasminogen or plasmin. CONCLUSIONS AND IMPLICATIONS: Plasminogen stimulates ASM cell proliferation in a manner mediated by uPA and involving multiple signalling pathways downstream of plasmin. Targeting mediators of plasminogen-evoked ASM responses, such as uPA or annexin A2, may be useful in the treatment of asthma.

Secreted factors from human mast cells trigger inflammatory cytokine production by human airway smooth muscle cells.

BACKGROUND: A notable feature of allergic asthma is the infiltration of mast cells into smooth muscle in the human airway. Thus, mast cells and human airway smooth muscle (hASM) cells are likely to exhibit mutual functional modulation via direct cell-cell contact or through released factors. This study examined mast cell modulation of hASM cell cytokine release. METHODS: The mast cell line HMCα was used to model mast cell function. hASM cells were either co-cultured directly with resting or IgE/antigen-stimulated HMCα cells or treated with HMCα-conditioned media to examine the impact on cytokine release. The activation pathways triggered in hASM cells by the mast cell-derived factors were examined through the use of selective inhibitors and by Western blotting. RESULTS: HMCα cells, or their conditioned media, induced the expression of cytokines (IL-8 and IL-6) by hASM cells at both the mRNA and the protein level. Cytokine expression in hASM cells was greatly amplified when HMCα cells were IgE/antigen-activated. The effects of the conditioned media were not mediated by the chemokines MCP-1 and MIP-1α or by exosomes. While the mast cell-derived factor(s) increased p38(MAPK) phosphorylation in hASM cells, cytokine production was not inhibited by the p38(MAPK) inhibitor SB203580. hASM cell production of IL-8 induced by HMCα condition media but not IL-6 was, however, attenuated by the Src tyrosine kinase inhibitor PP2. CONCLUSIONS: Our study shows that the release of soluble mediators by activated mast cells can stimulate hASM cells to elicit production of proinflammatory cytokines that may then exacerbate airway inflammation in asthma.

Increased circulating immunosuppressive CD14(+)HLA-DR(-/low) cells correlate with clinical cancer stage and pathological grade in patients with bladder carcinoma.

This study investigated CD14(+)HLA-DR(-/low) cells in peripheral blood mononuclear cells (PBMCs) from 64 patients with bladder carcinoma (BC) and 14 healthy controls. Cell phenotypes were determined and CD14(+)HLA-DR(-/low) cells, CD14(+)HLA-DR(+) cells and PBMCs depleted of CD14(+)HLA-DR(-/low) cells were isolated. Proliferation of stimulated PBMCs and interferon-γ (IFN-γ) production after addition of CD14(+)HLA-DR(-/low) and CD14(+)HLA-DR(+) cells at different ratios were measured. IFN-γ production was also measured after addition of L-arginine and/or antitransforming growth factor-ß (TGF-ß) neutralizing monoclonal antibody, and in PBMCs depleted of CD14(+)HLA-DR(-/low) cells. The proportion of CD14(+)HLA-DR(-/low) cells in BC patients was significantly higher than in controls. CD14(+)HLA-DR(-/low) cells significantly decreased T-cell proliferation and IFN-γ production in a dose-dependent manner. This suppressive activity was partially reversed by L-arginine or anti-TGF-ß. Enhanced IFN-γ secretion was also seen in PBMCs depleted of CD14(+)HLA-DR(-/low) cells. The level of CD14(+)HLA-DR(-/low) cells was associated with gender, tumour size, number of tumours, cancer pathological grade and clinical stage. CD14(+)HLA-DR(-/low) cells may represent a subpopulation of myeloid-derived suppressor cells in BC patients.

[Urinary RBP and glucocorticoid hormone therapy sensibility in adult primary nephrotic syndrome].

OBJECTIVE: To clarify the relationship between the renal tubular function and the efficacy of glucocorticoid, in adult patients with primary nephrotic syndrome. METHODS: Pro- and post-therapy urinary RBP and NAG were determined double antibodies sandwich ELISA and color comparimetry with p-nitrate reductase, respectively, in eighty adult patients with primary nephritic syndrome, according to the concentrations of urinary protein, these patients were divided into three no remission group, partial remission group and fully remission group, fifty-one normal persons as control group. Renal tubular function parameters among groups were compared before and after therapy, and the results were analysed when those parameters were used to predict the sensibility of glucocorticoid therapy. RESULTS: 1. There were no significant differences in urinary RBP, NAG and protein levels before treatment among patient groups (P > 0.05); 2. There were significant decreases in urinary RBP and NAG following glucocorticoid therapy in those response to glucocorticoid (P < 0.01); 3. There were significant differences in urinary protein, RBP and NAG among three groups of patients with primary nephrotic syndrome after treatment. CONCLUSION: Determination of urinary RBP may predict the sensibility of the therapy in the adult patients with primary nephrotic syndrome and its diagnostic efficiency is better than urinary NAG.

[Effects on ang II receptor antagonist on experimental glomerulosclerosis].

OBJECTIVE: To observe the effects of angiotensin II receptor antagonist losartan in experimental glomerulosclerosis. METHODS: The 5/6 nephrectomized rats were randomly divided into losartan treatment group and control group, the rats with sham operation served as normal control. Urine proteins were measured in the 2nd, 4th and 6th week after operation, and serum BUN, creatinine, total protein and albumin were measured in the 6th week following operation. Renal pathologic changes were evaluated in the 6th week. RESULTS: Losartan not only reduced urine protein, serum creatinine and BUN(P < 0.01), but also significantly ameliorated glomerular mesangial proliferation and glomerular sclerosis. CONCLUSION: The results suggest that losartan can retard progression of glomerulosclerosis in 5/6 nephrectomized rats.

[Therapeutic effects of Chinese drugs on early renal damage of rats caused by fish bile].

The therapeutic effects of Salvia miltiorrhizae, Typha angustifolia, Rheum palmatum preparations on early renal damage of rats caused by fish bile were observed. These drugs were effective in reducing serum creatinine, urinary NAGase, count of necrosed epithelial cells of proximal tubule and that of glomerular filled with RBC in Bowman's space (P < 0.05), and also effective in increasing creatinine clearance (P < 0.05).

Effect of a traditional Chinese medicine, yin zhi huang, on bilirubin clearance and conjugation.

Oral administration of Yin Zhi Huang (YZH) daily for 3 days in rabbits accelerated plasma clearance of infused unconjugated bilirubin. A similar but less dramatic effect resulted from 3 days pretreatment with phenobarbital, 70 mg/kg/day orally. Similar doses were injected intraperitoneally in rats for 3 days, following which the bile ducts were ligated and bilirubin infused intravenously. Plasma clearance of unconjugated bilirubin and plasma appearance of conjugated bilirubin were faster, and hepatic bilirubin content was higher in both YZH- and phenobarbital-treated rats than in control animals. These observations indicate that YZH is as effective as phenobarbital in stimulating bilirubin metabolic pathways and suggest that the drugs may share common mechanisms of action.